promethazine/codeine (Rx)

Brand and Other Names:
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

promethazine/codeine

oral liquid: Schedule V

  • (6.25mg/10mg)/5mL

Cough

Temporary relief cough and upper respiratory tract symptoms associated with allergies or common cold

6.25 mg/10 mg (5 mL) PO q4-6hr; not to exceed 30 mL/24 hr

Renal Impairment

Caution; may need to initiate at a lower dose

Hepatic Impairment

Caution; may need to initiate at a lower dose

Administration

Administer with special measuring device for accurate dose

Dosage Forms & Strengths

Oral liquid: Schedule V

  • (6.25mg/10mg)/5mL

Cough

<12 years: Use contraindicated

12 years: 2.5-5 mL PO q4-6hr; not to exceed 30 mL/24hr

>12 years: 6.25 mg/10 mg (5 mL) PO q4-6hr; not to exceed 30 mL/24 hr

Administration

Administer with special measuring device for accurate dose

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Interactions

Interaction Checker

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            Contraindicated (2)

            • 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.

            • disopyramide

              promethazine and disopyramide both increase QTc interval. Contraindicated.

            Serious - Use Alternative (97)

            • abametapir

              abametapir will increase the level or effect of promethazine by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP2D6 substrates. If not feasible, avoid use of abametapir.

            • amiodarone

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

            • amisulpride

              promethazine and amisulpride both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.

            • anagrelide

              anagrelide and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

            • apomorphine

              promethazine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • arsenic trioxide

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

            • artemether/lumefantrine

              promethazine and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

            • asenapine

              asenapine and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

            • asenapine transdermal

              asenapine transdermal and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

            • 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.

            • bromocriptine

              promethazine decreases effects of bromocriptine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • buprenorphine

              buprenorphine and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

              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.

            • cabergoline

              promethazine decreases effects of cabergoline by pharmacodynamic antagonism. Contraindicated.

            • 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

              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.

              promethazine, 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.

            • chlorpromazine

              chlorpromazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.

            • clonidine

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

            • clarithromycin

              promethazine and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.

            • clomipramine

              promethazine and clomipramine both increase QTc interval. Avoid or Use Alternate Drug.

            • 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.

              dacomitinib will increase the level or effect of promethazine 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.

            • degarelix

              degarelix and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

            • 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.

            • dofetilide

              promethazine and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.

            • dopamine

              promethazine decreases effects of dopamine by pharmacodynamic antagonism. Contraindicated.

            • dosulepin

              promethazine and dosulepin both increase QTc interval. Avoid or Use Alternate Drug.

            • dronedarone

              promethazine and dronedarone both increase QTc interval. Avoid or Use Alternate Drug.

            • droperidol

              promethazine and droperidol both increase QTc interval. Avoid or Use Alternate Drug.

            • eliglustat

              eliglustat and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

            • 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. .

              promethazine, 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.

            • encorafenib

              encorafenib and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

            • 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.

            • entrectinib

              entrectinib and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

            • epinephrine

              epinephrine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.

            • epinephrine racemic

              epinephrine racemic and promethazine both increase QTc interval. Avoid or Use Alternate Drug.

            • eribulin

              eribulin and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

            • erythromycin base

              promethazine and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

              promethazine and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              promethazine and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin stearate

              promethazine and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

            • 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 decrease the level or effect of promethazine by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. Coadministration may decrease plasma concentrations of CYP2B6 substrates owing to fexinidazole inducing CYP2B6.

            • fingolimod

              fingolimod and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

            • fluconazole

              promethazine and fluconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • fluoxetine

              fluoxetine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • fluphenazine

              fluphenazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.

            • formoterol

              promethazine and formoterol both increase QTc interval. Avoid or Use Alternate Drug.

            • 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.

              givosiran will increase the level or effect of promethazine 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.

            • haloperidol

              promethazine and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.

            • 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.

            • isocarboxazid

              isocarboxazid increases effects of promethazine 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.

            • itraconazole

              promethazine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • 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.

            • ketoconazole

              promethazine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • levodopa

              promethazine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • levoketoconazole

              promethazine and levoketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • lisuride

              promethazine decreases effects of lisuride by pharmacodynamic antagonism. Contraindicated.

            • lofepramine

              promethazine and lofepramine both increase QTc interval. Avoid or Use Alternate Drug.

            • lumefantrine

              promethazine and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

            • mefloquine

              mefloquine increases toxicity of promethazine by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.

            • methyldopa

              promethazine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

            • 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

              methylene blue and promethazine 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

              promethazine, 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.

            • moxifloxacin

              promethazine and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • 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.

