Dosing & Uses
Dosage Forms & Strengths
promethazine/codeine
oral liquid: Schedule V
- (6.25mg/10mg)/5mL
Cough
Temporary relief cough and upper respiratory tract symptoms associated with allergies or common cold
6.25 mg/10 mg (5 mL) PO q4-6hr; not to exceed 30 mL/24 hr
Renal Impairment
Caution; may need to initiate at a lower dose
Hepatic Impairment
Caution; may need to initiate at a lower dose
Administration
Administer with special measuring device for accurate dose
Dosage Forms & Strengths
Oral liquid: Schedule V
- (6.25mg/10mg)/5mL
Cough
<12 years: Use contraindicated
12 years: 2.5-5 mL PO q4-6hr; not to exceed 30 mL/24hr
>12 years: 6.25 mg/10 mg (5 mL) PO q4-6hr; not to exceed 30 mL/24 hr
Administration
Administer with special measuring device for accurate dose
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (2)
- alvimopan
alvimopan, codeine. receptor binding competition. Contraindicated. Alvimopan is contraindicated in opioid tolerant patients (ie, those who have taken therapeutic doses of opioids for >7 consecutive days immediately prior to taking alvimopan). Patients recently exposed to opioids are expected to be more sensitive to the effects of alvimopan and therefore may experience abdominal pain, nausea and vomiting, and diarrhea. No significant interaction is expected with concurrent use of opioid analgesics and alvimopan in patients who received opioid analgesics for 7 or fewer consecutive days prior to alvimopan.
- disopyramide
promethazine and disopyramide both increase QTc interval. Contraindicated.
Serious - Use Alternative (108)
- acrivastine
acrivastine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- amiodarone
promethazine and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.
- amisulpride
amisulpride and codeine both increase sedation. Avoid or Use Alternate Drug.
promethazine and amisulpride both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered. - anagrelide
anagrelide and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
- asenapine
asenapine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- apomorphine
promethazine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- arsenic trioxide
promethazine and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.
- artemether/lumefantrine
promethazine and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.
- asenapine
asenapine and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
- asenapine transdermal
asenapine transdermal and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
asenapine transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate - avapritinib
avapritinib and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- benzhydrocodone/acetaminophen
benzhydrocodone/acetaminophen and promethazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- benzhydrocodone/acetaminophen
benzhydrocodone/acetaminophen, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
benzhydrocodone/acetaminophen and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate - bremelanotide
bremelanotide will decrease the level or effect of codeine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.
- brimonidine
brimonidine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- bromocriptine
promethazine decreases effects of bromocriptine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- buprenorphine
buprenorphine and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
buprenorphine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx. - buprenorphine buccal
buprenorphine buccal, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
buprenorphine buccal and promethazine both decrease QTc interval. Avoid or Use Alternate Drug. - buprenorphine subdermal implant
buprenorphine subdermal implant and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
buprenorphine subdermal implant and promethazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
buprenorphine subdermal implant and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate - buprenorphine transdermal
buprenorphine transdermal and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
buprenorphine transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
buprenorphine transdermal and promethazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate - buprenorphine, long-acting injection
buprenorphine, long-acting injection and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
buprenorphine, long-acting injection and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
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 - butorphanol
butorphanol, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- cabergoline
promethazine decreases effects of cabergoline by pharmacodynamic antagonism. Contraindicated.
- calcium/magnesium/potassium/sodium oxybates
codeine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
promethazine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. - chlorpromazine
chlorpromazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.
- clonidine
clonidine, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.
- clarithromycin
promethazine and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.
- clomipramine
promethazine and clomipramine both increase QTc interval. Avoid or Use Alternate Drug.
- dacomitinib
dacomitinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
dacomitinib will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities. - degarelix
degarelix and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
- diazepam intranasal
diazepam intranasal, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- dofetilide
promethazine and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.
- dopamine
promethazine decreases effects of dopamine by pharmacodynamic antagonism. Contraindicated.
- dosulepin
promethazine and dosulepin both increase QTc interval. Avoid or Use Alternate Drug.
- dronedarone
promethazine and dronedarone both increase QTc interval. Avoid or Use Alternate Drug.
- droperidol
promethazine and droperidol both increase QTc interval. Avoid or Use Alternate Drug.
- eliglustat
eliglustat and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
- eluxadoline
codeine, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions. .
promethazine, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions. - encorafenib
encorafenib and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
- fentanyl
fentanyl, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
fentanyl and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate - entrectinib
entrectinib and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
- epinephrine
epinephrine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.
- epinephrine racemic
epinephrine racemic and promethazine both increase QTc interval. Avoid or Use Alternate Drug.
- eribulin
eribulin and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
- erythromycin base
promethazine and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.
- erythromycin ethylsuccinate
promethazine and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.
- erythromycin lactobionate
promethazine and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.
- erythromycin stearate
promethazine and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.
- fentanyl
fentanyl and promethazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- fentanyl intranasal
fentanyl intranasal, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
fentanyl intranasal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
fentanyl intranasal and promethazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate - fentanyl iontophoretic transdermal system
fentanyl iontophoretic transdermal system and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
fentanyl iontophoretic transdermal system and promethazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate - fentanyl transdermal
fentanyl transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
fentanyl transdermal and promethazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
fentanyl transdermal, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation. - fentanyl transmucosal
fentanyl transmucosal, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
- fexinidazole
fexinidazole will decrease the level or effect of promethazine by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. Coadministration may decrease plasma concentrations of CYP2B6 substrates owing to fexinidazole inducing CYP2B6.
- fingolimod
fingolimod and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
- fluconazole
promethazine and fluconazole both increase QTc interval. Avoid or Use Alternate Drug.
- fluoxetine
fluoxetine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
- fluphenazine
fluphenazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.
- formoterol
promethazine and formoterol both increase QTc interval. Avoid or Use Alternate Drug.
- givosiran
givosiran will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
givosiran will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling. - haloperidol
promethazine and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.
- hydrocodone
hydrocodone, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- isocarboxazid
isocarboxazid increases effects of promethazine by Other (see comment). Avoid or Use Alternate Drug. Comment: Isocarboxazid should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .
isocarboxazid increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d. - itraconazole
promethazine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.
- linezolid
linezolid increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.
- ketoconazole
promethazine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.
- levodopa
promethazine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- levoketoconazole
promethazine and levoketoconazole both increase QTc interval. Avoid or Use Alternate Drug.
- lisuride
promethazine decreases effects of lisuride by pharmacodynamic antagonism. Contraindicated.
- lofepramine
promethazine and lofepramine both increase QTc interval. Avoid or Use Alternate Drug.
- lumefantrine
promethazine and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.
- mefloquine
mefloquine increases toxicity of promethazine by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.
- methyldopa
promethazine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.
- methylene blue
methylene blue and codeine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
methylene blue and promethazine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities - metoclopramide intranasal
promethazine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.
codeine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient. - moxifloxacin
promethazine and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.
- nalbuphine
nalbuphine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- nilotinib
promethazine and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.
- octreotide
promethazine and octreotide both increase QTc interval. Avoid or Use Alternate Drug.
- octreotide (Antidote)
promethazine and octreotide (Antidote) both increase QTc interval. Avoid or Use Alternate Drug.
- olopatadine intranasal
codeine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
promethazine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. - oxaliplatin
oxaliplatin and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
- ozanimod
ozanimod and codeine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.
- paroxetine
paroxetine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
- pentazocine
pentazocine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- perphenazine
perphenazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.
- phenelzine
phenelzine increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.
- pitolisant
promethazine decreases effects of pitolisant by Other (see comment). Avoid or Use Alternate Drug. Comment: Pitolisant increases histamine levels in the brain; therefore, H1 receptor antagonists that cross the blood-brain barrier may reduce the efficacy of pitolisant.
- pramipexole
promethazine decreases effects of pramipexole by pharmacodynamic antagonism. Contraindicated.
