methadone (Rx)

Brand and Other Names:Methadose, Dolophine
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

injectable solution: Schedule II

  • 10mg/mL

tablet: Schedule II

  • 5mg
  • 10mg

dispersible tablet: Schedule II

  • 40mg

oral solution: Schedule II

  • 5mg/5mL
  • 10mg/5mL

oral concentrate solution: Schedule II

  • 10mg/mL

Pain Management

Indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate

Opioid-naive patients: 2.5 mg PO q8-12hr; titrate slowly with dose increases no more frequent than every 3-5 days

Conversion from parenteral methadone to oral methadone

  • 1:2 Parenteral-to-PO ratio: 5 mg parenteral = 10 mg PO

Conversion from other oral opioids to oral or intravenous methadone

  • Total daily baseline oral estimated daily oral and intravanous methadone requirement as percent of morphine equivalent dose
  • < 100 mg morphine equivalent dose: Administer 20% to 30% oral methadone or 10-15% IV methdone as percent of morphine equivalent dose
  • 100-300 mg morphine equivalent dose: Administer 10% to 20% oral methadone or 5-10% IV methadone as percent of morphine equivalent dose
  • 300-600 mg morphine equivalent dose: administer 8% to 12% oral methadone or 4-6% IV methadone as percent of morphine equivalent dose
  • 600-1,000 mg morphine equivalent dose: administer 5% to 10% oral methadone or 3-5% IV methadone as percent of morphine equivalent dose
  • > 1,000 mg morphine equivalent dose: Administer < 5 % oral methadone or <3% IV methadone as percent of morphine equivalent dose
  • For patients on a single opioid, sum the current total daily dose of the opioid, convert it to a morphine equivalent dose according to specific conversion factor for that specific opioid, then multiply the Morphine equivalent dose by the corresponding percentage in the above conversion description to calculate the approximate oral and IV methadone daily dose; divide the total daily methadone dose derived from the conversion description above to reflect the intended dosing schedule (i.e., for administration every 8 hours, divide total daily methadone dose by 3)
  • For patients on a regimen of more than one opioid, calculate the approximate oral methadone dose for each opioid and sum the totals to obtain the approximate total methadone daily dose. Divide the total daily methadone dose derived from the conversion description above to reflect the intended dosing schedule (i.e., for administration every 8 hours, divide total daily methadone dose by 3)

Parenteral morphine to intravenous methadone conversion for chronic administration

  • Total daily baseline parenteral estimated daily parenteral methadone requirement as percent of total daily morphine dose
  • 10-30 mg total daily baseline parenteral morphine dose: Administer 40-66% parenteral methadone as percent of morphine dose
  • 30-50 mg total daily baseline parenteral morphine dose: Administer 27-66% parenteral methadone as percent of morphine dose
  • 50-100 mg total daily baseline parenteral morphine dose: Administer 22-50% parenteral methadone as percent of morphine dose
  • 100-200 mg total daily baseline parenteral morphine dose: Administer 15-34% parenteral methadone as percent of morphine dose
  • 200-500 mg total daily baseline parenteral morphine dose: Administer 10% to 20% parenteral methadone as percent of morphine dose
  • The total daily methadone dose derived from the conversion calculations above may be divided to reflect the intended dosing schedule (i.e., for administration every 8 hours, divide total daily methadone dose by 3)
  • Methadone dosing should not be based solely on these methadone conversion calculations; dose titration methods should always be individualized to account for the patient's prior opioid exposure, general medical condition, concomitant medication, and anticipated breakthrough medication use; the endpoint of titration is achievement of adequate pain relief, balanced against tolerability of opioid side effects; if a patient develops intolerable opioid related side effects, the methadone dose, or dosing interval, may need to be decreased; for patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid component of these products in the conversion; always round the dose down, if necessary, to the appropriate methadone tablet or IV formulation strength(s) available

Opioid-tolerant patients

  • Discontinue all other around-the-clock opioids
  • Substantial interpatient variability, see prescribing information for guidance

Opioid-tolerant definition

  • Patients who are opioid tolerant are those receiving, for 1 week or longer, at least 60 mg/day PO morphine, 25 mcg/hr transdermal fentanyl, 30 mg/day PO oxycodone, 8 mg/day PO hydromorphone, 25 mg/day PO oxymorphone, or an equianalgesic dose of another opioid
  • Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression

Detoxification

20-30 mg PO once daily or minimum dosage necessary to suppress withdrawal; may be titrated to 40 mg/day in divided doses and continued for 2-3 days, then decreased 20% daily as tolerated

Dosing Modifications

Renal impairment (CrCl <10mL/min): 50-75% of normal dose

Hepatic impairment: Not recommended in severe liver disease:

Dosing Considerations

Do not abruptly discontinue methadone in a physically dependent patient

Limitations of use

  • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve for patients whom alternative treatment options (eg, nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain
  • Not indicated for acute pain or as a PRN analgesic

Access to naloxone for opioid overdose

  • Assess need for naloxone upon initiating and renewing treatment
  • Consider prescribing naloxone
    • Based on patient’s risk factors for overdose (eg, concomitant use of CNS depressants, a history of opioid use disorder, prior opioid overdose); presence of risk factors should not prevent proper pain management
    • Household members (including children) or other close contacts at risk for accidental ingestion or overdose
  • Consult patients and caregivers on the following:
    • Availability of naloxone for emergency treatment of opioid overdose
    • Ways differ on how to obtain naloxone as permitted by individual state dispensing and prescribing requirements or guidelines (eg, by prescription, directly from a pharmacist, as part of a community-based program)

Dosage Forms & Strengths

injected solution: Schedule II

  • 10mg/mL

tablet: Schedule II

  • 5mg
  • 10mg
  • 40mg

dispersible tablet: Schedule II

  • 40mg

oral solution: Schedule II

  • 5mg/5mL
  • 10mg/5mL

Pain (Off-label)

0.7 mg/kg/day PO/SC/IV/IM divided q6hr PRN; not to exceed 10 mg/dose  

Opiate Withdrawal (Off-label)

Neonates: 0.05-0.2 mg/kg PO q12-24hr; reduce dose by 10-20% per week over 4-6 weeks; adjust tapering on signs and symptoms of withdrawal

Pain

2.5 mg PO/IM q8-12hr; titrate slowly with dose increases no more frequent than every 3-5 days

Detoxification

20-30 mg PO once daily or minimum dosage necessary to suppress withdrawal; may be titrated to 40 mg/day in divided doses and continued for 2-3 days, then decreased 20% daily as tolerated

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Interactions

Interaction Checker

and methadone

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            Contraindicated (9)

            • alvimopan

              alvimopan, methadone. receptor binding competition. Contraindicated. Alvimopan is contraindicated in opioid tolerant patients (ie, those who have taken therapeutic doses of opioids for >7 consecutive days immediately prior to taking alvimopan). Patients recently exposed to opioids are expected to be more sensitive to the effects of alvimopan and therefore may experience abdominal pain, nausea and vomiting, and diarrhea. No significant interaction is expected with concurrent use of opioid analgesics and alvimopan in patients who received opioid analgesics for 7 or fewer consecutive days prior to alvimopan.

