phenobarbital (Rx)

Brand and Other Names:
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet: Schedule IV

  • 15mg
  • 16.2mg
  • 30mg
  • 32.4mg
  • 60mg
  • 64.8mg
  • 97.2
  • 100mg

elixir: Schedule IV

  • 20mg/5mL

injectable solution: Schedule IV

  • 65mg/mL
  • 130mg/mL

Status Epilepticus

Typically used after benzodiazepines and phenytoin fail to abort status epilepticus

15-20 mg/kg IV loading dose infused at 25-100 mg/min; may repeat once after 10 min with additional 5-10 mg/kg; respiratory support may be necessary when maximum dose administered  

Seizures

All types of seizure disorders, including partial, tonic-clonic, and myoclonic seizures

1-3 mg/kg/day PO/IV in 1-2 divided doses initially; adjust accordingly to maintain at a therapeutic steady state level of 20 mg/L  

Sedation

30-120 mg/day PO divided BID/TID; do not exceed 400 mg/day

Hypnotic

100-320 mg/day PO/IV/IM; do not administer for >2 weeks

Insomnia

100-200 mg PO qHS; do not exceed 400 mg/day

Dosing Considerations

Antiepileptic therapeutic concentration range: 10-40 mcg/L (43-172 micromoles/L)

Long half-life permits once-daily dosing, if tolerated, for seizures; single daily dosing at bedtime recommended because of sedation

Dosage Forms & Strengths

tablet: Schedule IV

  • 15mg
  • 16.2mg
  • 30mg
  • 32.4mg
  • 60mg
  • 64.8mg
  • 97.2mg
  • 100mg

elixir: Schedule IV

  • 20mg/5mL

injectable solution: Schedule IV

  • 65mg/mL
  • 130mg/mL

Status Epilepticus

Infants and children: 15-20 mg/kg IV infused at a rate not to exceed 2 mg/kg/min; not to exceed 1000 mg/dose  

<60 kg: IV rate at <30 mg/min

May repeat with 5-10 mg/kg bolus dose after 15-30 min PRN; not to exceed cumulative dose of 40 mg/kg

Seizures

Neonates (<28 days): 3-5 mg/kg/day IV/PO in 1-2 divided doses

Infants: 5-6 mg/kg/day IV/PO in 1-2 divided doses

1-5 years: 6-8 mg/kg/day IV/PO in 1-2 divided doses

6-12 years: 4-6 mg/kg/day IV/PO in 1-2 divided doses

>12 years: 1-3 mg/kg/day IV/PO in 1-2 divided doses, OR 50-100 mg BID/TID

Sedation

2 mg/kg PO TID  

Hypnotic

3-5 mg/kg PO HS  

Preoperative Sedation

1-3 mg/kg PO/IV/IM 1-1.5 hours before procedure  

Dosing Considerations

<6 years: Potential toxic dose 8 mg/kg

Antiepileptic therapeutic concentration range: 15-30 mcg/L (43-129 micromoles/L)

Long half-life permits once-daily dosing, if tolerated, for seizures; single daily dosing at bedtime recommended because of sedation

Hyperbilirubinemia (Off-label)

Neonates: 5 mg/kg/day PO/IV qDay, OR divided q12hr for 3-6 days following birth

<12 years (chronic cholestasis): 1.5-4 mg/kg PO q12hr  

Encephalopathy (Orphan)

Orphan designation for treatment of neonatal hypoxic ischemic encephalopathy to prevent seizures

Orphan sponsor

  • Fera Pharmaceuticals, LLC; 134 Birch Hill Road; Locust Valley, NY 11560

Neonatal Seizures (Orphan)

Orphan designation for treatment of neonatal seizures

Sponsor

  • Renaissance SSA, LLC; 411 South State Street, Suite E100; Newtown, Pennsylvania 18940
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Interactions

Interaction Checker

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            Contraindicated (31)

            • artemether/lumefantrine

              phenobarbital will decrease the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with strong CYP3A4 inducers can result in decreased serum concentrations and loss of antimalarial efficacy

            • atazanavir

              phenobarbital will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • cabotegravir

              phenobarbital will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

            • calcium/magnesium/potassium/sodium oxybates

              phenobarbital, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Prescribing information for sodium oxybate states coadministration with alcohol or insomnia drugs is contraindicated because of additive CNS depression.

            • cariprazine

              phenobarbital will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • cobimetinib

              phenobarbital will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

            • darunavir

              phenobarbital will decrease the level or effect of darunavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with phenobarbital may result in loss of therapeutic effect and development of resistance to darunavir

            • dienogest/estradiol valerate

              phenobarbital will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • doravirine

              phenobarbital will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • elbasvir/grazoprevir

              phenobarbital will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              phenobarbital decreases levels of elvitegravir/cobicistat/emtricitabine/tenofovir DF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. May lead to loss of virologic response and possible resistance.

            • etravirine

              phenobarbital decreases levels of etravirine by increasing metabolism. Contraindicated.

            • fostemsavir

              phenobarbital will decrease the level or effect of fostemsavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of fostemsavir (prodrug) with strong CYP3A4 inducers significantly decreases temsavir (active moiety) plasma concentrations, which may lead to loss of virologic response and resistance.

            • isavuconazonium sulfate

              phenobarbital will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • ledipasvir/sofosbuvir

              phenobarbital will decrease the level or effect of ledipasvir/sofosbuvir by P-glycoprotein (MDR1) efflux transporter. Contraindicated. P-gp inducers decrease sofosbuvir levels, and therefore decrease conversion to sofosbuvir's active metabolite (GS-331007) responsible for 90% of pharmacologic effect

            • lonafarnib

              phenobarbital will decrease the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inducers is contraindicated.

            • lorlatinib

              phenobarbital will decrease the level or effect of lorlatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of lorlatinib with strong CYP3A inducers is contraindicated. Discontinue the strong CYP3A inducer for 3 plasma half-lives before initiating lorlatinib.

            • lumacaftor/ivacaftor

              phenobarbital will decrease the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A inducers have minimal effect on lumacaftor exposure, but decreased ivacaftor exposure (AUC) by 57%. This may reduce the effectiveness of lumacaftor/ivacaftor. Therefore, coadministration is not recommended.

            • lumefantrine

              phenobarbital will decrease the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with strong CYP3A4 inducers can result in decreased serum concentrations and loss of antimalarial efficacy

            • lurasidone

              phenobarbital decreases levels of lurasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated.

            • naloxegol

              phenobarbital will decrease the level or effect of naloxegol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Use of naloxegol with strong CYP3A4 inducers is not recommended

            • ombitasvir/paritaprevir/ritonavir & dasabuvir

              phenobarbital will decrease the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir by increasing metabolism. Contraindicated. Strong CYP2C8 inducers may reduce dasabuvir levels, and therefore decreased efficacy of Viekira Pak

              phenobarbital will decrease the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inducers may reduce partiaprevir and ritonavir levels, and therefore decreased efficacy of Viekira Pak

            • panobinostat

              phenobarbital decreases levels of panobinostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inducers can reduce panobinostat levels by ~70% and lead to treatment failure.

            • pirfenidone

              phenobarbital will decrease the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Use of strong CYP1A2 inducers should be discontinued before initiating pirfenidone and avoided during treatment

            • praziquantel

              phenobarbital decreases levels of praziquantel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP450 inducers significantly decrease praziquantel blood levels.

            • regorafenib

              phenobarbital, regorafenib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inducers decrease regorafenib levels and increase exposure of the active metabolite M-5.

            • rilpivirine

              phenobarbital decreases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Rilpivirine should not be co-administered with strong CYP 3A4 inducers. Potential for loss of virologic response and possible resistance to rilpivirine or to the NNRTI class.

            • roflumilast

              phenobarbital will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectiveness

              phenobarbital will decrease the level or effect of roflumilast by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectiveness

            • sodium oxybate

              phenobarbital, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Prescribing information for sodium oxybate states coadministration with alcohol or insomnia drugs is contraindicated because of additive CNS depression.

            • vandetanib

              phenobarbital decreases levels of vandetanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with potent CYP3A4 inducers; these drugs reduce exposure to vandetanib by up to 40%.

            • voriconazole

              phenobarbital decreases levels of voriconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            Serious - Use Alternative (163)

            • abemaciclib

              phenobarbital will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.

            • acalabrutinib

              phenobarbital will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.

            • afatinib

              phenobarbital decreases levels of afatinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Increase afatinib daily dose by 10 mg as tolerated if chronic therapy with P-gp inducer required; resume previous afatinib dose 2-3 days after P-gp inducer discontinued.

            • alosetron

              phenobarbital will decrease the level or effect of alosetron by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • alpelisib

              phenobarbital will decrease the level or effect of alpelisib by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration of alpelisib (CYP3A4 substrate) with strong CYP3A4 inducers.

              phenobarbital will decrease the level or effect of alpelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • antithrombin alfa

              phenobarbital decreases effects of antithrombin alfa by increasing metabolism. Avoid or Use Alternate Drug.

            • antithrombin III

              phenobarbital decreases effects of antithrombin III by increasing metabolism. Avoid or Use Alternate Drug.

            • apalutamide

              apalutamide will decrease the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP2C19 inducer, with drugs that are CYP2C19 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered.

            • apixaban

              phenobarbital will decrease the level or effect of apixaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • apremilast

              phenobarbital will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy

            • argatroban

              phenobarbital decreases effects of argatroban by increasing metabolism. Avoid or Use Alternate Drug.

            • avapritinib

              phenobarbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • axitinib

              phenobarbital decreases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Selection of concomitant medication with no or minimal CYP3A4 induction potential is recommended.

            • bedaquiline

              phenobarbital will decrease the level or effect of bedaquiline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of bedaquiline with strong CYP3A4 inducers due to potential for decreased therapeutic effect

            • bemiparin

              phenobarbital decreases effects of bemiparin by increasing metabolism. Avoid or Use Alternate Drug.

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, phenobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • berotralstat

              phenobarbital decreases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • bictegravir

              phenobarbital will decrease the level or effect of bictegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of strong CYP3A and UGT1A1 inducers can substantially decrease bictegravir plasma concentrations. This may result in the loss of therapeutic effect and development of resistance to bictegravir. Coadministration with another anticonvulsant should be considered.

            • bivalirudin

              phenobarbital decreases effects of bivalirudin by increasing metabolism. Avoid or Use Alternate Drug.

            • bosutinib

              phenobarbital decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85%.

            • bremelanotide

              bremelanotide will decrease the level or effect of phenobarbital by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

            • brigatinib

              phenobarbital will decrease the level or effect of brigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP3A4 inducers may decrease brigatinib efficacy.

            • cabozantinib

              phenobarbital will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.

            • capmatinib

              phenobarbital will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ceritinib

              phenobarbital decreases levels of ceritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • cobicistat

              phenobarbital will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is necessary, monitor for lack or loss of virologic response from cobicistat

            • copanlisib

              phenobarbital will decrease the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of copanlisib with strong CYP3A4 inducers.

            • dabigatran

              phenobarbital will decrease the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration. P-gp inducers reduce systemic exposure of dabigatran

            • dabrafenib

              phenobarbital decreases levels of dabrafenib by increasing metabolism. Avoid or Use Alternate Drug. Strong CYP2C8 inducers may decrease dabrafenib levels.

              phenobarbital decreases levels of dabrafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • dalteparin

              phenobarbital decreases effects of dalteparin by increasing metabolism. Avoid or Use Alternate Drug.