- prasugrel
codeine will decrease the level or effect of prasugrel by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Co-administration of opioid agonists delay and reduce absorption of prasugrel and its active metabolite presumably by slowing gastric emptying; consider the use of a parenteral anti-platelet agent in acute coronary syndrome patients requiring co-administration of opioid agonists
- procarbazine
procarbazine increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. MAOIs may potentiate CNS depression and hypotension. Do not use within 14 days of MAOI use. .
- prochlorperazine
prochlorperazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.
- promazine
promazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.
- quinidine
quinidine, promethazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Additive cardiac effects.
- rasagiline
rasagiline increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.
- ropinirole
promethazine decreases effects of ropinirole by pharmacodynamic antagonism. Contraindicated.
- selegiline transdermal
selegiline transdermal increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.
- selinexor
selinexor, codeine. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.
- siponimod
siponimod and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
- sodium oxybate
codeine, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
promethazine, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. - sufentanil SL
sufentanil SL, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- tetrabenazine
tetrabenazine and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.
- thioridazine
promethazine and thioridazine both increase QTc interval. Avoid or Use Alternate Drug.
- ticagrelor
codeine will decrease the level or effect of ticagrelor by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Co-administration of opioid agonists delay and reduce absorption of ticagrelor and its active metabolite presumably by slowing gastric emptying; consider the use of a parenteral anti-platelet agent in acute coronary syndrome patients requiring co-administration of opioid agonists
- tramadol
tramadol, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
- tranylcypromine
tranylcypromine increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.
tranylcypromine increases effects of promethazine by Other (see comment). Avoid or Use Alternate Drug. Comment: Tranylcypromine should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. Combination of tranylcypromine and promethazine may result in additive hypotensive effects. - tretinoin
promethazine, tretinoin. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.
- valerian
valerian and codeine both increase sedation. Avoid or Use Alternate Drug.
Monitor Closely (387)
- abiraterone
abiraterone increases levels of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
abiraterone increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate. - aclidinium
aclidinium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of aclidinium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - albuterol
codeine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- acrivastine
acrivastine and promethazine both increase sedation. Use Caution/Monitor.
- albiglutide
promethazine, albiglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.
- albuterol
promethazine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- alfentanil
promethazine and alfentanil both increase sedation. Use Caution/Monitor.
alfentanil and codeine both increase sedation. Use Caution/Monitor. - alprazolam
alprazolam and codeine both increase sedation. Use Caution/Monitor.
promethazine and alprazolam both increase sedation. Use Caution/Monitor. - amifampridine
promethazine increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.
- amiodarone
amiodarone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- amisulpride
amisulpride and promethazine both increase sedation. Use Caution/Monitor.
- amitriptyline
promethazine and amitriptyline both increase sedation. Use Caution/Monitor.
promethazine and amitriptyline both increase QTc interval. Use Caution/Monitor.
codeine and amitriptyline both increase sedation. Use Caution/Monitor. - amobarbital
amobarbital and codeine both increase sedation. Use Caution/Monitor.
promethazine and amobarbital both increase sedation. Use Caution/Monitor. - amoxapine
promethazine and amoxapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine and amoxapine both increase QTc interval. Use Caution/Monitor.
codeine and amoxapine both increase sedation. Use Caution/Monitor.
promethazine and amoxapine both increase sedation. Use Caution/Monitor. - anticholinergic/sedative combos
anticholinergic/sedative combos decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
anticholinergic/sedative combos decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of anticholinergic/sedative combos by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - apomorphine
codeine and apomorphine both increase sedation. Use Caution/Monitor.
- apomorphine
promethazine and apomorphine both increase sedation. Use Caution/Monitor.
- arformoterol
codeine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - aripiprazole
promethazine, aripiprazole. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
codeine and aripiprazole both increase sedation. Use Caution/Monitor.
aripiprazole and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine and aripiprazole both increase sedation. Use Caution/Monitor. - armodafinil
codeine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - artemether/lumefantrine
artemether/lumefantrine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
artemether/lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. - asenapine
promethazine, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
asenapine and promethazine both increase sedation. Use Caution/Monitor. - azelastine
azelastine and codeine both increase sedation. Use Caution/Monitor.
- asenapine transdermal
asenapine transdermal and promethazine both increase sedation. Use Caution/Monitor.
- atracurium
atracurium decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
atracurium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of atracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - atropine
atropine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
atropine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - atropine IV/IM
promethazine increases effects of atropine IV/IM by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
- avapritinib
avapritinib and promethazine both increase sedation. Use Caution/Monitor.
- azelastine
azelastine and promethazine both increase sedation. Use Caution/Monitor.
- azithromycin
promethazine and azithromycin both increase QTc interval. Use Caution/Monitor.
- baclofen
promethazine and baclofen both increase sedation. Use Caution/Monitor.
baclofen and codeine both increase sedation. Use Caution/Monitor. - belladonna alkaloids
belladonna alkaloids decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
belladonna alkaloids decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - belladonna and opium
codeine and belladonna and opium both increase sedation. Use Caution/Monitor.
- belladonna and opium
promethazine and belladonna and opium both increase sedation. Use Caution/Monitor.
belladonna and opium decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
belladonna and opium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of belladonna and opium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - benperidol
benperidol and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine and benperidol both increase sedation. Use Caution/Monitor.
codeine and benperidol both increase sedation. Use Caution/Monitor. - benzphetamine
promethazine, benzphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
codeine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - benztropine
promethazine increases effects of benztropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use. .
- brexanolone
brexanolone, codeine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- brexanolone
brexanolone, promethazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- brexpiprazole
brexpiprazole and codeine both increase sedation. Use Caution/Monitor.
brexpiprazole and promethazine both increase sedation. Use Caution/Monitor. - brimonidine
brimonidine and promethazine both increase sedation. Use Caution/Monitor.
- brivaracetam
brivaracetam and codeine both increase sedation. Use Caution/Monitor.
- brivaracetam
brivaracetam and promethazine both increase sedation. Use Caution/Monitor.
- brompheniramine
brompheniramine and promethazine both increase sedation. Use Caution/Monitor.
brompheniramine and codeine both increase sedation. Use Caution/Monitor. - buprenorphine
buprenorphine and codeine both increase sedation. Use Caution/Monitor.
promethazine and buprenorphine both increase sedation. Use Caution/Monitor. - buprenorphine buccal
promethazine and buprenorphine buccal both increase sedation. Use Caution/Monitor.
buprenorphine buccal and codeine both increase sedation. Use Caution/Monitor. - buprenorphine, long-acting injection
codeine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.
- bupropion
bupropion will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- bupropion
bupropion will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents the conversion of codeine to its active metabolite morphine.
- butabarbital
butabarbital and codeine both increase sedation. Use Caution/Monitor.
promethazine and butabarbital both increase sedation. Use Caution/Monitor. - butalbital
butalbital and codeine both increase sedation. Use Caution/Monitor.
promethazine and butalbital both increase sedation. Use Caution/Monitor. - butorphanol
butorphanol and codeine both increase sedation. Use Caution/Monitor.
promethazine and butorphanol both increase sedation. Use Caution/Monitor. - caffeine
promethazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - carbinoxamine
carbinoxamine and codeine both increase sedation. Use Caution/Monitor.
carbinoxamine and promethazine both increase sedation. Use Caution/Monitor. - cariprazine
promethazine, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- carisoprodol
carisoprodol and codeine both increase sedation. Use Caution/Monitor.
- carisoprodol
promethazine and carisoprodol both increase sedation. Use Caution/Monitor.
- celecoxib
celecoxib decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- cenobamate
cenobamate, codeine. Either increases effects of the other by sedation. Use Caution/Monitor.
cenobamate will decrease the level or effect of promethazine by affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP2B6 substrate, as needed, when coadministered with cenobamate.
cenobamate, promethazine. Either increases effects of the other by sedation. Use Caution/Monitor. - chloral hydrate
chloral hydrate and codeine both increase sedation. Use Caution/Monitor.
promethazine and chloral hydrate both increase sedation. Use Caution/Monitor. - chlordiazepoxide
chlordiazepoxide and codeine both increase sedation. Use Caution/Monitor.
promethazine and chlordiazepoxide both increase sedation. Use Caution/Monitor. - chloroquine
chloroquine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- chlorpheniramine
chlorpheniramine and promethazine both increase sedation. Use Caution/Monitor.
- chlorpheniramine
chlorpheniramine and codeine both increase sedation. Use Caution/Monitor.
- chlorpromazine
chlorpromazine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine
codeine and chlorpromazine both increase sedation. Use Caution/Monitor.
chlorpromazine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine and chlorpromazine both increase sedation. Use Caution/Monitor. - chlorzoxazone
chlorzoxazone and codeine both increase sedation. Use Caution/Monitor.
promethazine and chlorzoxazone both increase sedation. Use Caution/Monitor. - cigarette smoking
cigarette smoking decreases levels of promethazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.
- cimetidine
cimetidine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- cinacalcet
cinacalcet decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- cinnarizine
cinnarizine and codeine both increase sedation. Use Caution/Monitor.
cinnarizine and promethazine both increase sedation. Use Caution/Monitor. - cisatracurium
cisatracurium decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
cisatracurium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of cisatracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - clemastine
clemastine and codeine both increase sedation. Use Caution/Monitor.
- citalopram
citalopram and promethazine both increase serotonin levels. Use Caution/Monitor. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
- clemastine
clemastine and promethazine both increase sedation. Use Caution/Monitor.
- clobazam
codeine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
promethazine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
clobazam decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
clobazam will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly. - clomipramine
promethazine and clomipramine both increase sedation. Use Caution/Monitor.
codeine and clomipramine both increase sedation. Use Caution/Monitor.
clomipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine. - clonazepam
promethazine and clonazepam both increase sedation. Use Caution/Monitor.
clonazepam and codeine both increase sedation. Use Caution/Monitor. - clonidine
clonidine, promethazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.
- clorazepate
clorazepate and codeine both increase sedation. Use Caution/Monitor.
- clorazepate
promethazine and clorazepate both increase sedation. Use Caution/Monitor.
- clozapine
codeine and clozapine both increase sedation. Use Caution/Monitor.
promethazine and clozapine both increase sedation. Use Caution/Monitor.
clozapine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
clozapine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine. - cocaine topical
cocaine topical decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- codeine
promethazine and codeine both increase sedation. Use Caution/Monitor.
- cyclizine
promethazine increases effects of cyclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
cyclizine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
cyclizine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
cyclizine and codeine both increase sedation. Use Caution/Monitor.
cyclizine and promethazine both increase sedation. Use Caution/Monitor. - cyclobenzaprine
cyclobenzaprine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
promethazine increases effects of cyclobenzaprine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
cyclobenzaprine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
cyclobenzaprine and codeine both increase sedation. Use Caution/Monitor.
promethazine and cyclobenzaprine both increase sedation. Use Caution/Monitor. - cyproheptadine
cyproheptadine and codeine both increase sedation. Use Caution/Monitor.
cyproheptadine and promethazine both increase sedation. Use Caution/Monitor. - dantrolene
dantrolene and codeine both increase sedation. Use Caution/Monitor.
promethazine and dantrolene both increase sedation. Use Caution/Monitor. - daridorexant
codeine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
promethazine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. - darifenacin
darifenacin decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
darifenacin decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
promethazine increases effects of darifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
darifenacin decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor. - dasatinib
promethazine and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.
- desflurane
desflurane and codeine both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.
- desflurane
desflurane and promethazine both increase sedation. Use Caution/Monitor.
desflurane and promethazine both decrease QTc interval. Use Caution/Monitor. - desipramine
codeine and desipramine both increase sedation. Use Caution/Monitor.
promethazine and desipramine both increase QTc interval. Use Caution/Monitor.
desipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
promethazine and desipramine both increase sedation. Use Caution/Monitor. - desvenlafaxine
desvenlafaxine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg
desvenlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg - deutetrabenazine
deutetrabenazine and promethazine both decrease QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).
promethazine and deutetrabenazine both increase sedation. Use Caution/Monitor.
codeine and deutetrabenazine both increase sedation. Use Caution/Monitor. - dexchlorpheniramine
dexchlorpheniramine and codeine both increase sedation. Use Caution/Monitor.
dexchlorpheniramine and promethazine both increase sedation. Use Caution/Monitor. - dexfenfluramine
promethazine, dexfenfluramine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
codeine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - dexmedetomidine
promethazine and dexmedetomidine both increase sedation. Use Caution/Monitor.
dexmedetomidine and codeine both increase sedation. Use Caution/Monitor. - dexmethylphenidate
promethazine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine, dexmethylphenidate. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
codeine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - dextroamphetamine
promethazine, dextroamphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
codeine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - dextromoramide
codeine and dextromoramide both increase sedation. Use Caution/Monitor.
promethazine and dextromoramide both increase sedation. Use Caution/Monitor. - diamorphine
promethazine and diamorphine both increase sedation. Use Caution/Monitor.
codeine and diamorphine both increase sedation. Use Caution/Monitor. - diazepam
promethazine and diazepam both increase sedation. Use Caution/Monitor.
diazepam and codeine both increase sedation. Use Caution/Monitor. - diazepam intranasal
diazepam intranasal, promethazine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.
- diethylpropion
codeine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dicyclomine
dicyclomine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
dicyclomine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of dicyclomine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - diethylpropion
promethazine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine, diethylpropion. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only. - difelikefalin
difelikefalin and codeine both increase sedation. Use Caution/Monitor.
difelikefalin and promethazine both increase sedation. Use Caution/Monitor. - difenoxin hcl
promethazine and difenoxin hcl both increase sedation. Use Caution/Monitor.
codeine and difenoxin hcl both increase sedation. Use Caution/Monitor. - dimenhydrinate
dimenhydrinate and promethazine both increase sedation. Use Caution/Monitor.
dimenhydrinate and codeine both increase sedation. Use Caution/Monitor. - diphenhydramine
diphenhydramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
diphenhydramine and codeine both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine and promethazine both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - diphenoxylate hcl
promethazine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
codeine and diphenoxylate hcl both increase sedation. Use Caution/Monitor. - dipipanone
codeine and dipipanone both increase sedation. Use Caution/Monitor.
promethazine and dipipanone both increase sedation. Use Caution/Monitor. - dobutamine
promethazine, dobutamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
codeine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - dolasetron
promethazine and dolasetron both increase QTc interval. Modify Therapy/Monitor Closely.
- dopamine
codeine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- donepezil
donepezil and promethazine both decrease QTc interval. Use Caution/Monitor.
- donepezil transdermal
donepezil transdermal, promethazine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.
- dopamine
promethazine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine, dopamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only. - dopexamine
promethazine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - dosulepin
codeine and dosulepin both increase sedation. Use Caution/Monitor.
promethazine and dosulepin both increase sedation. Use Caution/Monitor. - doxepin
codeine and doxepin both increase sedation. Use Caution/Monitor.
promethazine and doxepin both increase sedation. Use Caution/Monitor.
promethazine and doxepin both increase QTc interval. Use Caution/Monitor. - doxylamine
doxylamine and codeine both increase sedation. Use Caution/Monitor.
promethazine and doxylamine both increase sedation. Use Caution/Monitor. - dronedarone
dronedarone decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- droperidol
droperidol and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine and droperidol both increase sedation. Use Caution/Monitor. - droperidol
codeine and droperidol both increase sedation. Use Caution/Monitor.
- duloxetine
duloxetine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- efavirenz
efavirenz and promethazine both decrease QTc interval. Use Caution/Monitor.
