promethazine (Rx)

Allergic Conditions

PO/PR: 25 mg at bedtime or 12.5 mg before meals and at bedtime (dosage range, 6.25-12.5 mg q8hr)

IV/IM: 25 mg; may be repeated in 2 hours when necessary; switch to PO as soon as possible

Nausea & Vomiting

PO/PR: 12.5-25 mg q4-6hr PRN

IV/IM: 12.5-25 mg q4-6hr PRN

Motion Sickness

25 mg PO/PR 30-60 minutes before departure and q8-12hr PRN; on succeeding travel days, 25 mg PO/PR every morning and every evening

Preoperative Sedation

50 mg PO/PR on night before procedure or 25-50 mg IV/IM combined with reduced doses of analgesics and atropinelike drugs

Postoperative Sedation

25-50 mg IV/IM/PO/PR combined with reduced doses of analgesics and atropinelike drugs

Obstetric Sedation

25-50 mg IV/IM in early labor; may be increased to 25-75 mg q2-4hr after labor established; not to exceed two doses or up to 100 mg/day during labor

Allergic Conditions (Off-label)

<2 years old: Contraindicated

≥2 years old: 25 mg PO/PR at bedtime or 12.5 mg q6hr; alternatively, 6.25-12.5 mg PO/PR q8hr

Nausea & Vomiting

<2 years old: Contraindicated

≥2 years old: 0.25-1 mg/kg PO/PR q4-6hr PRN; not to exceed 25 mg  

Motion Sickness

<2 years: Contraindicated

≥2 years: 12.5-25 mg PO/PR administered 30-60 minutes before departure and q8-12hr PRN or 0.5 mg/kg PO q12hr PRN  

Succeeding days of travel: 12.5-25 mg twice daily (upon arising or before evening meals)

Sedation

<2 years: Contraindicated

≥2 years: 12.5-25 mg PO/IM/PR at bedtime

Preoperative Sedation

<2 years: Contraindicated

≥2 years: 1 mg/kg PO/PR with reduced dose of analgesic and appropriate dose of atropinelike drug  

Postoperative Sedation

<2 years: Contraindicated

≥2 years: 12.5-25 mg with reduced dose of analgesic and appropriate dose of atropinelike drug

Contraindicated (9)

• disopyramide

  promethazine and disopyramide both increase QTc interval. Contraindicated.

• ibutilide

  promethazine and ibutilide both increase QTc interval. Contraindicated.

• indapamide

  promethazine and indapamide both increase QTc interval. Contraindicated.

• metrizamide

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

• pentamidine

  promethazine and pentamidine both increase QTc interval. Contraindicated.

• pimozide

  promethazine and pimozide both increase QTc interval. Contraindicated.

• procainamide

  promethazine and procainamide both increase QTc interval. Contraindicated.

• quinidine

  promethazine and quinidine both increase QTc interval. Contraindicated.

• sotalol

  promethazine and sotalol both increase QTc interval. Contraindicated.

Serious - Use Alternative (84)

• amiodarone

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

• amisulpride

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

• anagrelide

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

• apomorphine

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

• arsenic trioxide

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

• artemether/lumefantrine

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

• asenapine

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

• asenapine transdermal

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

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen and promethazine 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 buccal

  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 transdermal

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

• cabergoline

  promethazine decreases effects of cabergoline by pharmacodynamic antagonism. Contraindicated.

• calcium/magnesium/potassium/sodium oxybates

  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.

• 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 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.

• 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

  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.

• 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.

• 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 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.

• 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. .

• itraconazole

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

• 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 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.

• moxifloxacin

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

• 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

  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.

• paroxetine

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

• perphenazine

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

• 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.

• 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.

• ropinirole

  promethazine decreases effects of ropinirole by pharmacodynamic antagonism. Contraindicated.

• siponimod

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

• sodium oxybate

  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.

• 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.

• tranylcypromine

  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.

• tretinoin topical

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

• trifluoperazine

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

• trimipramine

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

• venlafaxine

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

• yohimbe

  yohimbe decreases effects of promethazine by pharmacodynamic antagonism. Contraindicated.

• ziprasidone

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

Monitor Closely (317)

• 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.

• 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.

• 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.

• alprazolam

  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.