            • dantrolene

              phenobarbital will decrease the level or effect of dantrolene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • darolutamide

              phenobarbital will increase the level or effect of darolutamide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a P-gp and CYP3A4 substrate. Avoid coadminstration of darolutamide with combined P-gp and strong or moderate CYP3A4 inducers.

            • deflazacort

              phenobarbital will decrease the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of deflazacort with moderate or strong CYP3A4 inducers.

            • dexlansoprazole

              phenobarbital will decrease the level or effect of dexlansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • dihydroergotamine

              phenobarbital will decrease the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • dihydroergotamine intranasal

              phenobarbital will decrease the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • dolutegravir

              phenobarbital will decrease the level or effect of dolutegravir by increasing metabolism. Avoid or Use Alternate Drug. Avoid coadministration; insufficient data to recommend dosage adjustment

            • dronedarone

              phenobarbital will decrease the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • duloxetine

              phenobarbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • duvelisib

              phenobarbital will decrease the level or effect of duvelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inducer decreases duvelisib area under the curve (AUC), which may reduce duvelisib efficacy.

            • edoxaban

              phenobarbital will decrease the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration of edoxaban with potent P-gp inducers

            • eliglustat

              phenobarbital will decrease the level or effect of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers significantly decreases eliglustat exposure; coadministration not recommended

            • elvitegravir

              phenobarbital will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

            • encorafenib

              phenobarbital will decrease the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • enoxaparin

              phenobarbital decreases effects of enoxaparin by increasing metabolism. Avoid or Use Alternate Drug.

            • entrectinib

              phenobarbital will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • enzalutamide

              phenobarbital will decrease the level or effect of enzalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erdafitinib

              phenobarbital will decrease the level or effect of erdafitinib by altering metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP2C9 or CYP3A4 inducers with erdafitinib.

            • ergotamine

              phenobarbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin base

              phenobarbital will decrease the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

              phenobarbital will decrease the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              phenobarbital will decrease the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin stearate

              phenobarbital will decrease the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • esomeprazole

              phenobarbital will decrease the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • eszopiclone

              phenobarbital will decrease the level or effect of eszopiclone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ethinylestradiol

              phenobarbital will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • everolimus

              phenobarbital will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              phenobarbital will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

            • fedratinib

              phenobarbital will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • fexinidazole

              phenobarbital will increase the level or effect of fexinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP450 inducers may significantly increase plasma concentrations of fexinidazole?s active metabolites: fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2). M2 plasma concentrations associated with increased QT prolongation risks.

            • finerenone

              phenobarbital will decrease the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • flurazepam

              phenobarbital will decrease the level or effect of flurazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • fondaparinux

              phenobarbital decreases effects of fondaparinux by increasing metabolism. Avoid or Use Alternate Drug.

            • fostamatinib

              phenobarbital will decrease the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • gilteritinib

              phenobarbital will decrease the level or effect of gilteritinib by Other (see comment). Avoid or Use Alternate Drug. Gilteritinib is a P-gp and CYP3A4 substrates. Coadministration of gilteritinib with a combined P-gp and strong CYP3A inducer decreases gilteritinib exposure and efficacy.

            • glasdegib

              phenobarbital will decrease the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of glasdegib with strong CYP3A inducers.

            • heparin

              phenobarbital decreases effects of heparin by increasing metabolism. Avoid or Use Alternate Drug.

            • hydrocodone

              hydrocodone, phenobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • ibrutinib

              phenobarbital decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

            • idelalisib

              phenobarbital will decrease the level or effect of idelalisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration; strong CYP3A4 inducers significantly decrease idelalisib systemic exposure

            • infigratinib

              phenobarbital will decrease the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • irinotecan

              phenobarbital will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • irinotecan liposomal

              phenobarbital will decrease the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • isocarboxazid

              isocarboxazid, phenobarbital. Other (see comment). Avoid or Use Alternate Drug. Comment: CNS depressants such as barbiturates should not be used in combination with isocarboxazid.

            • isosorbide dinitrate

              phenobarbital will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • isosorbide mononitrate

              phenobarbital will decrease the level or effect of isosorbide mononitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • istradefylline

              phenobarbital will decrease the level or effect of istradefylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of istradefylline with strong CYP3A4 inducers.

            • ivabradine

              phenobarbital will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.

            • ivacaftor

              phenobarbital decreases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers; systemic exposure of ivacaftor substantially reduced (ie, ~9-fold).

            • ivosidenib

              phenobarbital will decrease the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ivosidenib with strong CYP3A4 inducers decreased ivosidenib plasma concentrations.

            • ixazomib

              phenobarbital will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

            • larotrectinib

              phenobarbital will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

            • lefamulin

              phenobarbital will decrease the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lefamulin with strong or moderate CYP3A inducers unless the benefit outweighs risks. Monitor for reduced efficacy.

            • lemborexant

              phenobarbital will decrease the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • letermovir

              phenobarbital will decrease the level or effect of letermovir by Other (see comment). Avoid or Use Alternate Drug. Coadministration of letermovir with UCT1A1/3 inducers is not recommended.

              phenobarbital will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

            • lomitapide

              phenobarbital will decrease the level or effect of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lovastatin

              phenobarbital will decrease the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lurbinectedin

              phenobarbital will decrease the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • macimorelin

              phenobarbital will decrease the level or effect of macimorelin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for false positive test results if macimorelin and strong CYP3A4 inducers are coadministered. Discontinue strong CYP3A4 inducer, allowing for sufficient washout time, before testing.

            • macitentan

              phenobarbital will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • mestranol

              phenobarbital decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

            • methoxyflurane

              phenobarbital increases toxicity of methoxyflurane by increasing metabolism. Contraindicated. Increased metabolism of methoxyflurane to nephrotoxic compounds.

            • metoclopramide intranasal

              phenobarbital, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

            • midostaurin

              phenobarbital will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.

            • mobocertinib

              phenobarbital will decrease the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • modafinil

              phenobarbital will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • naldemedine

              phenobarbital will decrease the level or effect of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers.

            • neratinib

              phenobarbital will decrease the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inducers.

            • netupitant/palonosetron

              phenobarbital will decrease the level or effect of netupitant/palonosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Netupitant is mainly metabolized by CYP3A4; avoid use in patients who are chronically using a strong CYP3A4 inducer

            • nintedanib

              phenobarbital decreases levels of nintedanib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration, particularly for P-gp inducers that are also CYP3A4 inducers; nintedanib is a substrate of P-gp and to a less extent CYP3A4.

            • norethindrone

              phenobarbital will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

            • norethindrone acetate

              phenobarbital will decrease the level or effect of norethindrone acetate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

            • norethindrone transdermal

              phenobarbital will decrease the level or effect of norethindrone transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

            • olaparib

              phenobarbital will decrease the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olaparib with strong CYP3A4 inducers.

            • omeprazole

              phenobarbital will decrease the level or effect of omeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • osimertinib

              phenobarbital will decrease the level or effect of osimertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of osimertinib with strong CYP3A inducers.

            • ozanimod

              phenobarbital will decrease the level or effect of ozanimod by Other (see comment). Avoid or Use Alternate Drug. Coadministration of ozanimod (a CYP2C8 substrate) with strong CYP2C8 inducers decreases the exposure of the active metabolites (CC112273 and CC1084037) of ozanimod, which may decrease the effiicacy of ozanimod. Therefore, coadministration of ozanimod with strong CYP2C8 inducers is not recommended.

            • palbociclib

              phenobarbital will decrease the level or effect of palbociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease palbociclib plasma exposure by ~85%.

            • pemigatinib

              phenobarbital will decrease the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • perampanel

              phenobarbital will decrease the level or effect of perampanel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • pexidartinib

              phenobarbital will decrease the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • phenindione

              phenobarbital decreases effects of phenindione by increasing metabolism. Avoid or Use Alternate Drug.

            • pomalidomide

              phenobarbital decreases levels of pomalidomide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              phenobarbital decreases levels of pomalidomide by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • ponatinib

              phenobarbital decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.

            • pralsetinib

              phenobarbital will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

            • pretomanid

              phenobarbital will decrease the level or effect of pretomanid by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Pretomanid is a CYP3A4 substrate. Avoid coadministration of strong or moderate CYP3A4 inducers

            • protamine

              phenobarbital decreases effects of protamine by increasing metabolism. Avoid or Use Alternate Drug.

            • ranolazine

              phenobarbital will decrease the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ribociclib

              phenobarbital will decrease the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ribociclib with strong CYP3A inducers should be avoided.

            • rimegepant

              phenobarbital will decrease the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ripretinib

              phenobarbital will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.

            • rivaroxaban

              phenobarbital will decrease the level or effect of rivaroxaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • rolapitant

              phenobarbital will decrease the level or effect of rolapitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Long-term coadministration of strong CYP3A4 inducers with rolapitant may significantly decrease rolapitant efficacy.

            • romidepsin

              phenobarbital will decrease the level or effect of romidepsin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • selinexor

              selinexor, phenobarbital. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

            • selpercatinib

              phenobarbital will decrease the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • selumetinib

              phenobarbital will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • sildenafil

              phenobarbital will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potent CYP3A4 inducers are expected to cause substantial decreases in sildenafil plasma levels

            • silodosin

              phenobarbital will decrease the level or effect of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • simvastatin

              phenobarbital will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • siponimod

              phenobarbital will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • sirolimus

              phenobarbital will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • sofosbuvir

              phenobarbital will decrease the level or effect of sofosbuvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. P-gp inducers decrease sofosbuvir levels, and therefore decrease conversion to sofosbuvir's active metabolite (GS-331007) responsible for 90% of pharmacologic effect

            • sofosbuvir/velpatasvir

              phenobarbital will decrease the level or effect of sofosbuvir/velpatasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Sofosbuvir and velpatasvir are substrates of the drug transporter P-gp. Potent P-gp inducers may significantly decrease sofosbuvir and velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              phenobarbital will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              phenobarbital will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

            • sonidegib

              phenobarbital will decrease the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sonidegib with strong or moderate CYP3A4 inducers.

            • sorafenib

              phenobarbital will decrease the level or effect of sorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • sotorasib

              phenobarbital will decrease the level or effect of sotorasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • stiripentol

              phenobarbital will decrease the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of stiripentol with strong CYP3A4 inducers, increase stiripentol dose.

              phenobarbital will decrease the level or effect of stiripentol by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of stiripentol with strong CYP1A2 inducers, increase stiripentol dose.

              stiripentol, phenobarbital. Either increases effects of the other by sedation. Avoid or Use Alternate Drug. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

            • sufentanil SL

              sufentanil SL, phenobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • tamsulosin

              phenobarbital will decrease the level or effect of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tazemetostat

              phenobarbital will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tepotinib

              phenobarbital will decrease the level or effect of tepotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tetracycline

              phenobarbital will decrease the level or effect of tetracycline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tezacaftor

              phenobarbital will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tivozanib

              phenobarbital will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tizanidine

              phenobarbital will decrease the level or effect of tizanidine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • tolvaptan

              phenobarbital will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • trabectedin

              phenobarbital will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tucatinib

              phenobarbital will decrease the level or effect of tucatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              phenobarbital will decrease the level or effect of tucatinib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of tucatinib (a CYP2C8 substrate) with a strong or moderate CYP2C8 inducer decreases tucatinib plasma concentrations.