- eliglustat
eliglustat increases levels of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.
elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events. - ephedrine
promethazine, ephedrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
promethazine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - epinephrine
codeine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine decreases effects of epinephrine by pharmacodynamic antagonism. Use Caution/Monitor. Block pressor response to epinephrine, which may result in severe hypotension and tachycardia.
promethazine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine, epinephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only. - epinephrine racemic
promethazine decreases effects of epinephrine racemic by pharmacodynamic antagonism. Use Caution/Monitor. Block pressor response to epinephrine, which may result in severe hypotension and tachycardia.
codeine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - esketamine intranasal
esketamine intranasal, codeine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
esketamine intranasal, promethazine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. - estazolam
estazolam and codeine both increase sedation. Use Caution/Monitor.
promethazine and estazolam both increase sedation. Use Caution/Monitor. - ethanol
promethazine and ethanol both increase sedation. Use Caution/Monitor.
codeine and ethanol both increase sedation. Use Caution/Monitor. - etomidate
etomidate and codeine both increase sedation. Use Caution/Monitor.
etomidate and promethazine both increase sedation. Use Caution/Monitor. - fedratinib
fedratinib will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.
fedratinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary. - fenfluramine
promethazine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine, fenfluramine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
codeine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - fentanyl
fentanyl, promethazine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
- flibanserin
codeine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
- fentanyl intranasal
fentanyl intranasal, promethazine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
- fentanyl transdermal
fentanyl transdermal, promethazine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
- fentanyl transmucosal
fentanyl transmucosal, promethazine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
- fesoterodine
fesoterodine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
fesoterodine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of fesoterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - flavoxate
flavoxate decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
flavoxate decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of flavoxate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - flecainide
promethazine and flecainide both increase QTc interval. Modify Therapy/Monitor Closely.
- flibanserin
promethazine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
- fluoxetine
promethazine and fluoxetine both increase QTc interval. Use Caution/Monitor.
fluoxetine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine - fluphenazine
fluphenazine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine and fluphenazine both increase sedation. Use Caution/Monitor.
promethazine, fluphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
codeine and fluphenazine both increase sedation. Use Caution/Monitor. - flurazepam
flurazepam and codeine both increase sedation. Use Caution/Monitor.
promethazine and flurazepam both increase sedation. Use Caution/Monitor. - fluvoxamine
fluvoxamine and promethazine both increase QTc interval. Use Caution/Monitor.
- formoterol
codeine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- formoterol
promethazine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- foscarnet
promethazine and foscarnet both increase QTc interval. Modify Therapy/Monitor Closely.
- gabapentin
gabapentin, promethazine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
gabapentin, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation. - gabapentin enacarbil
gabapentin enacarbil, promethazine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
gabapentin enacarbil, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation. - ganaxolone
promethazine and ganaxolone both increase sedation. Use Caution/Monitor.
codeine and ganaxolone both increase sedation. Use Caution/Monitor. - gemifloxacin
gemifloxacin and promethazine both decrease QTc interval. Use Caution/Monitor.
- haloperidol
haloperidol decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
codeine and haloperidol both increase sedation. Use Caution/Monitor. - gilteritinib
gilteritinib and promethazine both decrease QTc interval. Use Caution/Monitor.
- glycopyrrolate
promethazine increases effects of glycopyrrolate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
- glycopyrrolate inhaled
glycopyrrolate inhaled decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
glycopyrrolate inhaled decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of glycopyrrolate inhaled by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - glycopyrronium tosylate topical
glycopyrronium tosylate topical, promethazine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.
- gotu kola
gotu kola increases effects of promethazine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- granisetron
granisetron and promethazine both decrease QTc interval. Use Caution/Monitor.
- guanfacine
guanfacine, promethazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.
- haloperidol
haloperidol and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine and haloperidol both increase sedation. Use Caution/Monitor.
promethazine, haloperidol. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction). - hawthorn
hawthorn increases effects of promethazine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- henbane
henbane decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
henbane decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of henbane by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - homatropine
homatropine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
homatropine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - hops
hops increases effects of promethazine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- hyaluronidase
promethazine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.
- hydromorphone
promethazine and hydromorphone both increase sedation. Use Caution/Monitor.
codeine and hydromorphone both increase sedation. Use Caution/Monitor. - hydroxyzine
hydroxyzine and codeine both increase sedation. Use Caution/Monitor.
hydroxyzine and promethazine both increase sedation. Use Caution/Monitor.
hydroxyzine and promethazine both decrease QTc interval. Use Caution/Monitor. - hyoscyamine
hyoscyamine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
hyoscyamine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of hyoscyamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - iloperidone
codeine and iloperidone both increase sedation. Use Caution/Monitor.
- hyoscyamine spray
promethazine increases effects of hyoscyamine spray by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
- iloperidone
iloperidone and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine and iloperidone both increase QTc interval. Modify Therapy/Monitor Closely.
promethazine and iloperidone both increase sedation. Use Caution/Monitor.
promethazine, iloperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction). - imipramine
promethazine and imipramine both increase sedation. Use Caution/Monitor.
codeine and imipramine both increase sedation. Use Caution/Monitor.
promethazine and imipramine both increase QTc interval. Use Caution/Monitor.
imipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine. - incobotulinumtoxinA
promethazine, incobotulinumtoxinA. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects.
- isoniazid
isoniazid decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- ipratropium
ipratropium decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
ipratropium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of ipratropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - isoflurane
isoflurane and promethazine both decrease QTc interval. Use Caution/Monitor.
- isoproterenol
codeine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine, isoproterenol. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only. - kava
kava increases effects of promethazine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- ketamine
ketamine and codeine both increase sedation. Use Caution/Monitor.
- ketamine
ketamine and promethazine both increase sedation. Use Caution/Monitor.
- ketoconazole
ketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- ketotifen, ophthalmic
codeine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
promethazine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor. - lapatinib
promethazine and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.
- lasmiditan
lasmiditan, codeine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
- lasmiditan
lasmiditan, promethazine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
- lemborexant
lemborexant will decrease the level or effect of promethazine by affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Monitor CYP2B6 substrate for adequate clinical response. Consider increasing the CYP2B6 substrate dose according to specific prescribing recommendations.
lemborexant, codeine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.
lemborexant, promethazine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects. - letermovir
letermovir increases levels of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- levalbuterol
promethazine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- levalbuterol
codeine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- levofloxacin
promethazine and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.
- levoketoconazole
levoketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- levorphanol
codeine and levorphanol both increase sedation. Use Caution/Monitor.
promethazine and levorphanol both increase sedation. Use Caution/Monitor. - liraglutide
promethazine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.
- lisdexamfetamine
codeine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- lisdexamfetamine
promethazine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine, lisdexamfetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only. - lithium
lithium, promethazine. Other (see comment). Use Caution/Monitor. Comment: Risk of neurotoxicity. Multiple mechanisms involved.
lithium and promethazine both decrease QTc interval. Use Caution/Monitor. - lofepramine
promethazine and lofepramine both increase sedation. Use Caution/Monitor.
codeine and lofepramine both increase sedation. Use Caution/Monitor. - lofexidine
promethazine and lofexidine both increase sedation. Use Caution/Monitor.
codeine and lofexidine both increase sedation. Use Caution/Monitor. - lopinavir
lopinavir decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- loprazolam
promethazine and loprazolam both increase sedation. Use Caution/Monitor.
- loprazolam
loprazolam and codeine both increase sedation. Use Caution/Monitor.
- lorazepam
promethazine and lorazepam both increase sedation. Use Caution/Monitor.
lorazepam and codeine both increase sedation. Use Caution/Monitor. - lorcaserin
lorcaserin will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
lorcaserin will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. - lormetazepam
lormetazepam and codeine both increase sedation. Use Caution/Monitor.
promethazine and lormetazepam both increase sedation. Use Caution/Monitor. - loxapine
codeine and loxapine both increase sedation. Use Caution/Monitor.
loxapine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine, loxapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
promethazine and loxapine both increase sedation. Use Caution/Monitor. - loxapine inhaled
loxapine inhaled and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine, loxapine inhaled. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
codeine and loxapine inhaled both increase sedation. Use Caution/Monitor.
promethazine and loxapine inhaled both increase sedation. Use Caution/Monitor. - lumacaftor/ivacaftor
lumacaftor/ivacaftor, promethazine. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .
- lumefantrine
lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- lumefantrine
lumefantrine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- lurasidone
lurasidone, codeine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.
lurasidone increases effects of promethazine by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.; potendial for additive CNS effects .
promethazine, lurasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction). - maprotiline
promethazine and maprotiline both increase sedation. Use Caution/Monitor.
promethazine and maprotiline both increase QTc interval. Use Caution/Monitor.
codeine and maprotiline both increase sedation. Use Caution/Monitor. - marijuana
promethazine and marijuana both increase sedation. Use Caution/Monitor.
codeine and marijuana both increase sedation. Use Caution/Monitor. - meclizine
meclizine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
meclizine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of meclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - melatonin
codeine and melatonin both increase sedation. Use Caution/Monitor.
- melatonin
promethazine and melatonin both increase sedation. Use Caution/Monitor.
- meperidine
promethazine and meperidine both increase sedation. Use Caution/Monitor.
codeine and meperidine both increase sedation. Use Caution/Monitor. - meprobamate
codeine and meprobamate both increase sedation. Use Caution/Monitor.
promethazine and meprobamate both increase sedation. Use Caution/Monitor. - metaproterenol
promethazine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - metaxalone
promethazine and metaxalone both increase sedation. Use Caution/Monitor.
metaxalone and codeine both increase sedation. Use Caution/Monitor. - metformin
promethazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- methadone
codeine and methadone both increase sedation. Use Caution/Monitor.
- methadone
promethazine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.
promethazine and methadone both increase sedation. Use Caution/Monitor. - methamphetamine
codeine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine, methamphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
promethazine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - methocarbamol
promethazine and methocarbamol both increase sedation. Use Caution/Monitor.
methocarbamol and codeine both increase sedation. Use Caution/Monitor. - methoxsalen
methoxsalen, promethazine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.
- methylenedioxymethamphetamine
codeine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- methscopolamine
methscopolamine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
methscopolamine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of methscopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - methylenedioxymethamphetamine
promethazine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine, methylenedioxymethamphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only. - methylphenidate
promethazine, methylphenidate. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
- metoclopramide
promethazine and metoclopramide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
- midazolam
promethazine and midazolam both increase sedation. Use Caution/Monitor.
midazolam and codeine both increase sedation. Use Caution/Monitor. - midazolam intranasal
midazolam intranasal, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.
midazolam intranasal, promethazine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect. - midodrine
promethazine, midodrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
codeine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - mifepristone
mifepristone will increase the level or effect of promethazine by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.
- mirabegron
mirabegron will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- mirabegron
mirabegron will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- mirtazapine
mirtazapine and promethazine both decrease QTc interval. Use Caution/Monitor.
codeine and mirtazapine both increase sedation. Use Caution/Monitor.
promethazine and mirtazapine both increase sedation. Use Caution/Monitor. - modafinil
codeine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - molindone
promethazine, molindone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- morphine
codeine and morphine both increase sedation. Use Caution/Monitor.
- morphine
promethazine and morphine both increase sedation. Use Caution/Monitor.
- motherwort
codeine and motherwort both increase sedation. Use Caution/Monitor.
promethazine and motherwort both increase sedation. Use Caution/Monitor. - moxonidine
codeine and moxonidine both increase sedation. Use Caution/Monitor.
promethazine and moxonidine both increase sedation. Use Caution/Monitor. - nabilone
promethazine and nabilone both increase sedation. Use Caution/Monitor.
codeine and nabilone both increase sedation. Use Caution/Monitor. - nalbuphine
codeine and nalbuphine both increase sedation. Use Caution/Monitor.
promethazine and nalbuphine both increase sedation. Use Caution/Monitor. - norepinephrine
promethazine, norepinephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
codeine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - nortriptyline
promethazine and nortriptyline both increase QTc interval. Use Caution/Monitor.
promethazine and nortriptyline both increase sedation. Use Caution/Monitor.
codeine and nortriptyline both increase sedation. Use Caution/Monitor. - ofloxacin
promethazine and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.
- olanzapine
codeine and olanzapine both increase sedation. Use Caution/Monitor.
- olanzapine
olanzapine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine and olanzapine both increase sedation. Use Caution/Monitor.
promethazine, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
olanzapine and promethazine both decrease QTc interval. Use Caution/Monitor. - oliceridine
oliceridine, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- onabotulinumtoxinA
onabotulinumtoxinA decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
onabotulinumtoxinA decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - opium tincture
promethazine and opium tincture both increase sedation. Use Caution/Monitor.
codeine and opium tincture both increase sedation. Use Caution/Monitor. - orphenadrine
orphenadrine and codeine both increase sedation. Use Caution/Monitor.
promethazine and orphenadrine both increase sedation. Use Caution/Monitor. - oxazepam
oxazepam and codeine both increase sedation. Use Caution/Monitor.
promethazine and oxazepam both increase sedation. Use Caution/Monitor. - oxybutynin
oxybutynin decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
oxybutynin decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of oxybutynin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - oxycodone
codeine and oxycodone both increase sedation. Use Caution/Monitor.
- oxybutynin topical
oxybutynin topical decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
oxybutynin topical decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of oxybutynin topical by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - oxybutynin transdermal
oxybutynin transdermal decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
oxybutynin transdermal decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of oxybutynin transdermal by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - oxycodone
promethazine and oxycodone both increase sedation. Use Caution/Monitor.
- oxymorphone
codeine and oxymorphone both increase sedation. Use Caution/Monitor.
promethazine and oxymorphone both increase sedation. Use Caution/Monitor. - paliperidone
paliperidone and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine and paliperidone both increase sedation. Use Caution/Monitor.
promethazine, paliperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
codeine and paliperidone both increase sedation. Use Caution/Monitor.
promethazine and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely. - pancuronium
pancuronium decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
pancuronium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of pancuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - papaveretum
codeine and papaveretum both increase sedation. Use Caution/Monitor.
- papaveretum
promethazine and papaveretum both increase sedation. Use Caution/Monitor.
- papaverine
promethazine and papaverine both increase sedation. Use Caution/Monitor.
codeine and papaverine both increase sedation. Use Caution/Monitor. - paroxetine
promethazine and paroxetine both increase QTc interval. Use Caution/Monitor.
paroxetine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine. - passion flower
passion flower increases effects of promethazine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- peginterferon alfa 2b
peginterferon alfa 2b, codeine. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.
- pazopanib
promethazine and pazopanib both increase QTc interval. Use Caution/Monitor.
- peginterferon alfa 2b
peginterferon alfa 2b, promethazine. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.
- pegvisomant
codeine decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.
- pentazocine
codeine and pentazocine both increase sedation. Use Caution/Monitor.
promethazine and pentazocine both increase sedation. Use Caution/Monitor. - pentobarbital
promethazine and pentobarbital both increase sedation. Use Caution/Monitor.
pentobarbital and codeine both increase sedation. Use Caution/Monitor. - perampanel
perampanel and promethazine both increase sedation. Use Caution/Monitor.
perampanel and codeine both increase sedation. Use Caution/Monitor. - perphenazine
promethazine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
codeine and perphenazine both increase sedation. Use Caution/Monitor.
perphenazine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine and perphenazine both increase sedation. Use Caution/Monitor. - phendimetrazine
promethazine, phendimetrazine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
codeine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - phenelzine
phenelzine increases effects of promethazine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration of phenelzine and antihistamines may result in additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .
- phenobarbital
phenobarbital and codeine both increase sedation. Use Caution/Monitor.
- phenobarbital
promethazine and phenobarbital both increase sedation. Use Caution/Monitor.
- phentermine
promethazine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine, phentermine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
codeine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - phenylephrine
promethazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
codeine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - phenylephrine PO
promethazine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .
codeine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .
promethazine, phenylephrine PO. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only. - pholcodine
promethazine and pholcodine both increase sedation. Use Caution/Monitor.
codeine and pholcodine both increase sedation. Use Caution/Monitor. - pimavanserin
promethazine, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- pimozide
codeine and pimozide both increase sedation. Use Caution/Monitor.
- pimozide
pimozide and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine and pimozide both increase sedation. Use Caution/Monitor.
promethazine, pimozide. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction). - pirbuterol
codeine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - porfimer
promethazine, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.
- pregabalin
pregabalin, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- posaconazole
promethazine and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.
