codeine/chlorpheniramine (Rx)

Brand and Other Names:Tuzistra XR, Tuxarin ER
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

codeine/chlorpheniramine

extended-release oral suspension: Schedule III

  • (14.7mg/2.8mg)/5mL (equivalent to 20mg codeine phosphate and 4mg chlorpheniramine maleate)

tablet, extended-release: Schedule III

  • 40mg/5.6mg (equivalent to 54.3mg codeine phosphate and 8mg chlorpheniramine maleate)

Cough & Cold

Indicated for relief of cough and symptoms associated with upper respiratory tract allergies or common cold in adults (>18 years)

Suspension: 10 mL PO q12hr; not to exceed 2 doses (20 mL) in 24 hr

Tablet: 1 tablet PO q12hr; not to exceed 2 doses/24 hr

<18 years: Safety and efficacy not established

Dose selection for an elderly patient should be made with caution, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy

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Interactions

Interaction Checker

and codeine/chlorpheniramine

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            Contraindicated (1)

            • alvimopan

              alvimopan, codeine. 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.

            Serious - Use Alternative (46)

            • abametapir

              abametapir will increase the level or effect of chlorpheniramine 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.

            • apalutamide

              apalutamide will decrease the level or effect of chlorpheniramine 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.

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, codeine. 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 codeine 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, codeine. 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, codeine. 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, codeine. 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

              chlorpheniramine, 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.

              codeine, 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.

            • clonidine

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

            • eluxadoline

              chlorpheniramine, 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.

            • dacomitinib

              dacomitinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

            • diazepam intranasal

              diazepam intranasal, codeine. 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.

            • eluxadoline

              codeine, 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. .

            • fentanyl

              fentanyl, codeine. 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, codeine. 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, codeine. 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, codeine. 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 will increase the level or effect of chlorpheniramine 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.

            • givosiran

              givosiran will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.

            • hydrocodone

              hydrocodone, codeine. 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.

            • idelalisib

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

            • isocarboxazid

              isocarboxazid increases effects of chlorpheniramine by Other (see comment). Avoid or Use Alternate Drug. Comment: Isocarboxazid should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

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

            • linezolid

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

            • lonafarnib

              lonafarnib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

            • methylene blue

              methylene blue and codeine 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

              chlorpheniramine, 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.

              codeine, 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.

            • nalbuphine

              nalbuphine, codeine. 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.

            • olopatadine intranasal

              chlorpheniramine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • olopatadine intranasal

              codeine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • ozanimod

              ozanimod and codeine 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.

            • pentazocine

              pentazocine, codeine. 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 codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • prasugrel

              codeine will decrease the level or effect of prasugrel by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Co-administration of opioid agonists delay and reduce absorption of prasugrel and its active metabolite presumably by slowing gastric emptying; consider the use of a parenteral anti-platelet agent in acute coronary syndrome patients requiring co-administration of opioid agonists

            • procarbazine

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

            • rasagiline

              rasagiline increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

            • selegiline transdermal

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

            • selinexor

              selinexor, codeine. 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

              chlorpheniramine, 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.

              codeine, 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.

            • sufentanil SL

              sufentanil SL, codeine. 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.

            • tranylcypromine

              tranylcypromine increases effects of chlorpheniramine by Other (see comment). Avoid or Use Alternate Drug. Comment: Tranylcypromine should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

            • ticagrelor

              codeine will decrease the level or effect of ticagrelor by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Co-administration of opioid agonists delay and reduce absorption of ticagrelor and its active metabolite presumably by slowing gastric emptying; consider the use of a parenteral anti-platelet agent in acute coronary syndrome patients requiring co-administration of opioid agonists

            • tramadol

              tramadol, codeine. 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 codeine 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 chlorpheniramine 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.

            • valerian

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

            • voxelotor

              voxelotor will increase the level or effect of chlorpheniramine 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 (284)

            • abiraterone

              abiraterone increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.

