Dosing & Uses
Dosage Forms & Strengths
codeine/chlorpheniramine
extended-release oral suspension: Schedule III
- (14.7mg/2.8mg)/5mL (equivalent to 20mg codeine phosphate and 4mg chlorpheniramine maleate)
tablet, extended-release: Schedule III
- 40mg/5.6mg (equivalent to 54.3mg codeine phosphate and 8mg chlorpheniramine maleate)
Cough & Cold
Indicated for relief of cough and symptoms associated with upper respiratory tract allergies or common cold in adults (>18 years)
Suspension: 10 mL PO q12hr; not to exceed 2 doses (20 mL) in 24 hr
Tablet: 1 tablet PO q12hr; not to exceed 2 doses/24 hr
<18 years: Safety and efficacy not established
Dose selection for an elderly patient should be made with caution, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (1)
- alvimopan
alvimopan, codeine. receptor binding competition. Contraindicated. Alvimopan is contraindicated in opioid tolerant patients (ie, those who have taken therapeutic doses of opioids for >7 consecutive days immediately prior to taking alvimopan). Patients recently exposed to opioids are expected to be more sensitive to the effects of alvimopan and therefore may experience abdominal pain, nausea and vomiting, and diarrhea. No significant interaction is expected with concurrent use of opioid analgesics and alvimopan in patients who received opioid analgesics for 7 or fewer consecutive days prior to alvimopan.
Serious - Use Alternative (55)
- acrivastine
acrivastine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- amisulpride
amisulpride and codeine both increase sedation. Avoid or Use Alternate Drug.
- apalutamide
apalutamide will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
- asenapine
asenapine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- asenapine transdermal
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 codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
benzhydrocodone/acetaminophen and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
benzhydrocodone/acetaminophen, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. - bremelanotide
bremelanotide will decrease the level or effect of codeine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.
- buprenorphine subdermal implant
buprenorphine subdermal implant and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- brimonidine
brimonidine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- buprenorphine
buprenorphine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- buprenorphine buccal
buprenorphine buccal, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- buprenorphine subdermal implant
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 codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
buprenorphine transdermal and chlorpheniramine 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 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 chlorpheniramine 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.
- calcium/magnesium/potassium/sodium oxybates
chlorpheniramine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- 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.
- clonidine
clonidine, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.
- dacomitinib
dacomitinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- diazepam intranasal
diazepam intranasal, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- eluxadoline
chlorpheniramine, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions.
codeine, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions. . - fentanyl
fentanyl, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
- fexinidazole
fexinidazole will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
- fentanyl intranasal
fentanyl intranasal, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
- fentanyl transdermal
fentanyl transdermal, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
- fentanyl transmucosal
fentanyl transmucosal, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
- givosiran
givosiran will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- hydrocodone
hydrocodone, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- idelalisib
idelalisib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates
- isocarboxazid
isocarboxazid increases effects of chlorpheniramine by Other (see comment). Avoid or Use Alternate Drug. Comment: Isocarboxazid should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .
isocarboxazid increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d. - linezolid
linezolid increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.
- lonafarnib
lonafarnib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.
- methylene blue
methylene blue and codeine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
- metoclopramide intranasal
chlorpheniramine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.
codeine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient. - nalbuphine
nalbuphine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- olopatadine intranasal
chlorpheniramine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
- olopatadine intranasal
codeine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
- ozanimod
ozanimod and codeine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.
- pentazocine
pentazocine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- phenelzine
phenelzine increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.
- prasugrel
codeine will decrease the level or effect of prasugrel by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Co-administration of opioid agonists delay and reduce absorption of prasugrel and its active metabolite presumably by slowing gastric emptying; consider the use of a parenteral anti-platelet agent in acute coronary syndrome patients requiring co-administration of opioid agonists
- procarbazine
procarbazine increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. MAOIs may potentiate CNS depression and hypotension. Do not use within 14 days of MAOI use. .
- rasagiline
rasagiline increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.
- selegiline transdermal
selegiline transdermal increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.
- selinexor
selinexor, codeine. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.
- sodium oxybate
chlorpheniramine, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
codeine, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. - sufentanil SL
sufentanil SL, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- tranylcypromine
tranylcypromine increases effects of chlorpheniramine by Other (see comment). Avoid or Use Alternate Drug. Comment: Tranylcypromine should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .
- ticagrelor
codeine will decrease the level or effect of ticagrelor by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Co-administration of opioid agonists delay and reduce absorption of ticagrelor and its active metabolite presumably by slowing gastric emptying; consider the use of a parenteral anti-platelet agent in acute coronary syndrome patients requiring co-administration of opioid agonists
- tramadol
tramadol, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
- tranylcypromine
tranylcypromine increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.
- tucatinib
tucatinib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.
- valerian
valerian and codeine both increase sedation. Avoid or Use Alternate Drug.
- voxelotor
voxelotor will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.
Monitor Closely (294)
- abiraterone
abiraterone increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- acrivastine
acrivastine and chlorpheniramine both increase sedation. Use Caution/Monitor.
- albuterol
chlorpheniramine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - alfentanil
chlorpheniramine and alfentanil both increase sedation. Use Caution/Monitor.
alfentanil and codeine both increase sedation. Use Caution/Monitor. - alprazolam
alprazolam and codeine both increase sedation. Use Caution/Monitor.
chlorpheniramine and alprazolam both increase sedation. Use Caution/Monitor. - amifampridine
chlorpheniramine increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.
- amiodarone
amiodarone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- amisulpride
amisulpride and chlorpheniramine both increase sedation. Use Caution/Monitor.
- amitriptyline
chlorpheniramine and amitriptyline both increase sedation. Use Caution/Monitor.
codeine and amitriptyline both increase sedation. Use Caution/Monitor. - amobarbital
amobarbital will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
amobarbital and codeine both increase sedation. Use Caution/Monitor.
chlorpheniramine and amobarbital both increase sedation. Use Caution/Monitor. - amoxapine
codeine and amoxapine both increase sedation. Use Caution/Monitor.
chlorpheniramine and amoxapine both increase sedation. Use Caution/Monitor. - apomorphine
codeine and apomorphine both increase sedation. Use Caution/Monitor.
chlorpheniramine and apomorphine both increase sedation. Use Caution/Monitor. - arformoterol
chlorpheniramine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - aripiprazole
codeine and aripiprazole both increase sedation. Use Caution/Monitor.
chlorpheniramine and aripiprazole both increase sedation. Use Caution/Monitor. - armodafinil
codeine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlorpheniramine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - artemether/lumefantrine
artemether/lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- asenapine
asenapine and chlorpheniramine both increase sedation. Use Caution/Monitor.
- asenapine transdermal
asenapine transdermal and chlorpheniramine both increase sedation. Use Caution/Monitor.
- avapritinib
avapritinib and chlorpheniramine both increase sedation. Use Caution/Monitor.
- azelastine
azelastine and codeine both increase sedation. Use Caution/Monitor.
azelastine and chlorpheniramine both increase sedation. Use Caution/Monitor. - baclofen
chlorpheniramine and baclofen both increase sedation. Use Caution/Monitor.
baclofen and codeine both increase sedation. Use Caution/Monitor. - belladonna and opium
codeine and belladonna and opium both increase sedation. Use Caution/Monitor.
chlorpheniramine and belladonna and opium both increase sedation. Use Caution/Monitor. - belzutifan
belzutifan will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.
- benperidol
codeine and benperidol both increase sedation. Use Caution/Monitor.
- benperidol
chlorpheniramine and benperidol both increase sedation. Use Caution/Monitor.
- benzphetamine
chlorpheniramine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - brexanolone
brexanolone, codeine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
brexanolone, chlorpheniramine. Either increases toxicity of the other by sedation. Use Caution/Monitor. - brexpiprazole
brexpiprazole and chlorpheniramine both increase sedation. Use Caution/Monitor.
brexpiprazole and codeine both increase sedation. Use Caution/Monitor. - brimonidine
brimonidine and chlorpheniramine both increase sedation. Use Caution/Monitor.
- brivaracetam
brivaracetam and codeine both increase sedation. Use Caution/Monitor.
- brivaracetam
brivaracetam and chlorpheniramine both increase sedation. Use Caution/Monitor.
- brompheniramine
brompheniramine and codeine both increase sedation. Use Caution/Monitor.
brompheniramine and chlorpheniramine both increase sedation. Use Caution/Monitor. - buprenorphine
buprenorphine and codeine both increase sedation. Use Caution/Monitor.
chlorpheniramine and buprenorphine both increase sedation. Use Caution/Monitor. - buprenorphine buccal
chlorpheniramine and buprenorphine buccal both increase sedation. Use Caution/Monitor.
buprenorphine buccal and codeine both increase sedation. Use Caution/Monitor. - buprenorphine, long-acting injection
codeine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.
- butabarbital
chlorpheniramine and butabarbital both increase sedation. Use Caution/Monitor.
- bupropion
bupropion will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents the conversion of codeine to its active metabolite morphine.
- butabarbital
butabarbital and codeine both increase sedation. Use Caution/Monitor.
- butalbital
chlorpheniramine and butalbital both increase sedation. Use Caution/Monitor.
butalbital and codeine both increase sedation. Use Caution/Monitor. - butorphanol
butorphanol and codeine both increase sedation. Use Caution/Monitor.
chlorpheniramine and butorphanol both increase sedation. Use Caution/Monitor. - caffeine
chlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - carbinoxamine
carbinoxamine and chlorpheniramine both increase sedation. Use Caution/Monitor.
carbinoxamine and codeine both increase sedation. Use Caution/Monitor. - carisoprodol
carisoprodol and codeine both increase sedation. Use Caution/Monitor.
chlorpheniramine and carisoprodol both increase sedation. Use Caution/Monitor. - celecoxib
celecoxib decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- cenobamate
cenobamate will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
cenobamate, chlorpheniramine. Either increases effects of the other by sedation. Use Caution/Monitor. - cenobamate
cenobamate, codeine. Either increases effects of the other by sedation. Use Caution/Monitor.
- chloral hydrate
chloral hydrate and codeine both increase sedation. Use Caution/Monitor.
chlorpheniramine and chloral hydrate both increase sedation. Use Caution/Monitor. - chlordiazepoxide
chlorpheniramine and chlordiazepoxide both increase sedation. Use Caution/Monitor.
chlordiazepoxide and codeine both increase sedation. Use Caution/Monitor. - chloroquine
chloroquine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- chlorpromazine
chlorpheniramine and chlorpromazine both increase sedation. Use Caution/Monitor.
- chlorpheniramine
chlorpheniramine and codeine both increase sedation. Use Caution/Monitor.
- chlorpromazine
codeine and chlorpromazine both increase sedation. Use Caution/Monitor.
chlorpromazine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine - chlorzoxazone
chlorzoxazone and codeine both increase sedation. Use Caution/Monitor.
chlorpheniramine and chlorzoxazone both increase sedation. Use Caution/Monitor. - cimetidine
cimetidine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- cinnarizine
chlorpheniramine and cinnarizine both increase sedation. Use Caution/Monitor.
- cinacalcet
cinacalcet decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- cinnarizine
cinnarizine and codeine both increase sedation. Use Caution/Monitor.