- pralidoxime
pralidoxime decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
pralidoxime decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of pralidoxime by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - pregabalin
pregabalin, promethazine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- primaquine
primaquine and promethazine both decrease QTc interval. Use Caution/Monitor.
- primidone
promethazine and primidone both increase sedation. Use Caution/Monitor.
primidone and codeine both increase sedation. Use Caution/Monitor. - procarbazine
procarbazine, promethazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Excessive sedation.
- prochlorperazine
codeine and prochlorperazine both increase sedation. Use Caution/Monitor.
- prochlorperazine
prochlorperazine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine and prochlorperazine both increase sedation. Use Caution/Monitor. - promethazine
promethazine and codeine both increase sedation. Use Caution/Monitor.
- propafenone
propafenone will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- propantheline
propantheline decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
propantheline decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of propantheline by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - propofol
propofol and promethazine both increase sedation. Use Caution/Monitor.
propofol and codeine both increase sedation. Use Caution/Monitor. - propylhexedrine
codeine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine, propylhexedrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only. - protriptyline
codeine and protriptyline both increase sedation. Use Caution/Monitor.
promethazine and protriptyline both increase QTc interval. Use Caution/Monitor.
promethazine and protriptyline both increase sedation. Use Caution/Monitor. - pseudoephedrine
promethazine, pseudoephedrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
- quazepam
quazepam and codeine both increase sedation. Use Caution/Monitor.
- quazepam
promethazine and quazepam both increase sedation. Use Caution/Monitor.
- quetiapine
codeine and quetiapine both increase sedation. Use Caution/Monitor.
promethazine and quetiapine both increase sedation. Use Caution/Monitor.
promethazine and quetiapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine, quetiapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction). - quinidine
quinidine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
quinidine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. - ramelteon
codeine and ramelteon both increase sedation. Use Caution/Monitor.
promethazine and ramelteon both increase sedation. Use Caution/Monitor. - ranolazine
promethazine and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.
- remimazolam
remimazolam, codeine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.
- rapacuronium
rapacuronium decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
rapacuronium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of rapacuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - ribociclib
ribociclib will increase the level or effect of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- risperidone
promethazine and risperidone both increase sedation. Use Caution/Monitor.
codeine and risperidone both increase sedation. Use Caution/Monitor.
promethazine, risperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
promethazine and risperidone both increase QTc interval. Modify Therapy/Monitor Closely.
promethazine and risperidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. - ritonavir
ritonavir will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- rocuronium
rocuronium decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
rocuronium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of rocuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - rolapitant
rolapitant will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.
rolapitant will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration. - salmeterol
codeine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - scopolamine
scopolamine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
scopolamine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of scopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - scullcap
codeine and scullcap both increase sedation. Use Caution/Monitor.
- scullcap
promethazine and scullcap both increase sedation. Use Caution/Monitor.
- secobarbital
secobarbital and codeine both increase sedation. Use Caution/Monitor.
promethazine and secobarbital both increase sedation. Use Caution/Monitor. - selegiline
selegiline increases toxicity of codeine by unknown mechanism. Modify Therapy/Monitor Closely. Potential for increased CNS depression, drowsiness, dizziness or hypotension, so use with any MAOI should be cautious.
- serdexmethylphenidate/dexmethylphenidate
promethazine, serdexmethylphenidate/dexmethylphenidate. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
- sertraline
sertraline decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
sertraline and promethazine both decrease QTc interval. Use Caution/Monitor. - sevoflurane
sevoflurane and promethazine both decrease QTc interval. Use Caution/Monitor.
sevoflurane and codeine both increase sedation. Use Caution/Monitor.
sevoflurane and promethazine both increase sedation. Use Caution/Monitor. - shepherd's purse
promethazine and shepherd's purse both increase sedation. Use Caution/Monitor.
codeine and shepherd's purse both increase sedation. Use Caution/Monitor. - smoking
smoking decreases levels of promethazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.
- stiripentol
stiripentol, codeine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.
- solifenacin
solifenacin decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
solifenacin decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of solifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
solifenacin and promethazine both decrease QTc interval. Use Caution/Monitor. - sparsentan
sparsentan will decrease the level or effect of promethazine by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Sparsentan (a CYP2B6 inducer) decreases exposure of CYP2B6 substrates and reduces efficacy related to these substrates.
- stiripentol
stiripentol, promethazine. affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP2B6 inhibitor and inducer. Monitor CYP2B6 substrates coadministered with stiripentol for increased or decreased effects. CYP2B6 substrates may require dosage adjustment.
stiripentol, promethazine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence. - sufentanil
codeine and sufentanil both increase sedation. Use Caution/Monitor.
promethazine and sufentanil both increase sedation. Use Caution/Monitor. - sulfamethoxazole
promethazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
- suvorexant
suvorexant and codeine both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary
- sunitinib
sunitinib and promethazine both decrease QTc interval. Use Caution/Monitor.
- tacrolimus
tacrolimus and promethazine both decrease QTc interval. Use Caution/Monitor.
- tapentadol
promethazine and tapentadol both increase sedation. Use Caution/Monitor.
codeine and tapentadol both increase sedation. Use Caution/Monitor. - telavancin
promethazine and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.
- temazepam
temazepam and codeine both increase sedation. Use Caution/Monitor.
- temazepam
promethazine and temazepam both increase sedation. Use Caution/Monitor.
- terbinafine
terbinafine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.
terbinafine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug. - terbutaline
codeine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - tetrabenazine
promethazine and tetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely.
- thioridazine
thioridazine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
codeine and thioridazine both increase sedation. Use Caution/Monitor. - thioridazine
promethazine and thioridazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine and thioridazine both increase sedation. Use Caution/Monitor. - thiothixene
promethazine and thiothixene both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
codeine and thiothixene both increase sedation. Use Caution/Monitor.
promethazine, thiothixene. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
promethazine and thiothixene both increase sedation. Use Caution/Monitor. - ticlopidine
ticlopidine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- tiotropium
tiotropium decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
tiotropium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of tiotropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - tobacco use
tobacco use decreases levels of promethazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.
- tolterodine
tolterodine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
tolterodine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of tolterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - topiramate
codeine and topiramate both increase sedation. Modify Therapy/Monitor Closely.
promethazine and topiramate both increase sedation. Modify Therapy/Monitor Closely. - tramadol
promethazine and tramadol both increase sedation. Use Caution/Monitor.
codeine and tramadol both increase sedation. Use Caution/Monitor. - tranylcypromine
tranylcypromine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- trazodone
promethazine and trazodone both increase QTc interval. Use Caution/Monitor.
promethazine and trazodone both increase sedation. Use Caution/Monitor. - trazodone
codeine and trazodone both increase sedation. Use Caution/Monitor.
- triazolam
promethazine and triazolam both increase sedation. Use Caution/Monitor.
triazolam and codeine both increase sedation. Use Caution/Monitor. - triclofos
triclofos and codeine both increase sedation. Use Caution/Monitor.
promethazine and triclofos both increase sedation. Use Caution/Monitor. - trifluoperazine
promethazine, trifluoperazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
codeine and trifluoperazine both increase sedation. Use Caution/Monitor.
promethazine and trifluoperazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine and trifluoperazine both increase sedation. Use Caution/Monitor. - trihexyphenidyl
trihexyphenidyl decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of trihexyphenidyl by pharmacodynamic synergism. Use Caution/Monitor. Potential for additive anticholinergic effects. - trimipramine
codeine and trimipramine both increase sedation. Use Caution/Monitor.
- trimethoprim
promethazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
- trimipramine
promethazine and trimipramine both increase sedation. Use Caution/Monitor.
- triprolidine
promethazine and triprolidine both increase sedation. Use Caution/Monitor.
triprolidine and codeine both increase sedation. Use Caution/Monitor. - tropisetron
promethazine and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.
- venlafaxine
venlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- trospium chloride
trospium chloride decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
trospium chloride decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of trospium chloride by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - valbenazine
valbenazine and promethazine both decrease QTc interval. Use Caution/Monitor.