            • albuterol

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

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

            • alfentanil

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

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

            • alprazolam

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

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

            • amifampridine

              chlorpheniramine increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

            • amiodarone

              amiodarone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • amitriptyline

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

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

            • amobarbital

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

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

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

            • amoxapine

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

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

            • apomorphine

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

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

            • arformoterol

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

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

            • aripiprazole

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

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

            • armodafinil

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

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

            • artemether/lumefantrine

              artemether/lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • azelastine

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

            • azelastine

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

            • baclofen

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

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

            • belladonna and opium

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

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

            • belzutifan

              belzutifan will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

            • benperidol

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

            • benperidol

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

            • benzphetamine

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

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

            • brexanolone

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

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

            • brompheniramine

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

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

            • buprenorphine

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

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

            • buprenorphine buccal

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

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

            • buprenorphine, long-acting injection

              codeine 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

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

            • bupropion

              bupropion will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents the conversion of codeine to its active metabolite morphine.

            • butabarbital

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

            • butalbital

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

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

            • butorphanol

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

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

            • caffeine

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

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

            • carbinoxamine

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

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

            • carisoprodol

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

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

            • celecoxib

              celecoxib decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • cenobamate

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

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

            • cenobamate

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

            • chloral hydrate

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

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

            • chlordiazepoxide

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

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

            • chloroquine

              chloroquine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • chlorpromazine

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

            • chlorpheniramine

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

            • chlorpromazine

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

              chlorpromazine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine

            • chlorzoxazone

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

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

            • cimetidine

              cimetidine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • cinnarizine

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

            • cinacalcet

              cinacalcet decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • cinnarizine

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

            • clemastine

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

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

            • clobazam

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

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

              clobazam decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • clomipramine

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

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

              clomipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • clonazepam

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

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

            • clorazepate

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

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

            • clozapine

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

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

              clozapine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • cocaine topical

              cocaine topical decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • codeine

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

            • crofelemer

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

            • cyclizine

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

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

            • cyclobenzaprine

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

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

            • cyproheptadine

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

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

            • dabrafenib

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

            • dantrolene

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

            • dantrolene

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

            • daridorexant

              chlorpheniramine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

              codeine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • darifenacin

              darifenacin decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • desflurane

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

            • desflurane

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

            • desipramine

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

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

              desipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • desvenlafaxine

              desvenlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • deutetrabenazine

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

            • deutetrabenazine

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

            • dexchlorpheniramine

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

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

            • dexfenfluramine

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

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

            • dexmedetomidine

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

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

            • dexmethylphenidate

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

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

            • dextroamphetamine

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

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

            • dextromoramide

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

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

            • diamorphine

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

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

            • diazepam

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

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

            • diazepam intranasal

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

            • diethylpropion

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

            • diethylpropion

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

            • difelikefalin

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

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

            • difenoxin hcl

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

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

            • dimenhydrinate

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

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

            • diphenhydramine

              diphenhydramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

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

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

            • diphenoxylate hcl

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

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

            • dipipanone

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

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

            • dobutamine

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

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

            • donepezil transdermal

              donepezil transdermal, chlorpheniramine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

            • dopamine

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

            • dopamine

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

            • dopexamine

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

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

            • dosulepin

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

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

            • doxepin

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

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

            • doxylamine

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

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

            • dronedarone

              dronedarone decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • droperidol

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

            • droperidol

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

            • duloxetine

              duloxetine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • efavirenz

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

            • elagolix

              elagolix will decrease the level or effect of chlorpheniramine 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.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

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

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • ephedrine

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

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

            • epinephrine

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

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

            • epinephrine racemic

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

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

            • esketamine intranasal

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

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

            • estazolam

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

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

            • ethanol

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

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

            • etomidate

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

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

            • fedratinib

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

              fedratinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • fenfluramine

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

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

            • fentanyl

              fentanyl, chlorpheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • flibanserin

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

            • fentanyl intranasal

              fentanyl intranasal, chlorpheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • fentanyl transdermal

              fentanyl transdermal, chlorpheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • fentanyl transmucosal

              fentanyl transmucosal, chlorpheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • flibanserin

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

            • fluoxetine

              fluoxetine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine

            • fluphenazine

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

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

            • flurazepam

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

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

            • formoterol

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

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

            • fosphenytoin

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

            • gabapentin

              gabapentin, codeine. 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

              gabapentin, chlorpheniramine. 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, codeine. 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, chlorpheniramine. 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.