            • ubrogepant

              phenobarbital will decrease the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ulipristal

              phenobarbital will decrease the level or effect of ulipristal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • upadacitinib

              phenobarbital will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.

            • valbenazine

              phenobarbital will decrease the level or effect of valbenazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Concomitant use not recommended.

            • valerian

              valerian increases effects of phenobarbital by pharmacodynamic synergism. Avoid or Use Alternate Drug. May enhance CNS depression.

            • velpatasvir

              phenobarbital will decrease the level or effect of velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • vemurafenib

              phenobarbital decreases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • venetoclax

              phenobarbital will decrease the level or effect of venetoclax by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of venetoclax with strong or moderate CYP3A inducers. Consider alternative treatment with agents that have less CYP3A induction.

            • voclosporin

              phenobarbital will decrease the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • vorapaxar

              phenobarbital decreases levels of vorapaxar by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • vortioxetine

              phenobarbital will decrease the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • voxelotor

              phenobarbital will decrease the level or effect of voxelotor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor is primarily metabolized by CYP3A4. Avoid coadministration with moderate or strong CYP3A4 inducers. If unable to avoid coadministration, increase voxelotor dose (see Dosage Modifications).

            • voxilaprevir

              phenobarbital will decrease the level or effect of voxilaprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • warfarin

              phenobarbital decreases effects of warfarin by increasing metabolism. Avoid or Use Alternate Drug.

            • zanubrutinib

              phenobarbital will decrease the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            Monitor Closely (432)

            • abiraterone

              phenobarbital decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.

            • acebutolol

              phenobarbital decreases levels of acebutolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • albuterol

              phenobarbital increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • alfentanil

              phenobarbital and alfentanil both increase sedation. Use Caution/Monitor.

            • alitretinoin

              phenobarbital will decrease the level or effect of alitretinoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • almotriptan

              phenobarbital will decrease the level or effect of almotriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • alprazolam

              phenobarbital will decrease the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital and alprazolam both increase sedation. Use Caution/Monitor.

            • amikacin

              phenobarbital will decrease the level or effect of amikacin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • amiodarone

              phenobarbital will decrease the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • amitriptyline

              phenobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              phenobarbital will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              phenobarbital and amitriptyline both increase sedation. Use Caution/Monitor.

            • amlodipine

              phenobarbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • amobarbital

              amobarbital and phenobarbital both increase sedation. Use Caution/Monitor.

            • amoxapine

              phenobarbital and amoxapine both increase sedation. Use Caution/Monitor.

            • apomorphine

              phenobarbital and apomorphine both increase sedation. Use Caution/Monitor.

            • aprepitant

              phenobarbital will decrease the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • arformoterol

              phenobarbital increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • aripiprazole

              phenobarbital will decrease the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital and aripiprazole both increase sedation. Use Caution/Monitor.

            • armodafinil

              phenobarbital increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • artesunate

              phenobarbital will decrease the level or effect of artesunate by increasing metabolism. Use Caution/Monitor. Coadministration may decrease AUC and peak plasma concentration of active artesunate metabolite (DHA) by inducing UGT. Monitor for decreased efficacy.

            • atenolol

              phenobarbital decreases levels of atenolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • atogepant

              phenobarbital will decrease the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Recommended atogepant dosage with concomitant use of strong or moderate CYP3A4 inducers is 30 mg or 60 mg qDay.

            • atorvastatin

              phenobarbital will decrease the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of atorvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • avanafil

              phenobarbital will decrease the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. For patients with ED, monitor response carefully because of potential for decreased effectiveness.

            • avatrombopag

              phenobarbital will decrease the level or effect of avatrombopag by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. When treating ITP, coadministration of avatrombopag with a moderate or strong dual CYP2C9/3A4 inducer requires an increased avatrombopag starting dose. Refer to drug monograph for specific recommendations.

            • azelastine

              azelastine and phenobarbital both increase sedation. Use Caution/Monitor.

            • baclofen

              phenobarbital and baclofen both increase sedation. Use Caution/Monitor.

            • bazedoxifene/conjugated estrogens

              phenobarbital will decrease the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              phenobarbital decreases levels of bazedoxifene/conjugated estrogens by increasing metabolism. Use Caution/Monitor. A reduction in bazedoxifene exposure may be associated with an increase risk of endometrial hyperplasia.

            • belladonna and opium

              phenobarbital and belladonna and opium both increase sedation. Use Caution/Monitor.

            • benazepril

              phenobarbital, benazepril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects.

            • bendamustine

              phenobarbital decreases levels of bendamustine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Concentrations of active metabolites may be increased.

            • benperidol

              phenobarbital and benperidol both increase sedation. Use Caution/Monitor.

            • benzhydrocodone/acetaminophen

              phenobarbital will decrease the level or effect of benzhydrocodone/acetaminophen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with benzhydrocodone (prodrug of hydrocodone); plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression.

            • benzphetamine

              phenobarbital increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • betaxolol

              phenobarbital decreases levels of betaxolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • bexarotene

              phenobarbital will decrease the level or effect of bexarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • bisoprolol

              phenobarbital decreases levels of bisoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • blinatumomab

              blinatumomab increases levels of phenobarbital by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

            • bortezomib

              phenobarbital will decrease the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • brentuximab vedotin

              phenobarbital decreases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • brexanolone

              brexanolone, phenobarbital. Either increases toxicity of the other by sedation. Use Caution/Monitor.

            • brexpiprazole

              phenobarbital will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

            • brivaracetam

              phenobarbital will decrease the level or effect of brivaracetam by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Brivaracetam plasma concentration decreased by 19%.

            • brodalumab

              brodalumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, brodalumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of brodalumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • bromocriptine

              phenobarbital will decrease the level or effect of bromocriptine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • brompheniramine

              brompheniramine and phenobarbital both increase sedation. Use Caution/Monitor.

            • budesonide

              phenobarbital will decrease the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of budesonide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • bupivacaine implant

              phenobarbital, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.

            • buprenorphine

              phenobarbital and buprenorphine both increase sedation. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • buprenorphine buccal

              phenobarbital and buprenorphine buccal both increase sedation. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of buprenorphine buccal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • buprenorphine subdermal implant

              phenobarbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

            • buprenorphine transdermal

              phenobarbital will decrease the level or effect of buprenorphine transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • buprenorphine, long-acting injection

              phenobarbital will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • bupropion

              phenobarbital will decrease the level or effect of bupropion by increasing metabolism. Use Caution/Monitor. Decrease levels of bupropion.

            • buspirone

              phenobarbital will decrease the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • butabarbital

              butabarbital and phenobarbital both increase sedation. Use Caution/Monitor.

            • butalbital

              butalbital and phenobarbital both increase sedation. Use Caution/Monitor.

            • butorphanol

              phenobarbital and butorphanol both increase sedation. Use Caution/Monitor.

            • cabazitaxel

              phenobarbital will decrease the level or effect of cabazitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of strong CYP3A4 inducers may decrease cabazitaxel concentrations. Avoid coadministration.

            • caffeine

              phenobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • calcifediol

              phenobarbital, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

            • calcitriol

              phenobarbital will decrease the level or effect of calcitriol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • canagliflozin

              phenobarbital decreases levels of canagliflozin by increasing metabolism. Use Caution/Monitor. Coadministration with potent UGT enzyme inducers: Consider increasing dose to 300 mg qDay if 100 mg/day tolerate and additional glycemic control required (eGFR must be >60 mL/min/1.73 m2 to increase dose); if eGFR <60 mL/min/1.73 m2, consider using a different antihyperglycemic agent.

            • cannabidiol

              phenobarbital will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

              cannabidiol will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • captopril

              phenobarbital, captopril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.

            • carbamazepine

              phenobarbital will decrease the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • carbinoxamine

              carbinoxamine and phenobarbital both increase sedation. Use Caution/Monitor.

            • carisoprodol

              phenobarbital and carisoprodol both increase sedation. Use Caution/Monitor.

            • carvedilol

              phenobarbital will decrease the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              phenobarbital decreases levels of carvedilol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • celiprolol

              phenobarbital decreases levels of celiprolol by increasing metabolism. Use Caution/Monitor. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • cenobamate

              cenobamate will increase the level or effect of phenobarbital by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Concomitant use of phenobarbital with multiple doses of cenobamate 200 mg qDay increased carbamazepine mean Cmax and AUC by 34% and 37%. Consider a dose reduction of phenobarbital, as clinically appropriate, when used concomitantly with cenobamate.

              cenobamate will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider a dose reduction of CYP2C19 substrates, as clinically appropriate, when used concomitantly with cenobamate.

              cenobamate, phenobarbital. Either increases effects of the other by sedation. Use Caution/Monitor.

            • chloral hydrate

              phenobarbital and chloral hydrate both increase sedation. Use Caution/Monitor.

            • chloramphenicol

              chloramphenicol increases levels of phenobarbital by decreasing metabolism. Use Caution/Monitor.

            • chlordiazepoxide

              phenobarbital and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • chloroquine

              phenobarbital will decrease the level or effect of chloroquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • chlorpheniramine

              chlorpheniramine and phenobarbital both increase sedation. Use Caution/Monitor.

            • chlorpromazine

              phenobarbital and chlorpromazine both increase sedation. Use Caution/Monitor.

            • chlorzoxazone

              phenobarbital and chlorzoxazone both increase sedation. Use Caution/Monitor.

            • cilostazol

              phenobarbital will decrease the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cinacalcet

              phenobarbital will decrease the level or effect of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cinnarizine

              cinnarizine and phenobarbital both increase sedation. Use Caution/Monitor.

            • citalopram

              phenobarbital will decrease the level or effect of citalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clemastine

              clemastine and phenobarbital both increase sedation. Use Caution/Monitor.

            • clobazam

              phenobarbital, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

            • clobetasone

              phenobarbital will decrease the level or effect of clobetasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of clobetasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • clomipramine

              phenobarbital will decrease the level or effect of clomipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              phenobarbital and clomipramine both increase sedation. Use Caution/Monitor.

            • clonazepam

              phenobarbital and clonazepam both increase sedation. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clopidogrel

              phenobarbital will increase the level or effect of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of clopidogrel to its active metabolite. Monitor patients for potential increase in antiplatelet effects when CYP3A4 inducers are used in combination with clopidogrel

            • clorazepate

              phenobarbital and clorazepate both increase sedation. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of clorazepate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clozapine

              phenobarbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital and clozapine both increase sedation. Use Caution/Monitor.

            • codeine

              phenobarbital and codeine both increase sedation. Use Caution/Monitor.

            • colchicine

              phenobarbital will decrease the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • conivaptan

              phenobarbital will decrease the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • conjugated estrogens

              phenobarbital will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • conjugated estrogens, vaginal

              phenobarbital will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • cortisone

              phenobarbital will decrease the level or effect of cortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of cortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • crizotinib

              phenobarbital decreases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inducers should be avoided. .

            • cyclizine

              cyclizine and phenobarbital both increase sedation. Use Caution/Monitor.

            • cyclobenzaprine

              phenobarbital and cyclobenzaprine both increase sedation. Use Caution/Monitor.

            • cyclophosphamide

              phenobarbital will decrease the level or effect of cyclophosphamide by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.

