Dosing & Uses
Dosage Forms & Strengths
codeine/guaifenesin
Schedule V
oral liquid
- (6.3mg/100mg)/5mL
- (8mg/200mg)/5mL
- (10mg/200mg)/5mL
- (10mg/100mg)/5mL
- (10mg/300mg)/5mL
oral solution
- (10mg/100mg)/5mL
- (7.5mg/225mg)/5mL
oral syrup
- (10mg/100mg)/5mL
Cough
Temporary control of cough caused by minor throat and bronchial irritation
Loosens mucus and thins bronchial secretions
5 mL [(6.3mg/100mg)/5mL] PO q4-6hr; not to exceed 90 mL/day
5-7.5 mL [(7.5mg/225mg)/5mL] PO q4hr; not to exceed 45 mL/day
10 mL [(8mg-10mg)/100 mg - 200 mg)]/5 mL PO q4hr; not to exceed 60 mL/day
5 mL [(10mg/300mg)/5 mL] PO q4hr; not to exceed 40 mL/day
5 mL [(20 mg/200 mg)/5 mL] PO q4-6hr; not to exceed 30 mL/day
Dosage Forms & Strengths
codeine/guaifenesin
Schedule V
liquid
- (6.3mg/100mg)/5mL
- (8mg/200mg)/5mL
- (10mg/100mg)/5mL
- (10mg/200mg)/5mL
- (10mg/300mg)/5mL
oral solution
- (10mg/100mg)/5mL
- (7.5mg/225mg)/5mL
oral syrup
- (10mg/100mg)/5mL
Cough
Temporary control of cough caused by minor throat and bronchial irritation
Loosens mucus and thins bronchial secretions
<12 years
- Not recommended
≥12 years
- 5 mL [(6.3mg/100mg)/5mL] PO q4-6hr; not to exceed 90 mL/day
- 5-7.5 mL [(7.5mg/225mg)/5mL] PO q4hr; not to exceed 45 mL/day
- 10 mL [(8mg-10mg)/100 mg - 200 mg)]/5 mL PO q4hr; not to exceed 60 mL/day
- 5 mL [(10mg/300mg)/5 mL] PO q4hr; not to exceed 40 mL/day
- 5 mL [(20 mg/200 mg)/5 mL] PO q4-6hr; not to exceed 30 mL/day
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 (35)
- benzhydrocodone/acetaminophen
benzhydrocodone/acetaminophen, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- bremelanotide
bremelanotide will decrease the level or effect of codeine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.
- 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.
- butorphanol
butorphanol, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- calcium/magnesium/potassium/sodium oxybates
codeine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- 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
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.
- 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.
- isocarboxazid
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.
- 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
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.
- 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
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.
- 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.
- valerian
valerian and codeine both increase sedation. Avoid or Use Alternate Drug.
Monitor Closely (225)
- 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.
- albuterol
codeine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- alfentanil
alfentanil and codeine both increase sedation. Use Caution/Monitor.
- alprazolam
alprazolam and codeine both increase sedation. Use Caution/Monitor.
- amiodarone
amiodarone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- amitriptyline
codeine and amitriptyline both increase sedation. Use Caution/Monitor.
- amobarbital
amobarbital and codeine both increase sedation. Use Caution/Monitor.
- amoxapine
codeine and amoxapine both increase sedation. Use Caution/Monitor.
- apomorphine
codeine and apomorphine both increase sedation. Use Caution/Monitor.
- arformoterol
codeine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- aripiprazole
codeine 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.
- artemether/lumefantrine
artemether/lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- azelastine
azelastine and codeine both increase sedation. Use Caution/Monitor.
- baclofen
baclofen and codeine both increase sedation. Use Caution/Monitor.
- belladonna and opium
codeine and belladonna and opium both increase sedation. Use Caution/Monitor.
- benperidol
codeine and benperidol both increase sedation. Use Caution/Monitor.
