1. Clinical Overview
A fixed-dose combination analgesic containing Paracetamol (Acetaminophen), a centrally-acting non-opioid analgesic and antipyretic, and Codeine Phosphate, a weak opioid analgesic and antitussive. This combination provides synergistic pain relief by acting on multiple pathways. Paracetamol acts on central COX inhibition and the endocannabinoid system, while Codeine is a prodrug metabolized to morphine, acting on mu-opioid receptors. It is indicated for moderate to severe pain not adequately controlled by non-opioids alone.
| Onset | Duration | Bioavailability |
|---|---|---|
| Oral: 30-45 minutes for analgesic effect. | Approximately 4-6 hours. | Paracetamol: ~85-98%. Codeine: ~40-70% (subject to CYP2D6 polymorphism). |
2. Mechanism of Action
The combination provides additive/synergistic analgesia through distinct and complementary mechanisms. Paracetamol exerts central analgesic and antipyretic effects via presumed inhibition of prostaglandin synthesis in the CNS, modulation of the serotonergic and endocannabinoid systems. Codeine is a prodrug converted by CYP2D6 to morphine, which acts as an agonist primarily at central mu-opioid receptors, altering the perception of and emotional response to pain.
3. Indications & Uses
- Moderate to severe acute pain (e.g., post-operative pain, trauma, musculoskeletal pain)
- Pain associated with conditions like osteoarthritis flare-ups, back pain
4. Dosage & Administration
Adult Dosage: One tablet (Paracetamol 650mg + Codeine 30mg) every 4-6 hours as needed for pain. Maximum: 4 tablets in 24 hours (Paracetamol 2600mg, Codeine 120mg). Duration should be limited to the shortest period necessary, typically 3-5 days.
Administration: Take with or without food. Swallow whole with a glass of water. Do not crush, chew, or break the tablet. Can be taken with food if GI upset occurs. Do not consume alcohol. Use exactly as prescribed; do not increase dose or frequency.
5. Side Effects
Common side effects may include:
- Dizziness
- Drowsiness/sedation
- Nausea
- Vomiting
- Constipation
- Dry mouth
- Sweating
- Lightheadedness
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Alcohol / CNS Depressants (Benzodiazepines, Barbiturates) | Additive CNS depression, respiratory depression, sedation; increased risk of hepatotoxicity with alcohol. | Major |
| Other Opioids (Morphine, Tramadol) | Additive opioid effects, increased risk of respiratory depression, constipation, CNS depression. | Major |
| MAO Inhibitors (Phenelzine, Selegiline) | Risk of serotonin syndrome, excitatory reactions, severe hypertension or hypotension. | Contraindicated |
| Serotonergic Drugs (SSRIs, SNRIs, TCAs, Triptans) | Increased risk of serotonin syndrome. | Moderate to Major |
| Anticholinergics (Atropine, Antihistamines) | Increased risk of urinary retention, severe constipation, paralytic ileus. | Moderate |
| Muscle Relaxants | Enhanced neuromuscular blockade and respiratory depression. | Moderate |
| Warfarin | Paracetamol may potentiate anticoagulant effect with chronic high doses (>2g/day for several days); monitor INR. | Moderate |
| Enzyme Inducers (Rifampicin, Carbamazepine, Phenytoin) | Increased metabolism of codeine to morphine (potential for increased effect/toxicity) and increased conversion of paracetamol to NAPQI (hepatotoxicity risk). | Moderate |
| CYP2D6 Inhibitors (Fluoxetine, Paroxetine, Quinidine) | Reduced conversion of codeine to morphine, diminishing analgesic effect. | Moderate |
| Domperidone, Metoclopramide | Antagonistic effects on GI motility. | Minor |
7. Patient Counselling
- DO take exactly as prescribed by your doctor.
- DO inform your doctor about all other medicines, vitamins, and herbal products you are taking.
- DO store the medicine in a safe, locked place out of reach of children and pets.
- DO NOT crush, chew, or break the tablet.
- DO NOT consume alcohol in any form while on this medication.
- DO NOT drive or operate heavy machinery until you know how it affects you.
- DO NOT share this medicine with anyone else, even if they have similar symptoms.
- DO NOT take for longer than prescribed.
- DO NOT take other paracetamol-containing products (cold & flu remedies, other painkillers).
8. Toxicology & Storage
Overdose: TRIPHASIC: Phase 1 (0-24h): Nausea, vomiting, pallor, lethargy, diaphoresis. Phase 2 (24-72h): Apparent improvement, but rising liver enzymes (AST/ALT), right upper quadrant pain. Phase 3 (72-96h): Peak hepatotoxicity (jaundice, coagulopathy, encephalopathy), renal failure, hypoglycemia, coma. Codeine overdose adds: Respiratory depression (cyanosis, apnea), extreme somnolence progressing to stupor/coma, skeletal muscle flaccidity, bradycardia, hypotension, circulatory collapse, cardiac arrest.
Storage: Store below 30°C, in a cool, dry place, protected from light and moisture. Keep in the original blister pack or container. Keep out of reach and sight of children and others for whom it is not prescribed. Do not flush or pour down the drain. Dispose of unused medication through a take-back program or as per pharmacy instructions.