Codeine is a naturally occurring phenanthrene alkaloid and opioid prodrug, primarily used for its analgesic, antitussive, and antidiarrheal properties. In India, it is a Schedule H1 drug under the Drugs and Cosmetics Rules, indicating high potential for abuse and dependence. Its therapeutic effects are mediated through conversion to morphine in the liver via the cytochrome P450 2D6 (CYP2D6) enzyme. Its efficacy is highly variable due to genetic polymorphisms in this enzyme.
Adult: Analgesia: 15-60 mg every 4-6 hours as needed. Max: 360 mg/day. Antitussive: 10-20 mg every 4-6 hours. Max: 120 mg/day. Always use the lowest effective dose for the shortest duration.
Note: Take orally with or without food. Taking with food may reduce GI upset. Do not crush, chew, or break sustained-release formulations. Swallow whole with a glass of water. For combination products, adhere to the dosing schedule of the other component (e.g., paracetamol max 4g/day).
Codeine is a prodrug. Its primary analgesic and antitussive effects are mediated through its active metabolite, morphine. Morphine acts as an agonist, primarily at the mu-opioid receptor (MOR), and to a lesser extent at kappa and delta receptors in the central nervous system (CNS). Activation of these G-protein coupled receptors inhibits adenylate cyclase, reduces neurotransmitter release (e.g., substance P), and hyperpolarizes neurons by opening potassium channels, leading to decreased pain signal transmission and modulation of the cough center.
Pregnancy: Category C (US FDA). Use only if potential benefit justifies potential fetal risk. Prolonged use during pregnancy can cause neonatal opioid withdrawal syndrome (NOWS). Avoid during labor/delivery as it may cause respiratory depression in the neonate.
Driving: IMPAIRS ABILITY. Causes drowsiness, dizziness, and altered judgment. Patients must not drive or operate heavy machinery until they know how the drug affects them.
| CNS Depressants (Alcohol, Benzodiazepines, Barbiturates, other Opioids) | Additive CNS depression, profound sedation, respiratory depression, coma, death. | Major |
| MAO Inhibitors (Phenelzine, Tranylcypromine) | Potentially fatal reactions: serotonin syndrome, excitability, hyperpyrexia, rigidity. | Contraindicated |
| Serotonergic Drugs (SSRIs, SNRIs, TCAs, Tramadol, Triptans) | Increased risk of serotonin syndrome. | Major |
| CYP2D6 Inhibitors (Fluoxetine, Paroxetine, Quinidine, Bupropion) | Reduced conversion to morphine, decreased analgesic effect. | Moderate |
| CYP3A4 Inducers (Rifampicin, Carbamazepine, Phenytoin, St. John's Wort) | Increased metabolism of codeine, potentially reducing efficacy. | Moderate |
| CYP3A4 Inhibitors (Ketoconazole, Clarithromycin, Ritonavir, Grapefruit juice) | Decreased metabolism, increased codeine levels and side effects. | Moderate |
| Anticholinergics (Atropine, Antihistamines, TCAs) | Increased risk of urinary retention, severe constipation, paralytic ileus. | Moderate |
| Muscle Relaxants | Enhanced neuromuscular blocking action, increased respiratory depression. | Moderate |
Same composition (Codeine (NA)), different brands: