Acetaminophen and Codeine

Acetaminophen and Codeine Brand Names

Capital and Codeine | Cocet | Cocet Plus | Tylenol with Codeine | Tylenol with Codeine No.3 | Tylenol with Codeine No.4 | TY-PAP with Codeine | Vopac

What is Acetaminophen and Codeine

Acetaminophen and codeine are used together to treat mild to moderate pain. Acetaminophen is a non-salicylate analgesic with similar analgesic potency as NSAIDs, and codeine is an oral semisynthetic opiate agonist derived from the opioid alkaloid, thebaine.

The combination of acetaminophen and codeine produces additive analgesia as compared to the same doses of either agent alone.

Combinations containing higher doses of one or both components give progressively increasing analgesia. However, dosage escalation of this combination is limited by the maximum dose and “ceiling effect” of acetaminophen.

The combination of acetaminophen and opioid analgesics may achieve a “dose-sparing” effect such that lower doses of both agents produce pain relief with fewer side effects.

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 and codeine-containing products in all pediatric patients for any indication.

Indications

• cough
• mild pain
• moderate pain

Side Effects

1. abdominal pain
2. acute generalized exanthematous pustulosis (AGEP)
3. adrenocortical insufficiency
4. agranulocytosis
5. amenorrhea
6. anaphylactic shock
7. anaphylactoid reactions
8. angioedema
9. anorexia
10. bleeding
11. cardiac arrest
12. confusion
13. constipation
14. contact dermatitis
15. dizziness
16. drowsiness
17. dysphoria
18. edema
19. elevated hepatic enzymes
20. encephalopathy
21. euphoria
22. exfoliative dermatitis
23. flushing
24. gonadal suppression
25. hallucinations
26. headache
27. hepatic failure
28. hepatic necrosis
29. hepatotoxicity
30. hyperamylasemia
31. hyponatremia
32. hypoprothrombinemia
33. hypotension
34. impotence (erectile dysfunction)
35. infertility
36. interstitial nephritis
37. jaundice
38. libido decrease
39. maculopapular rash
40. miosis
41. nausea
42. neonatal opioid withdrawal syndrome
43. neutropenia
44. orthostatic hypotension
45. palpitations
46. pancytopenia
47. physiological dependence
48. pruritus
49. psychological dependence
50. purpura
51. rash
52. renal failure (unspecified)
53. renal papillary necrosis
54. renal tubular necrosis
55. respiratory arrest
56. respiratory depression
57. restlessness
58. serotonin syndrome
59. SIADH
60. syncope
61. thrombocytopenia
62. thrombocytosis
63. tolerance
64. toxic epidermal necrolysis
65. urticaria
66. vomiting
67. withdrawal

Monitoring Parameters

• LFTs
• serum creatinine/BUN: in chronic use or acute toxicity

Contraindications

• abrupt discontinuation
• accidental exposure
• acetaminophen hypersensitivity
• adenoidectomy
• adrenal insufficiency
• alcoholism
• anemia
• Asian patients
• asthma
• Black patients
• bladder obstruction
• bone marrow suppression
• breast-feeding
• cardiac arrhythmias
• cardiac disease
• Caucasian patients
• children
• chronic obstructive pulmonary disease (COPD)
• coadministration with other CNS depressants
• constipation
• diarrhea
• driving or operating machinery
• ethanol intoxication
• G6PD deficiency
• geriatric
• GI disease
• GI obstruction
• head trauma
• hepatic disease
• hepatitis
• Hispanic patients
• hypotension
• hypothyroidism
• hypovolemia
• ileus
• immunosuppression
• increased intracranial pressure
• infants
• infection
• inflammatory bowel disease
• labor
• MAOI therapy
• myxedema
• neonatal opioid withdrawal syndrome
• neonates
• neuromuscular disease
• obesity
• obstetric delivery
• oliguria
• opiate agonist hypersensitivity
• potential for overdose or poisoning
• pregnancy
• prostatic hypertrophy
• pulmonary disease
• renal disease
• renal impairment
• respiratory depression
• respiratory infection
• sleep apnea
• substance abuse
• sulfite hypersensitivity
• tonsillectomy
• ulcerative colitis
• urethral stricture
• urinary retention

Interactions

• Abacavir; Lamivudine, 3TC; Zidovudine, ZDV
• Abiraterone
• Acetaminophen; Aspirin, ASA; Caffeine
• Acetaminophen; Butalbital
• Acetaminophen; Butalbital; Caffeine
• Acetaminophen; Butalbital; Caffeine; Codeine
• Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
• 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
• Antacids
• Anticholinergics
• Apalutamide
• Apomorphine
• Apraclonidine
• Aprepitant, Fosaprepitant
• Aripiprazole
• Artemether; Lumefantrine
• Articaine; Epinephrine
• Asenapine
• Aspirin, ASA
• Aspirin, ASA; Butalbital; Caffeine
• Aspirin, ASA; Butalbital; Caffeine; Codeine
• Aspirin, ASA; Caffeine; Dihydrocodeine
• Aspirin, ASA; Caffeine; Orphenadrine
• Aspirin, ASA; Carisoprodol
• Aspirin, ASA; Carisoprodol; Codeine
• Aspirin, ASA; Citric Acid; Sodium Bicarbonate
• Aspirin, ASA; Dipyridamole
• Aspirin, ASA; Omeprazole
• Aspirin, ASA; Oxycodone
• Aspirin, ASA; Pravastatin
• 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
• Boceprevir
• Bosentan
• Brexpiprazole
• Brigatinib
• Brimonidine
• Brimonidine; Brinzolamide
• Brimonidine; Timolol
• Brompheniramine
• Brompheniramine; Carbetapentane; Phenylephrine
• Brompheniramine; Dextromethorphan; Guaifenesin
• Brompheniramine; Guaifenesin; Hydrocodone
• Brompheniramine; Hydrocodone; Pseudoephedrine
• Brompheniramine; Pseudoephedrine
• Bumetanide
• Bupivacaine
• Bupivacaine Liposomal
• Bupivacaine; Lidocaine
• Buprenorphine
• Buprenorphine; Naloxone
• Bupropion
• Bupropion; Naltrexone
• Buspirone
• Busulfan
• 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
• Charcoal
• 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
• Cholestyramine
• Choline Salicylate; Magnesium Salicylate
• 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
• Dapsone
• 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
• Diflunisal
• Diltiazem
• Dimenhydrinate
• Diphenhydramine
• Diphenhydramine; Hydrocodone; Phenylephrine
• Diphenhydramine; Ibuprofen
• Diphenhydramine; Naproxen
• Diphenhydramine; Phenylephrine
• Dolasetron
• Doxepin
• Doxylamine
• Doxylamine; Pyridoxine
• Dronabinol
• Dronedarone
• Droperidol
• Drospirenone; Ethinyl Estradiol
• Drospirenone; Ethinyl Estradiol; Levomefolate
• 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
• Ethinyl Estradiol
• Ethinyl Estradiol; Desogestrel
• Ethinyl Estradiol; Ethynodiol Diacetate
• Ethinyl Estradiol; Etonogestrel
• Ethinyl Estradiol; Levonorgestrel
• Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate
• Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate
• Ethinyl Estradiol; Norelgestromin
• Ethinyl Estradiol; Norethindrone
• Ethinyl Estradiol; Norethindrone Acetate
• Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate
• Ethinyl Estradiol; Norethindrone; Ferrous fumarate
• Ethinyl Estradiol; Norgestimate
• Ethinyl Estradiol; Norgestrel
• Ethotoin
• Etomidate
• Etravirine
• Everolimus
• Exenatide
• 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
• Hydantoins
• 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
• Hydroxyprogesterone
• Hydroxyzine
• Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
• Ibuprofen; Oxycodone
• Idelalisib
• Iloperidone
• Imatinib
• Imipramine
• Indapamide
• Indinavir
• Insulin Glargine; Lixisenatide
• Isavuconazonium
• Isocarboxazid
• Isoflurane
• Isoniazid, INH
• Isoniazid, INH; Pyrazinamide, PZA; Rifampin
• Isoniazid, INH; Rifampin
• Istradefylline
• Itraconazole
• Ketamine
• Ketoconazole
• Lamivudine, 3TC; Zidovudine, ZDV
• Lamotrigine
• Lanthanum Carbonate
• Lapatinib
• Larotrectinib
• Lasmiditan
• Lefamulin
• Lemborexant
• Letermovir
• Levobupivacaine
• Levocetirizine
• Levomilnacipran
• Lidocaine
• Lidocaine; Prilocaine
• Lincosamides
• Linezolid
• Lixisenatide
• Lofexidine
• Lomitapide
• Loop diuretics
• Loperamide
• Loperamide; Simethicone
• Lopinavir; Ritonavir
• Lorazepam
• Lorlatinib
• Loxapine
• Lumacaftor; Ivacaftor
• Lumateperone
• Lurasidone
• Magnesium Salicylate
• 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
• Mipomersen
• 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
• Omeprazole; Sodium Bicarbonate
• Ondansetron
• Oritavancin
• Orphenadrine
• Osilodrostat
• Oxazepam
• Oxycodone
• Oxymorphone
• Ozanimod
• Palbociclib
• Paliperidone
• Palonosetron
• Panobinostat
• Papaverine
• Paroxetine
• Peginterferon Alfa-2b
• Pegvisomant
• Penicillin G Benzathine; Penicillin G Procaine
• Penicillin G Procaine
• Pentazocine
• Pentazocine; Naloxone
• Pentobarbital
• Perampanel
• Perindopril; Amlodipine
• Perphenazine
• Perphenazine; Amitriptyline
• Phenelzine
• Phenobarbital
• Phenylephrine; Promethazine
• Phenytoin
• Pimozide
• Pneumococcal Vaccine, Polyvalent
• 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
• Salsalate
• Saquinavir
• Secobarbital
• Segesterone Acetate; Ethinyl Estradiol
• Selegiline
• Selpercatinib
• Serotonin-Receptor Agonists
• Serotonin-Receptor Antagonists
• Sertraline
• Sevoflurane
• Sildenafil
• Skeletal Muscle Relaxants
• Sodium Bicarbonate
• Sodium Oxybate
• Solifenacin
• Spironolactone
• St. John’s Wort, Hypericum perforatum
• Streptogramins
• Sulfinpyrazone
• Sumatriptan
• Suvorexant
• Tapentadol
• Tasimelteon
• Tazemetostat
• Telaprevir
• Telithromycin
• Telotristat Ethyl
• Temazepam
• Terbinafine
• Tetrabenazine
• Tetracaine
• Thalidomide
• Thiazide diuretics
• Thiopental
• Thioridazine
• Thiothixene
• Ticagrelor
• Tipranavir
• Tizanidine
• tobacco
• Tolterodine
• Torsemide
• Tramadol
• Trandolapril; Verapamil
• Tranylcypromine
• Trazodone
• Triamterene
• Triazolam
• Tricyclic antidepressants
• Trifluoperazine
• Trimethobenzamide
• Trimetrexate
• Trimipramine
• Triprolidine
• Trospium
• Tucatinib
• Valerian, Valeriana officinalis
• Valproic Acid, Divalproex Sodium
• Vemurafenib
• Venlafaxine
• Verapamil
• Vigabatrin
• Vilazodone
• Voriconazole
• Vortioxetine
• Voxelotor
• Warfarin
• Zaleplon
• Ziconotide
• Zidovudine, ZDV
• Ziprasidone
• Zolmitriptan
• Zolpidem