PRESENTED BY:NUTHAN

Y12PHDO430

GENERIC NAME : PARACETAMOL (PCM) IUPAC NAME :

N-(4-hydroxyphenyl)acetamide ALTERNATE NAME : ACETAMINOPHEN THERAPEUTIC CLASS:

ANALGESIC,ANTIPYRETIC It’s therapeutic effects similar to salicylates,

but it lacks anti inflammatory, antiplatelet, and gastric ulcerative effects.

INDICATION: For temporary pain relief of fever, minor aches and pains.

• AVAILABLE DOSAGE FORM: FOR NEONATES & PAEDIATRICS

• PAIN (Oral route) :Dose may be given every 4–6 hours as necessary

(up to 5 times in 24 hours).

• Dosage for Self-medication of Pain in Children up to 11 Years of Age

Age Weight Oral Dose

≤3 months 2.7–5 kg 40 mg

4–11 months 5–8 kg 80 mg

12–23 months 8–11 kg 120 mg

2–3 years 11–16 kg 160 mg

4–5 years 16–21 kg 240 mg

6–8 years 22–27 kg 320 mg

9–10 years 27–32 kg 400 mg

11 years 33–43 kg 480 mg

For self-medication in children ≥12 years of age, 325–650 mg every 4-6 hours as necessary.

IV ROUTE (FOR PAIN):

Administer as single or repeated doses. Children 2–12 years of age: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours. Adolescents ≥13 years of age and weighing <50 kg: 15 mg/kg every

6 hours or 12.5 mg/kg every 4 hours. Adolescents ≥13 years of age and weighing ≥50 kg: 1 g every 6

hours or 650 mg every 4 hours. May switch between oral and IV acetaminophen without dosage

adjustment.

FEVER (Oral route) : Dose may be given every 4–6 hours as

necessary (up to 5 times in 24 hours)Dosage for Self-medication of Fever in Children up to 11 Years of Age

Age Weight Oral Dose

≤3 months 2.7–5 kg 40 mg

4–11 months 5–8 kg 80 mg

12–23 months 8–11 kg 120 mg

2–3 years 11–16 kg 160 mg

• For self-medication in children ≥12 years of age, 650 mg every 4–6 hours

or 1 g every 6 hours as necessary.

RECTAL ROUTE: Dose may be given every 4 hours as necessary (up to 5 times in 24 hours).

IV ROUTE: Administer as single or repeated doses.

• Children 2–12 years of age: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours.

• Adolescents ≥13 years of age and weighing <50 kg: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours.

• Adolescents ≥13 years of age and weighing ≥50 kg: 1 g every 6 hours or 650 mg every 4 hours. May switch between oral and IV acetaminophen without dosage adjustment.

4–5 years 16–21 kg 240 mg

6–8 years 22–27 kg 320 mg

9–10 years 27–32 kg 400 mg

11 years 33–43 kg 480 mg

DOSE FOR ADULTS :

• Oral - For self-medication, 650 mg every 4–6 hours or 1 g every 6 hours as necessary. Alternatively, 1.3 g as extended-release tablets every 8 hours.

• Rectal - 325–650 mg every 4 hours as necessary.

• IV - Administer as single or repeated doses.

• Adults weighing ≥50 kg: 1 g every 6 hours or 650 mg every 4 hours. May switch between oral and IV acetaminophen without dosage adjustment.

• Adults weighing <50 kg: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours.

• Pain Associated with Migraine Headache:

• Oral Acetaminophen, aspirin, and caffeine for self-medication: 2 tablets (each containing acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg) as a single dose.

• Pain Associated with Osteoarthritis: Oral Maximum 4 g daily.

• Fever : Oral or Rectal - Maximum 4 g daily. Some manufacturers recommend maximum oral dosage of 3 g daily. Self-medication should not exceed 3 days.

• IV - Adults weighing ≥50 kg: Maximum single dose is 1 g, minimum dosing interval is 4 hours, and maximum daily dosage is 4 g per 24-hour period.

• Adults weighing <50 kg: Maximum single dose is 15 mg/kg, minimum dosing interval is 4 hours, and maximum daily dosage is 75 mg/kg per 24-hour period.