• amisulpride

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

• amitriptyline

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

• amobarbital

  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.
  
  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

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

• arformoterol

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

• aripiprazole

  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.
  
  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).

• armodafinil

  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.

• 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.

• 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.

• 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

  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.

• benzphetamine

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

• benztropine

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

• brexanolone

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

• brexpiprazole

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

• brimonidine

  brimonidine and promethazine 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.

• buprenorphine

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

• buprenorphine buccal

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

• bupropion

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

• butabarbital

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

• butalbital

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

• butorphanol

  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.

• carbinoxamine

  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

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

• cenobamate

  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

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

• chlordiazepoxide

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

• chlorpheniramine

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

• chlorpromazine

  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

  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.

• cinnarizine

  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.

• 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

  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.
  
  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).

• clomipramine

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

• clonazepam

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

• clonidine

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

• clorazepate

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

• clozapine

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

• codeine

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

• cyclizine

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

• cyclobenzaprine

  promethazine and cyclobenzaprine both increase sedation. Use Caution/Monitor.
  
  cyclobenzaprine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  cyclobenzaprine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  promethazine increases effects of cyclobenzaprine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• cyproheptadine

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

• dantrolene

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

• daridorexant

  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 levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  darifenacin decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  promethazine increases effects of darifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• dasatinib

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

• desflurane

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

• desipramine

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

• deutetrabenazine

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

• dexchlorpheniramine

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

• dexfenfluramine

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

• dexmedetomidine

  promethazine and dexmedetomidine 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.

• dextroamphetamine

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

• dextromoramide

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

• diamorphine

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

• diazepam

  promethazine and diazepam 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.

• 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 promethazine both increase sedation. Use Caution/Monitor.

• difenoxin hcl

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

• dimenhydrinate

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

• diphenhydramine

  diphenhydramine and promethazine 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.
  
  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.

• dipipanone

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

• dobutamine

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

• dolasetron

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

• 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.

• dosulepin

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

• doxepin

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

• doxylamine

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

• 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.

• 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.

• ephedrine

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

• epinephrine

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

• epinephrine racemic

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

• esketamine intranasal

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

• estazolam

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

• ethanol

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

• etomidate

  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.

• 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.

• 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.

• 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.

• 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).

• flurazepam

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

• fluvoxamine

  fluvoxamine and promethazine both increase QTc interval. 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 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.

• ganaxolone

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

• gemifloxacin

  gemifloxacin and promethazine both decrease QTc interval. 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.

• hydroxyzine

  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.

• 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 QTc interval. Use Caution/Monitor.
  
  promethazine and imipramine both increase sedation. Use Caution/Monitor.

• 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.

• 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

  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 promethazine both increase sedation. Use Caution/Monitor.

• ketotifen, ophthalmic

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

• lapatinib

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

• 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, 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.

• levalbuterol

  promethazine 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.

• levorphanol

  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

  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.

• lofexidine

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

• loprazolam

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

• lorazepam

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

• lorcaserin

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

• lormetazepam

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

• loxapine

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

• loxapine inhaled

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

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

• lurasidone

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

• marijuana

  promethazine 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

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

• meperidine

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

• meprobamate

  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.

• metaxalone

  promethazine and metaxalone 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

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

• methamphetamine

  promethazine 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.

• methocarbamol

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

• methoxsalen

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

• 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 intranasal

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

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

• mirtazapine

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

• modafinil

  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

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

• motherwort

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

• moxonidine

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

• nabilone

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

• nalbuphine

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

• norepinephrine

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

• nortriptyline

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

• ofloxacin

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

• 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.

• 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.

• orphenadrine

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

• oxazepam

  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.

• 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

  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 QTc interval. Modify Therapy/Monitor Closely.
  
  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).

• 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

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

• papaverine

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

• paroxetine

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

• passion flower

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

• 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.

• pentazocine

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

• pentobarbital

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

• perampanel

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

• perphenazine

  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.
  
  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).

• phendimetrazine

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

• 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

  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.

• 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.

• phenylephrine PO

  promethazine 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.

• 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

  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

  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.

• 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.

• procarbazine

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

• 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.

• 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.

• propylhexedrine

  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

  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

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

• quetiapine

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

• quinidine

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

• ramelteon

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

• ranolazine

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

• 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.

