Codeine

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

  1. arthralgia
  2. bone pain
  3. cough
  4. dental pain
  5. diarrhea
  6. headache
  7. migraine
  8. mild pain
  9. moderate pain
  10. myalgia

Side Effects

  1. abdominal pain
  2. adrenocortical insufficiency
  3. agitation
  4. amenorrhea
  5. anorexia
  6. anxiety
  7. apnea
  8. biliary obstruction
  9. blurred vision
  10. bradycardia
  11. cardiac arrest
  12. confusion
  13. constipation
  14. diaphoresis
  15. diarrhea
  16. dizziness
  17. drowsiness
  18. dysphoria
  19. dyspnea
  20. edema
  21. euphoria
  22. flushing
  23. gastritis
  24. gonadal suppression
  25. hallucinations
  26. headache
  27. hyperamylasemia
  28. hypertension
  29. hyponatremia
  30. hypotension
  31. impotence (erectile dysfunction)
  32. infertility
  33. insomnia
  34. libido decrease
  35. miosis
  36. nausea
  37. neonatal opioid withdrawal syndrome
  38. orthostatic hypotension
  39. palpitations
  40. pancreatitis
  41. physiological dependence
  42. pruritus
  43. psychological dependence
  44. rash
  45. respiratory arrest
  46. respiratory depression
  47. restlessness
  48. seizures
  49. serotonin syndrome
  50. SIADH
  51. sinus tachycardia
  52. syncope
  53. tolerance
  54. urinary retention
  55. urticaria
  56. vertigo
  57. vomiting
  58. weakness
  59. withdrawal
  60. 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
  • Tazemetostat
  • Telithromycin
  • Telotristat Ethyl
  • Temazepam
  • Terbinafine
  • Tetrabenazine
  • Tetracaine
  • Thalidomide
  • Thiazide diuretics
  • Thiopental
  • Thioridazine
  • Thiothixene
  • Ticagrelor
  • Tipranavir
  • Tizanidine
  • Tolterodine
  • Torsemide
  • Tramadol
  • Trandolapril; Verapamil
  • Tranylcypromine
  • Trazodone
  • Triamterene
  • Triazolam
  • Tricyclic antidepressants
  • Trifluoperazine
  • Trimethobenzamide
  • Trimipramine
  • Triprolidine
  • Trospium
  • Tucatinib
  • Valerian, Valeriana officinalis
  • Valproic Acid, Divalproex Sodium
  • Venlafaxine
  • Verapamil
  • Vigabatrin
  • Vilazodone
  • Voriconazole
  • Vortioxetine
  • Voxelotor
  • Zaleplon
  • Ziconotide
  • Ziprasidone
  • Zolmitriptan
  • Zolpidem
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