            • cyclosporine

              phenobarbital will decrease the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of cyclosporine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • cyproheptadine

              cyproheptadine and phenobarbital both increase sedation. Use Caution/Monitor.

            • dantrolene

              phenobarbital and dantrolene both increase sedation. Use Caution/Monitor.

            • dapsone topical

              phenobarbital increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia.

            • darifenacin

              phenobarbital will decrease the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dasatinib

              phenobarbital will decrease the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • deferasirox

              phenobarbital decreases levels of deferasirox by Other (see comment). Use Caution/Monitor. Comment: Avoid concomitant use of potent UGT inducers with deferasirox. If co-administration is required then consider increasing initial dose of deferasirox to 30 mg/kg and monitor ferritin levels and clinical response.

            • deflazacort

              phenobarbital will decrease the level or effect of deflazacort by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • desipramine

              phenobarbital will decrease the level or effect of desipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              phenobarbital and desipramine both increase sedation. Use Caution/Monitor.

            • dexamethasone

              phenobarbital will decrease the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dexchlorpheniramine

              dexchlorpheniramine and phenobarbital both increase sedation. Use Caution/Monitor.

            • dexfenfluramine

              phenobarbital increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dexmedetomidine

              phenobarbital and dexmedetomidine both increase sedation. Use Caution/Monitor.

            • dexmethylphenidate

              phenobarbital increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dextroamphetamine

              phenobarbital increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dextromoramide

              phenobarbital and dextromoramide both increase sedation. Use Caution/Monitor.

            • diamorphine

              phenobarbital and diamorphine both increase sedation. Use Caution/Monitor.

            • diazepam

              phenobarbital will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital and diazepam both increase sedation. Use Caution/Monitor.

            • diazepam intranasal

              phenobarbital will decrease the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inducers may increase rate of diazepam elimination; therefore, efficacy of diazepam may be decreased.

              diazepam intranasal, phenobarbital. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

            • diethylpropion

              phenobarbital increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • difenoxin hcl

              phenobarbital and difenoxin hcl both increase sedation. Use Caution/Monitor.

            • digoxin

              phenobarbital will decrease the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • diltiazem

              phenobarbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dimenhydrinate

              dimenhydrinate and phenobarbital both increase sedation. Use Caution/Monitor.

            • diphenhydramine

              diphenhydramine and phenobarbital both increase sedation. Use Caution/Monitor.

            • diphenoxylate hcl

              phenobarbital and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • dipipanone

              phenobarbital and dipipanone both increase sedation. Use Caution/Monitor.

            • dobutamine

              phenobarbital increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • docetaxel

              phenobarbital will decrease the level or effect of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dopamine

              phenobarbital increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dopexamine

              phenobarbital increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dosulepin

              phenobarbital and dosulepin both increase sedation. Use Caution/Monitor.

            • doxepin

              phenobarbital and doxepin both increase sedation. Use Caution/Monitor.

            • doxorubicin

              phenobarbital will decrease the level or effect of doxorubicin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital decreases levels of doxorubicin by increasing elimination. Use Caution/Monitor.

            • doxorubicin liposomal

              phenobarbital will decrease the level or effect of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital decreases levels of doxorubicin liposomal by increasing elimination. Use Caution/Monitor.

            • doxycycline

              phenobarbital decreases levels of doxycycline by increasing metabolism. Use Caution/Monitor.

            • doxylamine

              phenobarbital and doxylamine both increase sedation. Use Caution/Monitor.

            • dronabinol

              phenobarbital will decrease the level or effect of dronabinol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Dronabinol is a CYP2C9 substrate.

              phenobarbital will decrease the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dronabinol is a CYP3A4 substrate.

            • droperidol

              phenobarbital and droperidol both increase sedation. Use Caution/Monitor.

            • dulaglutide

              dulaglutide, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Dulaglutide slows gastric emptying and may impact absorption of concomitantly administered oral medications; be particularly cautious when coadministered with drugs that have a narrow therapeutic index.

            • dupilumab

              dupilumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, dupilumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of dupilumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • duvelisib

              phenobarbital will decrease the level or effect of duvelisib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • elagolix

              elagolix will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak CYP2C19 inhibitor. Caution with sensitive CYP2C19 substrates.

              phenobarbital will decrease the level or effect of elagolix by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • eletriptan

              phenobarbital will decrease the level or effect of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • eltrombopag

              phenobarbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • enfortumab vedotin

              phenobarbital will decrease the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ephedrine

              phenobarbital increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epinephrine

              phenobarbital increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epinephrine racemic

              phenobarbital increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • erlotinib

              phenobarbital will decrease the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • escitalopram

              phenobarbital will decrease the level or effect of escitalopram by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of escitalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • eslicarbazepine acetate

              phenobarbital will decrease the level or effect of eslicarbazepine acetate by increasing metabolism. Use Caution/Monitor. Higher dosage of eslicarbazepine may be necessary

              eslicarbazepine acetate will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • esmolol

              phenobarbital decreases levels of esmolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • esomeprazole

              phenobarbital will decrease the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • estazolam

              phenobarbital and estazolam both increase sedation. Use Caution/Monitor.

            • estradiol

              phenobarbital will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • estradiol vaginal

              phenobarbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estrogens conjugated synthetic

              phenobarbital will decrease the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of estrogens conjugated synthetic by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • estrogens esterified

              phenobarbital will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estropipate

              phenobarbital will decrease the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ethanol

              phenobarbital and ethanol both increase sedation. Use Caution/Monitor.

            • ethosuximide

              phenobarbital will decrease the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ethotoin

              phenobarbital will decrease the level or effect of ethotoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • etomidate

              etomidate and phenobarbital both increase sedation. Use Caution/Monitor.

            • etonogestrel

              phenobarbital will decrease the level or effect of etonogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • etoposide

              phenobarbital will decrease the level or effect of etoposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • etravirine

              phenobarbital will decrease the level or effect of etravirine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • exemestane

              phenobarbital will decrease the level or effect of exemestane by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. For patients receiving exemestane with a potent CYP3A4 inducer the recommended dose of exemestane is 50 mg daily after a meal.

            • fedratinib

              fedratinib will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • felbamate

              phenobarbital will decrease the level or effect of felbamate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • felodipine

              phenobarbital will decrease the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fenfluramine

              phenobarbital increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of fenfluramine by Other (see comment). Modify Therapy/Monitor Closely. Coadministration with drugs that increase serotonin may increase the risk of serotonin syndrome.

            • fentanyl

              phenobarbital will decrease the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

            • fentanyl intranasal

              phenobarbital will decrease the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

            • fentanyl transdermal

              phenobarbital will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

            • fentanyl transmucosal

              phenobarbital will decrease the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

            • ferric maltol

              ferric maltol, phenobarbital. Either increases levels of the other by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ferric maltol with certain oral medications may decrease the bioavailability of either ferric maltol and some oral drugs. For oral drugs where reductions in bioavailability may cause clinically significant effects on its safety or efficacy, separate administration of ferric maltol from these drugs. Duration of separation may depend on the absorption of the medication concomitantly administered (eg, time to peak concentration, whether the drug is an immediate or extended release product).

            • fesoterodine

              phenobarbital will decrease the level or effect of fesoterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fexinidazole

              fexinidazole will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • flibanserin

              phenobarbital will decrease the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers substantially decrease flibanserin systemic exposure.

            • fludrocortisone

              phenobarbital will decrease the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of fludrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • fluphenazine

              phenobarbital and fluphenazine both increase sedation. Use Caution/Monitor.

            • flurazepam

              phenobarbital and flurazepam both increase sedation. Use Caution/Monitor.

            • fluticasone furoate

              phenobarbital will decrease the level or effect of fluticasone furoate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fluticasone inhaled

              phenobarbital will decrease the level or effect of fluticasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • formoterol

              phenobarbital increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • fosamprenavir

              phenobarbital will decrease the level or effect of fosamprenavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fosphenytoin

              phenobarbital will decrease the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • gefitinib

              phenobarbital will decrease the level or effect of gefitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase gefitinib to 500 mg daily if coadministered with a strong CYP3A4 inducer. Resume gefitinib dose at 250 mg/day 7 days after discontinuing the strong inducer.

            • gentamicin

              phenobarbital will decrease the level or effect of gentamicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • glecaprevir/pibrentasvir

              phenobarbital will decrease the level or effect of glecaprevir/pibrentasvir by increasing metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 and P-gp with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

              phenobarbital will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • glyburide

              phenobarbital decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inducers may increase glyburide metabolism.

            • gotu kola

              gotu kola increases effects of phenobarbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

            • guanfacine

              phenobarbital will decrease the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inducers significantly reduce guanfacine plasma concentrations and elimination half-life. If coadministered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response. For patients with ADHD, FDA-approved labeling for ER guanfacine recommends that, if coadministered, doubling the recommended dose of guanfacine should be considered.

            • guselkumab

              guselkumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • haloperidol

              phenobarbital and haloperidol both increase sedation. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of haloperidol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • hawthorn

              hawthorn increases effects of phenobarbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

            • hemin

              phenobarbital decreases effects of hemin by pharmacodynamic antagonism. Use Caution/Monitor. Drugs that increase delta-aminolevulinic acid synthetase may decrease hemin effect.

            • hops

              hops increases effects of phenobarbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

            • hydrocodone

              phenobarbital will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • hydrocortisone

              phenobarbital will decrease the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of hydrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • hydromorphone

              phenobarbital and hydromorphone both increase sedation. Use Caution/Monitor.

            • hydroxyprogesterone caproate

              phenobarbital will decrease the level or effect of hydroxyprogesterone caproate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • hydroxyzine

              hydroxyzine and phenobarbital both increase sedation. Use Caution/Monitor.

            • ifosfamide

              phenobarbital increases effects of ifosfamide by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Coadministration of ifosfamide with CYP2B6 inducers may increase metabolism of ifosfamide to its metabolite. Monitor for increased effects/toxicities if combined with CYP2B6 inducers.

              phenobarbital increases toxicity of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of ifosfamide to its active alkylating metabolites. CYP3A4 inducers may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde. Closely monitor patients taking ifosfamide with CYP3A4 inducers for toxicities and consider dose adjustment.

            • iloperidone

              phenobarbital will decrease the level or effect of iloperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital and iloperidone both increase sedation. Use Caution/Monitor.

            • imatinib

              phenobarbital will decrease the level or effect of imatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • imipramine

              phenobarbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              phenobarbital and imipramine both increase sedation. Use Caution/Monitor.

            • indinavir

              phenobarbital will decrease the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of indinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • isoproterenol

              phenobarbital increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • itraconazole

              phenobarbital will decrease the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ivermectin

              phenobarbital will decrease the level or effect of ivermectin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ixabepilone

              phenobarbital will decrease the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ixekizumab

              ixekizumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, ixekizumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of ixekizumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • kava

              kava increases effects of phenobarbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

            • ketamine

              ketamine and phenobarbital both increase sedation. Use Caution/Monitor.

            • ketotifen, ophthalmic

              phenobarbital and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

            • labetalol

              phenobarbital decreases levels of labetalol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • lamotrigine

              phenobarbital decreases levels of lamotrigine by increasing hepatic clearance. Use Caution/Monitor.

