1. Clinical Overview
Paracetamol (Acetaminophen) is a widely used, centrally-acting, non-opioid analgesic and antipyretic agent. It is a first-line treatment for mild to moderate pain and fever. Unlike NSAIDs, it has minimal anti-inflammatory activity and a favorable gastrointestinal safety profile. It is one of the most commonly used over-the-counter (OTC) medications in India and globally.
| Onset | Duration | Bioavailability |
|---|---|---|
| Oral: 30 to 60 minutes. | Approximately 4 to 6 hours. | Approximately 85-98% after oral administration. |
2. Mechanism of Action
The exact mechanism is not fully elucidated but is distinct from NSAIDs. It is a potent inhibitor of the cyclooxygenase (COX) pathways, particularly in the central nervous system. It is believed to act on the COX-3 isoform (a variant of COX-1) and other central pathways, including the serotonergic and cannabinoid systems, to produce analgesia and antipyresis. It has very weak peripheral anti-inflammatory effects.
3. Indications & Uses
- Mild to moderate pain (e.g., headache, toothache, musculoskeletal pain, dysmenorrhea)
- Fever (pyrexia) of any etiology
4. Dosage & Administration
Adult Dosage: 325-650 mg every 4-6 hours OR 500-1000 mg every 6-8 hours. Maximum daily dose: 4 grams (4000 mg).
Administration: Oral tablet/capsule to be taken with or without food, with a full glass of water. Do not crush or chew unless specified (e.g., dispersible tablets). Should not be taken for more than 3 days for fever or 5 days for pain without medical advice.
5. Side Effects
Common side effects may include:
- Nausea
- Epigastric discomfort/pain
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Warfarin | Chronic high-dose paracetamol (>2g/day for several days) may potentiate anticoagulant effect by reducing synthesis of vitamin K-dependent clotting factors. Increases INR risk. | Major |
| Isoniazid | Increases formation of toxic metabolite NAPQI by inducing CYP2E1, significantly increasing risk of hepatotoxicity, even at therapeutic doses. | Major |
| Carbamazepine, Phenytoin, Phenobarbital | Enzyme inducers increase formation of NAPQI, increasing hepatotoxicity risk. | Moderate |
| Probenecid | Inhibits glucuronidation, may slightly increase and prolong paracetamol effect. | Minor |
| Metoclopramide, Domperidone | May increase absorption rate of paracetamol. | Minor |
| Cholestyramine | Reduces absorption of paracetamol if taken within 1 hour. | Minor |
| Alcohol (Chronic abuse) | Induces CYP2E1 and depletes glutathione, dramatically increasing risk of hepatotoxicity. Contraindicated. | Major |
| Other Hepatotoxic Drugs (e.g., Rifampicin, Sodium Valproate) | Additive risk of liver damage. | Major |
7. Patient Counselling
- DO take exactly as directed. Do not exceed 4 grams (8 tablets of 500mg) in 24 hours.
- DO check all other medication labels (cold, flu, combination analgesics) for 'paracetamol' or 'acetaminophen' to avoid accidental overdose.
- DO seek immediate medical attention in case of accidental overdose, even if feeling well.
- DONT take with alcohol. Avoid alcohol during treatment.
- DONT use for more than 3 days for fever or 5 days for pain without consulting a doctor.
- DONT give to children under 2 years of age without consulting a pediatrician.
- DO inform your doctor if you have liver disease, kidney disease, or are a chronic alcohol consumer.
8. Toxicology & Storage
Overdose: Stage 1 (0-24h): Nausea, vomiting, anorexia, malaise, pallor, diaphoresis. Stage 2 (24-72h): Right upper quadrant pain, elevated liver enzymes (ALT/AST), prolonged PT/INR. Patient may appear to improve clinically. Stage 3 (72-96h): Peak hepatotoxicity - jaundice, hepatic encephalopathy, coagulopathy, renal failure, hypoglycemia, lactic acidosis. Stage 4 (4 days-2 weeks): Either recovery or death from multi-organ failure.
Storage: Store below 30°C, in a cool, dry place. Protect from light and moisture. Keep out of reach of children. Do not use after the expiry date printed on the pack.