- benzphetamine
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.
- brompheniramine
brompheniramine and codeine both increase sedation. Use Caution/Monitor.
- buprenorphine
buprenorphine and codeine both increase sedation. Use Caution/Monitor.
- buprenorphine buccal
buprenorphine buccal and codeine both increase sedation. Use Caution/Monitor.
- buprenorphine, long-acting injection
codeine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.
- bupropion
bupropion will 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
butalbital and codeine both increase sedation. Use Caution/Monitor.
- butorphanol
butorphanol and codeine both increase sedation. Use Caution/Monitor.
- caffeine
codeine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- carbinoxamine
carbinoxamine and codeine both increase sedation. Use Caution/Monitor.
- carisoprodol
carisoprodol and codeine both increase sedation. Use Caution/Monitor.
- celecoxib
celecoxib decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- cenobamate
cenobamate, codeine. Either increases effects of the other by sedation. Use Caution/Monitor.
- chloral hydrate
chloral hydrate and codeine both increase sedation. Use Caution/Monitor.
- chlordiazepoxide
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.
- 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.
- cimetidine
cimetidine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- cinacalcet
cinacalcet decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- cinnarizine
cinnarizine and codeine both increase sedation. Use Caution/Monitor.
- clemastine
clemastine and codeine both increase sedation. Use Caution/Monitor.
- clobazam
codeine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
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.
clomipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine. - clonazepam
clonazepam and codeine both increase sedation. Use Caution/Monitor.
- clorazepate
clorazepate and codeine both increase sedation. Use Caution/Monitor.
- clozapine
codeine 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
cocaine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- cyclizine
cyclizine and codeine both increase sedation. Use Caution/Monitor.
- cyclobenzaprine
cyclobenzaprine and codeine both increase sedation. Use Caution/Monitor.
- cyproheptadine
cyproheptadine and codeine both increase sedation. Use Caution/Monitor.
- dantrolene
dantrolene and codeine both increase sedation. Use Caution/Monitor.
- daridorexant
codeine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
- 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 codeine both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.
- desipramine
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
codeine and deutetrabenazine both increase sedation. Use Caution/Monitor.
- dexchlorpheniramine
dexchlorpheniramine and codeine both increase sedation. Use Caution/Monitor.
- dexfenfluramine
codeine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dexmedetomidine
dexmedetomidine and codeine both increase sedation. Use Caution/Monitor.
- dexmethylphenidate
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.
- dextromoramide
codeine and dextromoramide both increase sedation. Use Caution/Monitor.
- diamorphine
codeine and diamorphine both increase sedation. Use Caution/Monitor.
- diazepam
diazepam and codeine both increase sedation. Use Caution/Monitor.
- diethylpropion
codeine 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.
- difenoxin hcl
codeine and difenoxin hcl both increase sedation. Use Caution/Monitor.
- dimenhydrinate
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. - diphenoxylate hcl
codeine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
- dipipanone
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.
- dopamine
codeine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dopexamine
codeine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dosulepin
codeine and dosulepin both increase sedation. Use Caution/Monitor.
- doxepin
codeine and doxepin both increase sedation. Use Caution/Monitor.
- doxylamine
doxylamine and codeine 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
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.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
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
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.
- epinephrine racemic
codeine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- esketamine intranasal
esketamine intranasal, codeine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- estazolam
estazolam and codeine both increase sedation. Use Caution/Monitor.
- ethanol
codeine and ethanol both increase sedation. Use Caution/Monitor.
- etomidate
etomidate and codeine both increase sedation. Use Caution/Monitor.
- fedratinib
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
codeine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- flibanserin
codeine 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
codeine and fluphenazine both increase sedation. Use Caution/Monitor.
- flurazepam
flurazepam and codeine both increase sedation. Use Caution/Monitor.
- formoterol
codeine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. 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 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.
- ganaxolone
codeine and ganaxolone both increase sedation. Use Caution/Monitor.