• Inhibits the synthesis of prostaglandins in the CNS and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic regulating center.

• PREGNANCY RISK FACTOR: “B”

• LACTATION: Enters breast milk.

• PHARMACODYNAMICS/KINETCS:

- Onset of action : <1hour

- Duration: 4-6 hours

•Absorption: Tmax, Oral, immediate-release: within 1 hour, adults; within 0.5 hour, paediatrics.

•Tmax, Oral, extended-release, adults: 0.5 to 3 hours

•Tmax, Rectal, pediatrics: 107 minutes to 5.1 hours

•Bioavailability Oral: 85% to 98% ; PPB – 10-25%

MECHANISM OF ACTION:

Distribution: Vd, adults: 0.7 to 1 L/kgVd, paediatrics: 0.7 to 1.2 L/kg ; Protein binding: 10% to 25% Metabolism: Liver: extensive N-acetyl-p-benzoquinone imine: major Excretion: Bile: 2.6% Renal: less than 5% unchanged Dialyzable: Yes (hemodialysis) Total body: adults, 0.27 L/hr/kg; paediatrics, 0.12 to 0.34 L/hr/kg Elimination Half LifeAdults: 2 to 3 hours Neonates: 4 to 11 hours Children: 1.5 to 4.2 hours

Dose Adjustments:

•Renal impairment, severe (GFR less than 10 mL/min): increase dosing

interval to every 8 hours for adults and children ; (CrCl 30 mL/min or less) a longer dosing interval and a reduced total daily dose may be warranted.

•Renal impairment, moderate (GFR 10 to 50 mL/min): adult, increase

dosing interval to every 6 hours; pediatric, give usual weight- or age-based dose.

•Renal impairment, mild (GFR greater than 50 mL/min): adult, increase

dosing interval to every 4 hours; pediatric, give usual weight- or age-based dose.

•Dialysis: supplemental doses not required following hemodialysis or peritoneal dialysis.

•Hepatic impairment severe: including active liver disease: use is

contraindicated.

•Hepatic impairment: reduction of the total daily dose may be warranted.

•Geriatric: prolonged half-life in elderly patients; no specific dosage adjustment is necessary based on current kinetic data.

Contraindications: •Active and severe hepatic disease

•Hypersensitivity to acetaminophen or any other components of the product

•Severe hepatic impairment

Drug-Drug Interaction: ACETAMINOPHEN and ISONIAZID may result in an increased risk of

hepatotoxicity. Concurrent use of ACETAMINOPHEN and PNEUMOCOCCAL 13-

VALENT VACCINE, DIPHTHERIA CONJUGATE may result in an inadequate immunologic response to the vaccine.

Concurrent use of ACETAMINOPHEN and IMATINIB may result in increased acetaminophen levels.

Concurrent use of ACETAMINOPHEN and WARFARIN may result in an increased risk of bleeding.

Concurrent use of ACETAMINOPHEN and PHENYTOIN may result in decreased acetaminophen effectiveness and an increased risk of hepatotoxicity.

ADVERSE EFFECTS:

Common:

• Dermatologic: Pruritus (5% or greater )

• Gastrointestinal: Constipation (5% or greater ), Nausea (adult, 34%; paediatric, 5% or greater ), Vomiting (adult, 15%; paediatric, 5% or greater )

• Neurologic: Headache (1% to 10% ), Insomnia (1% to 7% )

• Psychiatric: Agitation (5% or greater )

• Respiratory: Atelectasis (5% or greater )

Serious:

• Dermatologic: Acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, Toxic epidermal necrolysis

• Hepatic: Liver failure

• Respiratory: Pneumonitis

OVER DOSAGE / TOXICITY :

SYMPTOMS:

Hepatic necrosis, Renal tubular necrosis with acute toxicity.

Anaemia and GI disturbances with chronic toxicity.

TREATEMNT:

Acetylcysteine 140mg/kg orally (loading dose) followed by 70mg/kg every 4 hours for 17 doses.

Activated charcoal is very effective at binding acetaminophen.