            • ganaxolone

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

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

            • glycopyrronium tosylate topical

              glycopyrronium tosylate topical, chlorpheniramine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.

            • haloperidol

              haloperidol decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

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

            • gotu kola

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

            • haloperidol

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

            • hawthorn

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

            • hops

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

            • hyaluronidase

              chlorpheniramine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

            • hydromorphone

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

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

            • hydroxyzine

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

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

            • iloperidone

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

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

              iloperidone increases levels of chlorpheniramine 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.

            • imipramine

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

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

              imipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • isoniazid

              isoniazid decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • isoproterenol

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

            • isoproterenol

              codeine 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 chlorpheniramine 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.

            • kava

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

            • ketamine

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

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

            • ketoconazole

              ketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • ketotifen, ophthalmic

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

            • ketotifen, ophthalmic

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

            • lasmiditan

              lasmiditan, chlorpheniramine. 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.

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

            • lemborexant

              lemborexant, codeine. 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.

              lemborexant, chlorpheniramine. 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.

            • letermovir

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

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

            • levalbuterol

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

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

            • levoketoconazole

              levoketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • levorphanol

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

            • levorphanol

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

            • lisdexamfetamine

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

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

            • lofepramine

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

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

            • lofexidine

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

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

            • lopinavir

              lopinavir decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • loprazolam

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

            • loprazolam

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

            • lorazepam

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

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

            • lorcaserin

              lorcaserin will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • lormetazepam

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

            • lormetazepam

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

            • loxapine

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

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

            • loxapine inhaled

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

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

            • lumefantrine

              lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • lurasidone

              lurasidone, chlorpheniramine. 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.

            • lurasidone

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

            • maprotiline

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

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

            • marijuana

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

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

            • melatonin

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

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

            • meperidine

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

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

            • meprobamate

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

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

            • metaproterenol

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

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

            • metaxalone

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

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

            • methadone

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

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

            • methamphetamine

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

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

            • methocarbamol

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

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

            • methylenedioxymethamphetamine

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

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

            • midazolam

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

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

            • midazolam intranasal

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

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

            • midodrine

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

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

            • mirabegron

              mirabegron will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • mirtazapine

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

            • mirtazapine

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

            • mitotane

              mitotane decreases levels of chlorpheniramine 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

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

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

            • morphine

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

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

            • motherwort

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

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

            • moxonidine

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

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

            • nabilone

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

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

            • nalbuphine

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

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

            • norepinephrine

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

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

            • nortriptyline

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

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

            • olanzapine

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

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

            • oliceridine

              oliceridine, codeine. 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.

            • opium tincture

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

            • opium tincture

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

            • orphenadrine

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

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

            • oxazepam

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

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

            • oxycodone

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

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

            • oxymorphone

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

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

            • paliperidone

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

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

            • papaveretum

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

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

            • papaverine

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

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

            • paroxetine

              paroxetine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • passion flower

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

            • peginterferon alfa 2b

              peginterferon alfa 2b, codeine. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.

            • pegvisomant

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

            • pentazocine

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

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

            • pentobarbital

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

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

            • perampanel

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

            • perphenazine

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

            • perphenazine

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

            • phendimetrazine

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

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

            • phenelzine

              phenelzine increases effects of chlorpheniramine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration of phenelzine and antihistamines may result in additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

            • phenobarbital

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

            • phenobarbital

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

            • phentermine

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

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

            • phenylephrine

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

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

            • phenylephrine PO

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

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

            • pholcodine

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

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

            • pimozide

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

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

            • pirbuterol

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

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

            • pregabalin

              pregabalin, codeine. 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.

              pregabalin, chlorpheniramine. 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

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

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

            • prochlorperazine

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

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

            • promethazine

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

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

            • propofol

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

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

            • propylhexedrine

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

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

            • protriptyline

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

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

            • quazepam

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

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

            • quetiapine

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

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

            • quinidine

              quinidine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • ramelteon

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

            • ramelteon

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

            • remimazolam

              remimazolam, codeine. 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.