- clemastine
chlorpheniramine and clemastine both increase sedation. Use Caution/Monitor.
clemastine and codeine both increase sedation. Use Caution/Monitor. - clobazam
chlorpheniramine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
codeine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
clobazam decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine. - clomipramine
codeine and clomipramine both increase sedation. Use Caution/Monitor.
chlorpheniramine and clomipramine both increase sedation. Use Caution/Monitor.
clomipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine. - clonazepam
chlorpheniramine and clonazepam both increase sedation. Use Caution/Monitor.
clonazepam and codeine both increase sedation. Use Caution/Monitor. - clorazepate
clorazepate and codeine both increase sedation. Use Caution/Monitor.
chlorpheniramine and clorazepate both increase sedation. Use Caution/Monitor. - clozapine
codeine and clozapine both increase sedation. Use Caution/Monitor.
chlorpheniramine and clozapine both increase sedation. Use Caution/Monitor.
clozapine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine. - cocaine topical
cocaine topical decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- codeine
chlorpheniramine and codeine both increase sedation. Use Caution/Monitor.
- crofelemer
crofelemer increases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.
- cyclizine
chlorpheniramine and cyclizine both increase sedation. Use Caution/Monitor.
cyclizine and codeine both increase sedation. Use Caution/Monitor. - cyclobenzaprine
chlorpheniramine and cyclobenzaprine both increase sedation. Use Caution/Monitor.
cyclobenzaprine and codeine both increase sedation. Use Caution/Monitor. - cyproheptadine
cyproheptadine and codeine both increase sedation. Use Caution/Monitor.
chlorpheniramine and cyproheptadine both increase sedation. Use Caution/Monitor. - dabrafenib
dabrafenib will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
- dantrolene
dantrolene and codeine both increase sedation. Use Caution/Monitor.
- dantrolene
chlorpheniramine and dantrolene both increase sedation. Use Caution/Monitor.
- daridorexant
chlorpheniramine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
codeine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. - darifenacin
darifenacin decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- desflurane
desflurane and chlorpheniramine both increase sedation. Use Caution/Monitor.
- desflurane
desflurane and codeine both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.
- desipramine
chlorpheniramine and desipramine both increase sedation. Use Caution/Monitor.
codeine and desipramine both increase sedation. Use Caution/Monitor.
desipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine. - desvenlafaxine
desvenlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg
- deutetrabenazine
chlorpheniramine and deutetrabenazine both increase sedation. Use Caution/Monitor.
- deutetrabenazine
codeine and deutetrabenazine both increase sedation. Use Caution/Monitor.
- dexchlorpheniramine
chlorpheniramine and dexchlorpheniramine both increase sedation. Use Caution/Monitor.
dexchlorpheniramine and codeine both increase sedation. Use Caution/Monitor. - dexfenfluramine
chlorpheniramine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - dexmedetomidine
chlorpheniramine and dexmedetomidine both increase sedation. Use Caution/Monitor.
dexmedetomidine and codeine both increase sedation. Use Caution/Monitor. - dexmethylphenidate
chlorpheniramine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - dextroamphetamine
codeine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlorpheniramine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - dextromoramide
chlorpheniramine and dextromoramide both increase sedation. Use Caution/Monitor.
codeine and dextromoramide both increase sedation. Use Caution/Monitor. - diamorphine
chlorpheniramine and diamorphine both increase sedation. Use Caution/Monitor.
codeine and diamorphine both increase sedation. Use Caution/Monitor. - diazepam
chlorpheniramine and diazepam both increase sedation. Use Caution/Monitor.
diazepam and codeine both increase sedation. Use Caution/Monitor. - diazepam intranasal
diazepam intranasal, chlorpheniramine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.
- diethylpropion
codeine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- diethylpropion
chlorpheniramine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- difelikefalin
difelikefalin and codeine both increase sedation. Use Caution/Monitor.
difelikefalin and chlorpheniramine both increase sedation. Use Caution/Monitor. - difenoxin hcl
chlorpheniramine and difenoxin hcl both increase sedation. Use Caution/Monitor.
codeine and difenoxin hcl both increase sedation. Use Caution/Monitor. - dimenhydrinate
chlorpheniramine and dimenhydrinate both increase sedation. Use Caution/Monitor.
dimenhydrinate and codeine both increase sedation. Use Caution/Monitor. - diphenhydramine
diphenhydramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
diphenhydramine and codeine both increase sedation. Use Caution/Monitor.
chlorpheniramine and diphenhydramine both increase sedation. Use Caution/Monitor. - diphenoxylate hcl
codeine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
chlorpheniramine and diphenoxylate hcl both increase sedation. Use Caution/Monitor. - dipipanone
chlorpheniramine and dipipanone both increase sedation. Use Caution/Monitor.
codeine and dipipanone both increase sedation. Use Caution/Monitor. - dobutamine
codeine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlorpheniramine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - donepezil transdermal
donepezil transdermal, chlorpheniramine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.
- dopamine
codeine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dopamine
chlorpheniramine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dopexamine
chlorpheniramine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - dosulepin
chlorpheniramine and dosulepin both increase sedation. Use Caution/Monitor.
codeine and dosulepin both increase sedation. Use Caution/Monitor. - doxepin
codeine and doxepin both increase sedation. Use Caution/Monitor.
chlorpheniramine and doxepin both increase sedation. Use Caution/Monitor. - doxylamine
doxylamine and codeine both increase sedation. Use Caution/Monitor.
chlorpheniramine and doxylamine both increase sedation. Use Caution/Monitor. - dronedarone
dronedarone decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- droperidol
chlorpheniramine and droperidol both increase sedation. Use Caution/Monitor.
- droperidol
codeine and droperidol both increase sedation. Use Caution/Monitor.