            • eliglustat

              methadone increases levels of eliglustat by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated. If coadministered with strong or moderate CYP2D6 inhibitors, reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive and intermediate metabolizers; eliglustat is contraindiated if strong or moderate CYP2D6 inhibitors are given concomitantly with strong or moderate CYP3A inhibitors.

            • itraconazole

              itraconazole will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. QT interval prolongation and serious arrhythmia (torsades de pointes) have occurred in patients using methadone concomitantly with oral itraconazole and/or other CYP3A4 inhibitors.

            • ketoconazole

              ketoconazole will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

              ketoconazole and methadone both increase QTc interval. Contraindicated.

            • lefamulin

              lefamulin will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lefamulin is contraindicated with CYP3A substrates know to prolong the QT interval.

            • rasagiline

              rasagiline increases toxicity of methadone by unknown mechanism. Contraindicated. Risk of hypotension, hyperpyrexia, somnolence, or death.

            • ribociclib

              ribociclib will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • safinamide

              methadone, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • selegiline

              selegiline increases toxicity of methadone by unknown mechanism. Contraindicated. At least 14 days should elapse between discontinuation of selegiline and initiation of analgesic.

            Serious - Use Alternative (89)

            • abametapir

              abametapir will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • alfuzosin

              alfuzosin and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • amiodarone

              amiodarone and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • apalutamide

              apalutamide will decrease the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 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. Adjust dose according to prescribing information if needed.

            • apomorphine

              apomorphine and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • aripiprazole

              aripiprazole and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • arsenic trioxide

              arsenic trioxide and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • artemether

              artemether and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • atomoxetine

              atomoxetine and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, methadone. 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.

            • bremelanotide

              bremelanotide will decrease the level or effect of methadone 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.

            • buprenorphine

              buprenorphine, methadone. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • buprenorphine buccal

              buprenorphine buccal, methadone. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • butorphanol

              butorphanol, methadone. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • calcium/magnesium/potassium/sodium oxybates

              methadone, calcium/magnesium/potassium/sodium oxybates. Either increases effects 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.

            • carbamazepine

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

            • chloroquine

              chloroquine increases toxicity of methadone by QTc interval. Avoid or Use Alternate Drug.

            • cimetidine

              cimetidine will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              cimetidine increases effects of methadone by decreasing metabolism. Avoid or Use Alternate Drug.

            • clarithromycin

              clarithromycin will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • clonidine

              clonidine, methadone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

            • diazepam intranasal

              diazepam intranasal, methadone. 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.

            • disopyramide

              disopyramide and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • eluxadoline

              methadone, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions. .

            • entrectinib

              methadone and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • enzalutamide

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

            • eribulin

              eribulin and methadone both increase QTc interval. Avoid or Use Alternate Drug. Potential for enhanced QTc-prolonging effects; if concurrent use is necessary then ECG monitoring is recommended.

            • erythromycin base

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

            • erythromycin ethylsuccinate

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

            • erythromycin lactobionate

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

            • erythromycin stearate

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

            • escitalopram

              escitalopram increases toxicity of methadone by QTc interval. Avoid or Use Alternate Drug.

            • ethotoin

              ethotoin decreases levels of methadone by increasing metabolism. Contraindicated.

            • fentanyl

              fentanyl, methadone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

            • fentanyl intranasal

              fentanyl intranasal, methadone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

            • fentanyl transdermal

              fentanyl transdermal, methadone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

            • fentanyl transmucosal

              fentanyl transmucosal, methadone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

            • fexinidazole

              fexinidazole and methadone both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels and/or prolong QT interval.

              fexinidazole will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fosphenytoin

              fosphenytoin decreases levels of methadone by increasing metabolism. Contraindicated.

            • glasdegib

              methadone and glasdegib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, monitor for increased risk of QTc interval prolongation.

            • hydrocodone

              hydrocodone, methadone. 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.

            • hydroxychloroquine sulfate

              hydroxychloroquine sulfate and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • ibutilide

              ibutilide and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • idelalisib

              idelalisib will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • indapamide

              indapamide and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • inotuzumab

              inotuzumab and methadone both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.

            • isocarboxazid

              isocarboxazid increases toxicity of methadone by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • ivosidenib

              ivosidenib and methadone both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation.

              ivosidenib will decrease the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • linezolid

              linezolid increases toxicity of methadone by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • lonafarnib

              methadone will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

            • lopinavir

              lopinavir will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • macimorelin

              macimorelin and methadone both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.

            • methylene blue

              methylene blue and methadone both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • metoclopramide intranasal

              methadone, 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.

            • mifepristone

              mifepristone will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • nalbuphine

              nalbuphine, methadone. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • nefazodone

              nefazodone will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ondansetron

              methadone and ondansetron both increase QTc interval. Avoid or Use Alternate Drug. Avoid with congenital long QT syndrome; ECG monitoring recommended with concomitant medications that prolong QT interval, electrolyte abnormalities, CHF, or bradyarrhythmias.

            • ozanimod

              ozanimod and methadone both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

            • panobinostat

              methadone and panobinostat both increase QTc interval. Avoid or Use Alternate Drug. Panobinostat is known to significantly prolong QT interval. Panobinostat prescribing information states use with drugs known to prolong QTc is not recommended.

            • pentamidine

              methadone and pentamidine both increase QTc interval. Avoid or Use Alternate Drug.

            • pentazocine

              pentazocine, methadone. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • phenelzine

              phenelzine increases toxicity of methadone by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • phenytoin

              phenytoin decreases levels of methadone by increasing metabolism. Contraindicated.

            • pimozide

              methadone and pimozide both increase QTc interval. Avoid or Use Alternate Drug.

            • pitolisant

              methadone and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.

            • ponesimod

              ponesimod, methadone. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

            • procainamide

              methadone and procainamide both increase QTc interval. Avoid or Use Alternate Drug.

            • procarbazine

              procarbazine increases toxicity of methadone by unknown mechanism. Avoid or Use Alternate Drug. MAOIs may potentiate CNS depression and hypotension. Do not use within 14 days of MAOI use. .

            • quinidine

              quinidine and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • ribociclib

              ribociclib and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • rifabutin

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

            • rifampin

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

            • romidepsin

              methadone and romidepsin both increase QTc interval. Avoid or Use Alternate Drug.

            • saquinavir

              saquinavir, methadone. Either increases toxicity of the other by QTc interval. Avoid or Use Alternate Drug. Increased risk of PR prolongation and cardiac arrhythmias.

              saquinavir will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • selegiline transdermal

              selegiline transdermal increases toxicity of methadone by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

            • selinexor

              selinexor, methadone. 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.

            • sodium oxybate

              methadone, sodium oxybate. Either increases effects 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.

            • sotalol

              methadone and sotalol both increase QTc interval. Avoid or Use Alternate Drug.

            • St John's Wort

              St John's Wort will decrease the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • sufentanil SL

              sufentanil SL, methadone. 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.

            • tramadol

              tramadol, methadone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

            • tranylcypromine

              tranylcypromine increases toxicity of methadone by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • tucatinib

              tucatinib will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • umeclidinium bromide/vilanterol inhaled

              methadone increases toxicity of umeclidinium bromide/vilanterol inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

            • valerian

              valerian and methadone both increase sedation. Avoid or Use Alternate Drug.

            • vandetanib

              methadone, vandetanib. Either increases toxicity of the other by QTc interval. Avoid or Use Alternate Drug. Avoid coadministration with drugs known to prolong QT interval; if a drug known to prolong QT interval must be used, more frequent ECG monitoring is recommended.

            • vemurafenib

              vemurafenib and methadone both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.

            • vilanterol/fluticasone furoate inhaled

              methadone increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

            • voxelotor

              voxelotor will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            Monitor Closely (327)

            • abacavir

              abacavir will decrease the level or effect of methadone by unknown mechanism. Use Caution/Monitor. Monitor for opioid withdrawal symptoms.

            • albuterol

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

              albuterol and methadone both increase QTc interval. Use Caution/Monitor.

            • alfentanil

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

            • alfuzosin

              methadone and alfuzosin both increase QTc interval. Use Caution/Monitor.

            • alprazolam

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

            • amitriptyline

              amitriptyline and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • amobarbital

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

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

            • amoxapine

              amoxapine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • apomorphine

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

            • aprepitant

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

            • arformoterol

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

              arformoterol and methadone both increase QTc interval. Use Caution/Monitor.

            • aripiprazole

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

              methadone, aripiprazole. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • armodafinil

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

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

            • artemether/lumefantrine

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

              artemether/lumefantrine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

            • asenapine

              methadone, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • atazanavir

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

            • avapritinib

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

            • axitinib

              methadone increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • azelastine

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

            • baclofen

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

            • bedaquiline

              methadone and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely

            • belladonna and opium

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

            • benperidol

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

            • benzphetamine

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

            • bosentan

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

            • bosutinib

              bosutinib and methadone both increase QTc interval. Use Caution/Monitor.

            • brexanolone

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

            • brexpiprazole

              methadone will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

            • brompheniramine

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

            • budesonide

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

            • buprenorphine

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

            • buprenorphine buccal

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

            • buprenorphine, long-acting injection

              methadone increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.

            • butabarbital

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

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

            • butalbital

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

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

            • butorphanol

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

            • caffeine

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

            • cannabidiol

              cannabidiol will increase the level or effect of methadone by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • capecitabine

              capecitabine and methadone both increase QTc interval. Use Caution/Monitor.

            • carbinoxamine

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

            • cariprazine

              methadone, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • carisoprodol

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

            • cenobamate

              cenobamate will decrease the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • chloral hydrate

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

            • chlordiazepoxide

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

            • chlorpheniramine

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

            • chlorpromazine

              chlorpromazine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • chlorzoxazone

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

            • cinnarizine

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

            • ciprofloxacin

              ciprofloxacin and methadone both increase QTc interval. Use Caution/Monitor. Ciprofloxacin elicits minimal effects on QT interval. Caution if used in combination with other drugs known to affect QT interval or in patients with other risk factors.

            • citalopram

              methadone and citalopram both increase QTc interval. Use Caution/Monitor. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome like reactions. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • clarithromycin

              clarithromycin and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

            • clemastine

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

            • clobazam

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

            • clomipramine

              clomipramine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • clonazepam

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

            • clorazepate

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

            • clozapine

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

              methadone, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • cobicistat

              cobicistat will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Methadone dose may require an adjustment

            • codeine

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

            • conivaptan

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

            • cortisone

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

            • crizotinib

              crizotinib increases levels of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • crofelemer

              crofelemer increases levels of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • cyclizine

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

            • cyclobenzaprine

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

            • cyclosporine

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

            • cyproheptadine

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

            • dabrafenib

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

            • dantrolene

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

            • darifenacin

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

            • darunavir

              darunavir will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Carefully titrate dose when initiating buprenorphine, buprenorphine/naloxone, or methadone with patients taking darunavir/cobicstat. When initiating cobicistat in patients taking buprenorphine, buprenorphine/naloxone, or methadone, adjust dose for buprenorphine, buprenorphine/naloxone, or methadone and monitor clinical signs and symptoms.

            • dasatinib

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

              dasatinib and methadone both increase QTc interval. Use Caution/Monitor.

            • deferasirox

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

            • desflurane

              desflurane and methadone both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.

            • desipramine

              desipramine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • deutetrabenazine

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

            • dexamethasone

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

            • dexchlorpheniramine

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

            • dexfenfluramine

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

            • dexmedetomidine

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

            • dexmethylphenidate

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

            • dextroamphetamine

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

            • dextromoramide

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

            • DHEA, herbal

              DHEA, herbal will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • diamorphine

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

            • diazepam

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

            • dichlorphenamide

              dichlorphenamide and methadone both decrease serum potassium. Use Caution/Monitor.

            • didanosine

              methadone decreases levels of didanosine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • diethylpropion

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

            • difenoxin hcl

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

            • diltiazem

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

            • dimenhydrinate

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

            • diphenhydramine

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

            • diphenoxylate hcl

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

            • dipipanone

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

            • dobutamine

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

            • dofetilide

              dofetilide and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

            • dolasetron

              dolasetron and methadone both increase QTc interval. Use Caution/Monitor.

            • dopamine

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

            • dopexamine

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

            • dosulepin

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

            • doxepin

              doxepin and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • doxylamine

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

            • dronedarone

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

              dronedarone and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

            • droperidol

              droperidol and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • duvelisib

              duvelisib will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

            • efavirenz

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

            • elagolix

              elagolix decreases levels of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • eltrombopag

              eltrombopag increases levels of methadone by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.

            • elvitegravir

              elvitegravir decreases levels of methadone by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Dosage of methadone may need to be increased.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • encorafenib

              encorafenib, methadone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • ephedrine

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

            • epinephrine

              epinephrine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • epinephrine racemic

              epinephrine racemic and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • erythromycin base

              erythromycin base and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

            • erythromycin lactobionate

              erythromycin lactobionate and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

            • erythromycin stearate

              erythromycin stearate and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

            • esketamine intranasal

              esketamine intranasal, methadone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

            • eslicarbazepine acetate

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

            • estazolam

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

            • ethanol

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

            • etomidate

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

            • etravirine

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

            • ezogabine

              ezogabine, methadone. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.

            • fedratinib

              fedratinib will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fenfluramine

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

            • finerenone

              methadone will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

            • flecainide

              flecainide and methadone both increase QTc interval. Use Caution/Monitor.

            • flibanserin

              methadone and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

              methadone will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

            • fluconazole

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

              fluconazole and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

            • fludrocortisone

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

            • fluoxetine

              fluoxetine and methadone both increase QTc interval. Use Caution/Monitor.

            • fluphenazine

              fluphenazine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

              methadone, fluphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • flurazepam

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

            • fluvoxamine

              fluvoxamine and methadone both increase QTc interval. Use Caution/Monitor.

            • formoterol

              formoterol and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • fosamprenavir

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

            • foscarnet

              foscarnet and methadone both increase QTc interval. Use Caution/Monitor.

            • fosphenytoin

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

            • gabapentin

              gabapentin, methadone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • gabapentin enacarbil

              gabapentin enacarbil, methadone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • gemtuzumab

              methadone and gemtuzumab both increase QTc interval. Use Caution/Monitor.

            • goserelin

              goserelin increases toxicity of methadone by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

            • grapefruit

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

            • griseofulvin

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

            • haloperidol

              haloperidol and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

              methadone, haloperidol. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • histrelin

              histrelin increases toxicity of methadone by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

            • hydrocortisone

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

            • hydromorphone

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

            • hydroxyzine

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

              hydroxyzine increases toxicity of methadone by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

            • iloperidone

              iloperidone and methadone both increase QTc interval. Use Caution/Monitor.

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

              iloperidone increases levels of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

              methadone, iloperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • imipramine

              imipramine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • indacaterol, inhaled

              indacaterol, inhaled, methadone. QTc interval. Use Caution/Monitor. Drugs that are known to prolong the QTc interval may have an increased the risk of ventricular arrhythmias.

            • indinavir

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

            • isoniazid

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

            • isoproterenol

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

            • istradefylline

              istradefylline will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • ketamine

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

            • ketotifen, ophthalmic

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

            • lapatinib

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

              lapatinib and methadone both increase QTc interval. Use Caution/Monitor.

            • lasmiditan

              lasmiditan, methadone. 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

              methadone will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.

              lemborexant, methadone. 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.

            • lenvatinib

              methadone and lenvatinib both increase QTc interval. Use Caution/Monitor. Lenvatinib prescribing information recommends monitoring ECG closely when coadministered with QT prolonging drugs.

            • letermovir

              letermovir increases levels of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • leuprolide

              leuprolide increases toxicity of methadone by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

            • levalbuterol

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

            • levofloxacin

              levofloxacin and methadone both increase QTc interval. Use Caution/Monitor.

            • levorphanol

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

            • lisdexamfetamine

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

            • lofepramine

              lofepramine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • lofexidine

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

              methadone and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended.

            • lomitapide

              methadone increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

            • loprazolam

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

            • lorazepam

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

            • lorlatinib

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

            • lormetazepam

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

            • loxapine

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

              methadone, loxapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • loxapine inhaled

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

              methadone, loxapine inhaled. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • lumefantrine

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

              lumefantrine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

            • lurasidone

              lurasidone, methadone. 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.

              methadone, lurasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • maprotiline

              maprotiline and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • maraviroc

              maraviroc increases levels of methadone by QTc interval. Use Caution/Monitor. Potential for increased toxicity. Increased risk of QT prolongation and cardiac arrhythmias.

            • marijuana

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

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

            • melatonin

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

            • meperidine

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

            • meprobamate

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

            • metaproterenol

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

            • metaxalone

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

            • methamphetamine

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

            • methocarbamol

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

            • methylenedioxymethamphetamine

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

            • methylprednisolone

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

            • metronidazole

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

            • miconazole vaginal

              miconazole vaginal will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • midazolam

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

            • midazolam intranasal

              methadone will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

              midazolam intranasal, methadone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of benzodiazepines and opioids increases risk of respiratory depression. Use only in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required.

            • midodrine

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

            • mifepristone

              mifepristone will increase the level or effect of methadone by Other (see comment). Modify Therapy/Monitor Closely. Inhibits CYP2C8/2C9; use smallest recommended doses for substrates and monitor; combination may increase QT interval. Use alternatives if available

            • mirtazapine

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

            • mitotane

              mitotane decreases levels of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • modafinil

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

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

            • molindone

              methadone, molindone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • morphine

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

            • motherwort

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

            • moxifloxacin

              methadone and moxifloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

            • moxonidine

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

            • nabilone

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

            • nafcillin

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

            • nalbuphine

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

            • nelfinavir

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

            • nevirapine

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

            • nifedipine

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

            • nilotinib

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

              methadone and nilotinib both increase QTc interval. Modify Therapy/Monitor Closely.

            • norepinephrine

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

            • nortriptyline

              nortriptyline and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • octreotide

              methadone and octreotide both increase QTc interval. Modify Therapy/Monitor Closely.

            • octreotide (Antidote)

              methadone and octreotide (Antidote) both increase QTc interval. Modify Therapy/Monitor Closely.

            • ofloxacin

              methadone and ofloxacin both increase QTc interval. Use Caution/Monitor.

            • olanzapine

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

              methadone, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • oliceridine

              methadone will increase the level or effect of oliceridine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

              oliceridine, methadone. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. 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.

            • olodaterol inhaled

              methadone and olodaterol inhaled both increase QTc interval. Use Caution/Monitor. Drugs that prolong the QTc interval and may potentiate the effects of beta2 agonists on the cardiovascular system; increased risk of ventricular arrhythmias

            • opium tincture

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

            • orphenadrine

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

            • osilodrostat

              osilodrostat and methadone both increase QTc interval. Use Caution/Monitor.

            • osimertinib

              osimertinib and methadone both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.

            • oxaliplatin

              oxaliplatin will increase the level or effect of methadone by Other (see comment). Use Caution/Monitor. Monitor for ECG changes if therapy is initiated in patients with drugs known to prolong QT interval.

            • oxazepam

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

            • oxcarbazepine

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

            • oxycodone

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

            • oxymorphone

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

            • ozanimod

              ozanimod and methadone both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.

            • paliperidone

              methadone and paliperidone both increase QTc interval. Use Caution/Monitor.

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

              methadone, paliperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • papaveretum

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

            • papaverine

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

            • paroxetine

              methadone and paroxetine both increase QTc interval. Use Caution/Monitor.

            • pasireotide

              methadone and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.

            • peginterferon alfa 2b

              peginterferon alfa 2b will increase the level or effect of methadone by unknown mechanism. Use Caution/Monitor. Methadone levels may be elevated, increasing the pharmacologic effects and adverse reactions. Monitor patients for signs and symptoms of increased narcotic effects and adjust methadone dose as needed.

