Atopen

Approved Uses:

• Fever: Reduction of elevated body temperature due to infections, post-vaccination reactions, or inflammatory conditions.
• Mild to moderate pain, including:
• Headache (tension-type, migraine)
• Toothache and other dental pain
• Musculoskeletal pain (e.g., sprains, strains, low back pain)
• Osteoarthritis and other mild joint pain
• Dysmenorrhea (menstrual pain)
• Postoperative pain
• Pharyngitis and sore throat discomfort
• Pain associated with cold and flu

Clinically Accepted Off-Label Uses:

• Neonatal fever and mild pain under specialist supervision
• Chronic non-cancer pain in patients unable to use NSAIDs
• Mild cancer-related pain as part of multimodal pain control
• Adjunctive treatment in febrile seizures (not for prevention)
• Pain and fever management during pregnancy
• Antipyretic use following childhood vaccinations

রেজিস্টার্ড চিকিৎসকের পরামর্শ ছাড়া ওষুধ সেবন করবেন না।

Adults and Adolescents (12 years and older or body weight ≥50 kg):

• Oral or rectal: 500–1000 mg every 4 to 6 hours as needed
  Maximum single dose: 1000 mg
  Maximum daily dose: 4000 mg (3 g preferred for long-term use)
• Extended-release tablets (665 mg): 2 tablets every 8 hours
  Maximum daily dose: 3990 mg
• Intravenous (IV) infusion:
  1000 mg every 6 hours or 650 mg every 4 hours
  Infuse over 15 minutes
  Maximum daily dose: 4000 mg

Children (2 months to <12 years):

• Oral or rectal: 10–15 mg/kg per dose every 4 to 6 hours
  Maximum: 60 mg/kg/day or 4 doses in 24 hours
• IV dosing:
• Body weight 10–50 kg: 15 mg/kg every 6 hours or 7.5 mg/kg every 4 hours
• Maximum daily dose: 75 mg/kg/day, not exceeding 3750 mg

Neonates and Infants (<2 months):

• Oral or rectal: 7.5–10 mg/kg every 6 to 8 hours
  Maximum daily dose: 30–40 mg/kg
  Use only under strict medical supervision

Elderly:

• No routine dose adjustment if liver and kidney function are normal
• Consider lower maximum dose (≤3000 mg/day) due to increased hepatic sensitivity

Renal Impairment:

• Mild to moderate: no adjustment
• Severe impairment (CrCl <30 mL/min): increase dosing interval to every 6–8 hours
  Use with caution in chronic use
  IV: minimum interval of 6 hours

Hepatic Impairment:

• Mild to moderate: reduce maximum daily dose to ≤2000 mg
• Severe hepatic impairment or active liver disease: contraindicated

Paracetamol primarily acts in the central nervous system by inhibiting the synthesis of prostaglandins via an unidentified variant of the cyclooxygenase enzyme, possibly COX-3. This inhibition reduces the hypothalamic temperature set point, producing antipyresis, and increases pain threshold by decreasing prostaglandin-mediated sensitization of nociceptors. It lacks significant peripheral anti-inflammatory activity due to weak inhibition of peripheral COX enzymes.

• Absorption: Rapid and nearly complete after oral administration; peak plasma levels reached within 30–60 minutes.
• Bioavailability: 63–89%, depending on formulation and gastric emptying.
• Distribution: Volume of distribution ~0.9–1.0 L/kg; plasma protein binding <25%.
• Metabolism: Hepatic metabolism via glucuronidation and sulfation pathways; 5–10% metabolized by CYP2E1 to a hepatotoxic intermediate (NAPQI), which is detoxified by glutathione.
• Excretion: Primarily excreted in urine (>90%) as conjugated metabolites; <5% excreted unchanged.
• Half-life: 2 to 3 hours in healthy individuals; prolonged in overdose or liver dysfunction.

Pregnancy: Considered safe when used at recommended doses. No evidence of teratogenicity or fetal harm in human studies. Preferred analgesic/antipyretic during pregnancy.

Lactation: Paracetamol is excreted into breast milk in very small amounts. Considered compatible with breastfeeding; no adverse effects on infants have been documented.

Caution: Avoid prolonged or high-dose use. Always use the lowest effective dose for the shortest necessary duration.

• Analgesic and antipyretic
• Non-opioid, non-salicylate compound

• Hypersensitivity to paracetamol or any excipients
• Severe hepatic impairment or active liver disease
• History of liver damage following prior paracetamol use
• Use with other paracetamol-containing products

• Hepatotoxicity: Risk increases with overdose, chronic use, alcoholism, fasting, or malnutrition.
• Severe skin reactions: May rarely cause Stevens-Johnson syndrome, toxic epidermal necrolysis, or AGEP; discontinue immediately if rash appears.
• Alcohol use: Chronic alcohol consumption induces CYP2E1 and increases hepatotoxicity risk.
• Malnutrition: Increased susceptibility to liver injury due to reduced glutathione stores.
• Drug overdose: High risk of liver damage and death. Early treatment with N-acetylcysteine (NAC) is critical.
• Monitoring: Consider liver function tests in long-term or high-dose use.

রেজিস্টার্ড চিকিৎসকের পরামর্শ ছাড়া ওষুধ সেবন করবেন না।

Common:

• Nausea
• Vomiting
• Abdominal pain
• Headache

Less Common:

• Skin rash
• Pruritus
• Constipation
• Transient increases in liver enzymes

Serious/Rare:

• Hepatic failure
• Anaphylaxis
• Stevens-Johnson syndrome, toxic epidermal necrolysis
• Thrombocytopenia, neutropenia, pancytopenia
• Acute kidney injury (in overdose or prolonged use)

• Alcohol: Increases the risk of liver toxicity via induction of CYP2E1.
• CYP Enzyme Inducers (e.g., phenytoin, carbamazepine, rifampin): Increase risk of hepatotoxicity by elevating toxic metabolite formation.
• Warfarin and other coumarins: Prolonged use may increase INR; monitor coagulation parameters.
• Cholestyramine: Reduces absorption of paracetamol if given within 1 hour.
• Metoclopramide and domperidone: May enhance absorption by increasing gastric emptying.
• Probenecid: Inhibits glucuronidation, increasing paracetamol plasma levels.

Enzyme systems involved: primarily CYP2E1, minor involvement of CYP1A2 and CYP3A4.

• FDA: Strengthened warnings regarding liver toxicity. Recommends not exceeding 4000 mg/day and avoiding multiple paracetamol-containing products.
• EMA: Issued alerts on rare but serious skin reactions and emphasized the need to educate users on overdose risks.
• MHRA (UK): Reiterated the importance of avoiding overdose from multiple OTC formulations.
• WHO: Reaffirms paracetamol’s role as a first-line analgesic/antipyretic in all age groups, including pregnant women.
• TGA (Australia): Encourages limiting daily doses to ≤3000 mg when used for extended periods.

• Oral tablets, capsules, and syrups: Store at 15–30°C; protect from moisture and light.
• IV solution: Store at 20–25°C; do not refrigerate or freeze. Use within prescribed time after opening.
• Suppositories: Store below 25°C in a cool, dry place.
• Suspensions: Shake well before use. Protect from excessive heat and freezing.
• Keep all formulations out of reach of children.