Paracetamol

Therapeutic Class

Indications

Adult Doses

Pain or fever:

Oral, rectal: 325-650 mg every 4-6 hours or 1000 mg 3-4 times/day; do not exceed 4 g/day.

I.V.:

<50 kg: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours; maximum single dose: 750 mg/dose; maximum daily dose: 75 mg/kg/day (≤3.75 g/day)

≥50 kg: 650 mg every 4 hours or 1000 mg every 6 hours; maximum single dose: 1000 mg/dose; maximum daily dose: 4 g/day

Pediatric Doses

Pain or fever:

Oral, rectal:

Children <12 years: 10-15 mg/kg/dose every 4-6 hours as needed; do not exceed 5 doses (2.6 g) in 24 hours; alternatively, the following age-based doses may be used; see table.

I.V.:

Children 2-12 years: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours; maximum single dose: 15 mg/kg/dose; maximum daily dose: 75 mg/kg/day (≤3.75 g/day).

Adolescents >12 years: See adult dosing.

Doses in Renal impairment

Oral:

Children:

Cl_cr <10 mL/minute: Administer every 8 hours.

Intermittent hemodialysis or peritoneal dialysis: Administer every 8 hours.

CRRT: No adjustments necessary.

Adults:

Cl_cr 10-50 mL/minute: Administer every 6 hours.

Cl_cr <10 mL/minute: Administer every 8 hours.

Intermittent hemodialysis or peritoneal dialysis: No adjustment necessary.

CRRT: Administer every 8 hours.

I.V.: Cl_cr ≤30 mL/minute: Use with caution; consider decreasing daily dose and extending dosing interval.

Doses in Hepatic impairment

Use with caution. Avoid chronic use in hepatic impairment.

Contraindications

Warnings / Precautions

Adverse Reactions

Drug Interactions

Food Interactions

Mechanism of Actions

Metabolism

Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4;

Inhibits CYP3A4 (weak)

Pharmacodynamics

Onset: <1 hr.
Duration: 4-6 hr.
Absorption: Incomplete; depends upon dosage form. Time to peak, serum: oral: 10-60 min; may be delayed in acute overdoses. Decreased rate of absorption with food.
Distribution: Present in most body tissues; crosses the placenta and enters the breast milk. Protein binding: 8-43% (at toxic doses).
Metabolism: Hepatic via glucuronic and sulphuric acid conjugation. At normal therapeutic levels, glucuronide metabolites are metabolised to reactive intermediate (acetylimidoquinone) which is conjugated with glutathione and inactivated; at toxic doses, glutathione conjugation is insufficient leading to increased acetylimidoquinone which may cause hepatic cell necrosis.
Excretion: Plasma half-life: 2.7 hr (adults); 1.5-2 hr (infants and children); 3.5 hr (neonates). Neonates, infants and children up ≤10 yr excrete less glucuronide than adults. Half-life may be longer after toxic doses. Excreted mainly via urine (2- 5% unchanged; 55% as glucuronide metabolites). Total body clearance: 18 L/hr.

Patient Counselling

Consult the treating physician if any of symptom mentioned in adverse drug reaction develop.

Self-medication (OTC use): When used for self-medication, patients should be instructed to contact healthcare provider if used for fever lasting >3 days or for pain lasting >10 days in adults or >5 days in children.

Administration

Suspension, oral: Shake well before pouring a dose.

Injection: For I.V. infusion only. 

Same I/V incompatible

Pregnancy Category

Lactation

Storage Conditions

Intravenous: Do not store above 30°C; do not freeze or refrigerate; if parenteral solution is diluted: use within an hr (infusion time included). 

Oral: Do not store above 30°C; do not freeze or refrigerate.

Rectal: Do not store above 30°C; do not freeze or refrigerate.

ATC Classification

GenericPedia Classification

Storage

Intravenous: Do not store above 30°C; do not freeze or refrigerate; if parenteral solution is diluted: use within an hr (infusion time included). 

Oral: Do not store above 30°C; do not freeze or refrigerate.

Rectal: Do not store above 30°C; do not freeze or refrigerate.

Available As