- haloperidol
haloperidol decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
codeine and haloperidol both increase sedation. Use Caution/Monitor. - hydromorphone
codeine and hydromorphone both increase sedation. Use Caution/Monitor.
- hydroxyzine
hydroxyzine and codeine both increase sedation. Use Caution/Monitor.
- iloperidone
codeine and iloperidone both increase sedation. Use Caution/Monitor.
- imipramine
codeine 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
codeine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- ketamine
ketamine and codeine both increase sedation. Use Caution/Monitor.
- ketoconazole
ketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- ketotifen, ophthalmic
codeine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
- lasmiditan
lasmiditan, codeine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
- 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.
- letermovir
letermovir increases levels of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- levalbuterol
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
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.
- lofepramine
codeine and lofepramine both increase sedation. Use Caution/Monitor.
- lofexidine
codeine and lofexidine both increase sedation. Use Caution/Monitor.
- lopinavir
lopinavir decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- loprazolam
loprazolam and codeine both increase sedation. Use Caution/Monitor.
- lorazepam
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
lormetazepam and codeine both increase sedation. Use Caution/Monitor.
- loxapine
codeine and loxapine both increase sedation. Use Caution/Monitor.
- loxapine inhaled
codeine 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, 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
codeine and maprotiline both increase sedation. Use Caution/Monitor.
- marijuana
codeine and marijuana both increase sedation. Use Caution/Monitor.
- melatonin
codeine and melatonin both increase sedation. Use Caution/Monitor.
- meperidine
codeine and meperidine both increase sedation. Use Caution/Monitor.
- meprobamate
codeine and meprobamate both increase sedation. Use Caution/Monitor.
- metaproterenol
codeine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- metaxalone
metaxalone and codeine both increase sedation. Use Caution/Monitor.
- methadone
codeine and methadone both increase sedation. Use Caution/Monitor.
- methamphetamine
codeine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- methocarbamol
methocarbamol and codeine both increase sedation. Use Caution/Monitor.
- methylenedioxymethamphetamine
codeine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- midazolam
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.
- midodrine
codeine 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
codeine and mirtazapine both increase sedation. Use Caution/Monitor.
- modafinil
codeine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- morphine
codeine and morphine both increase sedation. Use Caution/Monitor.
- motherwort
codeine and motherwort both increase sedation. Use Caution/Monitor.
- moxonidine
codeine and moxonidine both increase sedation. Use Caution/Monitor.
- nabilone
codeine and nabilone both increase sedation. Use Caution/Monitor.
- nalbuphine
codeine 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.
- nortriptyline
codeine and nortriptyline both increase sedation. Use Caution/Monitor.
- olanzapine
codeine 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
codeine and opium tincture both increase sedation. Use Caution/Monitor.
- orphenadrine
orphenadrine and codeine both increase sedation. Use Caution/Monitor.
- oxazepam
oxazepam and codeine both increase sedation. Use Caution/Monitor.
- oxycodone
codeine and oxycodone both increase sedation. Use Caution/Monitor.
- oxymorphone
codeine and oxymorphone both increase sedation. Use Caution/Monitor.
- paliperidone
codeine and paliperidone both increase sedation. Use Caution/Monitor.
- papaveretum
codeine and papaveretum both increase sedation. Use Caution/Monitor.
- papaverine
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.
- 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
codeine and pentazocine both increase sedation. Use Caution/Monitor.
- pentobarbital
pentobarbital and codeine both increase sedation. Use Caution/Monitor.
- perampanel
perampanel and codeine 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.
- phenobarbital
phenobarbital and codeine both increase sedation. Use Caution/Monitor.
- phentermine
codeine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- phenylephrine
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. .
- pholcodine
codeine and pholcodine both increase sedation. Use Caution/Monitor.
- pimozide
codeine 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.
- 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.
