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
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• Rizatriptan
• Rolapitant
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• Ropivacaine
• Rotigotine
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• Selegiline
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• Serotonin-Receptor Agonists
• Serotonin-Receptor Antagonists
• Sertraline
• Sevoflurane
• Sildenafil
• Skeletal Muscle Relaxants
• Sodium Oxybate
• Solifenacin
• Spironolactone
• St. John’s Wort, Hypericum perforatum
• Streptogramins
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• Tapentadol
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