            • nilotinib

              promethazine and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • octreotide

              promethazine and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

            • octreotide (Antidote)

              promethazine and octreotide (Antidote) both increase QTc interval. Avoid or Use Alternate Drug.

            • oxaliplatin

              oxaliplatin and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

            • 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.

            • paroxetine

              paroxetine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • 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.

            • perphenazine

              perphenazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.

            • 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.

            • pitolisant

              promethazine decreases effects of pitolisant by Other (see comment). Avoid or Use Alternate Drug. Comment: Pitolisant increases histamine levels in the brain; therefore, H1 receptor antagonists that cross the blood-brain barrier may reduce the efficacy of pitolisant.

            • pramipexole

              promethazine decreases effects of pramipexole by pharmacodynamic antagonism. Contraindicated.

            • 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. .

            • prochlorperazine

              prochlorperazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.

            • promazine

              promazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.

            • quinidine

              quinidine, promethazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Additive cardiac effects.

            • rasagiline

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

            • ropinirole

              promethazine decreases effects of ropinirole by pharmacodynamic antagonism. Contraindicated.

            • 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.

            • siponimod

              siponimod and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

            • sodium oxybate

              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.

              promethazine, 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.

            • thioridazine

              promethazine and thioridazine both increase QTc interval. Avoid or Use Alternate Drug.

            • 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.

              tranylcypromine increases effects of promethazine 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. Combination of tranylcypromine and promethazine may result in additive hypotensive effects.

            • tretinoin

              promethazine, tretinoin. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

            • valerian

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

            Monitor Closely (377)

            • abiraterone

              abiraterone increases levels of promethazine 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.

              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.

            • aclidinium

              aclidinium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of aclidinium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • albuterol

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

            • albiglutide

              promethazine, albiglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.

            • albuterol

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

            • alfentanil

              promethazine 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.

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

            • amifampridine

              promethazine 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

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

              promethazine and amitriptyline both increase QTc interval. Use Caution/Monitor.

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

            • amobarbital

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

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

            • amoxapine

              promethazine and amoxapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              promethazine and amoxapine both increase QTc interval. Use Caution/Monitor.

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

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

            • anticholinergic/sedative combos

              anticholinergic/sedative combos decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              anticholinergic/sedative combos decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of anticholinergic/sedative combos by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • apomorphine

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

            • apomorphine

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

            • arformoterol

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

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

            • aripiprazole

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

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

              aripiprazole and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              promethazine 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.

              promethazine 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 promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

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

            • asenapine

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

            • azelastine

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

            • atracurium

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

              atracurium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of atracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • atropine

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

              atropine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • atropine IV/IM

              promethazine increases effects of atropine IV/IM by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • azelastine

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

            • azithromycin

              promethazine and azithromycin both increase QTc interval. Use Caution/Monitor.

            • baclofen

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

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

            • belladonna alkaloids

              belladonna alkaloids decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              belladonna alkaloids decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • belladonna and opium

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

            • belladonna and opium

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

              belladonna and opium decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              belladonna and opium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of belladonna and opium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • benperidol

              benperidol and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

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

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

            • benzphetamine

              promethazine, benzphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

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

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

            • benztropine

              promethazine increases effects of benztropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use. .

            • brexanolone

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

            • brexanolone

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

            • brompheniramine

              brompheniramine and promethazine 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.

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

            • buprenorphine buccal

              promethazine 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.

            • bupropion

              bupropion will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. 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.

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

            • butalbital

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

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

            • butorphanol

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

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

            • caffeine

              promethazine 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 codeine both increase sedation. Use Caution/Monitor.

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

            • cariprazine

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

            • carisoprodol

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

            • carisoprodol

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

              cenobamate will decrease the level or effect of promethazine by affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP2B6 substrate, as needed, when coadministered with cenobamate.

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

            • chloral hydrate

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

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

            • chlordiazepoxide

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

              promethazine and chlordiazepoxide 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.

            • chlorpheniramine

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

            • chlorpheniramine

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

            • chlorpromazine

              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

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

              chlorpromazine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

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

            • chlorzoxazone

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

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

            • cigarette smoking

              cigarette smoking decreases levels of promethazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.

            • 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.

            • 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.

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

            • cisatracurium

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

              cisatracurium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of cisatracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • clemastine

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

            • citalopram

              citalopram and promethazine both increase serotonin levels. Use Caution/Monitor. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.

            • clemastine

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

            • clobazam

              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).

              promethazine, 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.

              clobazam will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.

