acetaminophen (OTC)

Frequency Not Defined

Angioedema

Disorientation

Dizziness

Pruritic maculopapular rash

Rash

Hyperammonemia

Stevens-Johnson syndrome

Toxic epidermal necrolysis

Urticaria

Gastrointestinal hemorrhage

Laryngeal edema

Agranulocytosis

Leukopenia

Neutropenia

Pancytopenia

Thrombocytopenia

Thrombocytopenic purpura

Hepatotoxicity

Liver failure

Nephrotoxicity

Pneumonitis

Anaphylactoid

Contraindications

Hypersensitivity

Severe active liver disease

Cautions

Hypersensitivity and anaphylactic reactions reported; discontinue immediately if symptoms of allergic or hypersensitivity reactions occur

Acetaminophen is available in many dosage forms and products, check label carefully to avoid overdose

Use caution in patients with hepatic impairment or active liver disease

Risk of hepatotoxicity is higher in patients taking chronic high dose, or use of more than one acetaminophen-containing product

Use caution in patients with severe renal impairment; consider dosage adjustments

Consumption of 3 or more alcoholic drinks/day may increase risk of liver damage

Use with caution in patients with G6PD deficiency

Use caution in patients with chronic malnutrition

Risk for rare, but serious skin reactions that can be fatal; these reactions include Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP); symptoms may include skin redness, blisters and rash

Limit acetaminophen dose from all sources and routes to <4 g/day in adults

Pregnancy

Drug crosses placenta and can be detected in cord blood, newborn serum, and urine immediately after delivery

Increased risk of teratogenic effects not reported following maternal use of drug during pregnancy

Use of normal doses during pregnancy not associated with increased risk of miscarriage or still birth; however, increase in fetal death or spontaneous abortion may be seen with maternal overdose if treatment delayed

Wheezing and asthma in early childhood associated with frequent maternal use of drug during pregnancy

Lactation

Drug is excreted in milk; in general, breastfeeding is generally acceptable if relative infant dose (RID) is <10%; avoid breastfeeding when RID>25%

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Acts on hypothalamus to produce antipyresis

May work peripherally to block pain impulse generation; may also inhibit prostaglandin synthesis in CNS

Pharmacokinetics

Peak Plasma Time: 10-60 min (PO immediate-release); 60-120 min (PO extended-release); 6 hr (PO 500 mg, conventional tablet); 8 hr (PO 650 mg, extended-release tablet)

Peak Plasma Concentration: 2.1 mcg/mL (PO 500 mg, conventional tablet); 1.8 mcg/mL (PO 650 mg, extended-release tablet)

Onset: 1 hr

Distribution: 1 L/kg

Protein Bound: 10 to 25%

Metabolism: Liver (microsomal enzyme systems); conjugation (glucuronic/sulfuric acid)

Metabolites: N-acetyl-p-benzoquinoneimine, N-acetylimidoquinone, NAPQI; further metabolized via conjugation with glutathione

Half-life elimination: 1.25-3 hr (adolescents); 2-5 hr (children); 4 hr (infants); 7 hr (neonates); 2-3 hr (adults)

Excretion: urine (principally as acetaminophen glucuronide with acetaminophen sulfate/mercaptate)