promethazine/codeine (Rx)

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

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

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 (107)

• 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.

• acrivastine

  acrivastine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• amiodarone

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

• amisulpride

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

• asenapine

  asenapine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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.
  
  asenapine transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• avapritinib

  avapritinib and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen and promethazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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.
  
  benzhydrocodone/acetaminophen and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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.

• brimonidine

  brimonidine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

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

• buprenorphine subdermal implant

  buprenorphine subdermal implant and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine subdermal implant and promethazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine subdermal implant and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  buprenorphine transdermal and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine transdermal and promethazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  buprenorphine, long-acting injection and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• 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.

• cabergoline

  promethazine decreases effects of cabergoline by pharmacodynamic antagonism. Contraindicated.

• 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.

• olopatadine intranasal

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

• 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.

• tetrabenazine

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

• 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 (387)

• 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.

• acrivastine

  acrivastine and promethazine both increase sedation. 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.

• amisulpride

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

• 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).
  
  asenapine and promethazine both increase sedation. Use Caution/Monitor.

• azelastine

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

• asenapine transdermal

  asenapine transdermal and promethazine 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.

• avapritinib

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

• 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.

• brexpiprazole

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

• brimonidine

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

• brivaracetam

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

• brivaracetam

  brivaracetam and promethazine both increase 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 topical

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

• codeine

  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. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).
  
  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.

• sparsentan

  sparsentan will decrease the level or effect of promethazine by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Sparsentan (a CYP2B6 inducer) decreases exposure of CYP2B6 substrates and reduces efficacy related to these substrates.

• 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.

• valbenazine

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

• 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.

• abametapir

  Serious - Use Alternative (1)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.

• abiraterone

  Monitor Closely (2)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

  Monitor Closely (2)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.

• acrivastine

  Monitor Closely (1)acrivastine and promethazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)acrivastine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• albiglutide

  Monitor Closely (1)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

  Monitor Closely (2)codeine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  promethazine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• alfentanil

  Monitor Closely (2)promethazine and alfentanil both increase sedation. Use Caution/Monitor.
  
  alfentanil and codeine both increase sedation. Use Caution/Monitor.

• alprazolam

  Monitor Closely (2)alprazolam and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and alprazolam both increase sedation. Use Caution/Monitor.

• alvimopan

  Contraindicated (1)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.

• amifampridine

  Monitor Closely (1)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

  Monitor Closely (1)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.Serious - Use Alternative (1)promethazine and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)amiodarone will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• amisulpride

  Monitor Closely (1)amisulpride and promethazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)amisulpride and codeine both increase sedation. Avoid or Use Alternate Drug.
  
  promethazine and amisulpride both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.

• amitriptyline

  Monitor Closely (3)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.Minor (2)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.

• amobarbital

  Monitor Closely (2)amobarbital and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and amobarbital both increase sedation. Use Caution/Monitor.

• amoxapine

  Monitor Closely (4)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.Minor (3)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.

• anagrelide

  Serious - Use Alternative (1)anagrelide and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• anticholinergic/sedative combos

  Monitor Closely (3)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

  Monitor Closely (2)promethazine and apomorphine both increase sedation. Use Caution/Monitor.
  
  codeine and apomorphine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)promethazine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

• arformoterol

  Monitor Closely (2)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

  Monitor Closely (4)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

  Monitor Closely (2)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.

• arsenic trioxide

  Serious - Use Alternative (1)promethazine and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

• artemether/lumefantrine

  Monitor Closely (2)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.Serious - Use Alternative (1)promethazine and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

• asenapine

  Monitor Closely (2)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).
  
  asenapine and promethazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)asenapine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  asenapine and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.Minor (2)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.

• asenapine transdermal

  Monitor Closely (1)asenapine transdermal and promethazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)asenapine transdermal and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
  
  asenapine transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• ashwagandha

  Minor (1)ashwagandha increases effects of promethazine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• atracurium

  Monitor Closely (3)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

  Monitor Closely (3)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.Minor (1)promethazine increases toxicity of atropine by unknown mechanism. Minor/Significance Unknown.

• atropine IV/IM

  Monitor Closely (1)promethazine increases effects of atropine IV/IM by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.Minor (1)promethazine increases toxicity of atropine IV/IM by unknown mechanism. Minor/Significance Unknown.

• avapritinib

  Monitor Closely (1)avapritinib and promethazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)avapritinib and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• azelastine

  Monitor Closely (2)azelastine and codeine both increase sedation. Use Caution/Monitor.
  
  azelastine and promethazine both increase sedation. Use Caution/Monitor.

• azithromycin

  Monitor Closely (1)promethazine and azithromycin both increase QTc interval. Use Caution/Monitor.

• baclofen

  Monitor Closely (2)promethazine and baclofen both increase sedation. Use Caution/Monitor.
  
  baclofen and codeine both increase sedation. Use Caution/Monitor.

• belladonna alkaloids

  Monitor Closely (3)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

  Monitor Closely (5)promethazine and belladonna and opium both increase sedation. Use Caution/Monitor.
  
  codeine 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.
  
  promethazine increases effects of belladonna and opium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna and opium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

• benazepril

  Minor (1)promethazine increases effects of benazepril by unspecified interaction mechanism. Minor/Significance Unknown. Enhanced hypotensive effects.

• benperidol

  Monitor Closely (3)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.

• benzhydrocodone/acetaminophen

  Serious - Use Alternative (3)benzhydrocodone/acetaminophen and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  benzhydrocodone/acetaminophen and promethazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  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.

• benzphetamine

  Monitor Closely (3)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

  Monitor Closely (1)promethazine increases effects of benztropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use. .

• bremelanotide

  Serious - Use Alternative (1)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.

• brexanolone

  Monitor Closely (2)brexanolone, codeine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
  
  brexanolone, promethazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  Monitor Closely (2)brexpiprazole and codeine both increase sedation. Use Caution/Monitor.
  
  brexpiprazole and promethazine both increase sedation. Use Caution/Monitor.