- primidone
primidone and codeine both increase sedation. Use Caution/Monitor.
- prochlorperazine
codeine and prochlorperazine both increase sedation. Use Caution/Monitor.
- promethazine
promethazine and codeine both increase sedation. Use Caution/Monitor.
- propofol
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.
- protriptyline
codeine and protriptyline both increase sedation. Use Caution/Monitor.
- quazepam
quazepam and codeine both increase sedation. Use Caution/Monitor.
- quetiapine
codeine 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
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.
- 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.
- 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
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.
- secobarbital
secobarbital and codeine 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.
- 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
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.
- sufentanil
codeine 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
codeine and tapentadol both increase sedation. Use Caution/Monitor.
- temazepam
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
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. - thiothixene
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
codeine and topiramate both increase sedation. Modify Therapy/Monitor Closely.
- tramadol
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
codeine and trazodone both increase sedation. Use Caution/Monitor.
- triazolam
triazolam and codeine both increase sedation. Use Caution/Monitor.
- triclofos
triclofos and codeine both increase sedation. Use Caution/Monitor.
- trifluoperazine
codeine and trifluoperazine both increase sedation. Use Caution/Monitor.
- trimipramine
codeine and trimipramine both increase sedation. Use Caution/Monitor.
- triprolidine
triprolidine and codeine both increase sedation. Use Caution/Monitor.
- venlafaxine
venlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- xylometazoline
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.
- ziconotide
codeine and ziconotide both increase sedation. Use Caution/Monitor.
- ziprasidone
codeine and ziprasidone both increase sedation. Use Caution/Monitor.
- zotepine
codeine and zotepine both increase sedation. Use Caution/Monitor.
Minor (21)
- asenapine
asenapine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- brimonidine
brimonidine increases effects of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.
- dextroamphetamine
dextroamphetamine increases effects of codeine by unspecified interaction mechanism. Minor/Significance Unknown.
- eucalyptus
codeine 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.
- 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. - 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.
- 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.
- sage
codeine and sage both increase sedation. Minor/Significance Unknown.
- sertraline
sertraline decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
- thioridazine
thioridazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
- tipranavir
tipranavir will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- venlafaxine
venlafaxine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
- ziconotide
ziconotide, codeine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.
Adverse Effects
>10%
Codeine
- Drowsiness
- Constipation
1-10%
Codeine
- Bradycardia, hypotension, tachycardia
- Confusion, dizziness, false feeling of well being, headache, lightheadedness, malaise, paradoxical CNS stimulation, restlessness, weakness
- Rash, urticaria
- Anorexia, nausea, vomiting, xerostomia
- LFT's increased
- Ureteral spasm, urination decreased
- Dyspnea
- Burning at injection site, blurred vision, histamine release
Frequency Not Defined
Codeine (serious)
- Hypotension, with IV use
- Seizure, with excessive doses
- Anaphylactoid reaction (rare)
- Respiratory depression
Guaifensesin
- Headache
- Rash
- Nausea
- Vomiting
Warnings
Contraindications
Codeine
- Absolute: Acute abdominal condition, diarrhea associated with toxins, pseudomembranous colitis, respiratory depression
- Relative: Asthma (acute), inflammatory bowel disease, respiratory impairment
Guaifenesin
- Do not use as self-medication in chronic or persistent coughs
- Hypersensitivity
Cautions
Use caution in cardiac arrhythmias, emotional lability, gallbladder disease, hepatic impairment, renal impairment, surethral stricture, urinary tract surgery
Ibuprofen is more effective than codeine for pain from musculoskeletal injuries in children
Children are particularly sensitive to the respiratory depressant effects of codeine; because of risk of life-threatening respiratory depression and death, the use of codeine products is contraindicated in children less than 12 years of age, and in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy
Use in children also exposes them to risks of addiction, abuse, and misuse, which can lead to overdose and death; because benefits of symptomatic treatment of cough associated with allergies or common cold do not outweigh risks of use of codeine in pediatric patients, use is not indicated in patients younger than 18 years of age
Life-threatening respiratory depression and death have occurred in children who received codeine; codeine is subject to variability in metabolism based upon CYP2D6 genotype; based upon post-marketing reports, children < 12 years appear to be more susceptible to respiratory depressant effects of codeine, particularly if there are risk factors for respiratory depression; cases of death have been reported in the post-operative period following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being ultra-rapid metabolizers of codeine
Children with obstructive sleep apnea who are treated with codeine for post-tonsillectomy and/or adenoidectomy pain may be particularly sensitive to its respiratory depressant effect; because of risk of life-threatening respiratory depression and death: codeine is contraindicated in all children younger than 12 years of age; it is also contraindicated for post-operative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy
Avoid the use of codeine in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to respiratory depressant effects of codeine; 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.