- duloxetine
duloxetine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- efavirenz
efavirenz will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- elagolix
elagolix will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.
elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events. - ephedrine
chlorpheniramine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - epinephrine
codeine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlorpheniramine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - epinephrine racemic
chlorpheniramine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - esketamine intranasal
esketamine intranasal, chlorpheniramine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
esketamine intranasal, codeine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. - estazolam
estazolam and codeine both increase sedation. Use Caution/Monitor.
chlorpheniramine and estazolam both increase sedation. Use Caution/Monitor. - ethanol
chlorpheniramine and ethanol both increase sedation. Use Caution/Monitor.
codeine and ethanol both increase sedation. Use Caution/Monitor. - etomidate
etomidate and chlorpheniramine both increase sedation. Use Caution/Monitor.
etomidate and codeine both increase sedation. Use Caution/Monitor. - fedratinib
fedratinib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
fedratinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary. - fenfluramine
chlorpheniramine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - fentanyl
fentanyl, chlorpheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
- flibanserin
codeine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
- fentanyl intranasal
fentanyl intranasal, chlorpheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
- fentanyl transdermal
fentanyl transdermal, chlorpheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
- fentanyl transmucosal
fentanyl transmucosal, chlorpheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
- flibanserin
chlorpheniramine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
- fluoxetine
fluoxetine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine
- fluphenazine
chlorpheniramine and fluphenazine both increase sedation. Use Caution/Monitor.
codeine and fluphenazine both increase sedation. Use Caution/Monitor. - flurazepam
chlorpheniramine and flurazepam both increase sedation. Use Caution/Monitor.
flurazepam and codeine both increase sedation. Use Caution/Monitor. - formoterol
chlorpheniramine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - fosphenytoin
fosphenytoin will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- gabapentin
gabapentin, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- gabapentin
gabapentin, chlorpheniramine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- gabapentin enacarbil
gabapentin enacarbil, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
gabapentin enacarbil, chlorpheniramine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation. - ganaxolone
codeine and ganaxolone both increase sedation. Use Caution/Monitor.
chlorpheniramine and ganaxolone both increase sedation. Use Caution/Monitor. - glycopyrronium tosylate topical
glycopyrronium tosylate topical, chlorpheniramine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.
- haloperidol
haloperidol decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
codeine and haloperidol both increase sedation. Use Caution/Monitor. - gotu kola
gotu kola increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- haloperidol
chlorpheniramine and haloperidol both increase sedation. Use Caution/Monitor.
- hawthorn
hawthorn increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- hops
hops increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- hyaluronidase
chlorpheniramine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.
- hydromorphone
chlorpheniramine and hydromorphone both increase sedation. Use Caution/Monitor.
codeine and hydromorphone both increase sedation. Use Caution/Monitor. - hydroxyzine
chlorpheniramine and hydroxyzine both increase sedation. Use Caution/Monitor.
hydroxyzine and codeine both increase sedation. Use Caution/Monitor. - iloperidone
codeine and iloperidone both increase sedation. Use Caution/Monitor.
chlorpheniramine and iloperidone both increase sedation. Use Caution/Monitor.
iloperidone increases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4. - imipramine
codeine and imipramine both increase sedation. Use Caution/Monitor.
chlorpheniramine and imipramine both increase sedation. Use Caution/Monitor.
imipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine. - isoniazid
isoniazid decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- isoproterenol
chlorpheniramine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- isoproterenol
codeine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- istradefylline
istradefylline will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
- kava
kava increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- ketamine
ketamine and codeine both increase sedation. Use Caution/Monitor.
ketamine and chlorpheniramine both increase sedation. Use Caution/Monitor. - ketoconazole
ketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- ketotifen, ophthalmic
chlorpheniramine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
- ketotifen, ophthalmic
codeine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
- lasmiditan
lasmiditan, chlorpheniramine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
lasmiditan, codeine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions. - lemborexant
lemborexant, codeine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.
lemborexant, chlorpheniramine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects. - lenacapavir
lenacapavir will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- letermovir
letermovir increases levels of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- letermovir
letermovir increases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- levalbuterol
chlorpheniramine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - levoketoconazole
levoketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- levorphanol
chlorpheniramine and levorphanol both increase sedation. Use Caution/Monitor.
- levorphanol
codeine and levorphanol both increase sedation. Use Caution/Monitor.
- lisdexamfetamine
codeine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlorpheniramine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - lofepramine
chlorpheniramine and lofepramine both increase sedation. Use Caution/Monitor.
codeine and lofepramine both increase sedation. Use Caution/Monitor. - lofexidine
codeine and lofexidine both increase sedation. Use Caution/Monitor.
chlorpheniramine and lofexidine both increase sedation. Use Caution/Monitor. - lopinavir
lopinavir decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- loprazolam
chlorpheniramine and loprazolam both increase sedation. Use Caution/Monitor.
- loprazolam
loprazolam and codeine both increase sedation. Use Caution/Monitor.
- lorazepam
chlorpheniramine and lorazepam both increase sedation. Use Caution/Monitor.
lorazepam and codeine both increase sedation. Use Caution/Monitor. - lorcaserin
lorcaserin will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- lormetazepam
chlorpheniramine and lormetazepam both increase sedation. Use Caution/Monitor.
- lormetazepam
lormetazepam and codeine both increase sedation. Use Caution/Monitor.
- loxapine
chlorpheniramine and loxapine both increase sedation. Use Caution/Monitor.
codeine and loxapine both increase sedation. Use Caution/Monitor. - loxapine inhaled
codeine and loxapine inhaled both increase sedation. Use Caution/Monitor.
chlorpheniramine and loxapine inhaled both increase sedation. Use Caution/Monitor. - lumefantrine
lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- lurasidone
lurasidone, chlorpheniramine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.
- lurasidone
lurasidone, codeine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.