• brimonidine

  Monitor Closely (1)brimonidine and promethazine both increase sedation. Use Caution/Monitor.Minor (2)brimonidine increases effects of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.
  
  brimonidine increases effects of promethazine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.Serious - Use Alternative (1)brimonidine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• brivaracetam

  Monitor Closely (2)brivaracetam and codeine both increase sedation. Use Caution/Monitor.
  
  brivaracetam and promethazine both increase sedation. Use Caution/Monitor.

• bromocriptine

  Serious - Use Alternative (1)promethazine decreases effects of bromocriptine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

• brompheniramine

  Monitor Closely (2)brompheniramine and promethazine both increase sedation. Use Caution/Monitor.
  
  brompheniramine and codeine both increase sedation. Use Caution/Monitor.

• buprenorphine

  Monitor Closely (2)buprenorphine and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and buprenorphine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)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

  Monitor Closely (2)promethazine and buprenorphine buccal both increase sedation. Use Caution/Monitor.
  
  buprenorphine buccal and codeine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)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.
  
  buprenorphine buccal and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• buprenorphine subdermal implant

  Serious - Use Alternative (3)buprenorphine subdermal implant and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine subdermal implant and promethazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine subdermal implant and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  Serious - Use Alternative (3)buprenorphine transdermal and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine transdermal and promethazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  Monitor Closely (1)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.Serious - Use Alternative (1)buprenorphine, long-acting injection and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• bupropion

  Monitor Closely (2)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.
  
  bupropion will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Minor (1)promethazine increases toxicity of bupropion by unspecified interaction mechanism. Minor/Significance Unknown. May lower seizure threshold; keep bupropion dose as low as possible.

• butabarbital

  Monitor Closely (2)butabarbital and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and butabarbital both increase sedation. Use Caution/Monitor.

• butalbital

  Monitor Closely (2)butalbital and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and butalbital both increase sedation. Use Caution/Monitor.

• butorphanol

  Monitor Closely (2)butorphanol and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and butorphanol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)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.

• cabergoline

  Serious - Use Alternative (1)promethazine decreases effects of cabergoline by pharmacodynamic antagonism. Contraindicated.

• caffeine

  Monitor Closely (2)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.

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (2)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.

• captopril

  Minor (1)promethazine increases effects of captopril by unspecified interaction mechanism. Minor/Significance Unknown.

• carbinoxamine

  Monitor Closely (2)carbinoxamine and codeine both increase sedation. Use Caution/Monitor.
  
  carbinoxamine and promethazine both increase sedation. Use Caution/Monitor.

• cariprazine

  Monitor Closely (1)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

  Monitor Closely (2)carisoprodol and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and carisoprodol both increase sedation. Use Caution/Monitor.

• celecoxib

  Monitor Closely (1)celecoxib decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Minor (1)celecoxib will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• cenobamate

  Monitor Closely (3)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, codeine. Either increases effects of the other by sedation. Use Caution/Monitor.
  
  cenobamate, promethazine. Either increases effects of the other by sedation. Use Caution/Monitor.

• chasteberry

  Minor (1)chasteberry decreases effects of promethazine by pharmacodynamic antagonism. Minor/Significance Unknown. (Theoretical interaction).

• chloral hydrate

  Monitor Closely (2)chloral hydrate and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and chloral hydrate both increase sedation. Use Caution/Monitor.

• chlordiazepoxide

  Monitor Closely (2)chlordiazepoxide and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• chloroquine

  Monitor Closely (1)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.Minor (2)chloroquine increases levels of promethazine by decreasing metabolism. Minor/Significance Unknown.
  
  chloroquine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• chlorpheniramine

  Monitor Closely (2)chlorpheniramine and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and promethazine both increase sedation. Use Caution/Monitor.

• chlorpromazine

  Monitor Closely (4)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.Serious - Use Alternative (1)chlorpromazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.

• chlorzoxazone

  Monitor Closely (2)chlorzoxazone and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and chlorzoxazone both increase sedation. Use Caution/Monitor.

• cigarette smoking

  Monitor Closely (1)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

  Monitor Closely (1)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.Minor (1)cimetidine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• cinacalcet

  Monitor Closely (1)cinacalcet decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• cinnarizine

  Monitor Closely (2)cinnarizine and codeine both increase sedation. Use Caution/Monitor.
  
  cinnarizine and promethazine both increase sedation. Use Caution/Monitor.

• cisatracurium

  Monitor Closely (3)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.

• citalopram

  Monitor Closely (1)citalopram and promethazine both increase serotonin levels. Use Caution/Monitor. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.

• clarithromycin

  Serious - Use Alternative (1)promethazine and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.

• clemastine

  Monitor Closely (2)clemastine and promethazine both increase sedation. Use Caution/Monitor.
  
  clemastine and codeine both increase sedation. Use Caution/Monitor.

• clobazam

  Monitor Closely (4)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

  Monitor Closely (3)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.Serious - Use Alternative (1)promethazine and clomipramine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)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.

• clonazepam

  Monitor Closely (2)promethazine and clonazepam both increase sedation. Use Caution/Monitor.
  
  clonazepam and codeine both increase sedation. Use Caution/Monitor.

• clonidine

  Monitor Closely (1)clonidine, promethazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.Serious - Use Alternative (1)clonidine, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• clorazepate

  Monitor Closely (2)clorazepate and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and clorazepate both increase sedation. Use Caution/Monitor.

• clozapine

  Monitor Closely (5)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 topical

  Monitor Closely (1)cocaine topical decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• codeine

  Monitor Closely (1)promethazine and codeine both increase sedation. Use Caution/Monitor.

• cyclizine

  Monitor Closely (5)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

  Monitor Closely (5)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

  Monitor Closely (2)cyproheptadine and codeine both increase sedation. Use Caution/Monitor.
  
  cyproheptadine and promethazine both increase sedation. Use Caution/Monitor.