• risperidone

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

• 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.

• salmeterol

  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

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

• secobarbital

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

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

• sevoflurane

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

• shepherd's purse

  promethazine 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.

• 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

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

• sulfamethoxazole

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

• 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.

• telavancin

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

• temazepam

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

• terbinafine

  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

  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

  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.
  
  promethazine 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).

• 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

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

• tramadol

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

• trazodone

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

• triazolam

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

• triclofos

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

• trifluoperazine

  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.
  
  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).

• 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.

• 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.

• tropisetron

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

• 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

  promethazine 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.

• yohimbine

  promethazine 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.

• ziconotide

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

• ziprasidone

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

• zotepine

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

Minor (65)

• 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.

• ashwagandha

  ashwagandha increases effects of promethazine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance 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.

• 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

  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.

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

• imidapril

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

• 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 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.

• metyrapone

  promethazine decreases effects of metyrapone by unspecified interaction mechanism. 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 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 promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• 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 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.

• 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

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

• sertraline

  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 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.

• trandolapril

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

• 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.

• abiraterone

  Monitor Closely (1)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.

• 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.

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

• alfentanil

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

• alprazolam

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

• 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

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

• amitriptyline

  Monitor Closely (2)promethazine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  promethazine 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 (1)promethazine and amobarbital both increase sedation. Use Caution/Monitor.

• amoxapine

  Monitor Closely (3)promethazine and amoxapine both increase QTc interval. Use Caution/Monitor.
  
  promethazine and amoxapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. 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 (1)promethazine 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 (1)promethazine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• aripiprazole

  Monitor Closely (3)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).
  
  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 (1)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 (1)artemether/lumefantrine will increase the level or effect of promethazine 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 (1)asenapine and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.Minor (1)asenapine will increase the level or effect of promethazine 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 (1)asenapine transdermal and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• 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.

• azelastine

  Monitor Closely (1)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 (1)promethazine and baclofen 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 (4)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.
  
  promethazine and belladonna and opium both increase sedation. Use Caution/Monitor.

• benazepril

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

• benperidol

  Monitor Closely (2)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.

• benzhydrocodone/acetaminophen

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

• benzphetamine

  Monitor Closely (2)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.
  
  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. .

• brexanolone

  Monitor Closely (1)brexanolone, promethazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

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

• brimonidine

  Monitor Closely (1)brimonidine and promethazine both increase sedation. Use Caution/Monitor.Minor (1)brimonidine increases effects of promethazine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

• brivaracetam

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

• buprenorphine

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

• buprenorphine buccal

  Monitor Closely (1)promethazine and buprenorphine buccal both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine buccal and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• buprenorphine subdermal implant

  Serious - Use Alternative (2)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 transdermal

  Serious - Use Alternative (2)buprenorphine transdermal and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
  
  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

  Serious - Use Alternative (2)buprenorphine, long-acting injection and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine, long-acting injection and promethazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• bupropion

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

• butalbital

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

• butorphanol

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

• cabergoline

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

• caffeine

  Monitor Closely (1)promethazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (1)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 (1)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 (1)promethazine and carisoprodol both increase sedation. Use Caution/Monitor.

• celecoxib

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

• cenobamate

  Monitor Closely (2)cenobamate, promethazine. 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.

• chasteberry

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

• chloral hydrate

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

• chlordiazepoxide

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

• chloroquine

  Minor (2)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.

• chlorpheniramine

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

• chlorpromazine

  Monitor Closely (2)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 (1)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

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

• cinnarizine

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

• clobazam

  Monitor Closely (2)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.
  
  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).

• clomipramine

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

• clonidine

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

• clorazepate

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

• clozapine

  Monitor Closely (3)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 and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  promethazine and clozapine both increase sedation. Use Caution/Monitor.

• codeine

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

• cyclizine

  Monitor Closely (4)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.
  
  promethazine increases effects of cyclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  cyclizine and promethazine both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  Monitor Closely (4)cyclobenzaprine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  cyclobenzaprine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  promethazine increases effects of cyclobenzaprine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  promethazine and cyclobenzaprine both increase sedation. Use Caution/Monitor.