Healthcare providers should choose lowest effective dose for shortest period of time and inform patients and caregivers about these risks and signs of opioid overdose
Dosage should not be increased if cough fails to respond; an unresponsive cough should be reevaluated in 5 days or sooner for possible underlying pathology, such as foreign body or lower respiratory tract disease
Therapy in patients with acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment is contraindicated
Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients
The active ingredients may produce marked drowsiness and impair mental and/or physical abilities required for performance of potentially hazardous tasks such as driving a car or operating machinery
Codeine is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus; the use of codeine may obscure the diagnosis or clinical course of patients with acute abdominal conditions; the concurrent use of anticholinergics may produce paralytic ileus
Codeine therapy may result in constipation or obstructive bowel disease, especially in patients with underlying intestinal motility disorders; use with caution in patients with underlying intestinal motility disorders
Avoid therapy in patients with head injury, intracranial lesions, or a pre-existing increase in intracranial pressure; in patients who may be susceptible to intracranial effects of CO2 retention may reduce respiratory drive, and resultant CO2 retention can further increase intracranial pressure; opioids also produce adverse reactions that may obscure clinical course of patients with head injuries
The codeine may increase frequency of seizures in patients with seizure disorders, and may increase risk of seizures occurring in other clinical settings associated with seizures; monitor patients with a history of seizure disorders for worsened seizure control during therapy
Use is contraindicated in patients receiving monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping such therapy; MAOIs may potentiate effects of codeine’s active metabolite, including respiratory depression, coma, and confusion
May cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients; there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) monitor these patients for signs of hypotension after initiating therapy
Not recommended for use in pregnant women; Prolonged use during pregnancy can result in withdrawal in the neonate; neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use; if adrenal insufficiency is suspected, confirm diagnosis with diagnostic testing as soon as possible; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean patient off of opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers
Guaifenesin is often included in combos, check brand name/other constituents
Pregnancy & Lactation
Pregnancy category: C; category D if used for prolonged periods or in high doses at term
Lactation: excreted in breast milk; caution advised
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
- Narcotic agonist analgesic with antitussive activity, mu receptor agonist
Guaifenesin
- Reduces viscosity of secretions by increasing amount of respiratory tract fluid
Absorption
Codeine
- Onset: 30-60 min
- Duration: 4-6 hr
Guaifenesin
- Onset: 30 min
- Duration: 4-6 hr
Distribution
Codeine
- Peak plasma time: 0.5-1 hr
- Protein bound: 25%
Metabolism
Codeine
- Inactive but metabolized to morphine by CYP2D6 (missing in 5-10% of population)
Guaifenesin
- Metabolism: Liver
- Metabolite: b-(2-methoxyphenoxy) lactic acid
Elimination
Codeine
- Half-life: 3-4 hr
- Excretion: urine, feces
Guaifenesin
- Half-life: 1 hr
- Excretion: Urine
Administration
Oral Administration
Give with food or milk if GI upset
Administer with special measuring device for accurate dose
Images
Formulary
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