• dacomitinib

  Serious - Use Alternative (2)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.

• dantrolene

  Monitor Closely (2)dantrolene and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and dantrolene both increase sedation. Use Caution/Monitor.

• daridorexant

  Monitor Closely (2)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

  Monitor Closely (4)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.Minor (1)darifenacin will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dasatinib

  Monitor Closely (1)promethazine and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.

• degarelix

  Serious - Use Alternative (1)degarelix and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• desflurane

  Monitor Closely (3)desflurane and promethazine both increase sedation. Use Caution/Monitor.
  
  desflurane and promethazine both decrease QTc interval. Use Caution/Monitor.
  
  desflurane and codeine both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.

• desipramine

  Monitor Closely (4)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.Minor (2)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.

• desvenlafaxine

  Monitor Closely (2)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

  Monitor Closely (3)deutetrabenazine and promethazine both decrease QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).
  
  promethazine and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  codeine and deutetrabenazine both increase sedation. Use Caution/Monitor.

• dexchlorpheniramine

  Monitor Closely (2)dexchlorpheniramine and codeine both increase sedation. Use Caution/Monitor.
  
  dexchlorpheniramine and promethazine both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  Monitor Closely (3)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

  Monitor Closely (2)promethazine and dexmedetomidine both increase sedation. Use Caution/Monitor.
  
  dexmedetomidine and codeine both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  Monitor Closely (3)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

  Monitor Closely (3)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.Minor (1)dextroamphetamine increases effects of codeine by unspecified interaction mechanism. Minor/Significance Unknown.

• dextromoramide

  Monitor Closely (2)codeine and dextromoramide both increase sedation. Use Caution/Monitor.
  
  promethazine and dextromoramide both increase sedation. Use Caution/Monitor.

• diamorphine

  Monitor Closely (2)promethazine and diamorphine both increase sedation. Use Caution/Monitor.
  
  codeine and diamorphine both increase sedation. Use Caution/Monitor.

• diazepam

  Monitor Closely (2)promethazine and diazepam both increase sedation. Use Caution/Monitor.
  
  diazepam and codeine both increase sedation. Use Caution/Monitor.

• diazepam intranasal

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• dicyclomine

  Monitor Closely (3)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

  Monitor Closely (3)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.
  
  codeine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  promethazine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• difelikefalin

  Monitor Closely (2)difelikefalin and codeine both increase sedation. Use Caution/Monitor.
  
  difelikefalin and promethazine both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  Monitor Closely (2)promethazine and difenoxin hcl both increase sedation. Use Caution/Monitor.
  
  codeine and difenoxin hcl both increase sedation. Use Caution/Monitor.

• dimenhydrinate

  Monitor Closely (2)dimenhydrinate and promethazine both increase sedation. Use Caution/Monitor.
  
  dimenhydrinate and codeine both increase sedation. Use Caution/Monitor.

• diphenhydramine

  Monitor Closely (6)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 decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  diphenhydramine and promethazine both increase sedation. Use Caution/Monitor.
  
  promethazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.Minor (1)diphenhydramine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• diphenoxylate hcl

  Monitor Closely (2)promethazine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
  
  codeine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

• dipipanone

  Monitor Closely (2)codeine and dipipanone both increase sedation. Use Caution/Monitor.
  
  promethazine and dipipanone both increase sedation. Use Caution/Monitor.

• disopyramide

  Contraindicated (1)promethazine and disopyramide both increase QTc interval. Contraindicated.

• dobutamine

  Monitor Closely (3)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.

• dofetilide

  Serious - Use Alternative (1)promethazine and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.

• dolasetron

  Monitor Closely (1)promethazine and dolasetron both increase QTc interval. Modify Therapy/Monitor Closely.

• donepezil

  Monitor Closely (1)donepezil and promethazine both decrease QTc interval. Use Caution/Monitor.

• donepezil transdermal

  Monitor Closely (1)donepezil transdermal, promethazine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

• dopamine

  Monitor Closely (3)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.
  
  codeine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  promethazine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)promethazine decreases effects of dopamine by pharmacodynamic antagonism. Contraindicated.

• dopexamine

  Monitor Closely (2)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

  Monitor Closely (2)codeine and dosulepin both increase sedation. Use Caution/Monitor.
  
  promethazine and dosulepin both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)promethazine and dosulepin both increase QTc interval. Avoid or Use Alternate Drug.

• doxepin

  Monitor Closely (3)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.Minor (2)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.

• doxylamine

  Monitor Closely (2)doxylamine and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and doxylamine both increase sedation. Use Caution/Monitor.

• dronedarone

  Monitor Closely (1)dronedarone decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Serious - Use Alternative (1)promethazine and dronedarone both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)dronedarone will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• droperidol

  Monitor Closely (3)promethazine and droperidol both increase sedation. Use Caution/Monitor.
  
  codeine and droperidol both increase sedation. Use Caution/Monitor.
  
  droperidol and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.Serious - Use Alternative (1)promethazine and droperidol both increase QTc interval. Avoid or Use Alternate Drug.

• duloxetine

  Monitor Closely (1)duloxetine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Minor (1)duloxetine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• efavirenz

  Monitor Closely (1)efavirenz and promethazine both decrease QTc interval. Use Caution/Monitor.

• eliglustat

  Monitor Closely (1)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.Serious - Use Alternative (1)eliglustat and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• eluxadoline

  Serious - Use Alternative (2)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.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (2)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.

• enalapril

  Minor (1)promethazine increases effects of enalapril by unspecified interaction mechanism. Minor/Significance Unknown.

• encorafenib

  Serious - Use Alternative (1)encorafenib and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• entrectinib

  Serious - Use Alternative (1)entrectinib and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• ephedrine

  Monitor Closely (3)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

  Monitor Closely (4)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, 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.
  
  promethazine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)epinephrine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.

• epinephrine racemic

  Monitor Closely (3)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.Serious - Use Alternative (1)epinephrine racemic and promethazine both increase QTc interval. Avoid or Use Alternate Drug.