            • pegvisomant

              methadone decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.

            • pentazocine

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

            • pentobarbital

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

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

            • perampanel

              perampanel and methadone both decrease sedation. Use Caution/Monitor.

            • perphenazine

              perphenazine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

              methadone, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • phendimetrazine

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

            • phenobarbital

              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.

            • phentermine

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

            • phenylephrine

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

            • phenylephrine PO

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

            • phenytoin

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

            • pholcodine

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

            • pimavanserin

              methadone, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • pimozide

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

              methadone, pimozide. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • pirbuterol

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

            • posaconazole

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

              methadone and posaconazole both increase QTc interval. Use Caution/Monitor.

            • prednisone

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

            • pregabalin

              pregabalin, methadone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • primidone

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

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

            • prochlorperazine

              prochlorperazine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • promazine

              promazine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

            • promethazine

              promethazine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • propofol

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

            • propylhexedrine

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

            • protriptyline

              protriptyline and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • quazepam

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

            • quetiapine

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

              quetiapine, methadone. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Avoid use with drugs that prolong QT and in patients with risk factors for prolonged QT interval. Postmarketing cases show QT prolongation with overdose in patients with concomitant illness or with drugs known to cause electrolyte imbalance or prolong QT.

              methadone, quetiapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • quinine

              methadone and quinine both increase QTc interval. Use Caution/Monitor.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ramelteon

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

            • ranolazine

              methadone and ranolazine both increase QTc interval. Use Caution/Monitor.

            • remimazolam

              remimazolam, methadone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

            • rifampin

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

            • rifapentine

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

            • rilpivirine

              rilpivirine, methadone. Other (see comment). Use Caution/Monitor. Comment: No dose adjustments are required when initiating co-administration of methadone with rilpivirine. However, clinical monitoring is recommended as methadone maintenance therapy may need to be adjusted in some patients.

              rilpivirine increases toxicity of methadone by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes.

            • risperidone

              methadone and risperidone both increase QTc interval. Use Caution/Monitor.

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

              methadone, risperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • ritonavir

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

              ritonavir decreases effects of methadone by Other (see comment). Use Caution/Monitor. Comment: Ritonavir may induce the metabolism of methadone and/or induce the p glycoprotein pathway that pumps drugs out of the CNS.

            • rucaparib

              rucaparib will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • rufinamide

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

            • salmeterol

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

            • schisandra

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

            • scullcap

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

            • secobarbital

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

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

            • selpercatinib

              selpercatinib increases toxicity of methadone by QTc interval. Use Caution/Monitor.

            • sevoflurane

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

            • shepherd's purse

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

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of methadone by QTc interval. Use Caution/Monitor. Consider predose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias. .

            • sodium sulfate/potassium sulfate/magnesium sulfate

              sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of methadone by QTc interval. Use Caution/Monitor. Consider predose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias. .

            • sorafenib

              sorafenib and methadone both increase QTc interval. Use Caution/Monitor.

            • stiripentol

              stiripentol, methadone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

              stiripentol will increase the level or effect of methadone by Other (see comment). Modify Therapy/Monitor Closely. Stiripentol is a CYP2C8 inhibitor. Consider dosage reduction for CYP2C8 substrates if adverse effects are experienced when coadministered.

              stiripentol, methadone. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

            • sufentanil

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

            • sulfamethoxazole

              sulfamethoxazole and methadone both increase QTc interval. Use Caution/Monitor.

            • suvorexant

              suvorexant and methadone both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

            • tamsulosin

              methadone increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • tapentadol

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

            • tazemetostat

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

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

            • tecovirimat

              tecovirimat will increase the level or effect of methadone 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.

              tecovirimat will decrease the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • telavancin

              methadone and telavancin both increase QTc interval. Use Caution/Monitor.

            • temazepam

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

            • terbutaline

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

            • teriflunomide

              teriflunomide increases levels of methadone by Other (see comment). Use Caution/Monitor. Comment: Teriflunomide inhibits CYP2C8; caution when coadministered with CYP2C8 substrates.

            • thioridazine

              thioridazine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • thiothixene

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

              methadone, thiothixene. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • tinidazole

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

            • tipranavir

              tipranavir decreases levels of methadone by increasing metabolism. Use Caution/Monitor.

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

            • topiramate

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

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

            • tramadol

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

            • trazodone

              trazodone and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • triazolam

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

            • triclabendazole

              triclabendazole and methadone both increase QTc interval. Use Caution/Monitor.

            • triclofos

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

            • trifluoperazine

              trifluoperazine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

              methadone, trifluoperazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • trimethoprim

              methadone and trimethoprim both increase QTc interval. Use Caution/Monitor.

            • trimipramine

              trimipramine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • triprolidine

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

            • triptorelin

              triptorelin increases toxicity of methadone by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

            • tropisetron

              methadone and tropisetron both increase QTc interval. Use Caution/Monitor.

            • venlafaxine

              methadone and venlafaxine both increase QTc interval. Use Caution/Monitor.

            • verapamil

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

            • voclosporin

              voclosporin, methadone. Either increases effects of the other by QTc interval. Use Caution/Monitor.

            • voriconazole

              voriconazole will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increased plasma concentrations of methadone have been associated with toxicity including QT prolongation. Frequent monitoring for adverse events and toxicity related to methadone is recommended during coadministration. Dose reduction of methadone may be needed.

              methadone and voriconazole both increase QTc interval. Use Caution/Monitor.

            • xylometazoline

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

            • yohimbine

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

            • zafirlukast

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

            • ziconotide

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

            • ziprasidone

              methadone and ziprasidone both increase QTc interval. Modify Therapy/Monitor Closely.

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

              methadone, ziprasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • zotepine

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

            Minor (12)

            • azithromycin

              azithromycin and methadone both increase QTc interval. Minor/Significance Unknown.

            • brimonidine

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

            • dextroamphetamine

              dextroamphetamine increases effects of methadone by unspecified interaction mechanism. Minor/Significance Unknown.

            • eucalyptus

              methadone and eucalyptus both increase sedation. Minor/Significance Unknown.

            • lidocaine

              lidocaine increases toxicity of methadone by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.

            • octreotide

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

            • octreotide (Antidote)

              octreotide (Antidote) decreases levels of methadone by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • pazopanib

              methadone and pazopanib both increase QTc interval. Minor/Significance Unknown.

            • ruxolitinib

              methadone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sage

              methadone and sage both increase sedation. Minor/Significance Unknown.

            • ziconotide

              ziconotide, methadone. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.

            • zidovudine

              methadone increases levels of zidovudine by decreasing renal clearance. Minor/Significance Unknown.