- maprotiline
chlorpheniramine and maprotiline both increase sedation. Use Caution/Monitor.
codeine and maprotiline both increase sedation. Use Caution/Monitor. - marijuana
chlorpheniramine and marijuana both increase sedation. Use Caution/Monitor.
codeine and marijuana both increase sedation. Use Caution/Monitor. - melatonin
chlorpheniramine and melatonin both increase sedation. Use Caution/Monitor.
codeine and melatonin both increase sedation. Use Caution/Monitor. - meperidine
codeine and meperidine both increase sedation. Use Caution/Monitor.
chlorpheniramine and meperidine both increase sedation. Use Caution/Monitor. - meprobamate
codeine and meprobamate both increase sedation. Use Caution/Monitor.
chlorpheniramine and meprobamate both increase sedation. Use Caution/Monitor. - metaproterenol
chlorpheniramine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - metaxalone
chlorpheniramine and metaxalone both increase sedation. Use Caution/Monitor.
metaxalone and codeine both increase sedation. Use Caution/Monitor. - methadone
chlorpheniramine and methadone both increase sedation. Use Caution/Monitor.
codeine and methadone both increase sedation. Use Caution/Monitor. - methamphetamine
chlorpheniramine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - methocarbamol
chlorpheniramine and methocarbamol both increase sedation. Use Caution/Monitor.
methocarbamol and codeine both increase sedation. Use Caution/Monitor. - methylenedioxymethamphetamine
chlorpheniramine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - midazolam
chlorpheniramine and midazolam both increase sedation. Use Caution/Monitor.
midazolam and codeine both increase sedation. Use Caution/Monitor. - midazolam intranasal
midazolam intranasal, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.
midazolam intranasal, chlorpheniramine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect. - midodrine
codeine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlorpheniramine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - mirabegron
mirabegron will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- mirtazapine
chlorpheniramine and mirtazapine both increase sedation. Use Caution/Monitor.
- mirtazapine
codeine and mirtazapine both increase sedation. Use Caution/Monitor.
- mitotane
mitotane decreases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.
- modafinil
codeine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlorpheniramine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - morphine
chlorpheniramine and morphine both increase sedation. Use Caution/Monitor.
codeine and morphine both increase sedation. Use Caution/Monitor. - motherwort
chlorpheniramine and motherwort both increase sedation. Use Caution/Monitor.
codeine and motherwort both increase sedation. Use Caution/Monitor. - moxonidine
codeine and moxonidine both increase sedation. Use Caution/Monitor.
chlorpheniramine and moxonidine both increase sedation. Use Caution/Monitor. - nabilone
codeine and nabilone both increase sedation. Use Caution/Monitor.
chlorpheniramine and nabilone both increase sedation. Use Caution/Monitor. - nalbuphine
codeine and nalbuphine both increase sedation. Use Caution/Monitor.
chlorpheniramine and nalbuphine both increase sedation. Use Caution/Monitor. - norepinephrine
codeine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlorpheniramine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - nortriptyline
codeine and nortriptyline both increase sedation. Use Caution/Monitor.
chlorpheniramine and nortriptyline both increase sedation. Use Caution/Monitor. - olanzapine
codeine and olanzapine both increase sedation. Use Caution/Monitor.
chlorpheniramine and olanzapine both increase sedation. Use Caution/Monitor. - oliceridine
oliceridine, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- opium tincture
chlorpheniramine and opium tincture both increase sedation. Use Caution/Monitor.
- opium tincture
codeine and opium tincture both increase sedation. Use Caution/Monitor.
- orphenadrine
orphenadrine and codeine both increase sedation. Use Caution/Monitor.
chlorpheniramine and orphenadrine both increase sedation. Use Caution/Monitor. - oxazepam
oxazepam and codeine both increase sedation. Use Caution/Monitor.
chlorpheniramine and oxazepam both increase sedation. Use Caution/Monitor. - oxycodone
chlorpheniramine and oxycodone both increase sedation. Use Caution/Monitor.
codeine and oxycodone both increase sedation. Use Caution/Monitor. - oxymorphone
codeine and oxymorphone both increase sedation. Use Caution/Monitor.
chlorpheniramine and oxymorphone both increase sedation. Use Caution/Monitor. - paliperidone
chlorpheniramine and paliperidone both increase sedation. Use Caution/Monitor.
codeine and paliperidone both increase sedation. Use Caution/Monitor. - papaveretum
codeine and papaveretum both increase sedation. Use Caution/Monitor.
chlorpheniramine and papaveretum both increase sedation. Use Caution/Monitor. - papaverine
chlorpheniramine and papaverine both increase sedation. Use Caution/Monitor.
codeine and papaverine both increase sedation. Use Caution/Monitor. - paroxetine
paroxetine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- passion flower
passion flower increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- peginterferon alfa 2b
peginterferon alfa 2b, codeine. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.
- pegvisomant
codeine decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.
- pentazocine
chlorpheniramine and pentazocine both increase sedation. Use Caution/Monitor.
codeine and pentazocine both increase sedation. Use Caution/Monitor. - pentobarbital
chlorpheniramine and pentobarbital both increase sedation. Use Caution/Monitor.
pentobarbital and codeine both increase sedation. Use Caution/Monitor. - perampanel
perampanel and codeine both increase sedation. Use Caution/Monitor.
- perphenazine
chlorpheniramine and perphenazine both increase sedation. Use Caution/Monitor.
- perphenazine
codeine and perphenazine both increase sedation. Use Caution/Monitor.
- phendimetrazine
codeine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlorpheniramine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - phenelzine
phenelzine increases effects of chlorpheniramine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration of phenelzine and antihistamines may result in additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .
- phenobarbital
phenobarbital and codeine both increase sedation. Use Caution/Monitor.
- phenobarbital
chlorpheniramine and phenobarbital both increase sedation. Use Caution/Monitor.