• eribulin

  Serious - Use Alternative (1)eribulin and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• erythromycin base

  Serious - Use Alternative (1)promethazine and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  Serious - Use Alternative (1)promethazine and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  Serious - Use Alternative (1)promethazine and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin stearate

  Serious - Use Alternative (1)promethazine and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

• esketamine intranasal

  Monitor Closely (2)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

  Monitor Closely (2)estazolam and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and estazolam both increase sedation. Use Caution/Monitor.

• ethanol

  Monitor Closely (2)promethazine and ethanol both increase sedation. Use Caution/Monitor.
  
  codeine and ethanol both increase sedation. Use Caution/Monitor.Minor (1)ethanol, promethazine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.

• etomidate

  Monitor Closely (2)etomidate and codeine both increase sedation. Use Caution/Monitor.
  
  etomidate and promethazine both increase sedation. Use Caution/Monitor.

• eucalyptus

  Minor (2)codeine and eucalyptus both increase sedation. Minor/Significance Unknown.
  
  promethazine and eucalyptus both increase sedation. Minor/Significance Unknown.

• famciclovir

  Minor (1)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.

• fedratinib

  Monitor Closely (2)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

  Monitor Closely (3)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

  Monitor Closely (1)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.Serious - Use Alternative (1)fentanyl, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl intranasal

  Monitor Closely (1)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.Serious - Use Alternative (1)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

  Monitor Closely (1)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.Serious - Use Alternative (1)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

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• fesoterodine

  Monitor Closely (3)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.

• fexinidazole

  Serious - Use Alternative (1)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

  Serious - Use Alternative (1)fingolimod and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• flavoxate

  Monitor Closely (3)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

  Monitor Closely (1)promethazine and flecainide both increase QTc interval. Modify Therapy/Monitor Closely.

• flibanserin

  Monitor Closely (2)promethazine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
  
  codeine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

• fluconazole

  Serious - Use Alternative (1)promethazine and fluconazole both increase QTc interval. Avoid or Use Alternate Drug.

• fluoxetine

  Monitor Closely (2)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 morphineSerious - Use Alternative (1)fluoxetine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.Minor (1)fluoxetine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• fluphenazine

  Monitor Closely (4)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.Serious - Use Alternative (1)fluphenazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.

• flurazepam

  Monitor Closely (2)flurazepam and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and flurazepam both increase sedation. Use Caution/Monitor.

• fluvoxamine

  Monitor Closely (1)fluvoxamine and promethazine both increase QTc interval. Use Caution/Monitor.

• formoterol

  Monitor Closely (2)codeine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  promethazine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)promethazine and formoterol both increase QTc interval. Avoid or Use Alternate Drug.

• foscarnet

  Monitor Closely (1)promethazine and foscarnet both increase QTc interval. Modify Therapy/Monitor Closely.

• fosinopril

  Minor (1)promethazine increases effects of fosinopril by unspecified interaction mechanism. Minor/Significance Unknown.

• gabapentin

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (2)promethazine and ganaxolone both increase sedation. Use Caution/Monitor.
  
  codeine and ganaxolone both increase sedation. Use Caution/Monitor.

• gemifloxacin

  Monitor Closely (1)gemifloxacin and promethazine both decrease QTc interval. Use Caution/Monitor.

• gilteritinib

  Monitor Closely (1)gilteritinib and promethazine both decrease QTc interval. Use Caution/Monitor.

• givosiran

  Serious - Use Alternative (2)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.

• glycopyrrolate

  Monitor Closely (1)promethazine increases effects of glycopyrrolate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.Minor (1)promethazine increases toxicity of glycopyrrolate by unknown mechanism. Minor/Significance Unknown.

• glycopyrrolate inhaled

  Monitor Closely (3)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.Minor (1)promethazine increases toxicity of glycopyrrolate inhaled by unknown mechanism. Minor/Significance Unknown.

• glycopyrronium tosylate topical

  Monitor Closely (1)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

  Monitor Closely (1)gotu kola increases effects of promethazine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• granisetron

  Monitor Closely (1)granisetron and promethazine both decrease QTc interval. Use Caution/Monitor.

• guanfacine

  Monitor Closely (1)guanfacine, promethazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• haloperidol

  Monitor Closely (5)codeine and haloperidol both increase sedation. Use Caution/Monitor.
  
  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).
  
  haloperidol decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Serious - Use Alternative (1)promethazine and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)haloperidol will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• hawthorn

  Monitor Closely (1)hawthorn increases effects of promethazine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• henbane

  Monitor Closely (3)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

  Monitor Closely (3)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

  Monitor Closely (1)hops increases effects of promethazine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• hyaluronidase

  Monitor Closely (1)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.

• hydrocodone

  Serious - Use Alternative (1)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.

• hydromorphone

  Monitor Closely (2)promethazine and hydromorphone both increase sedation. Use Caution/Monitor.
  
  codeine and hydromorphone both increase sedation. Use Caution/Monitor.

• hydroxyzine

  Monitor Closely (3)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

  Monitor Closely (3)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.

• hyoscyamine spray

  Monitor Closely (1)promethazine increases effects of hyoscyamine spray by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• ibutilide

  Contraindicated (1)promethazine and ibutilide both increase QTc interval. Contraindicated.

• iloperidone

  Monitor Closely (5)promethazine and iloperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  iloperidone and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  promethazine and iloperidone both increase sedation. Use Caution/Monitor.
  
  codeine 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).

• imatinib

  Minor (3)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

  Minor (1)promethazine increases effects of imidapril by unspecified interaction mechanism. Minor/Significance Unknown.

• imipramine

  Monitor Closely (4)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.Minor (2)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.

• incobotulinumtoxinA

  Monitor Closely (1)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.

• indapamide

  Contraindicated (1)promethazine and indapamide both increase QTc interval. Contraindicated.

• ipratropium

  Monitor Closely (3)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.

• isocarboxazid

  Serious - Use Alternative (2)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.

• isoflurane

  Monitor Closely (1)isoflurane and promethazine both decrease QTc interval. Use Caution/Monitor.

• isoniazid

  Monitor Closely (1)isoniazid decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• isoproterenol

  Monitor Closely (3)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.

• itraconazole

  Serious - Use Alternative (1)promethazine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

• kava

  Monitor Closely (1)kava increases effects of promethazine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• ketamine

  Monitor Closely (2)ketamine and codeine both increase sedation. Use Caution/Monitor.
  
  ketamine and promethazine both increase sedation. Use Caution/Monitor.

• ketoconazole

  Monitor Closely (1)ketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Serious - Use Alternative (1)promethazine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• ketotifen, ophthalmic

  Monitor Closely (2)codeine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
  
  promethazine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• lapatinib

  Monitor Closely (1)promethazine and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.

• lasmiditan

  Monitor Closely (2)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, 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

  Monitor Closely (3)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

  Monitor Closely (1)letermovir increases levels of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levalbuterol

  Monitor Closely (2)promethazine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• levodopa

  Serious - Use Alternative (1)promethazine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

• levofloxacin

  Monitor Closely (1)promethazine and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

• levoketoconazole

  Monitor Closely (1)levoketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Serious - Use Alternative (1)promethazine and levoketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• levorphanol

  Monitor Closely (2)codeine and levorphanol both increase sedation. Use Caution/Monitor.
  
  promethazine and levorphanol both increase sedation. Use Caution/Monitor.

• lidocaine

  Minor (1)lidocaine increases toxicity of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.

• linezolid

  Serious - Use Alternative (1)linezolid increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• liraglutide

  Monitor Closely (1)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

  Monitor Closely (3)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.
  
  codeine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  promethazine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lisinopril

  Minor (1)promethazine increases effects of lisinopril by unspecified interaction mechanism. Minor/Significance Unknown.

• lisuride

  Serious - Use Alternative (1)promethazine decreases effects of lisuride by pharmacodynamic antagonism. Contraindicated.

• lithium

  Monitor Closely (2)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

  Monitor Closely (2)promethazine and lofepramine both increase sedation. Use Caution/Monitor.
  
  codeine and lofepramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)promethazine and lofepramine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)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.

• lofexidine

  Monitor Closely (2)promethazine and lofexidine both increase sedation. Use Caution/Monitor.
  
  codeine and lofexidine both increase sedation. Use Caution/Monitor.

• lopinavir

  Monitor Closely (1)lopinavir decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• loprazolam

  Monitor Closely (2)promethazine and loprazolam both increase sedation. Use Caution/Monitor.
  
  loprazolam and codeine both increase sedation. Use Caution/Monitor.

• lorazepam

  Monitor Closely (2)promethazine and lorazepam both increase sedation. Use Caution/Monitor.
  
  lorazepam and codeine both increase sedation. Use Caution/Monitor.

• lorcaserin

  Monitor Closely (2)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

  Monitor Closely (2)lormetazepam and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and lormetazepam both increase sedation. Use Caution/Monitor.

• loxapine

  Monitor Closely (4)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

  Monitor Closely (4)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

  Monitor Closely (1)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

  Monitor Closely (2)lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  lumefantrine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)promethazine and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

• lurasidone

  Monitor Closely (3)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

  Monitor Closely (3)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.Minor (2)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

  Minor (2)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

  Monitor Closely (2)promethazine and marijuana both increase sedation. Use Caution/Monitor.
  
  codeine and marijuana both increase sedation. Use Caution/Monitor.Minor (2)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.

• meclizine

  Monitor Closely (3)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.

• mefloquine

  Serious - Use Alternative (1)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.

• melatonin

  Monitor Closely (2)promethazine and melatonin both increase sedation. Use Caution/Monitor.
  
  codeine and melatonin both increase sedation. Use Caution/Monitor.

• meperidine

  Monitor Closely (2)promethazine and meperidine both increase sedation. Use Caution/Monitor.
  
  codeine and meperidine both increase sedation. Use Caution/Monitor.

• meprobamate

  Monitor Closely (2)codeine and meprobamate both increase sedation. Use Caution/Monitor.
  
  promethazine and meprobamate both increase sedation. Use Caution/Monitor.

• metaproterenol

  Monitor Closely (2)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

  Monitor Closely (2)promethazine and metaxalone both increase sedation. Use Caution/Monitor.
  
  metaxalone and codeine both increase sedation. Use Caution/Monitor.

• metformin

  Monitor Closely (1)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

  Monitor Closely (3)promethazine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  codeine and methadone both increase sedation. Use Caution/Monitor.
  
  promethazine and methadone both increase sedation. Use Caution/Monitor.

• methamphetamine

  Monitor Closely (3)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.
  
  codeine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  promethazine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methocarbamol

  Monitor Closely (2)promethazine and methocarbamol both increase sedation. Use Caution/Monitor.
  
  methocarbamol and codeine both increase sedation. Use Caution/Monitor.

• methoxsalen

  Monitor Closely (1)methoxsalen, promethazine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.

• methscopolamine

  Monitor Closely (3)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.

• methyldopa

  Serious - Use Alternative (1)promethazine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

• methylene blue

  Serious - Use Alternative (2)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

• methylenedioxymethamphetamine

  Monitor Closely (3)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.
  
  codeine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  promethazine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methylphenidate

  Monitor Closely (1)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

  Monitor Closely (1)promethazine and metoclopramide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

• metoclopramide intranasal

  Serious - Use Alternative (2)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.

• metrizamide

  Contraindicated (1)promethazine, metrizamide. Mechanism: unknown. Contraindicated. Risk of seizure. D/C phenothiazine 24h before admin. of metrizamide.

• metyrapone

  Minor (1)promethazine decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.

• metyrosine

  Minor (1)metyrosine increases toxicity of promethazine by pharmacodynamic synergism. Minor/Significance Unknown. Increased extrapyramidal symptoms.

