What is Codeine
Codeine is an opiate agonist and is similar to other phenanthrene derivatives.
Codeine, alone or in combination with other drugs, is used both as an antitussive and as an analgesic for mild to moderate pain.
Codeine is a prodrug that must be hepatically metabolized to morphine to provide effective analgesia.
Codeine metabolism is highly variable and unpredictable, particularly in children younger than 12 years; therapeutic response to recommended doses can range from lack of effect in poor metabolizers to fatality in ultra-rapid metabolizers.
Codeine use is contraindicated in pediatric patients younger than 12 years.
The American Academy of Pediatrics (AAP) recommends against the use of codeine in all pediatric patients for any indication.
Codeine has a high oral bioavailability similar to levorphanol, oxycodone, and methadone.
Indications
- arthralgia
- bone pain
- cough
- dental pain
- diarrhea
- headache
- migraine
- mild pain
- moderate pain
- myalgia
Side Effects
- abdominal pain
- adrenocortical insufficiency
- agitation
- amenorrhea
- anorexia
- anxiety
- apnea
- biliary obstruction
- blurred vision
- bradycardia
- cardiac arrest
- confusion
- constipation
- diaphoresis
- diarrhea
- dizziness
- drowsiness
- dysphoria
- dyspnea
- edema
- euphoria
- flushing
- gastritis
- gonadal suppression
- hallucinations
- headache
- hyperamylasemia
- hypertension
- hyponatremia
- hypotension
- impotence (erectile dysfunction)
- infertility
- insomnia
- libido decrease
- miosis
- nausea
- neonatal opioid withdrawal syndrome
- orthostatic hypotension
- palpitations
- pancreatitis
- physiological dependence
- pruritus
- psychological dependence
- rash
- respiratory arrest
- respiratory depression
- restlessness
- seizures
- serotonin syndrome
- SIADH
- sinus tachycardia
- syncope
- tolerance
- urinary retention
- urticaria
- vertigo
- vomiting
- weakness
- withdrawal
- xerostomia
Monitoring Parameters
- laboratory monitoring not necessary
Contraindications
- abrupt discontinuation
- acute abdomen
- adenoidectomy
- adrenal insufficiency
- alcoholism
- angina
- Asian patients
- asthma
- biliary tract disease
- Black patients
- bladder obstruction
- breast-feeding
- cardiac arrhythmias
- cardiac disease
- Caucasian patients
- children
- chronic obstructive pulmonary disease (COPD)
- coadministration with other CNS depressants
- constipation
- cor pulmonale
- diarrhea
- driving or operating machinery
- geriatric
- GI disease
- GI obstruction
- head trauma
- heart failure
- hepatic disease
- Hispanic patients
- hypotension
- hypothyroidism
- hypovolemia
- hypoxemia
- ileus
- increased intracranial pressure
- infants
- inflammatory bowel disease
- jaundice
- labor
- MAOI therapy
- myxedema
- neonatal opioid withdrawal syndrome
- neonates
- neuromuscular disease
- obesity
- obstetric delivery
- oliguria
- opiate agonist hypersensitivity
- pregnancy
- prostatic hypertrophy
- pulmonary disease
- renal disease
- renal failure
- renal impairment
- respiratory depression
- respiratory infection
- respiratory insufficiency
- scoliosis
- seizure disorder
- seizures
- sleep apnea
- status asthmaticus
- substance abuse
- sulfite hypersensitivity
- tonsillectomy
- ulcerative colitis
- urethral stricture
- urinary retention
Interactions
- Abiraterone
- Acetaminophen; Butalbital
- Acetaminophen; Butalbital; Caffeine
- Acetaminophen; Butalbital; Caffeine; Codeine
- Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
- Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine
- Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine
- Acetaminophen; Dextromethorphan
- Acetaminophen; Dextromethorphan; Doxylamine
- Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine
- Acetaminophen; Dextromethorphan; Phenylephrine
- Acetaminophen; Dextromethorphan; Pseudoephedrine
- Acetaminophen; Diphenhydramine
- Acetaminophen; Hydrocodone
- Acetaminophen; Oxycodone
- Acetaminophen; Pentazocine
- Acetaminophen; Tramadol
- Acrivastine; Pseudoephedrine
- Aldesleukin, IL-2
- Aliskiren; Amlodipine
- Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ
- Aliskiren; Hydrochlorothiazide, HCTZ
- Almotriptan
- Alosetron
- Alprazolam
- Alvimopan
- Amide local anesthetics
- Amifampridine
- Amiloride
- Amiloride; Hydrochlorothiazide, HCTZ
- Amiodarone
- Amitriptyline
- Amitriptyline; Chlordiazepoxide
- Amlodipine
- Amlodipine; Atorvastatin
- Amlodipine; Benazepril
- Amlodipine; Celecoxib
- Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan
- Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan
- Amlodipine; Olmesartan
- Amlodipine; Telmisartan
- Amlodipine; Valsartan
- Amobarbital
- Amoxapine
- Amoxicillin; Clarithromycin; Lansoprazole
- Amoxicillin; Clarithromycin; Omeprazole
- Anticholinergics
- Apalutamide
- Apomorphine
- Apraclonidine
- Aprepitant, Fosaprepitant
- Aripiprazole
- Artemether; Lumefantrine
- Articaine; Epinephrine
- Asenapine
- Aspirin, ASA; Butalbital; Caffeine
- Aspirin, ASA; Butalbital; Caffeine; Codeine
- Aspirin, ASA; Caffeine; Orphenadrine
- Aspirin, ASA; Carisoprodol
- Aspirin, ASA; Carisoprodol; Codeine
- Aspirin, ASA; Oxycodone
- Atazanavir
- Atazanavir; Cobicistat
- Atenolol; Chlorthalidone
- Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
- Atropine; Difenoxin
- Atropine; Diphenoxylate
- Atropine; Hyoscyamine; Phenobarbital; Scopolamine
- Azelastine
- Azelastine; Fluticasone
- Azilsartan; Chlorthalidone
- Baclofen
- Barbiturates
- Belladonna Alkaloids; Ergotamine; Phenobarbital
- Benazepril; Hydrochlorothiazide, HCTZ
- Bendroflumethiazide; Nadolol
- Benzhydrocodone; Acetaminophen
- Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
- Benzonatate
- Bethanechol
- Bexarotene
- Bismuth Subcitrate Potassium; Metronidazole; Tetracycline
- Bismuth Subsalicylate
- Bismuth Subsalicylate; Metronidazole; Tetracycline
- Bisoprolol; Hydrochlorothiazide, HCTZ
- Bosentan
- Brexpiprazole
- Brigatinib
- Brimonidine
- Brimonidine; Brinzolamide
- Brimonidine; Timolol
- Brompheniramine
- Brompheniramine; Carbetapentane; Phenylephrine
- Brompheniramine; Dextromethorphan; Guaifenesin
- Brompheniramine; Dextromethorphan; Phenylephrine
- Brompheniramine; Guaifenesin; Hydrocodone
- Brompheniramine; Hydrocodone; Pseudoephedrine
- Brompheniramine; Pseudoephedrine
- Bumetanide
- Bupivacaine
- Bupivacaine Liposomal
- Bupivacaine; Lidocaine
- Buprenorphine
- Buprenorphine; Naloxone
- Bupropion
- Bupropion; Naltrexone
- Buspirone
- Butabarbital
- Butorphanol
- Candesartan; Hydrochlorothiazide, HCTZ
- Cannabidiol
- Capsaicin; Metaxalone
- Captopril; Hydrochlorothiazide, HCTZ
- Carbamazepine
- Carbetapentane; Chlorpheniramine
- Carbetapentane; Chlorpheniramine; Phenylephrine
- Carbetapentane; Diphenhydramine; Phenylephrine
- Carbetapentane; Guaifenesin
- Carbetapentane; Guaifenesin; Phenylephrine
- Carbetapentane; Phenylephrine
- Carbetapentane; Phenylephrine; Pyrilamine
- Carbetapentane; Pseudoephedrine
- Carbetapentane; Pyrilamine
- Carbinoxamine
- Carbinoxamine; Dextromethorphan; Pseudoephedrine
- Carbinoxamine; Hydrocodone; Phenylephrine
- Carbinoxamine; Hydrocodone; Pseudoephedrine
- Carbinoxamine; Phenylephrine
- Carbinoxamine; Pseudoephedrine
- Cariprazine
- Carisoprodol
- Celecoxib
- Cenobamate
- Ceritinib
- Cetirizine
- Cetirizine; Pseudoephedrine
- Chlophedianol; Dexbrompheniramine
- Chlophedianol; Dexchlorpheniramine; Pseudoephedrine