            • lansoprazole

              phenobarbital will decrease the level or effect of lansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lapatinib

              phenobarbital will decrease the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of lapatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lasmiditan

              lasmiditan, phenobarbital. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

            • lemborexant

              lemborexant, phenobarbital. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

            • lesinurad

              phenobarbital will decrease the level or effect of lesinurad by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

            • levalbuterol

              phenobarbital increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • levamlodipine

              phenobarbital will decrease the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Closely monitor blood pressure when amlodipine is coadministered with CYP3A4 inducers.

            • levonorgestrel intrauterine

              phenobarbital decreases levels of levonorgestrel intrauterine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levonorgestrel oral

              phenobarbital decreases levels of levonorgestrel oral by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

              phenobarbital will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. The efficacy of hormonal contraceptives may be reduced. Use an alternative method of contraception or a backup method when enzyme inducers are used with combined hormonal contraceptives (CHCs), and continue backup contraception for 28 days after discontinuing enzyme inducer to ensure contraceptive reliability.

            • levorphanol

              phenobarbital and levorphanol both increase sedation. Use Caution/Monitor.

            • lidocaine

              phenobarbital will decrease the level or effect of lidocaine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • linagliptin

              phenobarbital will decrease the level or effect of linagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of alternative treatments is strongly recommended when linagliptin is to be administered with a CYP3A4 inducer.

            • lisdexamfetamine

              phenobarbital increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lofepramine

              phenobarbital and lofepramine both increase sedation. Use Caution/Monitor.

            • lofexidine

              phenobarbital and lofexidine both increase sedation. Use Caution/Monitor.

            • loperamide

              phenobarbital will decrease the level or effect of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lopinavir

              phenobarbital will decrease the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • loprazolam

              phenobarbital and loprazolam both increase sedation. Use Caution/Monitor.

            • loratadine

              phenobarbital will decrease the level or effect of loratadine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lorazepam

              phenobarbital and lorazepam both increase sedation. Use Caution/Monitor.

            • lormetazepam

              phenobarbital and lormetazepam both increase sedation. Use Caution/Monitor.

            • losartan

              phenobarbital will decrease the level or effect of losartan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lovastatin

              phenobarbital will decrease the level or effect of lovastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • loxapine

              phenobarbital and loxapine both increase sedation. Use Caution/Monitor.

            • loxapine inhaled

              phenobarbital and loxapine inhaled both increase sedation. Use Caution/Monitor.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor, phenobarbital. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

            • lurasidone

              lurasidone, phenobarbital. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

            • maprotiline

              phenobarbital and maprotiline both increase sedation. Use Caution/Monitor.

            • maraviroc

              phenobarbital will decrease the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of maraviroc by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • marijuana

              phenobarbital and marijuana both increase sedation. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of marijuana by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • medroxyprogesterone

              phenobarbital will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Contraceptirve failure possible

            • mefloquine

              phenobarbital, mefloquine. Either decreases effects of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • melatonin

              phenobarbital and melatonin both increase sedation. Use Caution/Monitor.

            • meperidine

              phenobarbital and meperidine both increase sedation. Use Caution/Monitor.

            • meprobamate

              phenobarbital and meprobamate both increase sedation. Use Caution/Monitor.

            • mestranol

              phenobarbital will decrease the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of mestranol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • metaproterenol

              phenobarbital increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • metaxalone

              phenobarbital and metaxalone both increase sedation. Use Caution/Monitor.

            • methadone

              phenobarbital will decrease the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital and methadone both increase sedation. Use Caution/Monitor.

            • methamphetamine

              phenobarbital increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • methocarbamol

              phenobarbital and methocarbamol both increase sedation. Use Caution/Monitor.

            • methylenedioxymethamphetamine

              phenobarbital increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • methylphenidate

              methylphenidate will increase the level or effect of phenobarbital by unknown mechanism. Use Caution/Monitor. Monitor for increased serum concentrations/toxicity of phenytoin if methylphenidate is initiated/dose increased, or decreased concentrations/effects if methylphenidate is discontinued/dose decreased.

            • methylprednisolone

              phenobarbital will decrease the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of methylprednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • metoprolol

              phenobarbital decreases levels of metoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • mexiletine

              phenobarbital will decrease the level or effect of mexiletine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • midazolam

              phenobarbital will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital and midazolam both increase sedation. Use Caution/Monitor.

            • midazolam intranasal

              midazolam intranasal, phenobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

            • midodrine

              phenobarbital increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • mifepristone

              phenobarbital will decrease the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers have not been studied, coadministration not recommended by manufacturer

            • mipomersen

              mipomersen, phenobarbital. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

            • mirtazapine

              phenobarbital and mirtazapine both increase sedation. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • modafinil

              phenobarbital increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • morphine

              phenobarbital and morphine both increase sedation. Use Caution/Monitor.

            • motherwort

              phenobarbital and motherwort both increase sedation. Use Caution/Monitor.

            • moxonidine

              phenobarbital and moxonidine both increase sedation. Use Caution/Monitor.

            • nabilone

              phenobarbital and nabilone both increase sedation. Use Caution/Monitor.

            • nadolol

              phenobarbital decreases levels of nadolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • nalbuphine

              phenobarbital and nalbuphine both increase sedation. Use Caution/Monitor.

            • nateglinide

              phenobarbital will decrease the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • nebivolol

              phenobarbital decreases levels of nebivolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • nefazodone

              phenobarbital will decrease the level or effect of nefazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nelfinavir

              phenobarbital will decrease the level or effect of nelfinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • neomycin PO

              phenobarbital will decrease the level or effect of neomycin PO by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nevirapine

              phenobarbital, nevirapine. Either decreases effects of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nicardipine

              phenobarbital will decrease the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nifedipine

              phenobarbital will decrease the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • nilotinib

              phenobarbital will decrease the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of nilotinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nisoldipine

              phenobarbital will decrease the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • norepinephrine

              phenobarbital increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • norgestrel

              phenobarbital will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nortriptyline

              phenobarbital and nortriptyline both increase sedation. Use Caution/Monitor.

            • olanzapine

              phenobarbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              phenobarbital and olanzapine both increase sedation. Use Caution/Monitor.

            • oliceridine

              phenobarbital will decrease the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration with a CYP3A4 inducer is necessary, consider increasing oliceridine dose until stable drug effects are achieved; monitor for signs of opioid withdrawal. If inducer is discontinued, consider oliceridine dosage reduction and monitor for signs of respiratory depression.

            • omeprazole

              phenobarbital will decrease the level or effect of omeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • ondansetron

              phenobarbital will decrease the level or effect of ondansetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment for ondansetron is recommended for patients on these drugs.

            • opium tincture

              phenobarbital and opium tincture both increase sedation. Use Caution/Monitor.

            • oritavancin

              oritavancin will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Oritavancin is a weak CYP2C9 inhibitor; caution if coadministered with CYP2C9 substrates that have a narrow therapeutic index

            • orlistat

              orlistat decreases levels of phenobarbital by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Risk of convulsions.

            • orphenadrine

              phenobarbital and orphenadrine both increase sedation. Use Caution/Monitor.

            • osilodrostat

              phenobarbital will decrease the level or effect of osilodrostat by Other (see comment). Modify Therapy/Monitor Closely. Osilodrostat is a CYP3A4 and CYP2B6 subtrate. Monitor cortisol concentration and patient?s signs and symptoms during coadministration and discontinuation with strong CYP3A4 and/or CYP2B6 inducers. Adjust dose of osilodrostat if necessary.

            • ospemifene

              phenobarbital decreases levels of ospemifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital decreases levels of ospemifene by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • oxazepam

              phenobarbital and oxazepam both increase sedation. Use Caution/Monitor.

            • oxycodone

              phenobarbital and oxycodone both increase sedation. Use Caution/Monitor.

              phenobarbital decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • oxymorphone

              phenobarbital and oxymorphone both increase sedation. Use Caution/Monitor.

            • paclitaxel

              phenobarbital will decrease the level or effect of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of paclitaxel by Other (see comment). Use Caution/Monitor. Paclitaxel levels/efficacy may decrease when coadministered with CYP2C8 inducers

            • paclitaxel protein bound

              phenobarbital will decrease the level or effect of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of paclitaxel protein bound by Other (see comment). Use Caution/Monitor. Paclitaxel levels/efficacy may decrease when coadministered with CYP2C8 inducers

            • paliperidone

              phenobarbital will decrease the level or effect of paliperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              phenobarbital and paliperidone both increase sedation. Use Caution/Monitor.

            • papaveretum

              phenobarbital and papaveretum both increase sedation. Use Caution/Monitor.

            • papaverine

              phenobarbital and papaverine both increase sedation. Use Caution/Monitor.

            • parecoxib

              phenobarbital will decrease the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • paromomycin

              phenobarbital will decrease the level or effect of paromomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • passion flower

              passion flower increases effects of phenobarbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

            • pazopanib

              phenobarbital will decrease the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • penbutolol

              phenobarbital decreases levels of penbutolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • pentazocine

              phenobarbital and pentazocine both increase sedation. Use Caution/Monitor.

            • pentobarbital

              pentobarbital and phenobarbital both increase sedation. Use Caution/Monitor.

            • perphenazine

              phenobarbital and perphenazine both increase sedation. Use Caution/Monitor.

            • phendimetrazine

              phenobarbital increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phentermine

              phenobarbital increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenylephrine

              phenobarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenylephrine PO

              phenobarbital increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • phenytoin

              phenobarbital will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • pholcodine

              phenobarbital and pholcodine both increase sedation. Use Caution/Monitor.

            • pimavanserin

              phenobarbital will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration if possible. Monitor for reduced pimavanserin efficacy. An increase in pimavanserin dosage may be needed.

            • pimozide

              phenobarbital and pimozide both increase sedation. Use Caution/Monitor.

            • pindolol

              phenobarbital decreases levels of pindolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • pirbuterol

              phenobarbital increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pitolisant

              phenobarbital will decrease the level or effect of pitolisant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Pitolisant exposure is decreased by 50% if coadministered with strong CYP3A4 inducers. For patients stable on pitolisant 8.9 mg/day or 17.8 mg/day, double the pitolisant dose (ie, 17.8 mg or 35.6 mg, respectively) over 7 days. If the strong CYP3A4 inducer is discontinued, reduce pitolisant dosage by half.

            • polatuzumab vedotin

              phenobarbital will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

            • posaconazole

              phenobarbital will decrease the level or effect of posaconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              phenobarbital decreases levels of posaconazole by increasing metabolism. Use Caution/Monitor.

            • prednisolone

              phenobarbital will decrease the level or effect of prednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of prednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • prednisone

              phenobarbital will decrease the level or effect of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of prednisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • primaquine

              phenobarbital will decrease the level or effect of primaquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • primidone

              phenobarbital and primidone both increase sedation. Use Caution/Monitor.

            • prochlorperazine

              phenobarbital and prochlorperazine both increase sedation. Use Caution/Monitor.

            • progesterone intravaginal gel

              phenobarbital will decrease the level or effect of progesterone intravaginal gel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • progesterone micronized

              phenobarbital will decrease the level or effect of progesterone micronized by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • progesterone, natural

              phenobarbital will decrease the level or effect of progesterone, natural by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • promethazine

              promethazine and phenobarbital both increase sedation. Use Caution/Monitor.