• midazolam

  Monitor Closely (2)promethazine and midazolam both increase sedation. Use Caution/Monitor.
  
  midazolam and codeine both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (2)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

  Monitor Closely (3)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

  Monitor Closely (1)mifepristone will increase the level or effect of promethazine by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.

• mirabegron

  Monitor Closely (2)mirabegron will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  mirabegron will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• mirtazapine

  Monitor Closely (3)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

  Monitor Closely (2)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.

• moexipril

  Minor (1)promethazine increases effects of moexipril by unspecified interaction mechanism. Minor/Significance Unknown.

• molindone

  Monitor Closely (1)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

  Monitor Closely (2)codeine and morphine both increase sedation. Use Caution/Monitor.
  
  promethazine and morphine both increase sedation. Use Caution/Monitor.

• motherwort

  Monitor Closely (2)codeine and motherwort both increase sedation. Use Caution/Monitor.
  
  promethazine and motherwort both increase sedation. Use Caution/Monitor.

• moxifloxacin

  Serious - Use Alternative (1)promethazine and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• moxonidine

  Monitor Closely (2)codeine and moxonidine both increase sedation. Use Caution/Monitor.
  
  promethazine and moxonidine both increase sedation. Use Caution/Monitor.

• nabilone

  Monitor Closely (2)promethazine and nabilone both increase sedation. Use Caution/Monitor.
  
  codeine and nabilone both increase sedation. Use Caution/Monitor.

• nalbuphine

  Monitor Closely (2)codeine and nalbuphine both increase sedation. Use Caution/Monitor.
  
  promethazine and nalbuphine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)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.

• nettle

  Minor (1)nettle increases effects of promethazine by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.

• nilotinib

  Serious - Use Alternative (1)promethazine and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)nilotinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  nilotinib will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• norepinephrine

  Monitor Closely (3)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

  Monitor Closely (3)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.Minor (2)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.

• octreotide

  Serious - Use Alternative (1)promethazine and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

• octreotide (Antidote)

  Serious - Use Alternative (1)promethazine and octreotide (Antidote) both increase QTc interval. Avoid or Use Alternate Drug.

• ofloxacin

  Monitor Closely (1)promethazine and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

• olanzapine

  Monitor Closely (5)promethazine and olanzapine both increase sedation. Use Caution/Monitor.
  
  olanzapine and promethazine both decrease QTc interval. Use Caution/Monitor.
  
  codeine and olanzapine both increase sedation. Use Caution/Monitor.
  
  olanzapine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. 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).

• oliceridine

  Monitor Closely (1)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.

• olopatadine intranasal

  Serious - Use Alternative (2)codeine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
  
  promethazine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• onabotulinumtoxinA

  Monitor Closely (3)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

  Monitor Closely (2)promethazine and opium tincture both increase sedation. Use Caution/Monitor.
  
  codeine and opium tincture both increase sedation. Use Caution/Monitor.

• orphenadrine

  Monitor Closely (2)orphenadrine and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and orphenadrine both increase sedation. Use Caution/Monitor.

• oxaliplatin

  Serious - Use Alternative (1)oxaliplatin and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• oxazepam

  Monitor Closely (2)oxazepam and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and oxazepam both increase sedation. Use Caution/Monitor.

• oxybutynin

  Monitor Closely (3)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.Minor (1)oxybutynin increases toxicity of promethazine by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin topical

  Monitor Closely (3)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.Minor (1)oxybutynin topical increases toxicity of promethazine by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin transdermal

  Monitor Closely (3)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.Minor (1)oxybutynin transdermal increases toxicity of promethazine by unspecified interaction mechanism. Minor/Significance Unknown.

• oxycodone

  Monitor Closely (2)promethazine and oxycodone both increase sedation. Use Caution/Monitor.
  
  codeine and oxycodone both increase sedation. Use Caution/Monitor.

• oxymorphone

  Monitor Closely (2)codeine and oxymorphone both increase sedation. Use Caution/Monitor.
  
  promethazine and oxymorphone both increase sedation. Use Caution/Monitor.

• ozanimod

  Serious - Use Alternative (1)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.

• paliperidone

  Monitor Closely (5)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

  Monitor Closely (3)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

  Monitor Closely (2)promethazine and papaveretum both increase sedation. Use Caution/Monitor.
  
  codeine and papaveretum both increase sedation. Use Caution/Monitor.

• papaverine

  Monitor Closely (2)promethazine and papaverine both increase sedation. Use Caution/Monitor.
  
  codeine and papaverine both increase sedation. Use Caution/Monitor.

• parecoxib

  Minor (2)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.

• paroxetine

  Monitor Closely (2)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.Serious - Use Alternative (1)paroxetine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• passion flower

  Monitor Closely (1)passion flower increases effects of promethazine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• pazopanib

  Monitor Closely (1)promethazine and pazopanib both increase QTc interval. Use Caution/Monitor.

• peginterferon alfa 2b

  Monitor Closely (2)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.
  
  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

  Monitor Closely (1)codeine decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.

• pentamidine

  Contraindicated (1)promethazine and pentamidine both increase QTc interval. Contraindicated.

• pentazocine

  Monitor Closely (2)codeine and pentazocine both increase sedation. Use Caution/Monitor.
  
  promethazine and pentazocine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)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.

• pentobarbital

  Monitor Closely (2)promethazine and pentobarbital both increase sedation. Use Caution/Monitor.
  
  pentobarbital and codeine both increase sedation. Use Caution/Monitor.

• perampanel

  Monitor Closely (2)perampanel and promethazine both increase sedation. Use Caution/Monitor.
  
  perampanel and codeine both increase sedation. Use Caution/Monitor.

• perindopril

  Minor (1)promethazine increases effects of perindopril by unspecified interaction mechanism. Minor/Significance Unknown.

• perphenazine

  Monitor Closely (4)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.Serious - Use Alternative (1)perphenazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.Minor (3)perphenazine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  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.