- valerian
valerian increases effects of promethazine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- vecuronium
vecuronium decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
vecuronium decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of vecuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - venlafaxine
promethazine and venlafaxine both increase QTc interval. Use Caution/Monitor.
- voriconazole
promethazine and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.
- vorinostat
vorinostat and promethazine both decrease QTc interval. Use Caution/Monitor.
- xylometazoline
codeine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine, xylometazoline. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
promethazine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - yohimbine
codeine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine, yohimbine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
promethazine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - ziconotide
codeine and ziconotide both increase sedation. Use Caution/Monitor.
promethazine and ziconotide both increase sedation. Use Caution/Monitor. - ziprasidone
codeine and ziprasidone both increase sedation. Use Caution/Monitor.
promethazine and ziprasidone both increase sedation. Use Caution/Monitor.
promethazine, ziprasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
promethazine and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. - zotepine
promethazine and zotepine both increase sedation. Use Caution/Monitor.
codeine and zotepine both increase sedation. Use Caution/Monitor.
promethazine and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
Minor (76)
- amiodarone
amiodarone will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- amitriptyline
amitriptyline, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
amitriptyline, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects. - amoxapine
amoxapine, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
amoxapine, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.
promethazine, amoxapine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects. - asenapine
asenapine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
asenapine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown. - ashwagandha
ashwagandha increases effects of promethazine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.
- brimonidine
brimonidine increases effects of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.
- atropine
promethazine increases toxicity of atropine by unknown mechanism. Minor/Significance Unknown.
- atropine IV/IM
promethazine increases toxicity of atropine IV/IM by unknown mechanism. Minor/Significance Unknown.
- benazepril
promethazine increases effects of benazepril by unspecified interaction mechanism. Minor/Significance Unknown. Enhanced hypotensive effects.
- brimonidine
brimonidine increases effects of promethazine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.
- bupropion
promethazine increases toxicity of bupropion by unspecified interaction mechanism. Minor/Significance Unknown. May lower seizure threshold; keep bupropion dose as low as possible.
- captopril
promethazine increases effects of captopril by unspecified interaction mechanism. Minor/Significance Unknown.
- celecoxib
celecoxib will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- chasteberry
chasteberry decreases effects of promethazine by pharmacodynamic antagonism. Minor/Significance Unknown. (Theoretical interaction).
- chloroquine
chloroquine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
chloroquine increases levels of promethazine by decreasing metabolism. Minor/Significance Unknown. - cimetidine
cimetidine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- clomipramine
clomipramine, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
clomipramine, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects. - darifenacin
darifenacin will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- desipramine
desipramine, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
desipramine, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects. - dextroamphetamine
dextroamphetamine increases effects of codeine by unspecified interaction mechanism. Minor/Significance Unknown.
- diphenhydramine
diphenhydramine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- doxepin
doxepin, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
doxepin, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects. - dronedarone
dronedarone will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- duloxetine
duloxetine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- enalapril
promethazine increases effects of enalapril by unspecified interaction mechanism. Minor/Significance Unknown.
- ethanol
ethanol, promethazine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.
- eucalyptus
codeine and eucalyptus both increase sedation. Minor/Significance Unknown.
promethazine and eucalyptus both increase sedation. Minor/Significance Unknown. - famciclovir
promethazine, famciclovir. aldehyde dehydrogenase inhibition. Minor/Significance Unknown. The conversion of 6-deoxy penciclovir to penciclovir is catalyzed by aldehyde oxidase. Interactions with other drugs metabolized by this enzyme and/or inhibiting this enzyme could potentially occur. Clinical interaction studies of famciclovir with promethazine did not show relevant effects on the formation of penciclovir.
- fluoxetine
fluoxetine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
- fosinopril
promethazine increases effects of fosinopril by unspecified interaction mechanism. Minor/Significance Unknown.
- glycopyrrolate
promethazine increases toxicity of glycopyrrolate by unknown mechanism. Minor/Significance Unknown.
- glycopyrrolate inhaled
promethazine increases toxicity of glycopyrrolate inhaled by unknown mechanism. Minor/Significance Unknown.
- haloperidol
haloperidol will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- imatinib
imatinib decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
imatinib will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
imatinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown. - imidapril
promethazine increases effects of imidapril by unspecified interaction mechanism. Minor/Significance Unknown.
- lidocaine
lidocaine increases toxicity of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.
- imipramine
imipramine, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
imipramine, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects. - lisinopril
promethazine increases effects of lisinopril by unspecified interaction mechanism. Minor/Significance Unknown.
- lofepramine
lofepramine, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
lofepramine, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects. - maprotiline
maprotiline, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
maprotiline, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects. - maraviroc
maraviroc will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
maraviroc will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown. - marijuana
marijuana will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
marijuana will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown. - metyrapone
promethazine decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.
- nilotinib
nilotinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- metyrosine
metyrosine increases toxicity of promethazine by pharmacodynamic synergism. Minor/Significance Unknown. Increased extrapyramidal symptoms.
- moexipril
promethazine increases effects of moexipril by unspecified interaction mechanism. Minor/Significance Unknown.
- nettle
nettle increases effects of promethazine by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.
- nilotinib
nilotinib will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- nortriptyline
nortriptyline, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
nortriptyline, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects. - oxybutynin
oxybutynin increases toxicity of promethazine by unspecified interaction mechanism. Minor/Significance Unknown.
- oxybutynin topical
oxybutynin topical increases toxicity of promethazine by unspecified interaction mechanism. Minor/Significance Unknown.
- oxybutynin transdermal
oxybutynin transdermal increases toxicity of promethazine by unspecified interaction mechanism. Minor/Significance Unknown.
- parecoxib
parecoxib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
parecoxib will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown. - perindopril
promethazine increases effects of perindopril by unspecified interaction mechanism. Minor/Significance Unknown.
- perphenazine
perphenazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
perphenazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine. - perphenazine
perphenazine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- propafenone
propafenone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
propafenone decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine. - protriptyline
protriptyline, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
protriptyline, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects. - pyrimethamine
pyrimethamine increases levels of promethazine by decreasing metabolism. Minor/Significance Unknown.
- quinacrine
quinacrine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
quinacrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
quinacrine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown. - quinapril
promethazine increases effects of quinapril by unspecified interaction mechanism. Minor/Significance Unknown.
- ranolazine
ranolazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- ramipril
promethazine increases effects of ramipril by unspecified interaction mechanism. Minor/Significance Unknown.
- ranolazine
ranolazine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- ritonavir
ritonavir will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- sage
codeine and sage both increase sedation. Minor/Significance Unknown.
promethazine and sage both increase sedation. Minor/Significance Unknown. - sertraline
sertraline decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
sertraline will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown. - Siberian ginseng
Siberian ginseng increases effects of promethazine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.
- thioridazine
thioridazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
- thioridazine
thioridazine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- tipranavir
tipranavir will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
tipranavir will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown. - trandolapril
promethazine increases effects of trandolapril by unspecified interaction mechanism. Minor/Significance Unknown.
- venlafaxine
venlafaxine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
- trazodone
trazodone, promethazine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.
trazodone, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. - trimipramine
trimipramine, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
trimipramine, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects. - ziconotide
ziconotide, codeine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.