- phentermine
chlorpheniramine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - phenylephrine
chlorpheniramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - phenylephrine PO
codeine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .
chlorpheniramine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. . - pholcodine
chlorpheniramine and pholcodine both increase sedation. Use Caution/Monitor.
codeine and pholcodine both increase sedation. Use Caution/Monitor. - pimozide
codeine and pimozide both increase sedation. Use Caution/Monitor.
chlorpheniramine and pimozide both increase sedation. Use Caution/Monitor. - pirbuterol
codeine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlorpheniramine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - pregabalin
pregabalin, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
pregabalin, chlorpheniramine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation. - primidone
chlorpheniramine and primidone both increase sedation. Use Caution/Monitor.
primidone and codeine both increase sedation. Use Caution/Monitor. - prochlorperazine
chlorpheniramine and prochlorperazine both increase sedation. Use Caution/Monitor.
codeine and prochlorperazine both increase sedation. Use Caution/Monitor. - promethazine
chlorpheniramine and promethazine both increase sedation. Use Caution/Monitor.
promethazine and codeine both increase sedation. Use Caution/Monitor. - propofol
propofol and chlorpheniramine both increase sedation. Use Caution/Monitor.
propofol and codeine both increase sedation. Use Caution/Monitor. - propylhexedrine
codeine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlorpheniramine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - protriptyline
chlorpheniramine and protriptyline both increase sedation. Use Caution/Monitor.
codeine and protriptyline both increase sedation. Use Caution/Monitor. - quazepam
chlorpheniramine and quazepam both increase sedation. Use Caution/Monitor.
quazepam and codeine both increase sedation. Use Caution/Monitor. - quetiapine
codeine and quetiapine both increase sedation. Use Caution/Monitor.
chlorpheniramine and quetiapine both increase sedation. Use Caution/Monitor. - quinidine
quinidine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- ramelteon
chlorpheniramine and ramelteon both increase sedation. Use Caution/Monitor.
- ramelteon
codeine and ramelteon both increase sedation. Use Caution/Monitor.
- remimazolam
remimazolam, codeine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.
- ribociclib
ribociclib will increase the level or effect of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- risperidone
codeine and risperidone both increase sedation. Use Caution/Monitor.
chlorpheniramine and risperidone both increase sedation. Use Caution/Monitor. - ritonavir
ritonavir will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- rucaparib
rucaparib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- rolapitant
rolapitant will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.
- salmeterol
chlorpheniramine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - scullcap
codeine and scullcap both increase sedation. Use Caution/Monitor.
chlorpheniramine and scullcap both increase sedation. Use Caution/Monitor. - secobarbital
secobarbital and codeine both increase sedation. Use Caution/Monitor.
chlorpheniramine and secobarbital both increase sedation. Use Caution/Monitor. - selegiline
selegiline increases toxicity of codeine by unknown mechanism. Modify Therapy/Monitor Closely. Potential for increased CNS depression, drowsiness, dizziness or hypotension, so use with any MAOI should be cautious.
- sevoflurane
sevoflurane and chlorpheniramine both increase sedation. Use Caution/Monitor.
- sertraline
sertraline decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- sevoflurane
sevoflurane and codeine both increase sedation. Use Caution/Monitor.
- shepherd's purse
chlorpheniramine and shepherd's purse both increase sedation. Use Caution/Monitor.
codeine and shepherd's purse both increase sedation. Use Caution/Monitor. - stiripentol
stiripentol, codeine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.
stiripentol, chlorpheniramine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment. - sufentanil
codeine and sufentanil both increase sedation. Use Caution/Monitor.
chlorpheniramine and sufentanil both increase sedation. Use Caution/Monitor. - suvorexant
suvorexant and codeine both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary
- tapentadol
chlorpheniramine and tapentadol both increase sedation. Use Caution/Monitor.
- tapentadol
codeine and tapentadol both increase sedation. Use Caution/Monitor.
- tazemetostat
tazemetostat will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tecovirimat
tecovirimat will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
- temazepam
chlorpheniramine and temazepam both increase sedation. Use Caution/Monitor.
temazepam and codeine both increase sedation. Use Caution/Monitor. - terbinafine
terbinafine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.
- terbutaline
chlorpheniramine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- terbutaline
codeine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- thioridazine
thioridazine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
codeine and thioridazine both increase sedation. Use Caution/Monitor.
chlorpheniramine and thioridazine both increase sedation. Use Caution/Monitor. - thiothixene
chlorpheniramine and thiothixene both increase sedation. Use Caution/Monitor.
codeine and thiothixene both increase sedation. Use Caution/Monitor. - ticlopidine
ticlopidine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- topiramate
chlorpheniramine and topiramate both increase sedation. Modify Therapy/Monitor Closely.
- topiramate
codeine and topiramate both increase sedation. Modify Therapy/Monitor Closely.
- tramadol
chlorpheniramine and tramadol both increase sedation. Use Caution/Monitor.
codeine and tramadol both increase sedation. Use Caution/Monitor. - tranylcypromine
tranylcypromine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- trazodone
chlorpheniramine and trazodone both increase sedation. Use Caution/Monitor.
- trazodone
codeine and trazodone both increase sedation. Use Caution/Monitor.
- triazolam
chlorpheniramine and triazolam both increase sedation. Use Caution/Monitor.
triazolam and codeine both increase sedation. Use Caution/Monitor. - triclofos
triclofos and codeine both increase sedation. Use Caution/Monitor.
chlorpheniramine and triclofos both increase sedation. Use Caution/Monitor. - trifluoperazine
chlorpheniramine and trifluoperazine both increase sedation. Use Caution/Monitor.
codeine and trifluoperazine both increase sedation. Use Caution/Monitor. - trimipramine
codeine and trimipramine both increase sedation. Use Caution/Monitor.
chlorpheniramine and trimipramine both increase sedation. Use Caution/Monitor. - triprolidine
chlorpheniramine and triprolidine both increase sedation. Use Caution/Monitor.
triprolidine and codeine both increase sedation. Use Caution/Monitor. - valerian
valerian increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- venlafaxine
venlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- xylometazoline
chlorpheniramine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - yohimbine
codeine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlorpheniramine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - ziconotide
codeine and ziconotide both increase sedation. Use Caution/Monitor.
chlorpheniramine and ziconotide both increase sedation. Use Caution/Monitor. - ziprasidone
codeine and ziprasidone both increase sedation. Use Caution/Monitor.
chlorpheniramine and ziprasidone both increase sedation. Use Caution/Monitor. - zotepine
codeine and zotepine both increase sedation. Use Caution/Monitor.
chlorpheniramine and zotepine both increase sedation. Use Caution/Monitor.
Minor (27)
- acetazolamide
acetazolamide will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- asenapine
asenapine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- ashwagandha
ashwagandha increases effects of chlorpheniramine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.
- brimonidine
brimonidine increases effects of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.
brimonidine increases effects of chlorpheniramine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression. - cyclophosphamide
cyclophosphamide will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- dextroamphetamine
dextroamphetamine increases effects of codeine by unspecified interaction mechanism. Minor/Significance Unknown.
- eucalyptus
codeine and eucalyptus both increase sedation. Minor/Significance Unknown.
chlorpheniramine and eucalyptus both increase sedation. Minor/Significance Unknown. - fluoxetine
fluoxetine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
- larotrectinib
larotrectinib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- imatinib
imatinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
imatinib decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine. - levoketoconazole
levoketoconazole will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- lidocaine
lidocaine increases toxicity of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.
- maraviroc
maraviroc will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- marijuana
marijuana will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- nettle
nettle increases effects of chlorpheniramine by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.
- nilotinib
nilotinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- parecoxib
parecoxib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- perphenazine
perphenazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
perphenazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine. - propafenone
propafenone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
propafenone decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine. - quinacrine
quinacrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
quinacrine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine. - ranolazine
ranolazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- ribociclib
ribociclib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- sage
codeine and sage both increase sedation. Minor/Significance Unknown.
chlorpheniramine and sage both increase sedation. Minor/Significance Unknown. - Siberian ginseng
Siberian ginseng increases effects of chlorpheniramine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.
- sertraline
sertraline decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
- thioridazine
thioridazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
Adverse Effects
Frequency Not Defined
Allergic: Allergic laryngospasm, nasal stuffiness, bronchospastic allergic reaction, hives, itching, swelling of face
Body as a whole: Asthenia, feeling of relaxation, redness or flushing of the face, unusual tiredness, weakness
Cardiovascular: Fast or slow heartbeat, hypertension, hypotension, orthostatic hypotension, palpitations, shock-like state, syncope
Dermatological system: Skin rash, pruritus, erythema, urticaria, excessive perspiration, dermatitis
Endocrine system: Changes in glucose utilization, decreased lactation, early menses, glycosuria, gynecomastia, hypoglycemia, increased appetite, increased libido, pheochromocytoma stimulation
Gastrointestinal system: Nausea and vomiting, constipation, abdominal distension, abdominal pain, acute pancreatitis, dry mouth, dyspepsia, epigastric distress, loss of appetite, diarrhea, gastro-esophageal reflux, gastrointestinal hypomotility
Genitourinary system: Ureteral spasm, urinary retention, dysuria, urinary frequency, urinary hesitancy, irritative bladder symptom
Nervous system: Blurred vision, diplopia, visual disturbances, confusion, dizziness, depression, drowsiness, sedation, headache, euphoria, facial dyskinesia, false sense of well-being, feeling faint, lightheadedness, general feeling of discomfort or illness, excitability, nervousness, agitation, restlessness, somnolence, insomnia, dyskinesia, irritability, tremor
Respiratory: Dryness of the pharynx and respiratory passages, laryngismus, atelectasis, wheezing, troubled breathing, respiratory depression, hiccups
Special senses: Labyrinthitis, tinnitus, vertigo, hypermetropia, increased lacrimation, mydriasis, photophobia
Warnings
Black Box Warnings
Opioid analgesic risk evaluation and mitigation strategy (REMS)
- To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products; under requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers
-
Healthcare providers are strongly encouraged to:
- Complete a REMS-compliant education program
- Counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products
- Emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist
- Consider other tools to improve patient, household, and community safety
Addiction, abuse, and misuse
- Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death; assess each patient’s risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions
Life-threatening respiratory depression
- Serious, life-threatening, or fatal respiratory depression may occur
- Monitor for respiratory depression, especially during initiation or following a dose increase
Accidental ingestion
- Accidental ingestion of even 1 dose, especially by children, can result in a fatal overdose
Neonatal opioid withdrawal syndrome
- Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
- If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available
Ultra-rapid metabolism of codeine and other risk factors for life-threatening respiratory depression in children
- Respiratory depression and death reported in children who received codeine following tonsillectomy and/or adenoidectomy that were also ultra-rapid metabolizers of codeine due to CYP2D6 polymorphism
- Contraindicated in children <12 years and in children <18 years following tonsillectomy and/or adenoidectomy; avoid use in adolescents 12-18 years who have risk factors that may increase sensitivity to respiratory depressant effects of codeine
Interactions with drugs affecting cytochrome P450 isoenzymes
- Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors requires careful consideration of the effects on parent drug, codeine, and active metabolite, morphine
Risks from concomitant use with benzodiazepines or other CNS depressants
- Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death
- Reserve concomitant prescribing of codeine sulfate tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate
- Limit dosages and durations to minimum required
- Follow patients for signs and symptoms of respiratory depression and sedation
Contraindications
Known hypersensitivity to codeine, chlorpheniramine, or product components
Children <12 years
Post-operative management in children <18 years following tonsillectomy and/or adenoidectomy
Patients with significant respiratory depression, acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within last 14 days
Known or suspected gastrointestinal obstruction, including paralytic ileus
Persons known to be hypersensitive to other opioids exhibiting cross-sensitivity to codeine
Cautions