- Chloral Hydrate
- Chloramphenicol
- Chlorcyclizine
- Chlordiazepoxide
- Chlordiazepoxide; Clidinium
- Chloroprocaine
- Chlorothiazide
- Chlorpheniramine
- Chlorpheniramine; Codeine
- Chlorpheniramine; Dextromethorphan
- Chlorpheniramine; Dextromethorphan; Phenylephrine
- Chlorpheniramine; Dihydrocodeine; Phenylephrine
- Chlorpheniramine; Dihydrocodeine; Pseudoephedrine
- Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine
- Chlorpheniramine; Hydrocodone
- Chlorpheniramine; Hydrocodone; Phenylephrine
- Chlorpheniramine; Hydrocodone; Pseudoephedrine
- Chlorpheniramine; Phenylephrine
- Chlorpheniramine; Pseudoephedrine
- Chlorpromazine
- Chlorthalidone
- Chlorthalidone; Clonidine
- Chlorzoxazone
- Cimetidine
- Cinacalcet
- Ciprofloxacin
- Citalopram
- Clarithromycin
- Clemastine
- Clobazam
- Clomipramine
- Clonazepam
- Clonidine
- Clopidogrel
- Clorazepate
- Clozapine
- Cobicistat
- Codeine; Phenylephrine; Promethazine
- Codeine; Promethazine
- COMT inhibitors
- Conivaptan
- Crizotinib
- Crofelemer
- Cyclizine
- Cyclobenzaprine
- Cyclosporine
- Cyproheptadine
- Dabrafenib
- Dacomitinib
- Dalfopristin; Quinupristin
- Danazol
- Dantrolene
- Darifenacin
- Darunavir
- Darunavir; Cobicistat
- Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
- Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
- Delavirdine
- Desflurane
- Desipramine
- Desmopressin
- Desvenlafaxine
- Deutetrabenazine
- Dexamethasone
- Dexchlorpheniramine
- Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine
- Dexmedetomidine
- Dexpanthenol
- Dextromethorphan
- Dextromethorphan; Diphenhydramine; Phenylephrine
- Dextromethorphan; Guaifenesin
- Dextromethorphan; Guaifenesin; Phenylephrine
- Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate
- Dextromethorphan; Guaifenesin; Pseudoephedrine
- Dextromethorphan; Promethazine
- Dextromethorphan; Quinidine
- Diazepam
- Diltiazem
- Dimenhydrinate
- Diphenhydramine
- Diphenhydramine; Hydrocodone; Phenylephrine
- Diphenhydramine; Ibuprofen
- Diphenhydramine; Naproxen
- Diphenhydramine; Phenylephrine
- Dolasetron
- Doxepin
- Doxylamine
- Doxylamine; Pyridoxine
- Dronabinol
- Dronedarone
- Droperidol
- Duloxetine
- Efavirenz
- Efavirenz; Emtricitabine; Tenofovir
- Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
- Elagolix
- Elagolix; Estradiol; Norethindrone acetate
- Elbasvir; Grazoprevir
- Eletriptan
- Eliglustat
- Eltrombopag
- Eluxadoline
- Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
- Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
- Enalapril; Hydrochlorothiazide, HCTZ
- Enflurane
- Enzalutamide
- Eprosartan; Hydrochlorothiazide, HCTZ
- Erythromycin
- Erythromycin; Sulfisoxazole
- Escitalopram
- Esketamine
- Eslicarbazepine
- Estazolam
- Eszopiclone
- Ethacrynic Acid
- Ethanol
- Ethotoin
- Etomidate
- Etravirine
- Everolimus
- Fedratinib
- Fesoterodine
- Flibanserin
- Fluconazole
- Fluoxetine
- Fluoxetine; Olanzapine
- Fluphenazine
- Flurazepam
- Fluvoxamine
- Fosamprenavir
- Fosinopril; Hydrochlorothiazide, HCTZ
- Fosphenytoin
- Fospropofol
- Fostamatinib
- Frovatriptan
- Furosemide
- Gabapentin
- General anesthetics
- Givosiran
- Granisetron
- grapefruit juice
- Guaifenesin; Hydrocodone
- Guaifenesin; Hydrocodone; Pseudoephedrine
- Guanabenz
- Guanfacine
- Haloperidol
- Halothane
- Homatropine; Hydrocodone
- Hydralazine; Hydrochlorothiazide, HCTZ
- Hydrochlorothiazide, HCTZ
- Hydrochlorothiazide, HCTZ; Irbesartan
- Hydrochlorothiazide, HCTZ; Lisinopril
- Hydrochlorothiazide, HCTZ; Losartan
- Hydrochlorothiazide, HCTZ; Methyldopa
- Hydrochlorothiazide, HCTZ; Metoprolol
- Hydrochlorothiazide, HCTZ; Moexipril
- Hydrochlorothiazide, HCTZ; Olmesartan