            • clomipramine

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

              codeine 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

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

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

            • clonidine

              clonidine, promethazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

            • clorazepate

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

            • clorazepate

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

            • clozapine

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

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

              clozapine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

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

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

            • cocaine

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

            • codeine

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

            • cyclizine

              promethazine increases effects of cyclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

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

              cyclizine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

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

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

            • cyclobenzaprine

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

              promethazine increases effects of cyclobenzaprine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              cyclobenzaprine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

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

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

            • cyproheptadine

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

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

            • dantrolene

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

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

            • daridorexant

              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.

              promethazine 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.

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

              promethazine increases effects of darifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              darifenacin decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

            • dasatinib

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

            • desflurane

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

            • desflurane

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

              desflurane and promethazine both decrease QTc interval. Use Caution/Monitor.

            • desipramine

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

              promethazine and desipramine both increase QTc interval. 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.

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

            • desvenlafaxine

              desvenlafaxine will increase the level or effect of promethazine 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

              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

              deutetrabenazine and promethazine both decrease QTc interval. Use Caution/Monitor.

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

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

            • dexchlorpheniramine

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

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

            • dexfenfluramine

              promethazine, dexfenfluramine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

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

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

            • dexmedetomidine

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

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

            • dexmethylphenidate

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

              promethazine, dexmethylphenidate. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

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

            • dextroamphetamine

              promethazine, dextroamphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

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

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

            • dextromoramide

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

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

            • diamorphine

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

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

            • diazepam

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

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

            • diazepam intranasal

              diazepam intranasal, promethazine. 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.

            • dicyclomine

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

              dicyclomine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of dicyclomine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • diethylpropion

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

              promethazine, diethylpropion. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • difelikefalin

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

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

            • difenoxin hcl

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

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

            • dimenhydrinate

              dimenhydrinate and promethazine 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.

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

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

              diphenhydramine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • diphenoxylate hcl

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

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

            • dipipanone

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

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

            • dobutamine

              promethazine, dobutamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

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

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

            • dolasetron

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

            • dopamine

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

            • donepezil

              donepezil and promethazine both decrease QTc interval. Use Caution/Monitor.

            • donepezil transdermal

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

            • dopamine

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

              promethazine, dopamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • dopexamine

              promethazine 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

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

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

            • doxepin

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

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

              promethazine and doxepin both increase QTc interval. Use Caution/Monitor.

            • doxylamine

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

              promethazine 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

              droperidol and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              promethazine 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 and promethazine both decrease QTc interval. Use Caution/Monitor.

            • eliglustat

              eliglustat increases levels of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of promethazine 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.

              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

              promethazine, ephedrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

              promethazine 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.

              promethazine decreases effects of epinephrine by pharmacodynamic antagonism. Use Caution/Monitor. Block pressor response to epinephrine, which may result in severe hypotension and tachycardia.

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

              promethazine, epinephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • epinephrine racemic

              promethazine decreases effects of epinephrine racemic by pharmacodynamic antagonism. Use Caution/Monitor. Block pressor response to epinephrine, which may result in severe hypotension and tachycardia.

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

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

            • esketamine intranasal

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

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

            • estazolam

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

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

            • ethanol

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

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

            • etomidate

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

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

            • fedratinib

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

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

              promethazine, fenfluramine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

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

            • fentanyl

              fentanyl, promethazine. 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, promethazine. 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, promethazine. 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, promethazine. 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.

            • fesoterodine

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

              fesoterodine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of fesoterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • flavoxate

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

              flavoxate decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of flavoxate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • flecainide

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

            • flibanserin

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

            • fluoxetine

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

              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

              fluphenazine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

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

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

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

            • flurazepam

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

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

            • fluvoxamine

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

            • formoterol

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

            • formoterol

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

            • foscarnet

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

            • gabapentin

              gabapentin, promethazine. 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, 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

              gabapentin enacarbil, promethazine. 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, 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.

            • ganaxolone

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

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

            • gemifloxacin

              gemifloxacin and promethazine both decrease QTc interval. Use Caution/Monitor.

            • 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.

            • gilteritinib

              gilteritinib and promethazine both decrease QTc interval. Use Caution/Monitor.

            • glycopyrrolate

              promethazine increases effects of glycopyrrolate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • glycopyrrolate inhaled

              glycopyrrolate inhaled decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              glycopyrrolate inhaled decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of glycopyrrolate inhaled by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • glycopyrronium tosylate topical

              glycopyrronium tosylate topical, promethazine. 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.

            • gotu kola

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

            • granisetron

              granisetron and promethazine both decrease QTc interval. Use Caution/Monitor.

            • guanfacine

              guanfacine, promethazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

            • haloperidol

              haloperidol and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

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

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

            • hawthorn

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

            • henbane

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

              henbane decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of henbane by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • homatropine

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

              homatropine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • hops

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

            • hyaluronidase

              promethazine 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

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

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

            • hydroxyzine

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

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

              hydroxyzine and promethazine both decrease QTc interval. Use Caution/Monitor.

