acetaminophen/diphenhydramine (OTC)

Frequency Not Defined

Hypotension

Tachycardia

Sedation

Sleepiness

Dermatologic rash

Increased appetite

Xerostomia

Anemia blood dyscrasias (neutropenia, pancytopenia, leukopenia)

Bilirubin and alkaline phosphatase may increase

Urinary retention

Contraindications

Hypersensitivity

Use within 14 days of MAO inhibitor therapy

G-6-PD deficiency

Severe hepatic impairment

Cautions

Acetaminophen: Hepatotoxicity possible in chronic alcoholics following various dose levels; severe or recurrent pain or high or continued fever may indicate a serious illness; contained in many OTC products and combined use with these products may result in toxicity due to cumulative doses exceeding recommended maximum dose

Acetaminophen: 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

Diphenhydramine: May cause significant confusional symptoms; not for administration to premature or full-term neonates

Pregnancy category: C

Lactation: excreted in breast milk, use caution

Pregnant or breastfeeding patients should seek advice of health professional before using OTC drugs

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

Acetaminophen blocks pain impulse generation peripherally & may inhibit the generation of prostaglandin in the CNS; reduces fever by inhibiting the hypothalamic heat-regulating center

Diphenhydramine competitively blocks histamine from binding to H1 receptors; significant antimuscarinic activity & penetrates CNS, which causes pronounced tendency to induce sedation

Pharmacokinetics

Acetaminophen

• Peak plasma time: 10-60 min (PO immediate release); 60-120 min (PO extended release); 6 hr (PO 500 mg tablet); 8 hr (PO 650 mg extended release tablet)
• Vd: 1 L/kg
• Protein binding: 10-25%
• Metabolism: Liver (microsomal enzyme systems); conjugation (glucuronic acid)
• Half-life: 1.25-3hr
• Excretion: Urine

Diphenhydramine

• Bioavailability: 42-62% (PO)
• Onset: 15-30 min
• Duration: 4-6 hr
• Peak plasma time: 2 hr (PO)
• Protein bound: 98.5%
• Vd: 22 L/kg (children); 17 L/kg (adults); 14 L/kg (Elderly)
• Half-life: 5 hr (children); 9 hr (adults); 13.5 hr (elderly)
• Excretion: Urine (50-75%)