BENADRYL PRESERVATIVE FREE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BENADRYL PRESERVATIVE FREE (BENADRYL PRESERVATIVE FREE).
Diphenhydramine competitively antagonizes histamine at H1-receptors on effector cells, leading to relief of allergic symptoms. It also possesses anticholinergic, antiemetic, sedative, and local anesthetic effects.
| Metabolism | Primarily metabolized by CYP2D6; undergoes N-demethylation and N-dealkylation in the liver. |
| Excretion | Primarily renal (90% as metabolites and unchanged drug); ~1% excreted in feces via bile. Unchanged diphenhydramine accounts for <5% of urinary recovery. |
| Half-life | Terminal elimination half-life: 4-8 hours (mean ~5 hours). Prolonged in hepatic impairment (up to 2-fold) and elderly (7-12 hours). |
| Protein binding | Approximately 78-85% bound, primarily to albumin. |
| Volume of Distribution | 3-5 L/kg (mean 4.5 L/kg). Indicates extensive tissue distribution with accumulation in lungs, spleen, and brain. |
| Bioavailability | Oral: 40-60% (first-pass metabolism). IV and IM: 100%. |
| Onset of Action | Intravenous: immediate (2-3 minutes); intramuscular: 15-30 minutes; oral: 15-30 minutes. |
| Duration of Action | Antihistaminic effects: 4-6 hours oral/IM; 2-4 hours IV. Sedative effects may persist up to 12 hours. |
| Molecular Weight | 255.35 |
25-50 mg IV/IM every 4-6 hours as needed; maximum single dose 100 mg, maximum daily dose 400 mg.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended; use with caution in severe renal impairment (GFR <10 mL/min) due to risk of accumulation. |
| Liver impairment | No specific Child-Pugh based adjustments; use with caution in severe hepatic impairment. |
| Pediatric use | Children >12 years: 25-50 mg IV/IM every 4-6 hours; maximum daily dose 300 mg. Children 6-12 years: 12.5-25 mg IV/IM every 4-6 hours; maximum daily dose 150 mg. Children <6 years: 5 mg/kg/day IV/IM divided every 6-8 hours, not to exceed 150 mg/day. |
| Geriatric use | Initiate at lowest effective dose (e.g., 25 mg) due to increased risk of sedation, dizziness, and anticholinergic effects; maximum daily dose 150 mg. |
| 1st trimester | Avoid unless clearly needed. Epidemiologic data do not show increased risk of major malformations, but use is not recommended due to lack of controlled studies. |
| 2nd trimester | Use with caution. Animal studies show no harm, but human data are limited. Consider risk-benefit. |
| 3rd trimester | Use with caution, especially near term. May cause uterine contractions or neonatal distress if used in high doses. |
Clinical note
Comprehensive clinical and safety monograph for BENADRYL PRESERVATIVE FREE (BENADRYL PRESERVATIVE FREE).
| Placental transfer | Diphenhydramine crosses the placenta. Transfer is likely moderate based on its molecular weight and lipophilicity. |
| Breastfeeding | Diphenhydramine is excreted into breast milk in small amounts; the American Academy of Pediatrics considers it compatible with breastfeeding, but it may cause drowsiness or irritability in the infant. Use lowest effective dose for shortest duration. |
■ FDA Black Box Warning
Not recommended for use in neonates or premature infants due to increased risk of paradoxical CNS excitation or seizures.
| Common Effects | Erythema skin redness Burning sensation Scaling Stinging sensation |
| Serious Effects |
Hypersensitivity to diphenhydramine or any componentPremature infantsNeonatesBreastfeeding infants (relative contraindication)Acute asthma attackConcurrent use with MAOIs (due to anticholinergic potentiation)
| Precautions | May cause marked drowsiness and impair cognitive/motor skills; avoid driving or operating machinery., Concurrent use with other CNS depressants (e.g., alcohol, benzodiazepines) potentiates sedation., Use caution in patients with glaucoma, prostatic hypertrophy, bladder neck obstruction, or asthma., Elderly patients are more sensitive to anticholinergic effects (e.g., confusion, urinary retention)., May cause paradoxical excitation in children. |
Loading safety data…
| Lactation Rating | L2 (probably compatible) or consider 'Safe' |
| Teratogenic Risk | FDA Pregnancy Category B. Animal studies have not demonstrated teratogenic effects; however, no adequate controlled studies in pregnant women. Diphenhydramine, the active ingredient, crosses the placenta. In first trimester, large epidemiologic studies have not shown a significant increase in major malformations, though a small risk for oral clefts has been suggested in some analyses. In second and third trimesters, exposure may be associated with transient neonatal withdrawal symptoms (tremors, irritability) if used near term. Use only if clearly needed. |
| Fetal Monitoring | No specific monitoring required but observe for maternal anticholinergic effects (dry mouth, urinary retention, sedation). Near term, monitor neonate for signs of withdrawal (tremors, irritability) or respiratory depression if used close to delivery. |
| Fertility Effects | No significant effects on fertility reported in animal studies. In humans, no well-documented impact on fertility. However, high doses may cause anticholinergic effects that could potentially affect reproductive function indirectly (e.g., vaginal dryness). |
| Food/Dietary |
| No specific food interactions are clinically relevant. Avoid alcohol and CNS depressant-containing foods (e.g., beverages with alcohol) due to additive sedative effects. |
| Clinical Pearls | BENADRYL PRESERVATIVE FREE (diphenhydramine injection, 50 mg/mL) is intended for deep intramuscular or slow intravenous administration. For IV use, inject at a rate not exceeding 25 mg/min to avoid hypotension and arrhythmias. In elderly patients, the anticholinergic side effects (confusion, urinary retention) are more pronounced; avoid use when possible. For anaphylaxis, epinephrine is first-line; diphenhydramine is adjunctive. Do not administer intra-arterially due to risk of gangrene. The preservative-free formulation is preferred for patients with sulfite sensitivity or neonates. Monitor for QT prolongation in patients at risk. |
| Patient Advice | This medication may cause drowsiness; do not drive or operate heavy machinery until you know how it affects you. · Avoid alcohol and other CNS depressants (e.g., sedatives, tranquilizers) as they can increase sedation. · Report any difficulty urinating, blurred vision, or rapid/pounding heartbeat to your healthcare provider. · Take exactly as prescribed; do not exceed the recommended dose. · For injection, the healthcare provider will administer it; do not attempt self-injection unless trained. · Keep out of reach of children; overdose may cause hallucinations, seizures, or coma. |