- Hydrochlorothiazide, HCTZ; Propranolol
- Hydrochlorothiazide, HCTZ; Quinapril
- Hydrochlorothiazide, HCTZ; Spironolactone
- Hydrochlorothiazide, HCTZ; Telmisartan
- Hydrochlorothiazide, HCTZ; Triamterene
- Hydrochlorothiazide, HCTZ; Valsartan
- Hydrocodone
- Hydrocodone; Ibuprofen
- Hydrocodone; Phenylephrine
- Hydrocodone; Potassium Guaiacolsulfonate
- Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine
- Hydrocodone; Pseudoephedrine
- Hydromorphone
- Hydroxyzine
- Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
- Ibuprofen; Oxycodone
- Idelalisib
- Iloperidone
- Imatinib
- Imipramine
- Indapamide
- Indinavir
- Isavuconazonium
- Isocarboxazid
- Isoflurane
- Isoniazid, INH
- Isoniazid, INH; Pyrazinamide, PZA; Rifampin
- Isoniazid, INH; Rifampin
- Istradefylline
- Itraconazole
- Ketamine
- Ketoconazole
- Lapatinib
- Larotrectinib
- Lasmiditan
- Lefamulin
- Lemborexant
- Letermovir
- Levobupivacaine
- Levocetirizine
- Levomilnacipran
- Lidocaine
- Lidocaine; Prilocaine
- Lincosamides
- Linezolid
- Lofexidine
- Loop diuretics
- Loperamide
- Loperamide; Simethicone
- Lopinavir; Ritonavir
- Lorazepam
- Lorlatinib
- Loxapine
- Lumacaftor; Ivacaftor
- Lumateperone
- Lurasidone
- Magnesium Salts
- Maprotiline
- Melatonin
- Meperidine; Promethazine
- Mephobarbital
- Mepivacaine
- Mepivacaine; Levonordefrin
- Meprobamate
- Metaxalone
- Methadone
- Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine
- Methocarbamol
- Methohexital
- Methyclothiazide
- Methyldopa
- Methylene Blue
- Metoclopramide
- Metolazone
- Metyrapone
- Metyrosine
- Midazolam
- Mifepristone
- Milnacipran
- Minocycline
- Mirabegron
- Mirtazapine
- Mitotane
- Modafinil
- Molindone
- Monoamine oxidase inhibitors
- Morphine
- Morphine; Naltrexone
- Nabilone
- Nafcillin
- Nalbuphine
- Naloxone
- Naltrexone
- Naproxen; Sumatriptan
- Naratriptan
- Nefazodone
- Nelfinavir
- Nesiritide, BNP
- Netupitant, Fosnetupitant; Palonosetron
- Nevirapine
- Nilotinib
- Nitroglycerin
- Nortriptyline
- Octreotide
- Olanzapine
- Ombitasvir; Paritaprevir; Ritonavir
- Omeprazole; Amoxicillin; Rifabutin
- Ondansetron
- Oritavancin
- Orphenadrine
- Osilodrostat
- Oxazepam
- Oxycodone
- Oxymorphone
- Ozanimod
- Palbociclib
- Paliperidone
- Palonosetron
- Panobinostat
- Papaverine
- Paroxetine
- Peginterferon Alfa-2b
- Pegvisomant
- Pentazocine
- Pentazocine; Naloxone
- Pentobarbital
- Perampanel
- Perindopril; Amlodipine
- Perphenazine
- Perphenazine; Amitriptyline
- Phenelzine
- Phenobarbital
- Phenylephrine; Promethazine
- Phenytoin
- Pimozide
- Posaconazole
- Potassium-sparing diuretics
- Pramipexole
- Pramlintide
- Prasugrel
- Pregabalin
- Prilocaine
- Prilocaine; Epinephrine
- Primidone
- Procarbazine
- Prochlorperazine
- Promethazine
- Propafenone
- Propofol
- Protriptyline
- Quazepam
- Quetiapine
- Quinidine
- Quinine
- Ramelteon
- Ranolazine
- Rasagiline
- Ribociclib
- Ribociclib; Letrozole
- Rifabutin
- Rifampin
- Rifapentine
- Rifaximin
- Risperidone
- Ritonavir
- Rizatriptan
- Rolapitant
- Ropinirole
- Ropivacaine
- Rotigotine
- Rucaparib
- Safinamide
- Saquinavir
- Secobarbital
- Selegiline
- Selpercatinib
- Serotonin-Receptor Agonists
- Serotonin-Receptor Antagonists
- Sertraline
- Sevoflurane
- Sildenafil
- Skeletal Muscle Relaxants
- Sodium Oxybate
- Solifenacin
- Spironolactone
- St. John’s Wort, Hypericum perforatum
- Streptogramins
- Sumatriptan
- Suvorexant
- Tapentadol
- Tasimelteon
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- Telithromycin
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- Temazepam
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- Tramadol
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