• phendimetrazine

  Monitor Closely (3)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

  Monitor Closely (1)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. .Serious - Use Alternative (1)phenelzine increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• phenobarbital

  Monitor Closely (2)phenobarbital and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and phenobarbital both increase sedation. Use Caution/Monitor.

• phentermine

  Monitor Closely (3)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

  Monitor Closely (3)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

  Monitor Closely (3)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

  Monitor Closely (2)promethazine and pholcodine both increase sedation. Use Caution/Monitor.
  
  codeine and pholcodine both increase sedation. Use Caution/Monitor.

• pimavanserin

  Monitor Closely (1)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

  Contraindicated (1)promethazine and pimozide both increase QTc interval. Contraindicated.Monitor Closely (4)pimozide and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. 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).
  
  promethazine and pimozide both increase sedation. Use Caution/Monitor.
  
  codeine and pimozide both increase sedation. Use Caution/Monitor.

• pirbuterol

  Monitor Closely (2)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.

• pitolisant

  Serious - Use Alternative (1)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.

• porfimer

  Monitor Closely (1)promethazine, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.

• posaconazole

  Monitor Closely (1)promethazine and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• pralidoxime

  Monitor Closely (3)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.

• pramipexole

  Serious - Use Alternative (1)promethazine decreases effects of pramipexole by pharmacodynamic antagonism. Contraindicated.

• prasugrel

  Serious - Use Alternative (1)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

• pregabalin

  Monitor Closely (2)pregabalin, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
  
  pregabalin, 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

  Monitor Closely (1)primaquine and promethazine both decrease QTc interval. Use Caution/Monitor.

• primidone

  Monitor Closely (2)promethazine and primidone both increase sedation. Use Caution/Monitor.
  
  primidone and codeine both increase sedation. Use Caution/Monitor.

• procainamide

  Contraindicated (1)promethazine and procainamide both increase QTc interval. Contraindicated.

• procarbazine

  Monitor Closely (1)procarbazine, promethazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Excessive sedation.Serious - Use Alternative (1)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

  Monitor Closely (3)codeine and prochlorperazine both increase sedation. Use Caution/Monitor.
  
  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.Serious - Use Alternative (1)prochlorperazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.

• promazine

  Serious - Use Alternative (1)promazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.

• promethazine

  Monitor Closely (1)promethazine and codeine both increase sedation. Use Caution/Monitor.

• propafenone

  Monitor Closely (1)propafenone will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Minor (2)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.

• propantheline

  Monitor Closely (3)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

  Monitor Closely (2)propofol and promethazine both increase sedation. Use Caution/Monitor.
  
  propofol and codeine both increase sedation. Use Caution/Monitor.

• propylhexedrine

  Monitor Closely (3)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

  Monitor Closely (3)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.Minor (2)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.

• pseudoephedrine

  Monitor Closely (1)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.

• pyrimethamine

  Minor (1)pyrimethamine increases levels of promethazine by decreasing metabolism. Minor/Significance Unknown.

• quazepam

  Monitor Closely (2)quazepam and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and quazepam both increase sedation. Use Caution/Monitor.

• quetiapine

  Monitor Closely (4)codeine and quetiapine both increase sedation. Use Caution/Monitor.
  
  promethazine and quetiapine both increase sedation. 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).
  
  promethazine and quetiapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

• quinacrine

  Minor (3)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

  Minor (1)promethazine increases effects of quinapril by unspecified interaction mechanism. Minor/Significance Unknown.

• quinidine

  Contraindicated (1)promethazine and quinidine both increase QTc interval. Contraindicated.Monitor Closely (2)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.Serious - Use Alternative (1)quinidine, promethazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Additive cardiac effects.

• ramelteon

  Monitor Closely (2)codeine and ramelteon both increase sedation. Use Caution/Monitor.
  
  promethazine and ramelteon both increase sedation. Use Caution/Monitor.

• ramipril

  Minor (1)promethazine increases effects of ramipril by unspecified interaction mechanism. Minor/Significance Unknown.

• ranolazine

  Monitor Closely (1)promethazine and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.Minor (2)ranolazine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  ranolazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rapacuronium

  Monitor Closely (3)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.

• rasagiline

  Serious - Use Alternative (1)rasagiline increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

• remimazolam

  Monitor Closely (1)remimazolam, codeine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

• ribociclib

  Monitor Closely (1)ribociclib will increase the level or effect of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• risperidone

  Monitor Closely (5)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

  Monitor Closely (1)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.Minor (1)ritonavir will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rocuronium

  Monitor Closely (3)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

  Monitor Closely (2)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.

• ropinirole

  Serious - Use Alternative (1)promethazine decreases effects of ropinirole by pharmacodynamic antagonism. Contraindicated.

• sage

  Minor (2)codeine and sage both increase sedation. Minor/Significance Unknown.
  
  promethazine and sage both increase sedation. Minor/Significance Unknown.

• salmeterol

  Monitor Closely (2)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

  Monitor Closely (3)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

  Monitor Closely (2)codeine and scullcap both increase sedation. Use Caution/Monitor.
  
  promethazine and scullcap both increase sedation. Use Caution/Monitor.

• secobarbital

  Monitor Closely (2)secobarbital and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and secobarbital both increase sedation. Use Caution/Monitor.

• selegiline

  Monitor Closely (1)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.

• selegiline transdermal

  Serious - Use Alternative (1)selegiline transdermal increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

• selinexor

  Serious - Use Alternative (1)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.

• serdexmethylphenidate/dexmethylphenidate

  Monitor Closely (1)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

  Monitor Closely (2)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.Minor (2)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.

• sevoflurane

  Monitor Closely (3)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

  Monitor Closely (2)promethazine and shepherd's purse both increase sedation. Use Caution/Monitor.
  
  codeine and shepherd's purse both increase sedation. Use Caution/Monitor.

• Siberian ginseng

  Minor (1)Siberian ginseng increases effects of promethazine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• siponimod

  Serious - Use Alternative (1)siponimod and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• smoking

  Monitor Closely (1)smoking decreases levels of promethazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.

