Paracetamol

Therapeutic Class
antipyretic
Indications

Treatment of mild-to-moderate pain and fever (analgesic/antipyretic)

I.V.: Additional indication: Management of moderate-to-severe pain when combined with opioid analgesia.

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.

Acetaminophen Dosing (Oral and Rectal Formulations)

Age

Dosage (mg)

Age

Dosage (mg)

0-3 mo

40

4-5 y

240

4-11 mo

80

6-8 y

320

1-2 y

120

9-10 y

400

2-3 y

160

11 y

480

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:

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

Intermittent hemodialysis or peritoneal dialysis: Administer every 8 hours.

CRRT: No adjustments necessary.

Adults:

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

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

Intermittent hemodialysis or peritoneal dialysis: No adjustment necessary.

CRRT: Administer every 8 hours.

I.V.: Clcr ≤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

Hypersensitivity to acetaminophen or any component of the formulation; severe hepatic impairment or severe active liver disease

Warnings / Precautions

Hepatotoxicity, Hypersensitivity/anaphylactic reactions, alcoholic liver disease, G6PD deficiency, Hepatic impairment, Hypovolemia, Renal impairment.

Limit dose to <4 g/day.

 

Adverse Reactions

Nausea, allergic reactions, skin rashes, acute renal tubular necrosis.
Potentially Fatal: Very rare, blood dyscrasias (e.g. thrombocytopenia, leucopenia, neutropenia, agranulocytosis); liver damage

Overdosage:

Consult local protocols.

Early symptoms: nausea and vomiting (normally settle within 24 hr of ingestion). After 24 hr symptoms may include right subcostal pain and tenderness, usually indicates development of hepatic necrosis. Liver damage is greatest 3-4 days after ingestion and may lead to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema and death.

Treatment: based on plasma concentration. Acetylcysteine protects the liver if administered within 24 hr after ingestion (most effective if given within 8 hr). Dose: 140 mg/kg orally (loading) followed by 70 mg/kg every 4 hr for 17 doses. Parenteral acetylcysteine is given to those unable to take oral dosing. Activated charcoal may be given if paracetamol is 150 mg/kg or 12 g (whichever is smaller) if it is thought that the paracetamol has been ingested within the previous hr.

Drug Interactions

Reduced absorption of cholestyramine within 1 hr of admin.

Accelerated absorption with metoclopramide.

Decreased effect with barbiturates, carbamazepine, hydantoins, rifampicin and sulfinpyrazone.

Paracetamol may increase effect of warfarin.
Potentially Fatal: Paracetamol increases the risk of liver damage in chronic alcoholics. Increased risk of toxicity with other hepatotoxic drugs or drugs which induce microsomal enzymes e.g. barbiturates, carbamazepine, hydantoins, rifampicin and sulfinpyrazone.

May produce false-positive test results for 5-hydroxyindoleacetic acid.

Food Interactions

Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.

Food: Rate of absorption may be decreased when given with food.

Herb/Nutraceutical: St John's wort may decrease acetaminophen levels.

Mechanism of Actions

Paracetamol exhibits analgesic action by peripheral blockage of pain impulse generation. It produces antipyresis by inhibiting the hypothalamic heat-regulating centre. Its weak anti-inflammatory activity is related to inhibition of prostaglandin synthesis in the CNS.

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
  • Chlorpromazine
  • Diazepam
  • Pregnancy Category

    IV:C

    Lactation

     Enters breast milk/use caution.

    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
    N02BE01
    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
  • Paracetamol 0.125 gm
  • Paracetamol 10 mg
  • Paracetamol 100 mg
  • Paracetamol 1000 mg
  • Paracetamol 12.5 mg
  • Paracetamol 120 mg
  • Paracetamol 125 mg
  • Paracetamol 15 mg
  • Paracetamol 150 mg
  • Paracetamol 156.25 mg
  • Paracetamol 160 mg
  • Paracetamol 162.5 mg
  • Paracetamol 162.50 mg
  • Paracetamol 165 mg
  • Paracetamol 170 mg
  • Paracetamol 240 mg
  • Paracetamol 250 mg
  • Paracetamol 300 mg
  • Paracetamol 320 mg
  • Paracetamol 325 mg
  • Paracetamol 330 mg
  • Paracetamol 333 mg
  • Paracetamol 350 mg
  • Paracetamol 375 mg
  • Paracetamol 400 mg
  • Paracetamol 450 mg
  • Paracetamol 50 mg
  • Paracetamol 500 mg
  • Paracetamol 500mg
  • Paracetamol 600 mg
  • Paracetamol 62.5 mg
  • Paracetamol 625 mg
  • Paracetamol 650 mg
  • Paracetamol 75 mg
  • Paracetamol 750 mg
  • Paracetamol 80 mg
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    2 Responses to Paracetamol

    1. April 24, 2013 at 4:20 pm #

      Good

    2. March 15, 2014 at 9:02 pm #

      1)what is the different bet. therapeutic class and generic pedia classification
      2)what does same I/V incompatible mean ?
      3)thanks for this website is the best without any exception.

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