Paracetamol for adults

Generic Name: Paracetamol
Alternative Name: Acetaminophen (used in the United States and Canada)
Drug Class: Analgesic and Antipyretic

Pharmaceutical Category: Non-opioid analgesic
Common Brand Names: Panadol, Tylenol, Excedrin (in combinations), Calpol (UK), Paramol (with dihydrocodeine), Anadin Extra (with aspirin and caffeine), Actifed (combination cold products)
Formulations: Oral tablets (standard and soluble), capsules, caplets, effervescent tablets, oral suspensions, suppositories, intravenous injection (paracetamol IV), combination products (e.g., with codeine or caffeine)
Route of Administration: Oral, rectal, or intravenous

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1. Mechanism of Action

Paracetamol acts primarily on the central nervous system, where it inhibits the cyclooxygenase (COX) enzymes, particularly COX-2, which play a role in the synthesis of prostaglandins, the chemical mediators of pain and fever. Its exact mechanism is still under research but includes:

• Antipyretic action: Acts on the hypothalamic heat-regulating center, reducing fever

• Analgesic effect: Central inhibition of prostaglandin synthesis

• Minimal anti-inflammatory activity due to limited peripheral COX inhibition

Unlike NSAIDs, paracetamol does not interfere with platelet aggregation, gastric mucosa, or renal perfusion, making it safer for the stomach and kidneys in standard doses.

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2. Therapeutic Indications in Adults

• Mild to moderate pain:

  • Headache

  • Toothache

  • Musculoskeletal pain (e.g., back pain, joint pain)

  • Dysmenorrhea (period pain)

  • Post-operative pain

  • Post-immunization discomfort

• Fever

• Chronic pain management (as adjunctive therapy)

• Osteoarthritis pain (especially in those unable to take NSAIDs)

• Often used in combination therapy with opioids (e.g., co-codamol) or NSAIDs

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3. Dosage and Administration (Adults)

Formulation	Strength	Typical Dosage	Max Dose (per 24 hrs)
Tablet/Caplet	500 mg	1–2 tablets every 4–6 hours	4,000 mg (8 × 500 mg tablets)
Soluble Tablet	500 mg or 1,000 mg	Same as above	4,000 mg
Oral Suspension	250 mg/5 mL or 500 mg/5 mL	10–20 mL (based on product)	4,000 mg
IV Form	1 g per infusion	1 g every 4–6 hrs	4 g (IV must be prescribed by physician)

General Rules:

• Minimum interval: 4 hours between doses

• Do not exceed 4 g/day (4000 mg)

• For underweight adults (<50 kg) or with hepatic impairment: max dose may be reduced to 60 mg/kg/day

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4. Pharmacokinetics

• Absorption: Rapid and complete orally

• Onset of action: ~30 minutes

• Peak effect: 1–2 hours

• Half-life: 1.5–3 hours in healthy adults

• Metabolism: Liver via conjugation (glucuronidation and sulfation); minor metabolism via CYP450 pathway producing NAPQI, a hepatotoxic metabolite

• Excretion: Renal (as metabolites)

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5. Contraindications

• Known hypersensitivity to paracetamol or any excipient

• Severe hepatic impairment or active liver disease

• Chronic alcoholism with acute liver dysfunction

• Use of other products containing paracetamol simultaneously (to avoid cumulative overdose)

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6. Warnings and Precautions

• Risk of hepatotoxicity with doses exceeding 4,000 mg/day

• Caution in patients with:

  • Hepatic impairment

  • Chronic alcoholism

  • Malnutrition or prolonged fasting (decreased glutathione availability)

  • Dehydration

• Alcohol potentiates hepatotoxic risk

• Avoid concurrent use with multiple paracetamol-containing products (e.g., cold and flu meds)

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7. Adverse Effects

Paracetamol is well-tolerated when used appropriately. Adverse effects are rare at therapeutic doses.

Common (1–10%)

• None typically reported

Uncommon (0.1–1%)

• Skin rash, pruritus

Rare (<0.1%)

• Liver toxicity/failure (from overdose)

• Allergic reactions, including urticaria, angioedema

• Thrombocytopenia, neutropenia, or pancytopenia (very rare)

• Anaphylaxis (extremely rare)

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8. Overdose and Toxicity

Paracetamol overdose is a medical emergency, with risk of fulminant hepatic necrosis.

Toxic Thresholds:

• 150 mg/kg (single dose) or >4 g/day chronically

Clinical Stages:

1. 0–24 hours: Nausea, vomiting, malaise, anorexia

2. 24–72 hours: Right upper quadrant pain, elevated liver enzymes

3. 72–96 hours: Liver failure, encephalopathy, jaundice, coagulopathy, renal failure

4. 4–14 days: Recovery or death

Antidote:

• N-acetylcysteine (NAC): Replenishes glutathione, binds toxic metabolite NAPQI

• Most effective within 8–10 hours of ingestion

• Activated charcoal if given <1 hour post-ingestion

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9. Drug Interactions

• Enzyme inducers (e.g., rifampin, phenytoin, carbamazepine): ↑ NAPQI production → ↑ hepatotoxicity risk

• Alcohol: ↑ hepatotoxicity via same mechanism

• Warfarin: Long-term use may potentiate INR → bleeding risk (monitor INR)

• Isoniazid: Additive hepatotoxicity

• Chloramphenicol: May ↑ its plasma concentration

• Probenecid: Reduces paracetamol clearance

• Anticonvulsants: Lower glutathione levels → ↑ risk in overdose

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10. Use in Special Populations

Elderly:

• Generally well-tolerated

• No dose adjustment needed unless hepatic impairment present

Pregnancy:

• Considered safe in all trimesters

• No known teratogenicity

• Preferred analgesic during pregnancy

Lactation:

• Safe; small amounts in breast milk

• No adverse effects in breastfeeding infants reported

Renal Impairment:

• Safe in mild to moderate impairment

• Severe impairment (CrCl <30 mL/min): Extend dose interval to every 6–8 hrs

• Avoid high doses

Hepatic Impairment:

• Use with great caution or avoid in moderate to severe liver disease

• Max dose: 2 g/day in mild liver dysfunction

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11. Clinical Comparisons (vs. Other Analgesics)

Drug	Antipyretic	Analgesic	Anti-inflammatory	GI Risk	Hepatic Risk
Paracetamol	Yes	Mild–moderate	No	Low	High (in overdose)
Ibuprofen	Yes	Mild–moderate	Yes	Moderate	Low
Aspirin	Yes	Mild–moderate	Yes	High	Moderate
Codeine	No	Moderate–strong	No	Moderate (with NSAIDs)	Moderate

Paracetamol is preferred over NSAIDs in:

• Peptic ulcer disease

• Pregnancy

• Patients on anticoagulants

• Elderly patients

• Hypertension or heart failure

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12. Common Combination Products (Caution Required)

• Co-codamol: Paracetamol + Codeine

• Paramol: Paracetamol + Dihydrocodeine

• Panadol Extra: Paracetamol + Caffeine

• Lemsip, Sudafed, etc.: Paracetamol + decongestants ± antihistamines
  Always check labels to avoid accidental overdose from multiple sources.

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13. Patient Counseling Points

• Take with or without food

• Do not exceed 8 tablets (4 g) per day

• Avoid duplicate use of cold/flu products with paracetamol

• Watch for signs of liver toxicity: yellow skin, nausea, fatigue

• Seek medical help immediately if overdose is suspected

• Not for use >3–5 days for pain or >3 days for fever without medical advice

• Do not drink excessive alcohol