• cyproheptadine

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

• dacomitinib

  Serious - Use Alternative (1)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 (1)promethazine and dantrolene both increase sedation. Use Caution/Monitor.

• daridorexant

  Monitor Closely (1)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 (3)darifenacin decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  darifenacin decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  promethazine increases effects of darifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.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 (2)desflurane and promethazine both decrease QTc interval. Use Caution/Monitor.
  
  desflurane and promethazine both increase sedation. Use Caution/Monitor.

• desipramine

  Monitor Closely (2)promethazine and desipramine both increase QTc interval. Use Caution/Monitor.
  
  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 (1)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

• deutetrabenazine

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

• dexchlorpheniramine

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

• dexfenfluramine

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

• dexmedetomidine

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

• dexmethylphenidate

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

• dextroamphetamine

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

• dextromoramide

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

• diamorphine

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

• diazepam

  Monitor Closely (1)promethazine and diazepam 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.

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

• difelikefalin

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

• difenoxin hcl

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

• dimenhydrinate

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

• diphenhydramine

  Monitor Closely (4)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.
  
  promethazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and promethazine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• diphenoxylate hcl

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

• dipipanone

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

• disopyramide

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

• dobutamine

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

• dosulepin

  Monitor Closely (1)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 (2)promethazine and doxepin both increase QTc interval. Use Caution/Monitor.
  
  promethazine and doxepin both increase sedation. 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 (1)promethazine and doxylamine both increase sedation. Use Caution/Monitor.

• dronedarone

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

• duloxetine

  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 (1)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 (1)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.

• 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 (2)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.

• epinephrine

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

• epinephrine racemic

  Monitor Closely (2)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.
  
  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 (1)esketamine intranasal, promethazine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• estazolam

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

• ethanol

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

• eucalyptus

  Minor (1)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 (1)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.

• fenfluramine

  Monitor Closely (2)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.
  
  promethazine 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.

• 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.

• 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.

• 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.

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

• fluphenazine

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

• flurazepam

  Monitor Closely (1)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 (1)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 (1)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 enacarbil

  Monitor Closely (1)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.

• ganaxolone

  Monitor Closely (1)promethazine 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 (1)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 (3)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 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.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.

• hydromorphone

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

• hydroxyzine

  Monitor Closely (2)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 (4)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).
  
  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.

• imatinib

  Minor (1)imatinib will increase the level or effect of promethazine 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 (2)promethazine and imipramine both increase QTc interval. Use Caution/Monitor.
  
  promethazine and imipramine both increase sedation. Use Caution/Monitor.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 (1)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. .

• isoflurane

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

• isoproterenol

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

• 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 (1)ketamine and promethazine both increase sedation. Use Caution/Monitor.

• ketoconazole

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

• ketotifen, ophthalmic

  Monitor Closely (1)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 (1)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 (2)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, 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.

• levalbuterol

  Monitor Closely (1)promethazine 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

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

• levorphanol

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

• 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 (2)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.
  
  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 (1)promethazine 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 (1)promethazine and lofexidine both increase sedation. Use Caution/Monitor.

• loprazolam

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

• lorazepam

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

• lorcaserin

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

• lormetazepam

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

• loxapine

  Monitor Closely (3)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).
  
  loxapine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  promethazine and loxapine both increase sedation. Use Caution/Monitor.

• loxapine inhaled

  Monitor Closely (3)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).
  
  loxapine inhaled and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. 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 (1)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 (2)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).
  
  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 .

• maprotiline

  Monitor Closely (2)promethazine and maprotiline both increase QTc interval. Use Caution/Monitor.
  
  promethazine 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 (1)maraviroc will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• marijuana

  Monitor Closely (1)promethazine and marijuana both increase sedation. Use Caution/Monitor.Minor (1)marijuana will increase the level or effect of promethazine 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 (1)promethazine and melatonin both increase sedation. Use Caution/Monitor.

• meperidine

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

• meprobamate

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

• metaproterenol

  Monitor Closely (1)promethazine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metaxalone

  Monitor Closely (1)promethazine and metaxalone 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 (2)promethazine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  promethazine and methadone both increase sedation. Use Caution/Monitor.