            • hyoscyamine

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

              hyoscyamine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of hyoscyamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • iloperidone

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

            • hyoscyamine spray

              promethazine increases effects of hyoscyamine spray by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • iloperidone

              iloperidone and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

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

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

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

            • imipramine

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

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

              promethazine and imipramine both increase QTc interval. 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.

            • incobotulinumtoxinA

              promethazine, incobotulinumtoxinA. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects.

            • isoniazid

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

            • ipratropium

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

              ipratropium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of ipratropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • isoflurane

              isoflurane and promethazine both decrease QTc interval. Use Caution/Monitor.

            • isoproterenol

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

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

              promethazine, isoproterenol. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • kava

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

            • ketamine

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

            • ketamine

              ketamine and promethazine 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

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

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

            • lapatinib

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

            • lasmiditan

              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.

            • lasmiditan

              lasmiditan, promethazine. 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 will decrease the level or effect of promethazine by affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Monitor CYP2B6 substrate for adequate clinical response. Consider increasing the CYP2B6 substrate dose according to specific prescribing recommendations.

              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, promethazine. 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.

            • levalbuterol

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

            • levalbuterol

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

            • levofloxacin

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

            • 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

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

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

            • liraglutide

              promethazine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.

            • lisdexamfetamine

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

            • lisdexamfetamine

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

              promethazine, lisdexamfetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • lithium

              lithium, promethazine. Other (see comment). Use Caution/Monitor. Comment: Risk of neurotoxicity. Multiple mechanisms involved.

              lithium and promethazine both decrease QTc interval. Use Caution/Monitor.

            • lofepramine

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

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

            • lofexidine

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

              codeine 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

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

            • loprazolam

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

            • lorazepam

              promethazine 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.

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

            • lormetazepam

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

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

            • loxapine

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

              loxapine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

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

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

            • loxapine inhaled

              loxapine inhaled and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

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

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

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

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor, promethazine. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .

            • lumefantrine

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

            • lumefantrine

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

            • 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.

              lurasidone increases effects of promethazine by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.; potendial for additive CNS effects .

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

            • maprotiline

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

              promethazine and maprotiline both increase QTc interval. Use Caution/Monitor.

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

            • marijuana

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

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

            • meclizine

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

              meclizine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of meclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • melatonin

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

            • melatonin

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

            • meperidine

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

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

            • meprobamate

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

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

            • metaproterenol

              promethazine 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

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

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

            • metformin

              promethazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

            • methadone

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

            • methadone

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

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

            • methamphetamine

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

              promethazine, methamphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

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

            • methocarbamol

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

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

            • methoxsalen

              methoxsalen, promethazine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.

            • methylenedioxymethamphetamine

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

            • methscopolamine

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

              methscopolamine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of methscopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • methylenedioxymethamphetamine

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

              promethazine, methylenedioxymethamphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • methylphenidate

              promethazine, methylphenidate. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • metoclopramide

              promethazine and metoclopramide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

            • midazolam

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

            • midodrine

              promethazine, midodrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

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

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

            • mifepristone

              mifepristone will increase the level or effect of promethazine by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.

            • mirabegron

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

            • mirabegron

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

            • mirtazapine

              mirtazapine and promethazine both decrease QTc interval. Use Caution/Monitor.

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

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

            • modafinil

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

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

            • molindone

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

            • morphine

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

            • morphine

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

            • motherwort

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

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

            • moxonidine

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

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

            • nabilone

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

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

            • nalbuphine

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

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

            • norepinephrine

              promethazine, norepinephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

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

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

            • nortriptyline

              promethazine and nortriptyline both increase QTc interval. Use Caution/Monitor.

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

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

            • ofloxacin

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

            • olanzapine

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

            • olanzapine

              olanzapine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

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

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

              olanzapine and promethazine both decrease QTc interval. 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.

            • onabotulinumtoxinA

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

              onabotulinumtoxinA decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • opium tincture

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

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

            • orphenadrine

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

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

            • oxazepam

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

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

            • oxybutynin

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

              oxybutynin decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of oxybutynin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • oxycodone

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

            • oxybutynin topical

              oxybutynin topical decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              oxybutynin topical decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of oxybutynin topical by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • oxybutynin transdermal

              oxybutynin transdermal decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              oxybutynin transdermal decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of oxybutynin transdermal by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • oxycodone

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

            • oxymorphone

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

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

            • paliperidone

              paliperidone and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

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

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

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

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

            • pancuronium

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

              pancuronium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of pancuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • papaveretum

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

            • papaveretum

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

            • papaverine

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

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

            • paroxetine

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

              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 promethazine 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.