            • ribociclib

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

            • risperidone

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

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

            • ritonavir

              ritonavir will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • rucaparib

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

            • rolapitant

              rolapitant will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

            • salmeterol

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

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

            • scullcap

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

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

            • secobarbital

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

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

            • selegiline

              selegiline increases toxicity of codeine by unknown mechanism. Modify Therapy/Monitor Closely. Potential for increased CNS depression, drowsiness, dizziness or hypotension, so use with any MAOI should be cautious.

            • sevoflurane

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

            • sertraline

              sertraline decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • sevoflurane

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

            • shepherd's purse

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

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

            • stiripentol

              stiripentol, codeine. 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.

              stiripentol, chlorpheniramine. 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.

            • sufentanil

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

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

            • suvorexant

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

            • tapentadol

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

            • tapentadol

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

            • tazemetostat

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

            • tecovirimat

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

            • temazepam

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

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

            • terbinafine

              terbinafine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

            • terbutaline

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

            • terbutaline

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

            • thioridazine

              thioridazine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

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

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

            • thiothixene

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

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

            • ticlopidine

              ticlopidine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • topiramate

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

            • topiramate

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

            • tramadol

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

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

            • tranylcypromine

              tranylcypromine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • trazodone

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

            • trazodone

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

            • triazolam

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

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

            • triclofos

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

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

            • trifluoperazine

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

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

            • trimipramine

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

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

            • triprolidine

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

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

            • valerian

              valerian increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

            • venlafaxine

              venlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • xylometazoline

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

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

            • yohimbine

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

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

            • ziconotide

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

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

            • ziprasidone

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

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

            • zotepine

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

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

            Minor (24)

            • asenapine

              asenapine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • ashwagandha

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

            • brimonidine

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

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

            • dextroamphetamine

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

            • eucalyptus

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

            • eucalyptus

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

            • fluoxetine

              fluoxetine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

            • imatinib

              imatinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              imatinib decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

            • levoketoconazole

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

            • lidocaine

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

            • maraviroc

              maraviroc will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • marijuana

              marijuana will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • nettle

              nettle increases effects of chlorpheniramine by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.

            • nilotinib

              nilotinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • parecoxib

              parecoxib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • perphenazine

              perphenazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              perphenazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

            • propafenone

              propafenone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              propafenone decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

            • quinacrine

              quinacrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              quinacrine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

            • ranolazine

              ranolazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • ribociclib

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

            • sage

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

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

            • Siberian ginseng

              Siberian ginseng increases effects of chlorpheniramine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

            • sertraline

              sertraline decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

            • thioridazine

              thioridazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

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            Adverse Effects

            Frequency Not Defined

            Allergic: Allergic laryngospasm, nasal stuffiness, bronchospastic allergic reaction, hives, itching, swelling of face

            Body as a whole: Asthenia, feeling of relaxation, redness or flushing of the face, unusual tiredness, weakness

            Cardiovascular: Fast or slow heartbeat, hypertension, hypotension, orthostatic hypotension, palpitations, shock-like state, syncope

            Dermatological system: Skin rash, pruritus, erythema, urticaria, excessive perspiration, dermatitis

            Endocrine system: Changes in glucose utilization, decreased lactation, early menses, glycosuria, gynecomastia, hypoglycemia, increased appetite, increased libido, pheochromocytoma stimulation

            Gastrointestinal system: Nausea and vomiting, constipation, abdominal distension, abdominal pain, acute pancreatitis, dry mouth, dyspepsia, epigastric distress, loss of appetite, diarrhea, gastro-esophageal reflux, gastrointestinal hypomotility

            Genitourinary system: Ureteral spasm, urinary retention, dysuria, urinary frequency, urinary hesitancy, irritative bladder symptom

            Nervous system: Blurred vision, diplopia, visual disturbances, confusion, dizziness, depression, drowsiness, sedation, headache, euphoria, facial dyskinesia, false sense of well-being, feeling faint, lightheadedness, general feeling of discomfort or illness, excitability, nervousness, agitation, restlessness, somnolence, insomnia, dyskinesia, irritability, tremor

            Respiratory: Dryness of the pharynx and respiratory passages, laryngismus, atelectasis, wheezing, troubled breathing, respiratory depression, hiccups

            Special senses: Labyrinthitis, tinnitus, vertigo, hypermetropia, increased lacrimation, mydriasis, photophobia

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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

            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

            Accidental ingestion

            • Accidental ingestion 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
            • 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

            Ultra-rapid metabolism of codeine and other risk factors for life-threatening respiratory depression in children

            • Respiratory depression and death reported in children who received codeine following tonsillectomy and/or adenoidectomy that were also ultra-rapid metabolizers of codeine due to CYP2D6 polymorphism
            • Contraindicated in children <12 years and in children <18 years following tonsillectomy and/or adenoidectomy; avoid use in adolescents 12-18 years who have risk factors that may increase sensitivity to respiratory depressant effects of codeine

            Interactions with drugs affecting cytochrome P450 isoenzymes

            • Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors requires careful consideration of the effects on parent drug, codeine, and active metabolite, morphine

            Risks from 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 of codeine sulfate tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate
            • Limit dosages and durations to minimum required
            • Follow patients for signs and symptoms of respiratory depression and sedation

            Contraindications

            Known hypersensitivity to codeine, chlorpheniramine, or product components

            Children <12 years

            Post-operative management in children <18 years following tonsillectomy and/or adenoidectomy

            Patients with significant respiratory depression, acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment

            Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within last 14 days

            Known or suspected gastrointestinal obstruction, including paralytic ileus

            Persons known to be hypersensitive to other opioids exhibiting cross-sensitivity to codeine

            Cautions

            Respiratory depression and death have occurred in children who received codeine in the postoperative period following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine (ie, multiple copies of the gene for CYP2D6 or high morphine concentrations) (see Black Box Warnings and Contraindications)

            Deaths have also occurred in nursing infants who were exposed to high levels of morphine in breast milk because their mothers were ultra-rapid metabolizers of codeine

            Avoid use in adolescents 12-18 years of age who have other risk factors that may increase sensitivity to respiratory depressant effects of codeine unless benefits outweigh risks; risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression; when prescribing codeine for adolescents, healthcare providers should choose lowest effective dose for shortest period of time and inform patients and caregivers about risks and the signs of morphine overdose

            Produces dose-related respiratory depression (fatalities reported) by directly acting on brain stem respiratory centers; may produce irregular and periodic breathing

            At least one death was reported in a nursing infant who was exposed to high levels of morphine in breast milk because mother was an ultra-rapid metabolizer of codeine; breastfeeding not recommended during treatment

            Potential for dependence and abuse

            Avoid use with head injuries; opioids produce adverse reactions that may obscure the clinical course of patients with head injuries

            Codeine and chlorpheniramine produce drowsiness and may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks (driving, operating machinery)

            Long-term use of opioids, including codeine, may result in constipation or obstructive bowel disease

            Caution with acute abdominal conditions since the codeine may obscure the diagnosis or clinical course of patients with acute abdominal conditions; concurrent use of other anticholinergics with codeine may produce paralytic ileus

            Caution in elderly or debilitated patients and those with asthma, persistent or chronic cough, hypothyroidism, Addison disease, prostatic hypertrophy, or urethral stricture

            Both codeine and chlorpheniramine are extensively metabolized by the liver; caution with severe hepatic impairment

            Concomitant use of opioids, with benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; because of these risks, avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol

            Avoid in patients with head injury, intra-cranial lesions, or increased intracranial pressure

            Avoid concurrent use of alcohol or other central nervous system depressants

            Measure dose only with an accurate mL measuring device

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            Pregnancy & Lactation

            Pregnancy

            Codeine

            • As with all opioids, administration of codeine to the mother shortly before delivery may result in some degree of respiratory depression in the newborn, especially if higher doses are used
            • Babies born to mothers who have been taking opioids regularly prior to delivery will be physically dependent
            • Withdrawal signs include irritability and excessive crying, tremors, hyperactive reflexes, increased respiratory rate, increased stools, sneezing, yawning, vomiting, and fever

            Labor and delivery

            • Use of codeine during labor may lead to respiratory depression in the neonate; opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate; use is not recommended in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate; opioid analgesics, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by increased rate of cervical dilation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression

            Chlorpheniramine

            • A retrospective study found a small, but statistically significant, association between maternal use of chlorpheniramine and inguinal hernia and eye or ear anomalies in children

            Lactation

            Codeine and its active metabolite, morphine, are present in human milk; there are published studies and cases that have reported excessive sedation, respiratory depression, and death in infants exposed to codeine via breast milk; women who are ultra-rapid metabolizers of codeine achieve higher than expected serum levels of morphine, potentially leading to higher levels of morphine in breast milk that can be dangerous in their breastfed infants

            Use caution if administered to a nursing woman; prescribe the lowest dose for shortest period of time to achieve desired effect; inform mothers when to seek immediate medical care and how to identify signs and symptoms of neonatal toxicity (eg, drowsiness or sedation, difficulty breastfeeding, breathing difficulties, and decreased tone)

            In women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and dose-dependent

            There is no information on effects of codeine milk production; because of potential for serious adverse reactions, including excess sedation, respiratory depression, and death in a breastfed infant, breastfeeding is not recommended during treatment

            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

            Codeine: Semisynthetic narcotic antitussive and analgesic with multiple actions qualitatively similar to those of morphine; believed to act centrally on the cough center

            Chlorpheniramine: Propylamine derivative antihistamine drug (H1 receptor antagonist) that also possesses anticholinergic and sedative activity; prevents released histamine from dilating capillaries and causing edema of the respiratory mucosa

            Absorption

            Peak plasma time

            • Codeine: 2.19 hr
            • Chlorpheniramine: 6.52 hr

            Peak plasma concentration

            • Codeine: 51.4 ng/mL
            • Chlorpheniramine: 7.84 ng/mL

            AUC

            • Codeine: 348.5 ng•h/mL
            • Chlorpheniramine: 304.3 ng•h/mL

            Distribution

            Protein bound

            • Codeine: 7-25%
            • Chlorpheniramine: 70%

            Vd

            • Codeine: 3-6 L/kg
            • Chlorpheniramine: 3.2 L/kg

            Metabolism

            Codeine

            • ~70-80% is metabolized by conjugation with glucuronic acid to codeine-6­glucuronide (C6G) and via O-demethylation to morphine (~5-10%) and N-demethylation to norcodeine (~10%) respectively
            • UDP-glucuronosyltransferase (UGT) 2B7 and 2B4 are the major enzymes mediating glucurodination of codeine to C6G
            • CYP2D6 and CYP3A4 are the major enzymes mediating O-demethylation and N-demethylation of codeine, respectively
            • Morphine and norcodeine are further metabolized by conjugation with glucuronic acid
            • Morphine and its M6 glucuronide conjugate are pharmacologically active
            • Whether C6G has pharmacological activity is unknown
            • Norcodeine and M3 glucuronide conjugate of morphine are generally not considered to be pharmacologically active

            Chlorpheniramine

            • Rapidly and extensively metabolized via demethylation in the liver, forming monodesmethyl and didesmethyl derivatives
            • Oxidative metabolism of chlorpheniramine is catalyzed by CYP2D6

            Elimination

            Half-life

            • Codeine: 5 hr
            • Chlorpheniramine: 21.45 hr

            Excretion

            • Codeine: 90% urine (~10% as unchanged drug)
            • Chlorpheniramine: Drug and its metabolites are primarily excreted through the kidneys, with large individual variation that depends on urine pH and flow rate

            Pharmacogenomics

            5-10% of codeine is metabolized to morphine by CYP2D6; the active morphine metabolite has a higher affinity for opioid receptors

            CYP2D6 poor metabolizers may not achieve adequate analgesia

            Ultra-rapid metabolizers (up to 7% of whites and up to 30% of Asian and African populations) may have increased toxicity due to rapid conversion

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            Administration

            Instructions

            Take with or without food

            Shake well before measuring dose

            Measure with an accurate mL measuring device; do not use a household teaspoon to measure the dose

            Storage

            Room temperature at 20-25°C (68-77°F); excursions permitted from 15-30°C (59-86°F)

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            Formulary

            FormularyPatient Discounts

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            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.
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            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            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.