Dosing & Uses
Dosing Form & Strengths
acetaminophen/diphenhydramine
tablet
- 325mg acetaminophen/12.5mg diphenhydramine hydrochloride (Percogesic)
- 325mg acetaminophen/50mg diphenhydramine hydrochloride (Unisom PM Pain Sleep Caps)
- 500mg acetaminophen/25mg diphenhydramine hydrochloride (Midol PM, Excedrin PM, Tylenol PM)
- 500mg acetaminophen/38mg diphenhydramine citrate (Midol PM, Excedrin PM, Tylenol PM)
- 500mg acetaminophen/12.5mg diphenhydramine hydrochloride (Percogesic Extra Strength, Tylenol Severe Allergy)
caplet
- 500mg acetaminophen/38mg diphenhydramine citrate (Excedrin PM)
- 500mg acetaminophen/50mg diphenhydramine hydrochloride (Legatrin PM)
- 500mg acetaminophen/25mg diphenhydramine hydrochloride (Mapap PM, Tylenol PM)
- 325mg acetaminophen/12.5mg diphenhydramine hydrochloride (Percogesic)
liquid
- 500mg acetaminophen/25mg diphenhydramine hydrochloride)/15mL (Tylenol PM)
gelcap
- 500mg acetaminophen/25mg diphenhydramine hydrochloride (Tylenol PM)
geltab
- 500mg acetaminophen/25mg diphenhydramine hydrochloride (Tylenol PM)
- 500mg acetaminophen/38mg diphenhydramine citrate (Excedrin PM)
oral powder
- 500mg acetaminophen/38mg diphenhydramine citrate per packet (Goody's Powder PM)
Pain with Sleeplessness
Excedrin PM
- 2 tabs/caps PO qHS
Tylenol PM
- 2 tabs/caps/geltabs/gelcaps PO qHS
Goody's PM
- 2 packets PO qHS PRN; may mix powders into glass or water or other liquid
Midol PM
- 2 tabs PO qHS PRN
Percogesic
- 1-2 tabs/caps PO q4hr PRN
Unisom
- 1 tab PO qHS
Dosing Form & Strengths
acetaminophen/diphenhydramine
tablet
- 325mg acetaminophen/12.5mg diphenhydramine hydrochloride (Percogesic)
- 325mg acetaminophen/50mg diphenhydramine hydrochloride (Unisom PM Pain Sleep Caps)
- 500mg acetaminophen/25mg diphenhydramine hydrochloride (Midol PM, Excedrin PM, Tylenol PM)
- 500mg acetaminophen/38mg diphenhydramine citrate (Midol PM, Excedrin PM, Tylenol PM)
- 500mg acetaminophen/12.5mg diphenhydramine hydrochloride (Percogesic Extra Strength, Tylenol Severe Allergy)
caplet
- 500mg acetaminophen/38mg diphenhydramine citrate (Excedrin PM)
- 500mg acetaminophen/50mg diphenhydramine hydrochloride (Legatrin PM)
- 500mg acetaminophen/25mg diphenhydramine hydrochloride (Mapap PM, Tylenol PM)
- 325mg acetaminophen/12.5mg diphenhydramine hydrochloride (Percogesic)
liquid
- 500mg acetaminophen/25mg diphenhydramine hydrochloride)/15mL (Tylenol PM)
gelcap
- 500mg acetaminophen/25mg diphenhydramine hydrochloride (Tylenol PM)
geltab
- 500mg acetaminophen/25mg diphenhydramine hydrochloride (Tylenol PM)
- 500mg acetaminophen/38mg diphenhydramine citrate (Excedrin PM)
oral powder
- 500mg acetaminophen/38mg diphenhydramine citrate per packet (Goody's Powder PM)
Pain with Sleeplessness
Excedrin PM
- <12 years: Safety and efficacy not established
- ≥12 years: 2 tabs/caps PO qHS
Tylenol PM
- <12 years: Safety and efficacy not established
- ≥12 years: 2 tabs/caps/geltabs/gelcaps PO qHS
Goody's PM
- <12 years: Safety and efficacy not established
- ≥12 years: 2 packets PO qHS PRN; may mix powders into glass or water or other liquid
Midol PM
- <12 years: Safety and efficacy not established
- ≥12 years: 2 tabs PO qHS PRN
Percogesic
- <12 years: Safety and efficacy not established
- ≥12 years: 1-2 tabs/caps PO q4hr PRN
Unisom
- 1 tab PO qHS
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Adverse Effects
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
Warnings
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 & Lactation
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.Pharmacology
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%)