1. Clinical Overview
Codeine is a naturally occurring phenanthrene alkaloid and opioid prodrug, classified as a weak opioid analgesic and antitussive. It exerts its therapeutic effects primarily through its active metabolite, morphine, formed via hepatic O-demethylation by the cytochrome P450 enzyme CYP2D6. In the Indian context, it is a Schedule H1 drug under the Drugs and Cosmetics Rules, 1945, requiring stringent prescription control and mandatory maintenance of records by pharmacists due to its abuse potential. It is indicated for the relief of mild to moderate pain and as an antitussive for non-productive cough.
| Onset | Duration | Bioavailability |
|---|---|---|
| Oral: 30 to 45 minutes for analgesia; 15 to 30 minutes for antitussive effect. | Approximately 4 to 6 hours for analgesia. | Approximately 50% due to significant first-pass metabolism. |
2. Mechanism of Action
Codeine is a prodrug. Its primary mechanism for analgesia and central antitussive effect is mediated through its active metabolite, morphine. Morphine acts as an agonist, predominantly at the mu-opioid receptor (MOR), and to a lesser extent at kappa and delta receptors in the central nervous system (CNS).
3. Indications & Uses
- Relief of mild to moderate pain where treatment with a non-opioid analgesic is not effective.
- Symptomatic relief of non-productive (dry) cough.
4. Dosage & Administration
Adult Dosage: Analgesia: 15mg to 60mg every 4 to 6 hours as needed. Maximum 240mg per 24 hours. Antitussive: 10mg to 20mg every 4 to 6 hours as needed. Maximum 120mg per 24 hours. (Note: 10mg strength is commonly used for antitussive purposes).
Administration: Oral administration. Can be taken with or without food. Taking with food may reduce gastrointestinal upset. Tablet should be swallowed whole with a glass of water. Do not crush, chew, or break sustained-release formulations (if available).
5. Side Effects
Common side effects may include:
- Nausea
- Vomiting
- Constipation
- Drowsiness/Sedation
- Dizziness/Lightheadedness
- Dry mouth
- Sweating
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| CNS Depressants (Alcohol, Benzodiazepines, other Opioids, Sedative-hypnotics) | Additive CNS and respiratory depression, profound sedation, coma, risk of death. | Major |
| MAO Inhibitors (Phenelzine, Tranylcypromine) | Potentially fatal serotonin syndrome, excitability, hyperpyrexia, rigidity. | Contraindicated |
| Serotonergic Drugs (SSRIs, SNRIs, TCAs, Triptans, Tramadol) | Increased risk of serotonin syndrome. | Major |
| CYP2D6 Inhibitors (Bupropion, Fluoxetine, Paroxetine, Quinidine) | Reduced conversion to morphine, decreased analgesic efficacy. | Moderate |
| CYP3A4 Inducers (Rifampicin, Carbamazepine, Phenytoin, St. John's Wort) | Increased metabolism to norcodeine, potentially reducing efficacy and altering side effect profile. | Moderate |
| CYP3A4 Inhibitors (Ketoconazole, Itraconazole, Clarithromycin, Ritonavir) | Decreased metabolism, increased codeine levels, risk of toxicity. | 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 |
7. Patient Counselling
- DO take exactly as prescribed by your doctor. Do not increase dose or frequency.
- DO inform all your doctors and dentists that you are taking codeine.
- DO store the medicine in a safe, secure place, out of reach of children and others.
- DONT consume alcohol or sleep-inducing medications (cold syrups, anxiety pills) while on codeine.
- DONT crush, chew, or break the tablet unless advised.
- DONT share your medicine with anyone else; it is a punishable offence under NDPS Act.
- DONT stop taking the medicine suddenly if used for a long time; consult your doctor for tapering.
8. Toxicology & Storage
Overdose: Triad of opioid overdose: 1) Respiratory depression (slow, shallow breathing, cyanosis, apnea). 2) CNS depression (profound sedation progressing to stupor, coma, flaccid skeletal muscles). 3) Miosis (pinpoint pupils; may be dilated in severe hypoxia). Other symptoms: Bradycardia, hypotension, hypothermia, circulatory collapse, cardiac arrest, pulmonary edema, seizures.
Storage: Store at room temperature (15°C to 30°C), protected from light and moisture. Keep in the original container, tightly closed. Keep out of reach and sight of children. Dispose of unused medication safely as per pharmacist's advice; do not flush or throw in household trash.