• sodium oxybate

  Serious - Use Alternative (2)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.

• solifenacin

  Monitor Closely (4)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.

• sotalol

  Contraindicated (1)promethazine and sotalol both increase QTc interval. Contraindicated.

• sparsentan

  Monitor Closely (1)sparsentan will decrease the level or effect of promethazine by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Sparsentan (a CYP2B6 inducer) decreases exposure of CYP2B6 substrates and reduces efficacy related to these substrates.

• stiripentol

  Monitor Closely (3)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, codeine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.
  
  stiripentol, 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

  Monitor Closely (2)codeine and sufentanil both increase sedation. Use Caution/Monitor.
  
  promethazine and sufentanil both increase sedation. Use Caution/Monitor.

• sufentanil SL

  Serious - Use Alternative (1)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.

• sulfamethoxazole

  Monitor Closely (1)promethazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• sunitinib

  Monitor Closely (1)sunitinib and promethazine both decrease QTc interval. Use Caution/Monitor.

• suvorexant

  Monitor Closely (1)suvorexant and codeine both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

• tacrolimus

  Monitor Closely (1)tacrolimus and promethazine both decrease QTc interval. Use Caution/Monitor.

• tapentadol

  Monitor Closely (2)promethazine and tapentadol both increase sedation. Use Caution/Monitor.
  
  codeine and tapentadol both increase sedation. Use Caution/Monitor.

• telavancin

  Monitor Closely (1)promethazine and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.

• temazepam

  Monitor Closely (2)promethazine and temazepam both increase sedation. Use Caution/Monitor.
  
  temazepam and codeine both increase sedation. Use Caution/Monitor.

• terbinafine

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (1)promethazine and tetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)tetrabenazine and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• thioridazine

  Monitor Closely (4)thioridazine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  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.
  
  codeine and thioridazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)promethazine and thioridazine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)thioridazine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  thioridazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• thiothixene

  Monitor Closely (4)promethazine and thiothixene both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. 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).
  
  codeine and thiothixene both increase sedation. Use Caution/Monitor.
  
  promethazine and thiothixene both increase sedation. Use Caution/Monitor.

• ticagrelor

  Serious - Use Alternative (1)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

• ticlopidine

  Monitor Closely (1)ticlopidine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• tiotropium

  Monitor Closely (3)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.

• tipranavir

  Minor (2)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.

• tobacco use

  Monitor Closely (1)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

  Monitor Closely (3)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

  Monitor Closely (2)codeine and topiramate both increase sedation. Modify Therapy/Monitor Closely.
  
  promethazine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• tramadol

  Monitor Closely (2)promethazine and tramadol both increase sedation. Use Caution/Monitor.
  
  codeine and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)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.

• trandolapril

  Minor (1)promethazine increases effects of trandolapril by unspecified interaction mechanism. Minor/Significance Unknown.

• tranylcypromine

  Monitor Closely (1)tranylcypromine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Serious - Use Alternative (2)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.

• trazodone

  Monitor Closely (3)promethazine and trazodone both increase QTc interval. Use Caution/Monitor.
  
  codeine and trazodone both increase sedation. Use Caution/Monitor.
  
  promethazine and trazodone both increase sedation. Use Caution/Monitor.Minor (2)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.

• tretinoin

  Serious - Use Alternative (1)promethazine, tretinoin. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• tretinoin topical

  Serious - Use Alternative (1)promethazine, tretinoin topical. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• triazolam

  Monitor Closely (2)promethazine and triazolam both increase sedation. Use Caution/Monitor.
  
  triazolam and codeine both increase sedation. Use Caution/Monitor.

• triclofos

  Monitor Closely (2)triclofos and codeine both increase sedation. Use Caution/Monitor.
  
  promethazine and triclofos both increase sedation. Use Caution/Monitor.

• trifluoperazine

  Monitor Closely (4)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.Serious - Use Alternative (1)promethazine and trifluoperazine both increase QTc interval. Avoid or Use Alternate Drug.

• trihexyphenidyl

  Monitor Closely (2)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.

• trimethoprim

  Monitor Closely (1)promethazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• trimipramine

  Monitor Closely (2)codeine and trimipramine both increase sedation. Use Caution/Monitor.
  
  promethazine and trimipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)promethazine and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)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.

• triprolidine

  Monitor Closely (2)promethazine and triprolidine both increase sedation. Use Caution/Monitor.
  
  triprolidine and codeine both increase sedation. Use Caution/Monitor.

• tropisetron

  Monitor Closely (1)promethazine and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.

• trospium chloride

  Monitor Closely (3)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.

• valbenazine

  Monitor Closely (1)valbenazine and promethazine both decrease QTc interval. Use Caution/Monitor.

• valerian

  Monitor Closely (1)valerian increases effects of promethazine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.Serious - Use Alternative (1)valerian and codeine both increase sedation. Avoid or Use Alternate Drug.

• vecuronium

  Monitor Closely (3)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

  Monitor Closely (2)promethazine and venlafaxine both increase QTc interval. Use Caution/Monitor.
  
  venlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)venlafaxine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.Minor (1)venlafaxine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• voriconazole

  Monitor Closely (1)promethazine and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• vorinostat

  Monitor Closely (1)vorinostat and promethazine both decrease QTc interval. Use Caution/Monitor.

• xylometazoline

  Monitor Closely (3)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.

• yohimbe

  Serious - Use Alternative (1)yohimbe decreases effects of promethazine by pharmacodynamic antagonism. Contraindicated.

• yohimbine

  Monitor Closely (3)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

  Monitor Closely (2)codeine and ziconotide both increase sedation. Use Caution/Monitor.
  
  promethazine and ziconotide both increase sedation. Use Caution/Monitor.Minor (1)ziconotide, codeine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.

• ziprasidone

  Monitor Closely (4)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.Serious - Use Alternative (1)promethazine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.

• zotepine

  Monitor Closely (3)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.