            • pazopanib

              promethazine and pazopanib both increase QTc interval. Use Caution/Monitor.

            • peginterferon alfa 2b

              peginterferon alfa 2b, promethazine. 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

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

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

            • pentobarbital

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

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

            • perampanel

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

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

            • perphenazine

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

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

              perphenazine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

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

            • phendimetrazine

              promethazine, phendimetrazine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

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

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

            • phenelzine

              phenelzine increases effects of promethazine 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

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

            • phentermine

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

              promethazine, phentermine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

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

            • phenylephrine

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

              promethazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

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

            • phenylephrine PO

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

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

              promethazine, phenylephrine PO. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • pholcodine

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

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

            • pimavanserin

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

            • pimozide

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

            • pimozide

              pimozide and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

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

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

            • pirbuterol

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

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

            • porfimer

              promethazine, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.

            • 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.

            • posaconazole

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

            • pralidoxime

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

              pralidoxime decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of pralidoxime by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • pregabalin

              pregabalin, promethazine. 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.

            • primaquine

              primaquine and promethazine both decrease QTc interval. Use Caution/Monitor.

            • primidone

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

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

            • procarbazine

              procarbazine, promethazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Excessive sedation.

            • prochlorperazine

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

            • prochlorperazine

              prochlorperazine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

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

            • promethazine

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

            • propafenone

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

            • propantheline

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

              propantheline decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of propantheline by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • propofol

              propofol and promethazine 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.

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

              promethazine, propylhexedrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • protriptyline

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

              promethazine and protriptyline both increase QTc interval. Use Caution/Monitor.

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

            • pseudoephedrine

              promethazine, pseudoephedrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • quazepam

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

            • quazepam

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

            • quetiapine

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

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

              promethazine and quetiapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

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

            • 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.

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

            • ramelteon

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

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

            • ranolazine

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

            • 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.

            • rapacuronium

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

              rapacuronium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of rapacuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • ribociclib

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

            • risperidone

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

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

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

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

              promethazine and risperidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. 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.

            • rocuronium

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

              rocuronium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of rocuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • rolapitant

              rolapitant will increase the level or effect of promethazine 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.

              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

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

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

            • scopolamine

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

              scopolamine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of scopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • scullcap

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

            • scullcap

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

            • secobarbital

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

              promethazine 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.

            • serdexmethylphenidate/dexmethylphenidate

              promethazine, serdexmethylphenidate/dexmethylphenidate. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • sertraline

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

              sertraline and promethazine both decrease QTc interval. Use Caution/Monitor.

            • sevoflurane

              sevoflurane and promethazine both decrease QTc interval. Use Caution/Monitor.

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

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

            • shepherd's purse

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

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

            • smoking

              smoking decreases levels of promethazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.

            • 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.

            • solifenacin

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

              solifenacin decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of solifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              solifenacin and promethazine both decrease QTc interval. Use Caution/Monitor.

            • stiripentol

              stiripentol, promethazine. affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP2B6 inhibitor and inducer. Monitor CYP2B6 substrates coadministered with stiripentol for increased or decreased effects. CYP2B6 substrates may require dosage adjustment.

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

            • sufentanil

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

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

            • sulfamethoxazole

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

            • suvorexant

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

            • sunitinib

              sunitinib and promethazine both decrease QTc interval. Use Caution/Monitor.

            • tacrolimus

              tacrolimus and promethazine both decrease QTc interval. Use Caution/Monitor.

            • tapentadol

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

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

            • telavancin

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

            • temazepam

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

            • temazepam

              promethazine and temazepam 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.

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

            • terbutaline

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

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

            • tetrabenazine

              promethazine and tetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely.

            • 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.

            • thioridazine

              promethazine and thioridazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

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

            • thiothixene

              promethazine and thiothixene both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

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

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

              promethazine 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.

            • tiotropium

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

              tiotropium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of tiotropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • tobacco use

              tobacco use decreases levels of promethazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.

            • tolterodine

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

              tolterodine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of tolterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • topiramate

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

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

            • tramadol

              promethazine 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

              promethazine and trazodone both increase QTc interval. Use Caution/Monitor.

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

            • trazodone

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

            • triazolam

              promethazine 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.

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

            • trifluoperazine

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

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

              promethazine and trifluoperazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

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

            • trihexyphenidyl

              trihexyphenidyl decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of trihexyphenidyl by pharmacodynamic synergism. Use Caution/Monitor. Potential for additive anticholinergic effects.

            • trimipramine

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

            • trimethoprim

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

            • trimipramine

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

            • triprolidine

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

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

            • tropisetron

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

            • venlafaxine

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

            • trospium chloride

              trospium chloride decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              trospium chloride decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of trospium chloride by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • valerian

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

            • vecuronium

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

              vecuronium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of vecuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • venlafaxine

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

            • voriconazole

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

            • vorinostat

              vorinostat and promethazine both decrease QTc interval. Use Caution/Monitor.

            • xylometazoline

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

              promethazine, xylometazoline. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

              promethazine 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.

              promethazine, yohimbine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

              promethazine 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.

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

            • ziprasidone

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

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

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

              promethazine and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

            • zotepine

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

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

              promethazine and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

            Minor (76)

            • amiodarone

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

            • amitriptyline

              amitriptyline, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amitriptyline, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • amoxapine

              amoxapine, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amoxapine, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

              promethazine, amoxapine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • asenapine

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

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

            • ashwagandha

              ashwagandha increases effects of promethazine 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.

            • atropine

              promethazine increases toxicity of atropine by unknown mechanism. Minor/Significance Unknown.

            • atropine IV/IM

              promethazine increases toxicity of atropine IV/IM by unknown mechanism. Minor/Significance Unknown.

            • benazepril

              promethazine increases effects of benazepril by unspecified interaction mechanism. Minor/Significance Unknown. Enhanced hypotensive effects.

            • brimonidine

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

            • bupropion

              promethazine increases toxicity of bupropion by unspecified interaction mechanism. Minor/Significance Unknown. May lower seizure threshold; keep bupropion dose as low as possible.

            • captopril

              promethazine increases effects of captopril by unspecified interaction mechanism. Minor/Significance Unknown.

            • celecoxib

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

            • chasteberry

              chasteberry decreases effects of promethazine by pharmacodynamic antagonism. Minor/Significance Unknown. (Theoretical interaction).

            • chloroquine

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

              chloroquine increases levels of promethazine by decreasing metabolism. Minor/Significance Unknown.

            • cimetidine

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

            • clomipramine

              clomipramine, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              clomipramine, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • darifenacin

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

            • desipramine

              desipramine, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              desipramine, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • dextroamphetamine

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

            • diphenhydramine

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

            • doxepin

              doxepin, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              doxepin, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • dronedarone

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

            • duloxetine

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

            • enalapril

              promethazine increases effects of enalapril by unspecified interaction mechanism. Minor/Significance Unknown.

            • ethanol

              ethanol, promethazine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.

            • eucalyptus

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

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

            • famciclovir

              promethazine, famciclovir. aldehyde dehydrogenase inhibition. Minor/Significance Unknown. The conversion of 6-deoxy penciclovir to penciclovir is catalyzed by aldehyde oxidase. Interactions with other drugs metabolized by this enzyme and/or inhibiting this enzyme could potentially occur. Clinical interaction studies of famciclovir with promethazine did not show relevant effects on the formation of penciclovir.

            • fluoxetine

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

            • fosinopril

              promethazine increases effects of fosinopril by unspecified interaction mechanism. Minor/Significance Unknown.

            • glycopyrrolate

              promethazine increases toxicity of glycopyrrolate by unknown mechanism. Minor/Significance Unknown.

            • glycopyrrolate inhaled

              promethazine increases toxicity of glycopyrrolate inhaled by unknown mechanism. Minor/Significance Unknown.

            • haloperidol

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

            • imatinib

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

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

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

            • imidapril

              promethazine increases effects of imidapril by unspecified interaction mechanism. Minor/Significance Unknown.

            • lidocaine

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

            • imipramine

              imipramine, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              imipramine, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • lisinopril

              promethazine increases effects of lisinopril by unspecified interaction mechanism. Minor/Significance Unknown.

            • lofepramine

              lofepramine, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              lofepramine, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • maprotiline

              maprotiline, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              maprotiline, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • maraviroc

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

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

            • marijuana

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

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

            • metyrapone

              promethazine decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.

            • nilotinib

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

            • metyrosine

              metyrosine increases toxicity of promethazine by pharmacodynamic synergism. Minor/Significance Unknown. Increased extrapyramidal symptoms.

            • moexipril

              promethazine increases effects of moexipril by unspecified interaction mechanism. Minor/Significance Unknown.

            • nettle

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

            • nilotinib

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

            • nortriptyline

              nortriptyline, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              nortriptyline, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • oxybutynin

              oxybutynin increases toxicity of promethazine by unspecified interaction mechanism. Minor/Significance Unknown.

            • oxybutynin topical

              oxybutynin topical increases toxicity of promethazine by unspecified interaction mechanism. Minor/Significance Unknown.

            • oxybutynin transdermal

              oxybutynin transdermal increases toxicity of promethazine by unspecified interaction mechanism. Minor/Significance Unknown.

            • parecoxib

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

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

            • perindopril

              promethazine increases effects of perindopril by unspecified interaction mechanism. 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.

            • perphenazine

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

            • 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.

            • protriptyline

              protriptyline, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              protriptyline, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • pyrimethamine

              pyrimethamine increases levels of promethazine by decreasing metabolism. Minor/Significance Unknown.

            • quinacrine

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

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

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

            • quinapril

              promethazine increases effects of quinapril by unspecified interaction mechanism. Minor/Significance Unknown.

            • ranolazine

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

            • ramipril

              promethazine increases effects of ramipril by unspecified interaction mechanism. Minor/Significance Unknown.

            • ranolazine

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

            • ritonavir

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

            • sage

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

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

            • sertraline

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

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

            • Siberian ginseng

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

            • thioridazine

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

            • thioridazine

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

            • tipranavir

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

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

            • trandolapril

              promethazine increases effects of trandolapril by unspecified interaction mechanism. Minor/Significance Unknown.

            • venlafaxine

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

            • trazodone

              trazodone, promethazine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.

              trazodone, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

            • trimipramine

              trimipramine, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              trimipramine, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • ziconotide

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

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            Adverse Effects

            >10% (Codeine)

            Constipation

            Drowsiness

            Frequency Not Defined (Promethazine)

            Sedation (common)

            Confusion (common)

            Disorientation (common)

            Adverse anticholinergic effects (dry mouth, blurred vision)

            Photosensitivity

            EPS

            Tachycardia

            Bradycardia

            Leukopenia (rare)

            Agranulocytosis (rare)

            Obstructive jaundice

            Frequency Not Defined (Codeine)

            Confusion

            Dizziness

            False feeling of well being

            Headache

            Lightheadedness

            Malaise

            Paradoxical CNS stimulation

            Restlessness

            Seizure (with excessive doses)

            Weakness

            Blurred vision

            Hypotension (especially with IV use)

            Tachycardia

            Bradycardia

            Dyspnea

            Respiratory depression

            Anorexia

            Nausea

            Vomiting

            Xerostomia

            Rash

            Urticaria

            Ureteral spasm

            Urination decreased

            LFT's increased

            Histamine release

            Anaphylactoid reaction (rare)

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            Warnings

            Black Box Warnings

            Because of the potential for fatal respiratory depression, do not administer promethazine and codeine concurrently to children <12 years of age

            Postmarketing cases of respiratory depression, including fatalities reported with use of promethazine in pediatric patients; children may be particularly sensitive to additive respiratory depressant effects when promethazine is combined with other respiratory depressants, including codeine

            Coadministration with benzodiazepines

            • 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 this drug combination 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
            • Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; risks from concomitant use with benzodiazepines or other CNS depressants; ultra- rapid metabolism of codeine and other risk factors for life-threatening respiratory depression in children; neonatal opioid withdrawal syndrome; interactions with drugs affecting cytochrome p450 isoenzymes; and hepatotoxicity

            Postoperative pain in children

            • Deaths have occurred in children with obstructive sleep apnea who receive codeine for postoperative pain following tonsillectomy and/or adenoidectomy
            • Contraindicated in children <12 years and in children < 18 years following tonsillectomy and/or adenoidectomy; avoid use in adolescents 12-18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine; codeine is converted to morphine by the liver; these children had evidence of being ultra-rapid metabolizers (via CYP2D6) of codeine, which is an inherited (genetic) ability that causes codeine to be converted rapidly into life-threatening or fatal amounts of morphine (see Pharmacology)
            • 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; avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol

            Contraindications

            Postoperative use in children following tonsillectomy and/or adenoidectomy (see Black Box Warnings)

            Promethazine

            • Hypersensitivity
            • Children <12 years (risk of potentially fatal respiratory depression)
            • Subcutaneous or intra-arterially administration
            • Benign prostatic hypertrophy
            • Narrow angle glaucoma
            • Pyloroduodenal obstruction, stenosing peptic ulcer, bladder neck obstruction
            • Severe CNS depression
            • Coma, severe respiratory depression

            Codeine

            • Absolute: acute abdominal condition, diarrhea associated w/ toxins, pseudomembranous colitis, respiratory depression
            • Relative: asthma (acute), inflammatory bowel disease, respiratory impairment
            • Children <12 years
            • Postoperative management in children <18 years following tonsillectomy and/or adenoidectomy
            • 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 the last 14 days
            • Significant respiratory depression
            • Porphyria
            • Treatment of lower respiratory tract symptoms, including asthma
            • Known or suspected gastrointestinal obstruction, including paralytic ileus