• methamphetamine

  Monitor Closely (2)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

  Monitor Closely (1)promethazine and methocarbamol 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 (1)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 (2)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.
  
  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 (1)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.

• 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 (1)promethazine and midazolam both increase sedation. Use Caution/Monitor.

• midazolam intranasal

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

• mirtazapine

  Monitor Closely (2)mirtazapine and promethazine both decrease QTc interval. Use Caution/Monitor.
  
  promethazine and mirtazapine both increase sedation. Use Caution/Monitor.

• modafinil

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

• motherwort

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

• nabilone

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

• nalbuphine

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

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

• norepinephrine

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

• nortriptyline

  Monitor Closely (2)promethazine and nortriptyline both increase QTc interval. Use Caution/Monitor.
  
  promethazine 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 (4)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.
  
  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.

• olopatadine intranasal

  Serious - Use Alternative (1)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 (1)promethazine and opium tincture both increase sedation. Use Caution/Monitor.

• orphenadrine

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

• oxymorphone

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

• paliperidone

  Monitor Closely (4)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).
  
  promethazine and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  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.

• 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 (1)promethazine and papaveretum both increase sedation. Use Caution/Monitor.

• papaverine

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

• parecoxib

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

• paroxetine

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

• pentamidine

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

• pentazocine

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

• pentobarbital

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

• perampanel

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

• perindopril

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

• perphenazine

  Monitor Closely (3)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).
  
  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 (1)perphenazine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• phendimetrazine

  Monitor Closely (2)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.
  
  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. .

• phenobarbital

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

• phentermine

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

• phenylephrine

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

• phenylephrine PO

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

• pholcodine

  Monitor Closely (1)promethazine 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 (3)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).
  
  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.

• pirbuterol

  Monitor Closely (1)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.

• pregabalin

  Monitor Closely (1)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 (1)promethazine and primidone 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.

• prochlorperazine

  Monitor Closely (2)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.

• propafenone

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

• 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 (1)propofol and promethazine both increase sedation. Use Caution/Monitor.

• propylhexedrine

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

• protriptyline

  Monitor Closely (2)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 (1)promethazine and quazepam both increase sedation. Use Caution/Monitor.

• quetiapine

  Monitor Closely (3)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.
  
  promethazine and quetiapine both increase sedation. Use Caution/Monitor.

• quinacrine

  Minor (1)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 (1)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 (1)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 (1)ranolazine will increase the level or effect of promethazine 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.

• risperidone

  Monitor Closely (4)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.
  
  promethazine and risperidone both increase sedation. Use Caution/Monitor.

• ritonavir

  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 (1)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.

• ropinirole

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

• sage

  Minor (1)promethazine and sage both increase sedation. Minor/Significance Unknown.

• salmeterol

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

• secobarbital

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

• 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 (1)sertraline and promethazine both decrease QTc interval. Use Caution/Monitor.Minor (1)sertraline will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• sevoflurane

  Monitor Closely (2)sevoflurane and promethazine both decrease QTc interval. Use Caution/Monitor.
  
  sevoflurane and promethazine both increase sedation. Use Caution/Monitor.

• shepherd's purse

  Monitor Closely (1)promethazine 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 (1)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 (2)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.
  
  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.

• sufentanil

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

• 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.

• tacrolimus

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

• tapentadol

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

• terbinafine

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

• thiothixene

  Monitor Closely (3)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 antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  promethazine and thiothixene both increase sedation. Use Caution/Monitor.

• 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 (1)tipranavir will increase the level or effect of promethazine 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 (1)promethazine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• tramadol

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

• trandolapril

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

• tranylcypromine

  Serious - Use Alternative (1)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 (2)promethazine and trazodone both increase QTc interval. 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 (1)promethazine and triazolam both increase sedation. Use Caution/Monitor.

• triclofos

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

• trifluoperazine

  Monitor Closely (3)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).
  
  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 (1)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 (1)promethazine and triprolidine 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.

• 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 (1)promethazine and venlafaxine both increase QTc interval. 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.

• 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 (2)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 (2)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 (1)promethazine and ziconotide both increase sedation. Use Caution/Monitor.

• ziprasidone

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

• zotepine

  Monitor Closely (2)promethazine and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  promethazine and zotepine both increase sedation. Use Caution/Monitor.