Respiratory depression and death have occurred in children who received codeine in the postoperative period following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine (ie, multiple copies of the gene for CYP2D6 or high morphine concentrations) (see Black Box Warnings and Contraindications)
Deaths have also occurred in nursing infants who were exposed to high levels of morphine in breast milk because their mothers were ultra-rapid metabolizers of codeine
Avoid use in adolescents 12-18 years of age who have other risk factors that may increase sensitivity to respiratory depressant effects of codeine unless benefits outweigh risks; risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression; when prescribing codeine for adolescents, healthcare providers should choose lowest effective dose for shortest period of time and inform patients and caregivers about risks and the signs of morphine overdose
Produces dose-related respiratory depression (fatalities reported) by directly acting on brain stem respiratory centers; may produce irregular and periodic breathing
At least one death was reported in a nursing infant who was exposed to high levels of morphine in breast milk because mother was an ultra-rapid metabolizer of codeine; breastfeeding not recommended during treatment
Potential for dependence and abuse
Avoid use with head injuries; opioids produce adverse reactions that may obscure the clinical course of patients with head injuries
Codeine and chlorpheniramine produce drowsiness and may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks (driving, operating machinery)
Long-term use of opioids, including codeine, may result in constipation or obstructive bowel disease
Caution with acute abdominal conditions since the codeine may obscure the diagnosis or clinical course of patients with acute abdominal conditions; concurrent use of other anticholinergics with codeine may produce paralytic ileus
Caution in elderly or debilitated patients and those with asthma, persistent or chronic cough, hypothyroidism, Addison disease, prostatic hypertrophy, or urethral stricture
Both codeine and chlorpheniramine are extensively metabolized by the liver; caution with severe hepatic impairment
Concomitant use of opioids, with benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; because of these risks, avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol
Avoid in patients with head injury, intra-cranial lesions, or increased intracranial pressure
Avoid concurrent use of alcohol or other central nervous system depressants
Measure dose only with an accurate mL measuring device
Pregnancy & Lactation
Pregnancy
Codeine
- As with all opioids, administration of codeine to the mother shortly before delivery may result in some degree of respiratory depression in the newborn, especially if higher doses are used
- Babies born to mothers who have been taking opioids regularly prior to delivery will be physically dependent
- Withdrawal signs include irritability and excessive crying, tremors, hyperactive reflexes, increased respiratory rate, increased stools, sneezing, yawning, vomiting, and fever
Labor and delivery
- Use of codeine during labor may lead to respiratory depression in the neonate; opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate; use is not recommended in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate; opioid analgesics, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by increased rate of cervical dilation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression
Chlorpheniramine
- A retrospective study found a small, but statistically significant, association between maternal use of chlorpheniramine and inguinal hernia and eye or ear anomalies in children
Lactation
Codeine and its active metabolite, morphine, are present in human milk; there are published studies and cases that have reported excessive sedation, respiratory depression, and death in infants exposed to codeine via breast milk; women who are ultra-rapid metabolizers of codeine achieve higher than expected serum levels of morphine, potentially leading to higher levels of morphine in breast milk that can be dangerous in their breastfed infants
Use caution if administered to a nursing woman; prescribe the lowest dose for shortest period of time to achieve desired effect; inform mothers when to seek immediate medical care and how to identify signs and symptoms of neonatal toxicity (eg, drowsiness or sedation, difficulty breastfeeding, breathing difficulties, and decreased tone)
In women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and dose-dependent
There is no information on effects of codeine milk production; because of potential for serious adverse reactions, including excess sedation, respiratory depression, and death in a breastfed infant, breastfeeding is not recommended during treatment
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Codeine: Semisynthetic narcotic antitussive and analgesic with multiple actions qualitatively similar to those of morphine; believed to act centrally on the cough center
Chlorpheniramine: Propylamine derivative antihistamine drug (H1 receptor antagonist) that also possesses anticholinergic and sedative activity; prevents released histamine from dilating capillaries and causing edema of the respiratory mucosa
Absorption
Peak plasma time
- Codeine: 2.19 hr
- Chlorpheniramine: 6.52 hr
Peak plasma concentration
- Codeine: 51.4 ng/mL
- Chlorpheniramine: 7.84 ng/mL
AUC
- Codeine: 348.5 ng•h/mL
- Chlorpheniramine: 304.3 ng•h/mL
Distribution
Protein bound
- Codeine: 7-25%
- Chlorpheniramine: 70%
Vd
- Codeine: 3-6 L/kg
- Chlorpheniramine: 3.2 L/kg
Metabolism
Codeine
- ~70-80% is metabolized by conjugation with glucuronic acid to codeine-6glucuronide (C6G) and via O-demethylation to morphine (~5-10%) and N-demethylation to norcodeine (~10%) respectively
- UDP-glucuronosyltransferase (UGT) 2B7 and 2B4 are the major enzymes mediating glucurodination of codeine to C6G
- CYP2D6 and CYP3A4 are the major enzymes mediating O-demethylation and N-demethylation of codeine, respectively
- Morphine and norcodeine are further metabolized by conjugation with glucuronic acid
- Morphine and its M6 glucuronide conjugate are pharmacologically active
- Whether C6G has pharmacological activity is unknown
- Norcodeine and M3 glucuronide conjugate of morphine are generally not considered to be pharmacologically active
Chlorpheniramine
- Rapidly and extensively metabolized via demethylation in the liver, forming monodesmethyl and didesmethyl derivatives
- Oxidative metabolism of chlorpheniramine is catalyzed by CYP2D6
Elimination
Half-life
- Codeine: 5 hr
- Chlorpheniramine: 21.45 hr
Excretion
- Codeine: 90% urine (~10% as unchanged drug)
- Chlorpheniramine: Drug and its metabolites are primarily excreted through the kidneys, with large individual variation that depends on urine pH and flow rate
Pharmacogenomics
5-10% of codeine is metabolized to morphine by CYP2D6; the active morphine metabolite has a higher affinity for opioid receptors
CYP2D6 poor metabolizers may not achieve adequate analgesia
Ultra-rapid metabolizers (up to 7% of whites and up to 30% of Asian and African populations) may have increased toxicity due to rapid conversion
Administration
Instructions
Take with or without food
Shake well before measuring dose
Measure with an accurate mL measuring device; do not use a household teaspoon to measure the dose
Storage
Room temperature at 20-25°C (68-77°F); excursions permitted from 15-30°C (59-86°F)
Images
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.