            Cautions

            Concomitant use of opioids, including promethazine HCl and codeine phosphate oral solution, 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

            Promethazine

            • Caution in CVD, asthma, hepatic impairment, peptic ulcer, respiratory impairment; the impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; avoid use of promethazine HCl and codeine phosphate oral solution in patients on these medications
            • Anaphylaxis in susceptible individuals
            • May impair ability to drive or perform hazardous tasks
            • Monitor closely with cardiovascular disease, hepatic impairment, Reye syndrome, history of sleep apnea
            • Depresses hypothalamic thermoregulatory mechanism; exposure to extreme temperatures may cause hypo- or hyperthermia
            • Antiemetic effect may obscure toxicity of chemotherapeutic drugs
            • Concomitant use of opioids, including promethazine HCl and codeine phosphate oral solution, with benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol
            • Convulsions have occurred with therapeutic doses and overdoses of promethazine hydrochloride in pediatric patients; promethazine may lower seizure threshold; it should be used with caution in persons with seizure disorders or in persons who are using concomitant medications, such as narcotics or local anesthetics, which may also affect seizure threshold
            • Promethazine is a phenothiazine; phenothiazines are associated with dystonic reactions; in pediatric patients who are acutely ill associated with dehydration, there is increased susceptibility to dystonias with promethazine HCl use
            • The respiratory-depressant effects of narcotic analgesics and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in presence of head injury, intracranial lesions, or a pre-existing increase in intracranial pressure; narcotics may produce adverse reactions which may obscure clinical course of patients with head injuries
            • A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) reported in association with promethazine HCl alone or in combination with antipsychotic drugs; 1) management of NMS should include immediate discontinuation of promethazine HCl, antipsychotic drugs, if any, and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available
            • Promethazine should be used with caution in patients with bone-marrow depression; leukopenia and agranulocytosis reported, usually when promethazine HCl has been used in association with other known marrow-toxic agents

            Codeine

            • Caution in cardiac arrhythmias, drug abuse/dependence, emotional lability, gallbladder disease, head injury, hepatic impairment, hypothyroidism, increased ICP, prostatic hypertrophy, renal impairment, seizures w/ epilepsy, urethral stricture, urinary tract surgery
            • Risk of life threatening side effects in nursing babies, especially if mother is an ultra rapid metabolizer of codeine
            • Codeine is subject to variability in metabolism based upon CYP2D6 genotype (described below), which can lead to an increased exposure to the active metabolite morphine
            • Avoid use of capsules 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
            • Dosage of codeine should not be increased if cough fails to respond; an unresponsive cough should be reevaluated in 5 days or sooner for possible underlying pathology, such as foreign body or lower respiratory tract disease
            • Narcotic analgesics or cough suppressants, including codeine, should not be used in patients with severe asthma or those with frequent asthma attacks
            • Codeine may produce orthostatic hypotension in ambulatory patients
            • Codeine may cause or aggravate constipation
            • Ibuprofen is more effective than codeine for pain from musculoskeletal injuries in children
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            Pregnancy & Lactation

            Pregnancy

            Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome; available data in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage

            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

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

            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

            Promethazine: Antidopaminergic effect due to blocking mesolimbic dopamine receptors and alpha-adrenergic receptors in the brain; antihistaminic effect due to blocking H1-receptors

            Codeine: Narcotic agonist analgesic with antitussive activity, mu receptor agonist

            Promethazine

            Onset: 20 min

            Duration: 4-6 hr

            Bioavailability: 25% (oral)

            Protein Bound: 93%

            Vd: 12.9-17.7 L/hr

            Metabolism: Hepatic P450 enzyme CYP2D6

            Metabolites: Promethazine sulfoxide and glucuronides (inactive)

            Excretion: Urine, feces

            Dialyzable: no

            Codeine

            Half-Life: 3-4 hr

            Onset: 30-60 min

            Metabolism: Inactive but metabolized to morphine by CYP2D6 (missing in 5-10% of population)

            Duration: 4-6 hr

            Peak Plasma Time: 0.5-1 hr

            Vd: 3-6 L/kg

            Bioavailability: 53%

            Protein Bound: 25%

            Excretion: Urine (90%), feces

            Pharmacogenomics

            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 Caucasians and up to 30% of Asian and African populations) may have increased toxicity due to rapid conversion

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            Images

            No images available for this drug.
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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            • View the formulary and any restrictions for each plan.
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            • Compare formulary status to other drugs in the same class.
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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.