            • propafenone

              phenobarbital decreases levels of propafenone by increasing metabolism. Use Caution/Monitor.

            • propofol

              propofol and phenobarbital both increase sedation. Use Caution/Monitor.

            • propranolol

              phenobarbital decreases levels of propranolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • propylhexedrine

              phenobarbital increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • protriptyline

              phenobarbital and protriptyline both increase sedation. Use Caution/Monitor.

            • quazepam

              phenobarbital and quazepam both increase sedation. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of quazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • quetiapine

              phenobarbital will decrease the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital and quetiapine both increase sedation. Use Caution/Monitor.

            • quinidine

              phenobarbital will decrease the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ramelteon

              phenobarbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              phenobarbital and ramelteon both increase sedation. Use Caution/Monitor.

            • rasagiline

              phenobarbital will decrease the level or effect of rasagiline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • repaglinide

              phenobarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifabutin

              phenobarbital will decrease the level or effect of rifabutin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • rifampin

              rifampin decreases levels of phenobarbital by increasing metabolism. Use Caution/Monitor.

            • riociguat

              phenobarbital will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment

            • risperidone

              phenobarbital will decrease the level or effect of risperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              phenobarbital and risperidone both increase sedation. Use Caution/Monitor.

            • ritonavir

              phenobarbital will decrease the level or effect of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of ritonavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ropinirole

              phenobarbital will decrease the level or effect of ropinirole by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • rucaparib

              rucaparib will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP2C19 substrates, if clinically indicated.

            • rufinamide

              phenobarbital decreases levels of rufinamide by increasing metabolism. Use Caution/Monitor.

            • ruxolitinib

              phenobarbital will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • salmeterol

              phenobarbital increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • saquinavir

              phenobarbital will decrease the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of saquinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sarilumab

              sarilumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.

            • scullcap

              phenobarbital and scullcap both increase sedation. Use Caution/Monitor.

            • secobarbital

              phenobarbital and secobarbital both increase sedation. Use Caution/Monitor.

            • secukinumab

              secukinumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, secukinumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of secukinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • selexipag

              phenobarbital will decrease the level or effect of selexipag by increasing metabolism. Modify Therapy/Monitor Closely. Increase selexipag dose (up to 2-fold) if coadministered with strong CYP2C8 inducers.

            • sevelamer

              sevelamer decreases levels of phenobarbital by increasing elimination. Use Caution/Monitor.

            • sevoflurane

              sevoflurane and phenobarbital both increase sedation. Use Caution/Monitor.

            • shepherd's purse

              phenobarbital and shepherd's purse both increase sedation. Use Caution/Monitor.

            • silodosin

              phenobarbital will decrease the level or effect of silodosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sirolimus

              phenobarbital will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • solifenacin

              phenobarbital will decrease the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sorafenib

              phenobarbital decreases levels of sorafenib by increasing metabolism. Use Caution/Monitor.

            • sotalol

              phenobarbital decreases levels of sotalol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • stiripentol

              stiripentol will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of CYP2C19 substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

            • streptomycin

              phenobarbital will decrease the level or effect of streptomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sufentanil

              phenobarbital and sufentanil both increase sedation. Use Caution/Monitor.

            • sufentanil SL

              phenobarbital decreases effects of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of CYP3A4 inducers may decrease sufentanil levels and efficacy, possibly precipitating withdrawal syndrome in patients who have developed physical dependence to sufentanil. Discontinuation of concomitantly used CYP3A4 inducers may increase sufentanil plasma concentration.

            • sunitinib

              phenobarbital will decrease the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • suvorexant

              phenobarbital will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers may decrease suvorexant efficacy; if increased suvorexant dose required, do not exceed 20 mg/day

            • tacrolimus

              phenobarbital will decrease the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tadalafil

              phenobarbital will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid combination in pulmonary HTN patients. For patients with ED, monitor response to tadalafil carefully because of potential for decreased effectiveness.

            • tamoxifen

              phenobarbital will decrease the level or effect of tamoxifen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tapentadol

              phenobarbital and tapentadol both increase sedation. Use Caution/Monitor.

            • tasimelteon

              phenobarbital will decrease the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration of tasimelteon with strong CYP3A4 inducers

            • tecovirimat

              tecovirimat will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Tecovirimat is a weak inhibitor of CYP2C8 and CYP2C19. Monitor for adverse effects if coadministered with sensitive substrates of these enzymes.

            • temazepam

              phenobarbital and temazepam both increase sedation. Use Caution/Monitor.

            • temsirolimus

              phenobarbital will decrease the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • teniposide

              phenobarbital will decrease the level or effect of teniposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • terbinafine

              phenobarbital will decrease the level or effect of terbinafine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of terbinafine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of terbinafine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • terbutaline

              phenobarbital increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tetracaine

              tetracaine, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.

            • thalidomide

              thalidomide increases effects of phenobarbital by unspecified interaction mechanism. Use Caution/Monitor. Increased sedative effects.

            • theophylline

              phenobarbital will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • thioridazine

              phenobarbital and thioridazine both increase sedation. Use Caution/Monitor.

            • thiothixene

              phenobarbital and thiothixene both increase sedation. Use Caution/Monitor.

            • tiagabine

              phenobarbital will decrease the level or effect of tiagabine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ticagrelor

              phenobarbital decreases levels of ticagrelor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid use of ticagrelor with potent CYP3A inducers.

            • timolol

              phenobarbital decreases levels of timolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • tinidazole

              phenobarbital will decrease the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tipranavir

              phenobarbital will decrease the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tobramycin

              phenobarbital will decrease the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tofacitinib

              phenobarbital will decrease the level or effect of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Loss of, or decreased response to tofacitinib may occur when coadministered with potent CYP3A4 inducers

            • tolterodine

              phenobarbital will decrease the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tolvaptan

              phenobarbital will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • topiramate

              phenobarbital and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • toremifene

              phenobarbital decreases levels of toremifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers increase rate of toremifene metabolism, lowering the steady-state concentration in serum.

            • tramadol

              phenobarbital and tramadol both increase sedation. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

            • trazodone

              phenobarbital will decrease the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital and trazodone both increase sedation. Use Caution/Monitor.

            • triamcinolone acetonide injectable suspension

              phenobarbital will decrease the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • triazolam

              phenobarbital will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital and triazolam both increase sedation. Use Caution/Monitor.

            • triclabendazole

              triclabendazole will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. If plasma concentrations of the CYP2C19 substrates are elevated during triclabendazole, recheck plasma concentration of the CYP2C19 substrates after discontinuation of triclabendazole.

            • triclofos

              phenobarbital and triclofos both increase sedation. Use Caution/Monitor.

            • trifluoperazine

              phenobarbital and trifluoperazine both increase sedation. Use Caution/Monitor.

            • trimipramine

              phenobarbital and trimipramine both increase sedation. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of trimipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • triprolidine

              triprolidine and phenobarbital both increase sedation. Use Caution/Monitor.

            • ustekinumab

              ustekinumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • vardenafil

              phenobarbital will decrease the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • verapamil

              phenobarbital will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • vilanterol/fluticasone furoate inhaled

              phenobarbital will decrease the level or effect of vilanterol/fluticasone furoate inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • vilazodone

              phenobarbital decreases levels of vilazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Consider increasing vilazodone dose up to 2-fold (not to exceed 80 mg/day) when coadministered with strong CYP3A4 inducers for >14 days.

            • vinblastine

              phenobarbital will decrease the level or effect of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vincristine

              phenobarbital will decrease the level or effect of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vincristine liposomal

              phenobarbital will decrease the level or effect of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vitamin D

              phenobarbital decreases effects of vitamin D by Other (see comment). Use Caution/Monitor. Comment: Vitamin D supplementation or dosage adjustments may be required in patients who are receiving chronic treatment with anticonvulsants.

            • vortioxetine

              phenobarbital increases levels of vortioxetine by increasing metabolism. Modify Therapy/Monitor Closely. Consider increasing the vortioxetine dose when coadministered with strong CYP inducers for >14 days; not to exceed 3 times original vortioxetine dose.

            • warfarin

              phenobarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • xylometazoline

              phenobarbital increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • yohimbine

              phenobarbital increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ziconotide

              phenobarbital and ziconotide both increase sedation. Use Caution/Monitor.

            • ziprasidone

              phenobarbital and ziprasidone both increase sedation. Use Caution/Monitor.

            • zotepine

              phenobarbital and zotepine both increase sedation. Use Caution/Monitor.

            Minor (150)

            • acetaminophen

              phenobarbital decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • acetaminophen IV

              phenobarbital decreases levels of acetaminophen IV by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • acetaminophen rectal

              phenobarbital decreases levels of acetaminophen rectal by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • acetazolamide

              acetazolamide, phenobarbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

            • alfentanil

              phenobarbital will decrease the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • alfuzosin

              phenobarbital will decrease the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • alosetron

              phenobarbital will decrease the level or effect of alosetron by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              phenobarbital will decrease the level or effect of alosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • alvimopan

              phenobarbital will decrease the level or effect of alvimopan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • ambrisentan

              phenobarbital will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • amitriptyline

              phenobarbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • amoxapine

              phenobarbital, amoxapine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • amphotericin B deoxycholate

              phenobarbital decreases levels of amphotericin B deoxycholate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • antipyrine

              phenobarbital will decrease the level or effect of antipyrine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • armodafinil

              phenobarbital will decrease the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              phenobarbital will decrease the level or effect of armodafinil by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • ascorbic acid

              phenobarbital decreases levels of ascorbic acid by increasing elimination. Minor/Significance Unknown.

            • asenapine

              phenobarbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • ashwagandha

              ashwagandha increases effects of phenobarbital by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

            • atracurium

              phenobarbital decreases effects of atracurium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • biotin

              phenobarbital decreases levels of biotin by unspecified interaction mechanism. Minor/Significance Unknown. Biotin supplementation may be necessary.

            • bosentan

              phenobarbital will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              phenobarbital will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • brimonidine

              brimonidine increases effects of phenobarbital by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

            • brinzolamide

              brinzolamide, phenobarbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

            • caffeine

              phenobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • celecoxib

              phenobarbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • cevimeline

              phenobarbital will decrease the level or effect of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • chloramphenicol

              phenobarbital decreases levels of chloramphenicol by increasing metabolism. Minor/Significance Unknown.

            • chlorpromazine

              phenobarbital decreases levels of chlorpromazine by increasing metabolism. Minor/Significance Unknown.

            • cimetidine

              phenobarbital will decrease the level or effect of cimetidine by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • cisatracurium

              phenobarbital decreases effects of cisatracurium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • clarithromycin

              phenobarbital will decrease the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              phenobarbital decreases levels of clarithromycin by increasing elimination. Minor/Significance Unknown.

            • clomipramine

              phenobarbital, clomipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • clotrimazole

              phenobarbital decreases levels of clotrimazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • cocaine

              phenobarbital will decrease the level or effect of cocaine by affecting hepatic enzyme CYP2B6 metabolism. Minor/Significance Unknown.

            • cyanocobalamin

              phenobarbital decreases levels of cyanocobalamin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • dapsone

              phenobarbital will decrease the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • desipramine

              phenobarbital, desipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • dexmethylphenidate

              dexmethylphenidate increases effects of phenobarbital by decreasing metabolism. Minor/Significance Unknown.