Adverse Effects
>10% (Codeine)
Constipation
Drowsiness
Frequency Not Defined (Promethazine)
Sedation (common)
Confusion (common)
Disorientation (common)
Adverse anticholinergic effects (dry mouth, blurred vision)
Photosensitivity
EPS
Tachycardia
Bradycardia
Leukopenia (rare)
Agranulocytosis (rare)
Obstructive jaundice
Frequency Not Defined (Codeine)
Confusion
Dizziness
False feeling of well being
Headache
Lightheadedness
Malaise
Paradoxical CNS stimulation
Restlessness
Seizure (with excessive doses)
Weakness
Blurred vision
Hypotension (especially with IV use)
Tachycardia
Bradycardia
Dyspnea
Respiratory depression
Anorexia
Nausea
Vomiting
Xerostomia
Rash
Urticaria
Ureteral spasm
Urination decreased
LFT's increased
Histamine release
Anaphylactoid reaction (rare)
Warnings
Black Box Warnings
Because of the potential for fatal respiratory depression, do not administer promethazine and codeine concurrently to children <12 years of age
Postmarketing cases of respiratory depression, including fatalities reported with use of promethazine in pediatric patients; children may be particularly sensitive to additive respiratory depressant effects when promethazine is combined with other respiratory depressants, including codeine
Coadministration with benzodiazepines
- Risks from concomitant use with benzodiazepines or other CNS depressants; concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; reserve concomitant prescribing of this drug combination and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to minimum required; follow patients for signs and symptoms of respiratory depression and sedation
- Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; risks from concomitant use with benzodiazepines or other CNS depressants; ultra- rapid metabolism of codeine and other risk factors for life-threatening respiratory depression in children; neonatal opioid withdrawal syndrome; interactions with drugs affecting cytochrome p450 isoenzymes; and hepatotoxicity
Postoperative pain in children
- Deaths have occurred in children with obstructive sleep apnea who receive codeine for postoperative pain following tonsillectomy and/or adenoidectomy
- Contraindicated in children <12 years and in children < 18 years following tonsillectomy and/or adenoidectomy; avoid use in adolescents 12-18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine; codeine is converted to morphine by the liver; these children had evidence of being ultra-rapid metabolizers (via CYP2D6) of codeine, which is an inherited (genetic) ability that causes codeine to be converted rapidly into life-threatening or fatal amounts of morphine (see Pharmacology)
- Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol
Contraindications
Postoperative use in children following tonsillectomy and/or adenoidectomy (see Black Box Warnings)
Promethazine
- Hypersensitivity
- Children <12 years (risk of potentially fatal respiratory depression)
- Subcutaneous or intra-arterially administration
- Benign prostatic hypertrophy
- Narrow angle glaucoma
- Pyloroduodenal obstruction, stenosing peptic ulcer, bladder neck obstruction
- Severe CNS depression
- Coma, severe respiratory depression
Codeine
- Absolute: acute abdominal condition, diarrhea associated w/ toxins, pseudomembranous colitis, respiratory depression
- Relative: asthma (acute), inflammatory bowel disease, respiratory impairment
- Children <12 years
- Postoperative management in children <18 years following tonsillectomy and/or adenoidectomy
- Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
- Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days
- Significant respiratory depression
- Porphyria
- Treatment of lower respiratory tract symptoms, including asthma
- Known or suspected gastrointestinal obstruction, including paralytic ileus
Cautions
Concomitant use of opioids, including promethazine HCl and codeine phosphate oral solution, with benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; because of these risks, avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol
Promethazine
- Caution in CVD, asthma, hepatic impairment, peptic ulcer, respiratory impairment; the impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; avoid use of promethazine HCl and codeine phosphate oral solution in patients on these medications
- Anaphylaxis in susceptible individuals
- May impair ability to drive or perform hazardous tasks
- Monitor closely with cardiovascular disease, hepatic impairment, Reye syndrome, history of sleep apnea
- Depresses hypothalamic thermoregulatory mechanism; exposure to extreme temperatures may cause hypo- or hyperthermia
- Antiemetic effect may obscure toxicity of chemotherapeutic drugs
- Concomitant use of opioids, including promethazine HCl and codeine phosphate oral solution, with benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol
- Convulsions have occurred with therapeutic doses and overdoses of promethazine hydrochloride in pediatric patients; promethazine may lower seizure threshold; it should be used with caution in persons with seizure disorders or in persons who are using concomitant medications, such as narcotics or local anesthetics, which may also affect seizure threshold
- Promethazine is a phenothiazine; phenothiazines are associated with dystonic reactions; in pediatric patients who are acutely ill associated with dehydration, there is increased susceptibility to dystonias with promethazine HCl use
- The respiratory-depressant effects of narcotic analgesics and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in presence of head injury, intracranial lesions, or a pre-existing increase in intracranial pressure; narcotics may produce adverse reactions which may obscure clinical course of patients with head injuries
- A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) reported in association with promethazine HCl alone or in combination with antipsychotic drugs; 1) management of NMS should include immediate discontinuation of promethazine HCl, antipsychotic drugs, if any, and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available
- Promethazine should be used with caution in patients with bone-marrow depression; leukopenia and agranulocytosis reported, usually when promethazine HCl has been used in association with other known marrow-toxic agents
Codeine
- Caution in cardiac arrhythmias, drug abuse/dependence, emotional lability, gallbladder disease, head injury, hepatic impairment, hypothyroidism, increased ICP, prostatic hypertrophy, renal impairment, seizures w/ epilepsy, urethral stricture, urinary tract surgery
- Risk of life threatening side effects in nursing babies, especially if mother is an ultra rapid metabolizer of codeine
- Codeine is subject to variability in metabolism based upon CYP2D6 genotype (described below), which can lead to an increased exposure to the active metabolite morphine
- Avoid use of capsules in adolescents 12-18 years of age who have other risk factors that may increase sensitivity to respiratory depressant effects of codeine unless benefits outweigh risks; risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression; when prescribing codeine for adolescents, healthcare providers should choose lowest effective dose for shortest period of time and inform patients and caregivers about risks and the signs of morphine overdose
- Dosage of codeine should not be increased if cough fails to respond; an unresponsive cough should be reevaluated in 5 days or sooner for possible underlying pathology, such as foreign body or lower respiratory tract disease
- Narcotic analgesics or cough suppressants, including codeine, should not be used in patients with severe asthma or those with frequent asthma attacks
- Codeine may produce orthostatic hypotension in ambulatory patients
- Codeine may cause or aggravate constipation
- Ibuprofen is more effective than codeine for pain from musculoskeletal injuries in children
Pregnancy & Lactation
Pregnancy
Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome; available data in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage
Labor and delivery
- Use of codeine during labor may lead to respiratory depression in the neonate; opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate; use is not recommended in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate; opioid analgesics, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by increased rate of cervical dilation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression
Lactation
Codeine and its active metabolite, morphine, are present in human milk; there are published studies and cases that have reported excessive sedation, respiratory depression, and death in infants exposed to codeine via breast milk; women who are ultra-rapid metabolizers of codeine achieve higher than expected serum levels of morphine, potentially leading to higher levels of morphine in breast milk that can be dangerous in their breastfed infants; in women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and dose-dependent; at least one death was reported in a nursing infant who was exposed to high levels of morphine in breast milk because mother was an ultra-rapid metabolizer of codeine; breastfeeding not recommended
There is no information on effects of codeine milk production; because of potential for serious adverse reactions, including excess sedation, respiratory depression, and death in a breastfed infant, breastfeeding is not recommended during treatment
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Promethazine: Antidopaminergic effect due to blocking mesolimbic dopamine receptors and alpha-adrenergic receptors in the brain; antihistaminic effect due to blocking H1-receptors
Codeine: Narcotic agonist analgesic with antitussive activity, mu receptor agonist
Promethazine
Onset: 20 min
Duration: 4-6 hr
Bioavailability: 25% (oral)
Protein Bound: 93%
Vd: 12.9-17.7 L/hr
Metabolism: Hepatic P450 enzyme CYP2D6
Metabolites: Promethazine sulfoxide and glucuronides (inactive)
Excretion: Urine, feces
Dialyzable: no
Codeine
Half-Life: 3-4 hr
Onset: 30-60 min
Metabolism: Inactive but metabolized to morphine by CYP2D6 (missing in 5-10% of population)
Duration: 4-6 hr
Peak Plasma Time: 0.5-1 hr
Vd: 3-6 L/kg
Bioavailability: 53%
Protein Bound: 25%
Excretion: Urine (90%), feces
Pharmacogenomics
10% of codeine is metabolized to morphine by CYP2D6; the active morphine metabolite has a higher affinity for opioid receptors
CYP2D6 poor metabolizers may not achieve adequate analgesia
Ultra-rapid metabolizers (up to 7% of Caucasians and up to 30% of Asian and African populations) may have increased toxicity due to rapid conversion
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