acetaminophen/aspirin/diphenhydramine (OTC)

Frequency Not Defined (Acetaminophen)

Angioedema, laryngeal edema

Pruritic maculopapular rash, urticaria

Agranulocytosis, leukopenia, neutropenia, pancytopenia, thrombocytopenia, thrombocytopenic purpura

Hepatotoxicity

May increase uric acid, chloride, glucose

May decrease sodium, calcium, bicarbonate

Anaphylactoid reaction

Frequency Not Defined (Aspirin)

Rash, urticaria

Dyspepsia, heartburn, nausea, stomach pain, vomiting

Tinnitus (high or chronic dose)

Frequency Not Defined (Diphenhydramine)

Sedation

Confusion

May decrease cognitive function in geriatric patients

Anticholinergic effects

Blurred vision

Diplopia

Xerostomia

Dry nasal mucosa

Pharyngeal dryness

Thick bronchial sputum

Constipation

Urinary retention

Agranulocytosis

Hemolytic anemia

Thrombocytopenia

Convulsions

Tachycardia

Palpitations

Hypotension

Nervousness

Restlessness

Euphoria

Vertigo

Menstrual irregularities

Anorexia

Neuritis

Tinnitus

Contraindications

Allergy to acetaminophen, aspirin, or diphenhydramine products

Coadministration with other acetaminophen containing medications; increased risk for severe hepatic impairment

Coadministration with other diphenhydramine containing products (even topical diphenhydramine)

Cautions

Acetaminophen

• Hepatic impairment or consumption of 3 or more alcoholic beverages/day may increase risk for liver damage (associated with acetaminophen)
• Do not take with other products that contain acetaminophen due to risk of additive toxicity/overdose
• 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

Aspirin

• Children and adolescents should not use aspirin for symptoms of viral infections (eg, chickenpox, influenza) due to risk for Reye syndrome
• Risk for GI bleeding
• Avoid with active peptic ulcer disease
• Avoid in severe renal impairment (ie, CrCl <10 mL/min)

Diphenhydramine

• May cause CNS depression, which can impair driving or operating heavy machinery
• May potentiate effects of sedatives such as alcohol
• Use caution in patients with angle-closure glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, thyroid dysfunction
• Elderly patients: Considered high-risk medication for this age group because it may increase risk of falls and has high incidence of anticholinergic effects; may exacerbate existing lower urinary tract conditions or benign prostatic hyperplasia; use in special situations may be appropriate; not recommended for treatment of insomnia, because tolerance develops and risk of anticholinergic effects increases

Pregnancy

Avoid aspirin (NSAIDs) during pregnancy, particularly in third trimester because of risk for premature closure of the ductus arteriosus

Lactation

Information below is from LactMed (a TOXNET database)

Aspirin

• Excreted in human breast milk as the salicylate metabolite
• Avoid high-dose during lactation; may take low-dose aspirin (ie, 75-162 mg/day) and avoid breastfeeding for 1-2 hr after dose to minimize antiplatelet effects on infant

Acetaminophen

• Excreted in low levels in human breast milk; amount in milk is much less than doses usually given to infants

Diphenhydramine

• No studies using modern assay methods to detect drug levels in breast milk have been reported
• Small, occasional doses of diphenhydramine would not be expected to cause any adverse effects in breastfed infants
• Larger doses or more prolonged use may cause effects in the infant or decrease the milk supply

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: Inhibits prostaglandin synthesis in CNS and may block peripheral pain impulse generation; acts on hypothalamus as antipyretic

Aspirin: Acts on hypothalamus to produce antipyresis; anti-inflammatory properties attributed to prostaglandin synthetase inhibition resulting in decreased formation of thromboxane A2

Diphenhydramine: Histamine H1-receptor antagonist with sedative properties

Instructions

Swallow caplet with full glass of water

Storage

Store at room temperature (20-25°C [68-77°F])

Close bottle cap tightly after use