            • diazepam

              phenobarbital will decrease the level or effect of diazepam by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • diclofenac

              phenobarbital will decrease the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • disopyramide

              phenobarbital will decrease the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • docetaxel

              phenobarbital will decrease the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • donepezil

              phenobarbital will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • dosulepin

              phenobarbital, dosulepin. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • doxepin

              phenobarbital, doxepin. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • dutasteride

              phenobarbital will decrease the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • efavirenz

              phenobarbital will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • eplerenone

              phenobarbital will decrease the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • erythromycin base

              phenobarbital decreases levels of erythromycin base by increasing elimination. Minor/Significance Unknown.

            • erythromycin ethylsuccinate

              phenobarbital decreases levels of erythromycin ethylsuccinate by increasing elimination. Minor/Significance Unknown.

            • erythromycin lactobionate

              phenobarbital decreases levels of erythromycin lactobionate by increasing elimination. Minor/Significance Unknown.

            • erythromycin stearate

              phenobarbital decreases levels of erythromycin stearate by increasing elimination. Minor/Significance Unknown.

            • ethosuximide

              ethosuximide decreases effects of phenobarbital by pharmacodynamic antagonism. Minor/Significance Unknown.

            • ethotoin

              phenobarbital decreases levels of ethotoin by increasing metabolism. Minor/Significance Unknown. Phenobarbital may occasionally not change or even increase (via competitive inhibition) phenytoin levels.

            • eucalyptus

              phenobarbital will decrease the level or effect of eucalyptus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              phenobarbital and eucalyptus both increase sedation. Minor/Significance Unknown.

            • felbamate

              felbamate increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown.

            • fexofenadine

              phenobarbital will decrease the level or effect of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • finasteride

              phenobarbital will decrease the level or effect of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • fluconazole

              phenobarbital decreases levels of fluconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • flurbiprofen

              phenobarbital will decrease the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • fluvastatin

              phenobarbital will decrease the level or effect of fluvastatin by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • folic acid

              folic acid decreases levels of phenobarbital by increasing metabolism. Minor/Significance Unknown.

              phenobarbital decreases levels of folic acid by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • fosphenytoin

              phenobarbital decreases levels of fosphenytoin by increasing metabolism. Minor/Significance Unknown. Phenobarbital may occasionally not change or even increase (via competitive inhibition) phenytoin levels.

            • frovatriptan

              phenobarbital will decrease the level or effect of frovatriptan by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • furosemide

              phenobarbital decreases levels of furosemide by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • galantamine

              phenobarbital will decrease the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • green tea

              phenobarbital will decrease the level or effect of green tea by increasing metabolism. Minor/Significance Unknown. Green tea products may contain caffeine. The metabolism of xanthines, such as caffeine, can be increased by concurrent use with barbiturates.

            • griseofulvin

              phenobarbital decreases levels of griseofulvin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • haloperidol

              haloperidol, phenobarbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hyperthermia if haloperidol admin. during barbiturate withdrawal.

            • ibuprofen

              phenobarbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • ibuprofen IV

              phenobarbital will decrease the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • imatinib

              phenobarbital will decrease the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • imipramine

              phenobarbital, imipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • isocarboxazid

              isocarboxazid increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

            • isradipine

              phenobarbital will decrease the level or effect of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • itraconazole

              phenobarbital will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              phenobarbital decreases levels of itraconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • ketoconazole

              phenobarbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              phenobarbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • L-methylfolate

              L-methylfolate decreases levels of phenobarbital by increasing metabolism. Minor/Significance Unknown.

              phenobarbital decreases levels of L-methylfolate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • lansoprazole

              phenobarbital will decrease the level or effect of lansoprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • levocarnitine

              phenobarbital decreases levels of levocarnitine by unspecified interaction mechanism. Minor/Significance Unknown.

            • levothyroxine

              phenobarbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

            • linezolid

              linezolid increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

            • liothyronine

              phenobarbital decreases levels of liothyronine by increasing metabolism. Minor/Significance Unknown.

            • lofepramine

              phenobarbital, lofepramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • loratadine

              phenobarbital will decrease the level or effect of loratadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • losartan

              phenobarbital will decrease the level or effect of losartan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • maprotiline

              phenobarbital, maprotiline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • meloxicam

              phenobarbital will decrease the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • methazolamide

              methazolamide, phenobarbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

            • methsuximide

              methsuximide decreases effects of phenobarbital by pharmacodynamic antagonism. Minor/Significance Unknown.

            • metyrapone

              phenobarbital decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.

            • miconazole vaginal

              phenobarbital decreases levels of miconazole vaginal by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • montelukast

              phenobarbital will decrease the level or effect of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nettle

              nettle increases effects of phenobarbital by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.

            • nimodipine

              phenobarbital will decrease the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nitrendipine

              phenobarbital will decrease the level or effect of nitrendipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nortriptyline

              phenobarbital, nortriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • onabotulinumtoxinA

              phenobarbital decreases effects of onabotulinumtoxinA by pharmacodynamic antagonism. Minor/Significance Unknown.

            • ondansetron

              phenobarbital will decrease the level or effect of ondansetron by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • oxcarbazepine

              phenobarbital decreases levels of oxcarbazepine by increasing metabolism. Minor/Significance Unknown.

            • oxybutynin

              phenobarbital will decrease the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • paclitaxel

              phenobarbital will decrease the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • paclitaxel protein bound

              phenobarbital will decrease the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pancuronium

              phenobarbital decreases effects of pancuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • pantoprazole

              phenobarbital will decrease the level or effect of pantoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • parecoxib

              phenobarbital will decrease the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • phenelzine

              phenelzine increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

            • phenytoin

              phenobarbital decreases levels of phenytoin by increasing metabolism. Minor/Significance Unknown. Phenobarbital may occasionally not change or even increase (via competitive inhibition) phenytoin levels.

            • pimozide

              phenobarbital will decrease the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pioglitazone

              phenobarbital will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • piroxicam

              phenobarbital will decrease the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • posaconazole

              phenobarbital decreases levels of posaconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • procarbazine

              procarbazine increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

            • propafenone

              phenobarbital will decrease the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • protriptyline

              phenobarbital, protriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • pyridoxine

              pyridoxine decreases levels of phenobarbital by increasing metabolism. Minor/Significance Unknown.

            • pyridoxine (Antidote)

              pyridoxine (Antidote) decreases levels of phenobarbital by increasing metabolism. Minor/Significance Unknown.

            • quinine

              phenobarbital will decrease the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • rabeprazole

              phenobarbital will decrease the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ramelteon

              phenobarbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              phenobarbital will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • rapacuronium

              phenobarbital decreases effects of rapacuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • riluzole

              phenobarbital will decrease the level or effect of riluzole by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • rocuronium

              phenobarbital decreases effects of rocuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • rose hips

              phenobarbital decreases levels of rose hips by increasing elimination. Minor/Significance Unknown.

            • sage

              phenobarbital and sage both increase sedation. Minor/Significance Unknown.

              sage decreases effects of phenobarbital by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction; some species of sage may cause convulsions.

            • saxagliptin

              phenobarbital will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • selegiline transdermal

              selegiline transdermal increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

            • Siberian ginseng

              Siberian ginseng increases effects of phenobarbital by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

            • succinylcholine

              phenobarbital decreases effects of succinylcholine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • sufentanil

              phenobarbital will decrease the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sulfamethoxazole

              phenobarbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • thioridazine

              thioridazine decreases levels of phenobarbital by unspecified interaction mechanism. Minor/Significance Unknown.

            • thyroid desiccated

              phenobarbital decreases levels of thyroid desiccated by increasing metabolism. Minor/Significance Unknown.

            • tiagabine

              phenobarbital decreases levels of tiagabine by increasing metabolism. Minor/Significance Unknown.

            • tibolone

              phenobarbital decreases levels of tibolone by increasing metabolism. Minor/Significance Unknown. Theoretical interaction.

            • tolbutamide

              phenobarbital will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • topiramate

              phenobarbital decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown.

            • tranylcypromine

              tranylcypromine increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

            • trazodone

              phenobarbital, trazodone. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • trimipramine

              phenobarbital, trimipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • valproic acid

              valproic acid increases levels of phenobarbital by unspecified interaction mechanism. Minor/Significance Unknown.

            • vecuronium

              phenobarbital decreases effects of vecuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • vinblastine

              phenobarbital will decrease the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • vincristine

              phenobarbital will decrease the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • vincristine liposomal

              phenobarbital will decrease the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • vinorelbine

              phenobarbital will decrease the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • warfarin

              phenobarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • zaleplon

              phenobarbital will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ziprasidone

              phenobarbital will decrease the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • zolpidem

              phenobarbital will decrease the level or effect of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • zonisamide

              phenobarbital will decrease the level or effect of zonisamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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            Adverse Effects

            Frequency Not Defined

            IV

            • Respiratory depression

            Common

            • Ataxia
            • Dizziness
            • Drowsiness
            • Dysarthria
            • Fatigue
            • Headache
            • Irritability
            • Nystagmus
            • Paresthesia restlessness
            • Vertigo
            • Geriatric patients: Excitement, confusion, depression
            • Pediatric patients: Paradoxical excitement/hyperactivity

            Less Common

            • Mental dullness
            • Constipation
            • Diarrhea
            • Nausea
            • Vomiting
            • Megaloblastic (folate-deficiency) anemia

            Uncommon

            • Rash
            • Hypocalcemia
            • Hepatotoxicity

            Rare

            • Stevens-Johnson syndrome
            • Rickets
            • Osteomalacia
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            Warnings

            Contraindications

            Hypersensitivity

            Porphyria

            Intra-arterial or subcutaneous administration

            Severe hepatic impairment

            Dyspnea or airway obstruction

            History of sedative hyponotic addiction

            Nephritic patients (large doses)

            Pregnancy/lactation

            Cautions

            Commercial injection is highly alkaline and may cause tissue necrosis if given SC or if it extravasates (if happens, treat with application of moist heat and injection of 0.5% procaine)

            May render oral contraceptives ineffective

            Paradoxical responses may occur, especially in pediatric patients and patients experiencing acute or chronic pain

            May cause CNS depression, causing physical and mental impairment; caution patient about performing tasks that require mental alertness

            May cause respiratory depression, especially with intravenous administration; use caution in patients with respiratory disease and status asthmaticus

            Withdraw therapy gradually; abrupt discontinuation, may increase seizure frequency

            Use caution in patients with severe anemia, patients experiencing depression, cardiac disease, hemodynamically unstable patients, hyperthyroidism, renal impairment, hypoadrenalism, and in patients with diabetes

            May mask important symptoms when used in patients with acute or chronic pain; use caution

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            Pregnancy & Lactation

            Pregnancy category: D

            Lactation: Do not nurse

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Depresses sensory and motor cortex, cerebellum

            Antiseizure activity occurs primarily where GABA mediates neurotransmission

            Hypnotic effects of barbiturates result from activity at GABA receptor in the polysynaptic midbrain reticular formation (controls CNS arousal)

            Off-label use for hyperbilirubinemia: Phenobarbital induces glucuronyl transferase and hepatic bilirubin-binding Y-protein to lower serum bilirubin concentrations

            Absorption

            Bioavailability: 70-90%

            Onset: 5 min (IV)

            Duration: 4-6 hr (IV/IM)