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            Adverse Effects

            Frequency Not Defined

            Agitation

            Angina pectoris

            Anticholinergic effects (dry mouth, palpitation, tachycardia)

            Bradycardia

            Cardiac arrest

            Coma

            Constipation

            Dizziness

            Dysphoria

            Euphoria

            Faintness

            Mental clouding or depression

            Myocardial infarction

            Nausea

            Pruritus, urticaria

            Nervousness

            QT-interval prolongation

            Respiratory arrest

            Respiratory/circulatory depression

            Restlessness

            Sedation

            Seizures

            Severe cardiac arrhythmias

            Shock

            ST-segment elevation

            Sweating, flushing, warmness of face/neck/upper thorax

            Syncope

            Urinary retention, oliguria

            Ventricular tachycardia

            Visual disturbances

            Vomiting

            Weakness

            Postmarketing Reports

            Confusion

            Disorientation

            Congenital oculomotor disorders

            Insomnia

            Hallucinations

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            Warnings

            Black Box Warnings

            Opioid analgesic risk evaluation and mitigation strategy (REMS)

            • To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products; under requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers
            • Healthcare providers are strongly encouraged to:
              • Complete a REMS-compliant education program
              • Counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products
              • Emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist
              • Consider other tools to improve patient, household, and community safety

            Detoxification and maintenance of dependence

            • For detoxification and maintenance of opioid dependence, methadone should be administered in accordance with the treatment standards cited in 42 CFR Section 8, including limitations on unsupervised administration

            Addiction, abuse, and misuse

            • Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death
            • Assess each patient’s risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions

            Life-threatening respiratory depression

            • Serious, life-threatening, or fatal respiratory depression may occur
            • Monitor for respiratory depression, especially during initiation or following a dose increase
            • Instruct patients to swallow tablet/capsule whole; crushing, chewing, snorting, injecting or dissolving can cause rapid release and absorption of a potentially fatal dose
            • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death

            Concomitant use with benzodiazepines or other CNS depressants

            • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death
            • Reserve concomitant prescribing with benzodiazepines or other CNS depressants for patients for whom alternatives to benzodiazepines or other CNS depressants are inadequate; limit dosages and durations to minimum required for patients being treated for pain; follow patients for signs and symptoms of respiratory depression and sedation; if patient is visibly sedated, evaluate cause of sedation, and consider delaying or omitting the daily methadone dose

            Accidental exposure

            • Accidental of even 1 dose, especially by children, can result in a fatal overdose

            Neonatal opioid withdrawal syndrome

            • Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
            • Syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight
            • Onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn
            • If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available

            Life-threatening QT prolongation

            • QT interval prolongation and serious arrhythmia (torsades de pointes) have occurred during treatment with methadone; closely monitor patients with risk factors for development of prolonged QT interval, a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction

            Cytochrome CYP450 interactions

            • Concomitant use with CYP3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors or discontinuation of concomitantly used CYP3A4 2B6, 2C19, or 2C9 inducers can result in fatal overdose

            Treatment for opioid addiction

            • Methadone products, when used for the treatment of opioid addiction in detoxification or maintenance programs, shall be dispensed only by certified opioid treatment programs as stipulated in 42 CFR 8.12

            Contraindications

            Hypersensitivity to methadone or formulation components; acute abdominal condition, toxin-mediated diarrhea, pseudomembranous colitis, respiratory depression; concurrent use of selegiline, hypercarbia, known or suspected gastrointestinal obstruction, including paralytic ileus, asthma (acute), significant respiratory impairment

            Acute pain or postoperative pain; pain that is mild or not expected to persist

            Cautions

            Schedule II opioid analgesics expose users to the risks of addiction, abuse, and misuse; there is a greater risk for overdose and death with extended-release opioids due to the larger amount of active opioid present (see Black Box Warnings)

            Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia; opioid use increases risk of CSA in a dose-dependent fashion; in patients who present with CSA, consider decreasing opioid dosage using best practices for opioid taper

            Addiction, abuse, and misuse risks are increased in patients with a personal or family history of substance abuse or mental illness (eg, major depression); the potential for these risks should not, however, prevent the prescribing of proper pain management in any given patient; intensive monitoring is necessary (see Black Box Warnings)

            Serious, life-threatening, or fatal respiratory depression reported (see Black Box Warnings)

            May cause constipation, which could cause problems in patients with unstable angina and patients post-myocardial infarction; consider preventive measures (sool softener, increased fiber in diet) to reduce potential for constipation

            Accidental exposure reported, including fatalities (see Black Box Warnings)

            Do not abruptly discontinue buprenorphine in a patient physically dependent on opioids; when discontinuing therapy, in a physically dependent patient, gradually taper the dosage; rapid tapering in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain

            Neonatal opioid withdrawal syndrome reported with long-term use during pregnancy (see Black Box Warnings)

            Interactions with CNS depressants (eg, alcohol, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids) can cause additive effects and increase risk for respiratory depression, profound sedation, and hypotension; deaths reported due to methadone abuse in conjunction with benzodiazepines

            Monitor for hypotension during dose initiation and titration; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may significantly increase hypotensive effects

            In patients with circulatory shock, therapy may cause vasodilation that can further reduce cardiac output and blood pressure; avoid therapy in patients with circulatory shock

            Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients

            Serotonin syndrome may occur with concomitant administration of serotonergic agents; monitor patients for symptoms of serotonin syndrome such as mental status changes, autonomic instability, neuromuscular changes, and/or GI symptoms

            Risk of QT interval prolongation at high doses

            Use caution in cardiac arrhythmias, drug abuse or dependence, emotional lability, gallbladder disease, head injury, prostatic hyperplasia,/urethral stricture, hepatic impairment, thyroid dysfunction, increased intracranial pressure, prostatic hypertrophy, adrenal insufficiency, history of depression or suicidal tendencies, renal function impairment, seizures with epilepsy, urethral stricture, patients who are morbidly obese, urinary tract surgery

            May cause CNS depression; use caution in performing tasks, which require mental alertness

            Not recommended to treat abdominal conditions; may obscure diagnosis or clinical course of patients with acute abdominal conditions

            Avoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist; mixed agonists/antagonist and partial agonist analgesics may reduce analgesic effect and/or may precipitate withdrawal symptoms; when discontinuing therapy, gradually taper dosage; do not abruptly discontinue therapy

            May obscure diagnosis or clinical course of patients with acute abdominal conditions; avoid use in patients with obstruction

            Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; may cause constriction of sphincter of Oddi

            Use with caution in patients with delirium tremens

            Opioid analgesic risk evaluation and mitigation strategy (REMS)

            • To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products
            • Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed; use the following link to obtain the Patient Counseling Guide (PCG): www.fda.gov/OpioidAnalgesicREMSPCG
            • Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
            • Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities
            • To obtain further information on opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com; the FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint

            Concomitant use with benzodiazepines or other CNS depressants

            • If concomitant use with benzodiazepines is warranted, strongly consider prescribing naloxone for emergency treatment of opioid overdose, as is recommended for all patients in methadone treatment for opioid use disorder
            • Concomitant use of methadone and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose and death; medication-assisted treatment of opioid use disorder, however, should not be categorically denied to patients taking these drugs; prohibiting or creating barriers to treatment can pose an even greater risk of morbidity and mortality due to opioid use disorder alone
            • Educate patients about risks of concomitant use of benzodiazepines, sedatives, opioid analgesics, or alcohol
            • Develop strategies to manage use of prescribed or illicit benzodiazepines or other CNS depressants at admission to methadone treatment, or if it emerges as a concern during treatment; adjustments to induction procedures and additional monitoring may be required
            • There is no evidence to support dose limitations or arbitrary caps of methadone as a strategy to address benzodiazepine use in methadone-treated patients; if a patient is sedated at time of methadone dosing, ensure that a medically-trained healthcare provider evaluates the cause of sedation, and delays or omits the methadone dose if appropriate
            • Cessation of benzodiazepines or other CNS depressants is preferred in most cases of concomitant use; in some cases monitoring in a higher level of care for taper may be appropriate. In others, gradually tapering a patient off a prescribed benzodiazepine or other CNS depressant or decreasing to lowest effective dose may be appropriate .
            • For patients in methadone treatment, benzodiazepines are not the treatment of choice for anxiety or insomnia; before co- prescribing benzodiazepines, ensure that patients are appropriately diagnosed and consider alternative medications and non-pharmacologic treatments to address anxiety or insomnia
            • Ensure that other healthcare providers prescribing benzodiazepines or other CNS depressants are aware of the patient’s methadone treatment and coordinate care to minimize the risks associated with concomitant use
            • In addition, take measures to confirm that patients are taking the medications prescribed and not diverting or supplementing with illicit drugs; toxicology screening should test for prescribed and illicit benzodiazepines

            Patient access to naloxone for emergency treatment of opioid overdose

            • Discuss availability of naloxone for emergency treatment of opioid overdose with patient and caregiver
            • Assess potential need for naloxone; consider prescribing for emergency treatment of opioid overdose
            • Because patients being treated for opioid use disorder have potential for relapse, putting them at risk for opioid overdose, strongly consider prescribing naloxone for emergency treatment of opioid overdose, both when initiating and renewing treatment
            • Also consider prescribing naloxone if patient has household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose
            • Advise patients and caregivers that naloxone may also be administered for a known or suspected overdose with therapy
            • Consult on availability and ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (eg, by prescription, directly from a pharmacist, or as part of a community-based program)
            • Educate patients regarding the signs and symptoms of respiratory depression and to call 911 or seek immediate emergency medical help in the event of a known or suspected overdose
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            Pregnancy & Lactation

            Pregnancy

            There are no adequate and well-controlled studies in pregnant women; untreated opioid addiction is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death; in addition, untreated opioid addiction often results in continued or relapsing illicit opioid use; neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy

            Pregnant women in methadone maintenance programs may have reduced incidence of obstetric and fetal complications and neonatal morbidity and mortality when compared to women using illicit drugs; untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes and risk of continued or relapsing illicit opioid use; these risks should be considered in women receiving maintenance treatment of opioid addiction; for women treated with pain severe enough to require daily, around-the-clock, long-term opioid treatment, therapy should be administered during pregnancy only if potential benefit justifies potential risk to fetus

            Infertility

            • Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; it is not known whether effects on fertility are reversible; reproductive function in human males may be decreased by methadone treatment; reductions in ejaculate volume and seminal vesicle and prostate secretions have been reported in methadone-treated individuals; in addition, reductions in serum testosterone levels and sperm motility, and abnormalities in sperm morphology have been reported

            Lactation

            Methadone present in low levels in human milk; did not show adverse reactions in breastfed infants; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for methadone and any potential adverse effects on the breastfed child from drug or from underlying maternal condition; advise breastfeeding women taking methadone to monitor the infant for increased drowsiness and breathing difficulties

            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

            Narcotic agonist-analgesic of opiate receptors; inhibits ascending pain pathways, thus altering perception and response to pain; produces analgesia, respiratory depression, and sedation

            Absorption

            Bioavailability: 36-100%

            Onset: PO, 0.5-1 hr; parenteral, 10-20 min

            Duration: 4-8 hr; repeated administration, 22-48 hr; overdosage, 36-48 hr

            Peak plasma time: 1-7.5 hr

            Distribution

            Protein bound: 85-90%

            Vd: 1-8 L/kg

            Metabolism

            Metabolized in liver via N-demethylation

            Elimination

            Half-life: 8-59 hr

            Excretion: Urine

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Methadose oral
            -
            40 mg tablet
            Methadone Intensol oral
            -
            10 mg/mL liquid
            methadone injection
            -
            10 mg/mL vial
            Diskets oral
            -
            40 mg tablet
            methadone oral
            -
            10 mg/mL liquid
            methadone oral
            -
            10 mg/mL liquid
            methadone oral
            -
            5 mg/5 mL solution
            methadone oral
            -
            10 mg/5 mL solution
            methadone oral
            -
            10 mg tablet
            methadone oral
            -
            5 mg tablet
            methadone oral
            -
            10 mg tablet
            methadone oral
            -
            5 mg tablet
            methadone oral
            -
            10 mg tablet
            methadone oral
            -
            10 mg tablet
            methadone oral
            -
            5 mg tablet
            methadone oral
            -
            10 mg tablet
            methadone oral
            -
            40 mg tablet
            methadone oral
            -
            10 mg tablet
            methadone oral
            -
            5 mg tablet
            methadone oral
            -
            10 mg tablet
            methadone oral
            -
            5 mg tablet
            methadone oral
            -
            10 mg tablet
            methadone oral
            -
            5 mg tablet

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Select a drug:
            Patient Education
            methadone injection

            METHADONE - INJECTION

            (METH-a-done)

            COMMON BRAND NAME(S): Dolophine

            WARNING: Methadone has a risk for abuse and addiction, which can lead to overdose and death. Methadone may also cause severe, possibly fatal, breathing problems and heartbeat problems. To lower your risk, your doctor should have you use the smallest dose of methadone that works, and use it for the shortest possible time. Do not increase your dose or use this medication more often than directed. See also How to Use section for more information about addiction.The risk for severe breathing problems or heartbeat problems is higher when you start this medication, when you are switching from another opioid to methadone, after a dose increase, or if you use the wrong dose/strength. Breathing problems from methadone may not happen right away after using a dose. Most heartbeat problems have happened in people using large doses of methadone for pain relief, but this problem can also occur in people getting smaller doses to treat opioid addiction. Using this medication with alcohol or other drugs that can cause drowsiness or breathing problems may cause very serious side effects, including death. Also, other medications can affect the removal of methadone from your body, which may affect how methadone works. Be sure you know how to use methadone and what other drugs you should avoid taking with it. See also Drug Interactions section. Get medical help right away if any of these very serious side effects occur: slow/shallow breathing, unusual lightheadedness, severe drowsiness/dizziness, difficulty waking up, fast/irregular heartbeat, fainting.Keep this medicine in a safe place to prevent theft, misuse, or abuse. If someone accidentally uses or swallows this drug, get medical help right away.Before using this medication, women of childbearing age should talk with their doctor(s) about the risks and benefits. Pregnancy may affect the amount of this drug in your body, so tell your doctor if you are pregnant or if you plan to become pregnant. During pregnancy, this medication should be used only when clearly needed. It may slightly increase the risk of birth defects if used during the first two months of pregnancy. Also, using it for a long time or in high doses near the expected delivery date may harm the unborn baby. To lessen the risk, use the smallest effective dose for the shortest possible time. Babies born to mothers who use this drug for a long time may develop severe (possibly fatal) withdrawal symptoms. Tell the doctor right away if you notice any symptoms in your newborn baby such as crying that doesn't stop, slow/shallow breathing, irritability, shaking, vomiting, diarrhea, poor feeding, or difficulty gaining weight.

            USES: This medication is used to treat moderate to severe pain. Methadone is an opioid medication. It acts on certain centers in the brain to relieve pain.This medication is also used to treat addiction to opioids (such as heroin) as part of an approved treatment program. It helps prevent withdrawal symptoms caused by stopping other opioids.

            HOW TO USE: See also Warning section.Read the Patient Information Leaflet that may be provided by your pharmacist before you start using methadone and each time you get a refill. If you have any questions, consult your doctor or pharmacist.Depending on your product, this medication is given by injection into a vein, into a muscle, or under the skin. Use it exactly as directed by your doctor. Read and learn all of the manufacturer's instructions for preparation and use. If you have any questions about using this medication properly, consult your doctor or pharmacist.The dosage is based on your medical condition and response to treatment.Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Before injecting each dose, clean the injection site with rubbing alcohol. If this medication is given into a muscle or under the skin, it is important to change the location of the injection site with each dose to avoid problem areas under the skin.Learn how to store and discard needles and medical supplies safely. Consult your pharmacist for more details.If nausea occurs, consult your doctor or pharmacist for ways to decrease it (such as lying down for 1 to 2 hours with as little head movement as possible).If you are using this medication for pain, remember that pain medications work best if they are used as the first signs of pain occur. If you wait until the pain has worsened, the medication may not work as well.Suddenly stopping this medication may cause withdrawal, especially if you have used it for a long time or in high doses. To prevent withdrawal, your doctor may lower your dose slowly. Tell your doctor or pharmacist right away if you have any withdrawal symptoms such as restlessness, mental/mood changes (including anxiety, trouble sleeping, thoughts of suicide), watering eyes, runny nose, nausea, diarrhea, sweating, muscle aches, or sudden changes in behavior.When this medication is used for a long time, it may not work as well. Your doctor may need to increase your dose or change your medication. Talk with your doctor if this medication stops working well.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). Use this medication exactly as prescribed to lower the risk of addiction. Ask your doctor or pharmacist for more details.Tell your doctor if your condition does not get better or if it gets worse.

            SIDE EFFECTS: See also Warning section.Nausea, vomiting, constipation, lightheadedness, dizziness, dry mouth, drowsiness, and increased sweating may occur. Pain, redness, or swelling at the injection site may occur if this medication is given into a muscle or under the skin. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.To prevent constipation, eat dietary fiber, drink enough water, and exercise. You may also need to take a laxative. Ask your pharmacist which type of laxative is right for you.To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.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.Tell your doctor right away if you have any serious side effects, including: interrupted breathing during sleep (sleep apnea), mental/mood changes (such as agitation, confusion, hallucinations), stomach/abdominal pain, difficulty urinating, signs of your adrenal glands not working well (such as loss of appetite, unusual tiredness, weight loss).Get medical help right away if you have any very serious side effects, including: seizure, severe drowsiness/difficulty waking up.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 using methadone, tell your doctor or pharmacist if you are allergic to it; 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: brain disorders (such as head injury, tumor, seizures), breathing problems (such as asthma, sleep apnea, chronic obstructive pulmonary disease-COPD), kidney disease, liver disease, mental/mood disorders (such as confusion, depression, thoughts of suicide), personal or family history of a substance use disorder (such as overuse of or addiction to drugs/alcohol), stomach/intestinal problems (such as blockage, constipation, diarrhea due to infection, paralytic ileus), difficulty urinating (such as due to enlarged prostate), disease of the pancreas (pancreatitis), gallbladder disease.Methadone may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can rarely cause serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using methadone, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using methadone safely.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).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 confusion, dizziness, drowsiness, slow/shallow breathing, and QT prolongation (see above).During pregnancy, this medication should be used only when clearly needed. It may harm an unborn baby. Discuss the risks and benefits with your doctor. (See also Warning section.)This drug passes into breast milk and may have undesirable effects on a nursing infant. Tell the doctor right away if your baby develops unusual sleepiness, difficulty feeding, or trouble breathing. Consult your doctor before breast-feeding or if you plan to stop breast-feeding.

            DRUG INTERACTIONS: See also Warning section.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: certain pain medications (mixed opioid agonist-antagonists such as pentazocine, nalbuphine, butorphanol), naltrexone.Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Do not take any MAO inhibitors (isocarboxazid, linezolid, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before and after treatment with this medication. Ask your doctor when to start or stop taking this medication.Other medications can affect the removal of methadone from your body, which may affect how methadone works. Examples include St. John's wort, azole antifungals (such as itraconazole), HIV drugs (such as ritonavir), macrolide antibiotics (such as erythromycin), rifamycins (such as rifampin), drugs used to treat seizures (such as carbamazepine), among others.The risk of serious side effects (such as slow/shallow breathing, severe drowsiness/dizziness) may be increased if this medication is used with other products that may also cause drowsiness or breathing problems. Tell your doctor or pharmacist if you are using other products such as other opioid pain or cough relievers (such as codeine, hydrocodone), alcohol, marijuana (cannabis), 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.This medication may interfere with certain laboratory tests (including amylase and lipase levels), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, give them naloxone if available, then call 911. If the person is awake and has no symptoms, 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: slow/shallow breathing, extreme drowsiness, slow heartbeat, severe dizziness, pinpoint pupils, coma.

            NOTES: Do not share this medication with others. Sharing it is against the law.This medication has been prescribed for your current condition only. Do not use it later for another condition unless told to do so by your doctor. A different medication may be necessary in those cases.Ask your doctor or pharmacist if you should have naloxone available to treat opioid overdose. Teach your family or household members about the signs of an opioid overdose and how to treat it.

            MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Use 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 medicines 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.

            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.