Diphenhydramine
Diphenhydramine hydrochloride
Brand names:Benadryl, Banophen, Sominex
A first-generation H1 antihistamine used as anaphylaxis adjunct (after epinephrine), for moderate allergic reactions, and for treatment of dystonic reactions from antipsychotic or metoclopramide administration. Significant sedation and anticholinergic effects limit operational use. Standard TCCC anaphylaxis bundle includes epinephrine, H1 blocker (diphenhydramine), and H2 blocker (famotidine or cimetidine).
Pharmacology and Actions
Diphenhydramine is a first-generation H1 antihistamine with significant central anticholinergic activity. Competitive antagonism at peripheral H1 receptors blocks histamine-mediated vasodilation, increased capillary permeability, and bronchospasm. Central H1 blockade and anticholinergic activity produce sedation. Also has antiemetic effect via central vestibular pathways and weak antitussive properties. The anticholinergic action makes it useful for acute dystonic reactions from dopamine antagonists (haloperidol, metoclopramide, prochlorperazine).
Indications
- Anaphylaxis adjunct (after epinephrine; H1 component of the H1/H2 combination)
- Moderate allergic reactions (urticaria, angioedema without airway compromise)
- Allergic contact dermatitis pruritus
- Acute dystonic reactions from dopamine antagonists
- Motion sickness (less common; dimenhydrinate or meclizine preferred)
- Insomnia (off-label, OTC PM sleep aids)
Absolute Contraindications
- Known hypersensitivity to diphenhydramine
- Acute asthma exacerbation (dries secretions)
- Neonates and premature infants
- Narrow-angle glaucoma
- Stenosing peptic ulcer
- Bladder neck obstruction
Precautions and Side Effects
Common: significant sedation (the dominant operational concern), dizziness, dry mouth, blurred vision, urinary retention, constipation. CNS: paradoxical excitation in children and some elderly; confusion in elderly. Cardiovascular: tachycardia, palpitations, rare QT prolongation. Anticholinergic burden: cognitive impairment, falls risk in elderly. Drug interactions: additive sedation with alcohol, opioids, benzodiazepines, and other CNS depressants; additive anticholinergic effects with TCAs, antipsychotics, and other antihistamines; MAOIs can prolong and intensify anticholinergic effects. Half-life 3 to 9 hours (longer in elderly). Pregnancy Category B (extensively used in pregnancy). Passes into breast milk; may cause infant sedation or reduce milk supply. AVOID IN ELDERLY (Beers criteria - high anticholinergic burden, falls risk). Pediatrics: paradoxical excitation possible; avoid in infants.
Adult Dosing
Pediatric Dosing
Children 2 to 5 years: 6.25 mg PO every 4 to 6 hours, max 37.5 mg per 24 hours. Children 6 to 11 years: 12.5 to 25 mg PO every 4 to 6 hours, max 150 mg per 24 hours. IV/IM: 1.25 mg/kg every 6 hours, max 50 mg per dose. Avoid in infants under 2 years.
Pharmacokinetics
Peak Effect: 1 to 4 hours.
Duration: 4 to 6 hours.
Storage and Handling
Store at room temperature (15 to 30 degrees C). Protect from light. Stable in standard EMS storage conditions. Tablets, capsules, oral solution, and injectable all robust in operational environments.
Reconstitution:
Injectable supplied as 50 mg/mL. For IV: can be given undiluted slowly (over 1 minute) or diluted in 10 to 20 mL of NS, D5W, or LR. IM: undiluted, deep muscular injection.
TCCC and TECC Role
Diphenhydramine is part of TCCC anaphylaxis management as the H1 component of the H1/H2 blocker adjunct after epinephrine. TCCC 2026 anaphylaxis protocol: epinephrine first (IM, repeated as needed), then H1 blocker (diphenhydramine 25 to 50 mg IV/IM), H2 blocker (famotidine or cimetidine), and corticosteroid (methylprednisolone or dexamethasone). Mission impact is substantial - significant sedation makes the operator non-mission-capable after administration. For moderate allergic reactions without anaphylaxis, second-generation antihistamines (loratadine, cetirizine, fexofenadine) preserve operational status.
Diphenhydramine's tactical relevance is concentrated in two scenarios: anaphylaxis adjunct after epinephrine, and emergency treatment of dystonic reactions (typically from metoclopramide, haloperidol, or prochlorperazine administration). For routine allergic complaints in operators who must remain functional, second-generation antihistamines (loratadine, cetirizine, fexofenadine) are vastly preferred - similar antihistamine efficacy with minimal sedation. Reserve diphenhydramine for situations where sedation is acceptable or where its specific anticholinergic profile is needed.
Treating diphenhydramine as a substitute for epinephrine in anaphylaxis. It is adjunctive only - epinephrine is the life-saving treatment; H1 blockade reduces cutaneous symptoms and modestly speeds resolution but does not prevent death from anaphylaxis. Giving diphenhydramine before or instead of epinephrine in a patient with airway, breathing, or circulatory compromise is dangerous. The other mistake is routine use for daily allergic complaints in operators - the sedation burden over a deployment is significant, and second-generation antihistamines accomplish the same goal without the operational cost.
This drug profile is provided as educational reference material for trained medical providers. It is not medical advice, not a substitute for formal training, and not a substitute for current published guidelines or medical direction.
Drug administration is governed by your scope of practice, agency standing orders, medical director protocols, and applicable state and federal regulations. Controlled substances are subject to additional handling, accountability, and documentation requirements per DEA and state law. Always verify dosing, indications, contraindications, and route of administration against current published guidelines and your local protocols before administration.
If this content is being viewed during a medical emergency, call 911 immediately and follow the direction of your local emergency dispatch and medical control. Do not use this reference as a substitute for emergency medical services.
Drug information evolves. Last reviewed dates and source citations are provided for each entry. Confirm currency against the cited source before clinical use.
Penn Tactical Solutions publishes this reference for educational purposes. PTS does not provide medical direction and does not assume responsibility for clinical decisions made in the field. Clinical responsibility rests with the administering provider, their medical director, and their agency.
Educational reference for trained medical providers. Not medical advice. Not a substitute for formal training, current published guidelines, or medical direction. Drug administration is governed by your scope of practice, agency standing orders, medical director protocols, and applicable state and federal regulations. Controlled substances require additional storage, accountability, and documentation per DEA and state law.
In a medical emergency, call 911. This reference is not a substitute for emergency medical services.
Verify dosing, indications, and contraindications against current published guidelines and your local protocols before administration. Confirm content currency against the source citation. Penn Tactical Solutions does not provide medical direction. Clinical responsibility rests with the administering provider, their medical director, and their agency.
Diphenhydramine
| IV/IO | 25 to 50 mg IV slow push over 1 minute. Standard anaphylaxis adjunct dose: 25 to 50 mg IV after epinephrine has been administered. For acute dystonia: 25 to 50 mg IV. (Immediate) |
| IM | 25 to 50 mg IM. Useful for anaphylaxis adjunct when IV access not available, and for acute dystonia. (20 to 30 minutes) |
| IN | None (None) |
| PO | 25 to 50 mg PO every 4 to 6 hours as needed. Maximum 300 mg per 24 hours. (15 to 30 minutes) |