            Peak plasma time: 8-12 hr

            Therapeutic plasma concentration: 10-40 mcg/mL; may require 3-4 weeks of treatment to achieve therapeutic levels

            Distribution

            Protein bound: 20-45%

            Metabolism

            Metabolized by hepatic oxidative hydroxylation

            Metabolites: Inactive

            Enzymes induced: CYP1A2, CYP2B6, CYP2C19, CYP2C9/10, CYP3A4

            Elimination

            Half-life: 50-140 hr

            Excretion: Urine (major)

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            Administration

            IV Incompatibilities

            Additive: Chlorpromazine, ephedrine, hydralazine, hydrocortisone Na-succinate, hydroxyzine, insulin, levorphanol, meperidine, morphine, norepinephrine, pentazocine, procaine, prochlorperazine, promazine, promethazine, streptomycin, vancomycin

            Syringe: Hydromorphone, ranitidine, sufentanil

            Y-site: Amphotericin B cholSO4

            IV Compatibilities

            Solution: Dextrose Ringer, dextrose LR, dextrose saline, Ringer, LR, NS, ½ NS, Na-lactate 1/6 M, D5W, D10W

            Additive: Amikacin, aminophylline, CaCl2, Ca-gluconate, colistimethate, dimenhydrinate, meropenem, polymyxin B, thiopental, verapamil

            Syringe: Caffeine, heparin

            Y-site: Doxapram, enalaprilat, fentanyl, fosphenytoin gatifloxacin, hydromorphone (may be incompatible at high concentrations of both), levofloxacin, linezolid, meropenem, methadone, morphine SO4, propofol, sufentanil

            IV Administration

            Slow injection at <60 mg/min

            May be given IM into large muscle but not SC

            Commercial injection is highly alkaline and can cause local tissue necrosis

            Stability

            Store intact vials at room temperature, protected from light

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            phenobarbital oral
            -
            100 mg tablet
            phenobarbital oral
            -
            97.2 mg tablet
            phenobarbital oral
            -
            97.2 mg tablet
            phenobarbital oral
            -
            64.8 mg tablet
            phenobarbital oral
            -
            32.4 mg tablet
            phenobarbital oral
            -
            16.2 mg tablet
            phenobarbital oral
            -
            20 mg/5 mL (4 mg/mL) elixir
            phenobarbital oral
            -
            100 mg tablet
            phenobarbital oral
            -
            60 mg tablet
            phenobarbital oral
            -
            16.2 mg tablet
            phenobarbital oral
            -
            32.4 mg tablet
            phenobarbital oral
            -
            64.8 mg tablet
            phenobarbital oral
            -
            32.4 mg tablet
            phenobarbital oral
            -
            16.2 mg tablet
            phenobarbital oral
            -
            15 mg tablet
            phenobarbital oral
            -
            32.4 mg tablet
            phenobarbital oral
            -
            16.2 mg tablet
            phenobarbital oral
            -
            32.4 mg tablet
            phenobarbital oral
            -
            97.2 mg tablet
            phenobarbital oral
            -
            16.2 mg tablet
            phenobarbital oral
            -
            64.8 mg tablet
            phenobarbital oral
            -
            32.4 mg tablet
            phenobarbital oral
            -
            30 mg tablet
            phenobarbital oral
            -
            64.8 mg tablet
            phenobarbital oral
            -
            97.2 mg tablet
            phenobarbital oral
            -
            15 mg tablet
            phenobarbital oral
            -
            20 mg/5 mL (4 mg/mL) elixir
            phenobarbital oral
            -
            30 mg tablet
            phenobarbital oral
            -
            30 mg tablet
            phenobarbital oral
            -
            64.8 mg tablet
            phenobarbital oral
            -
            64.8 mg tablet
            phenobarbital oral
            -
            97.2 mg tablet
            phenobarbital oral
            -
            97.2 mg tablet
            phenobarbital oral
            -
            100 mg tablet
            phenobarbital oral
            -
            60 mg tablet
            phenobarbital oral
            -
            30 mg tablet
            phenobarbital oral
            -
            15 mg tablet
            phenobarbital oral
            -
            97.2 mg tablet
            phenobarbital oral
            -
            64.8 mg tablet
            phenobarbital oral
            -
            15 mg tablet
            phenobarbital oral
            -
            15 mg tablet

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            phenobarbital oral

            PHENOBARBITAL - ORAL

            (fee-no-BARB-ih-tall)

            COMMON BRAND NAME(S): Luminal

            USES: This medication is used alone or with other medications to control seizures. Controlling and reducing seizures lets you do more of your normal daily activities, reduces your risk of harm when you lose consciousness, and lessens your risk for a possibly life-threatening condition of frequent, repeated seizures. Phenobarbital belongs to a class of drugs known as barbiturate anticonvulsants/hypnotics. It works by controlling the abnormal electrical activity in the brain that occurs during a seizure. This medication is also used for a short time (usually no more than 2 weeks) to help calm you or help you sleep during periods of anxiety. It works by affecting certain parts of the brain to cause calming.

            HOW TO USE: Take this medication by mouth with or without food, usually once daily at bedtime for seizure control, or as directed by your doctor. Take with food or milk if stomach upset occurs. If you are using the liquid form of this medication, measure the dose carefully using a special measuring device/cup. Do not use a household spoon because you may not get the correct dose.Dosage is based on your medical condition, phenobarbital blood levels, and response to treatment. The dosage in children may also be based on weight.Your doctor may direct you to start this medication at a low dose and gradually increase your dose to prevent side effects such as drowsiness and dizziness. Follow your doctor's instructions carefully. Do not take more or less of this drug than prescribed.It may take several weeks to reach the best dose for you and completely control your seizures. This medication works best when the amount of drug in your body is kept at a constant level. Take it at the same time(s) each day.Do not stop taking this medication (and other anticonvulsant medications) without consulting your doctor. Your seizures may worsen or cause a very severe seizure that is difficult to treat (status epilepticus) when this drug is suddenly stopped.If you suddenly stop using this medication, you may have withdrawal symptoms (such as anxiety, hallucinations, twitching, trouble sleeping). Withdrawal from phenobarbital can be severe and include seizures and (rarely) death. To help prevent withdrawal, your doctor may lower your dose slowly. Withdrawal is more likely if you have used phenobarbital for a long time or in high doses. Tell your doctor or pharmacist right away if you have withdrawal.Though it helps many people, this medication may sometimes cause addiction. This risk may be higher if you have a substance use disorder (such as overuse of or addiction to drugs/alcohol). Take this medication exactly as prescribed to lower the risk of addiction. Ask your doctor or pharmacist for more details.When this medication is used for a long time for anxiety or to help you sleep, it may not work as well. Phenobarbital should only be used for a short time for anxiety or sleep. Talk with your doctor if this medication stops working well.Tell your doctor if your anxiety or seizure control worsens (such as the number of seizures increases).

            SIDE EFFECTS: Dizziness, drowsiness, excitation, headache, tiredness, loss of appetite, nausea, or vomiting may occur as your body adjusts to the medication. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.A small number of people who take anticonvulsants for any condition (such as seizure, bipolar disorder, pain) may experience depression, suicidal thoughts/attempts, or other mental/mood problems. Tell your doctor right away if you or your family/caregiver notice any unusual/sudden changes in your mood, thoughts, or behavior including signs of depression, suicidal thoughts/attempts, thoughts about harming yourself.Tell your doctor right away if you have any serious side effects, including: staggering walk/clumsiness, double vision, fast/slow/shallow breathing, fainting, slow heartbeat, severe tiredness/weakness, pale skin.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking phenobarbital, tell your doctor or pharmacist if you are allergic to it; or to other barbiturates (such as primidone, secobarbital); or to other anti-seizure medications (such as carbamazepine, fosphenytoin, oxcarbazepine, phenytoin); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: certain hormone problems (adrenal disease such as Addison's disease), liver problems, kidney problems, lung disease (such as sleep apnea, chronic obstructive pulmonary disease-COPD), mental/mood disorders (such as depression, thoughts of suicide), personal or family history of a substance use disorder (such as overuse of or addiction to drugs/alcohol), personal/family history of a certain blood disorder (porphyria), certain vitamin deficiencies (folic acid, vitamin K).This drug may make you dizzy or drowsy. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).The liquid form of this product may contain alcohol or sugar. Caution is advised if you have diabetes, alcohol dependence, liver disease, or any other condition that requires you to limit/avoid these substances in your diet. Ask your doctor or pharmacist about using this product safely.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Older adults may be more sensitive to the side effects of this drug, especially drowsiness and dizziness. However, this drug can often cause excitement or confusion instead of drowsiness in older adults. Drowsiness, confusion, and dizziness can increase the risk of falling.Children may be more sensitive to the side effects of the drug. This drug can often cause excitement instead of drowsiness in young children.This medication is not recommended for use during pregnancy. It may harm an unborn baby. However, since untreated seizures are a serious condition that can harm both a pregnant woman and her unborn baby, do not stop taking this medication unless directed by your doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, immediately talk to your doctor about the benefits and risks of using this medication during pregnancy. Since birth control pills, patches, implants, and injections may not work if taken with this medication (see also Drug Interactions section), discuss reliable forms of birth control with your doctor.This medication may lower your folic acid and vitamin K levels, increasing the risk of spinal cord defects. Check with your doctor to make sure you are taking enough folic acid and vitamin K. Infants born to mothers who have been using this medication during pregnancy may also have symptoms such as fussiness, shaking, or bleeding. Tell the doctor right away if you notice any of these symptoms in your newborn.This medication passes into breast milk and may cause excessive sleepiness or feeding problems in the nursing infant. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: darunavir, etravirine, orlistat, rilpivirine.Other medications can affect the removal of phenobarbital from your body, which may affect how phenobarbital works. Examples include St. John's wort, among others.This medication can speed up the removal of other medications from your body, which may affect how they work. Examples of affected drugs include artemether/lumefantrine, asunaprevir, atazanavir, boceprevir, cobicistat, lurasidone, ranolazine, sofosbuvir, sorafenib, voriconazole, certain calcium channel blockers such as felodipine/nimodipine, among others.This medication may decrease the effectiveness of hormonal birth control such as pills, patch, or ring. This could cause pregnancy. Discuss with your doctor or pharmacist if you should use reliable backup birth control methods while using this medication. Also tell your doctor if you have any new spotting or breakthrough bleeding, because these may be signs that your birth control is not working well.The risk of serious side effects (such as slow/shallow breathing, severe drowsiness/dizziness) may be increased if this medication is taken with other products that may also cause drowsiness or breathing problems. Tell your doctor or pharmacist if you are taking other products such as opioid pain or cough relievers (such as codeine, hydrocodone), alcohol, marijuana (cannabis), other drugs for sleep or anxiety (such as alprazolam, lorazepam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), or antihistamines (such as cetirizine, diphenhydramine).Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.Phenobarbital is very similar to primidone. Do not use medications containing primidone while using phenobarbital.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe tiredness/dizziness, inability to wake up, very slow breathing rate.

            NOTES: Do not share this medication with others. Sharing it is against the law.Keep all medical appointments so that your doctor can monitor your progress or check for side effects. For long-term use, laboratory and/or medical tests (such as phenobarbital blood levels, blood counts, liver/kidney tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

            MISSED DOSE: If you are taking this medication to prevent seizures and miss a dose, take it as soon as you remember unless it is almost time for the next dose. In that case, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

            Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.