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diphenhydrAMINE (Monograph)

Brand names: AllerMax, Benadryl, Benadryl Allergy, Compoz, Diphenhist, ... show all 12 brands
Drug class: First Generation Antihistamines
- Antiparkinsonian Agents

Medically reviewed by Drugs.com on Oct 3, 2023. Written by ASHP.

Introduction

First generation antihistamine; an ethanolamine-derivative.a

Uses for diphenhydrAMINE

Acute Allergic Reactions

Amelioration of allergic reactions to blood or plasma.101

Adjunct to epinephrine and other standard measures for management of anaphylaxis after acute symptoms have been controlled.101 102 103

Used IV or IM for management of other uncomplicated allergic conditions of the immediate type when oral therapy is impossible or contraindicated.101

Allergic Rhinitis

Self-medication for temporary relief of rhinorrhea, sneezing, lacrimation, itching eyes, oronasopharyngeal irritation or itching, or cough associated with allergic rhinitis (e.g., hay fever) or other upper respiratory allergies.b o p q r s xx zz bbb

Used in fixed combination with other agents (e.g., acetaminophen, phenylephrine) for relief of rhinorrhea, sneezing, lacrimation, itching eyes, oronasopharyngeal itching, and/or other symptoms (e.g., headache, nasal/sinus congestion) associated with seasonal or perennial allergic rhinitis or other upper respiratory allergies.110 112 114

Use fixed-combination preparations only when symptoms amenable to each ingredient are present concurrently.b

Common Cold

Self-medication for temporary relief of symptoms associated with the common cold (e.g., rhinorrhea, sneezing, cough).d q s qq r ss ccc fff

Used in fixed combination with other agents (e.g., acetaminophen, phenylephrine) for symptomatic relief of rhinorrhea, sneezing, and/or other symptoms associated with the common cold (e.g., headache, minor aches and pains, sore throat, cough, nasal congestion).108 112 114

Insomnia

Self-medication for short-term (i.e., ≤2 weeks) management of occasional sleeplessness,v tt uu particularly in individuals who have difficulty falling asleep.104

Used in fixed combination with other agents (e.g., acetaminophen) for short-term management of occasional sleeplessness.107 109 111 113

Development of tolerance reported with repeated use.104

Dermatologic Disorders

Systemic antihistamines may be more effective than topical, especially if pruritus is generalized, and less likely to cause sensitivity reactions than when applied topically for pruritus associated with various dermatologic conditions.mm

Motion Sickness

Prevention and treatment of nausea, vomiting, and/or vertigo associated with motion sickness.101 hh ii jj kk ll

Parkinsonian Syndrome

May be useful as alternative therapy in the management of tremor early in the course of parkinsonian syndrome.kkk lll mmm Also may be useful in the management of drug-induced extrapyramidal reactions.mmm

Used IV for management of parkinsonian syndrome when oral therapy is impossible or contraindicated.101 Used specifically in geriatric patients who are unable to tolerate more potent agents; for mild cases of parkinsonism in younger patients; and in combination with centrally acting anticholinergic agents in other cases of parkinsonism.101

diphenhydrAMINE Dosage and Administration

Administration

Administer diphenhydramine hydrochloride orallys or by IV or deep IM injection.a

Administer diphenhydramine citrate-containing preparations orally.a

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

IV injection preferred over deep IM injection.a

IV use in a home-care setting should be employed under careful supervision.a

Rate of Administration

≤25 mg/minute.vv

Dosage

Available as diphenhydramine hydrochloride and diphenhydramine citrate; dosage is expressed in terms of diphenhydramine hydrochlorides or diphenhydramine citrate.a

Diphenhydramine citrate available only in fixed-combination preparations.a

12.5 mg diphenhydramine hydrochloride equivalent to 19 mg diphenhydramine citrate.a

Fixed-combination preparations do not permit individual titration of dosages.b When used in fixed combination with other agents (e.g., acetaminophen, phenylephrine), select a dosage that is within the usual therapeutic range for each ingredient.b Because combinations and dosage strengths vary for fixed-combination preparations, consult manufacturer’s product labeling for appropriate dosage of the specific preparation.

Pediatric Patients

Allergic Conditions and the Common Cold
Acute Allergic Reactions
IV or IM

Children >1 month of age: 5 mg/kg daily or 150 mg/m2 daily (up to a maximum of 300 mg daily) divided in 4 doses.vv

Alternatively, 1–2 mg/kg recommended by some experts.102 103

Allergic Rhinitis and the Common Cold
Oral

Self-medication in children 2–5 years of age: 6.25 mg every 4–6 hours (as diphenhydramine hydrochloride) or 9.5 mg every 4 hours (as diphenhydramine citrate) when directed by a clinician; do not exceed 37.5 mg (as diphenhydramine hydrochloride) or 57 mg (as diphenhydramine citrate) in 24 hours.q ww yy (See Pediatric Use under Cautions.)

Self-medication in children 6–11 years of age: 12.5–25 mg every 4–6 hours (as diphenhydramine hydrochloride) or 19 mg every 4 hours (as diphenhydramine citrate); do not exceed 150 mg (as diphenhydramine hydrochloride) or 76 mg (as diphenhydramine citrate) in 24 hours.q s ww

Self-medication in children ≥12 years of age: 25–50 mg every 4–6 hours (as diphenhydramine hydrochloride)q s ww or 38 mg every 4 hours (as diphenhydramine citrate);yy aaa do not exceed 300 mg (as diphenhydramine hydrochloride) or 152 mg (as diphenhydramine citrate) in 24 hours.q s ww yy aaa

Insomnia
Oral

Children 2–11 years of age† [off-label]: 1 mg/kg (as diphenhydramine hydrochloride) 30 minutes before retiring; do not exceed 50 mg.n

Self-medication in children ≥12 years of age: 50 mg (as diphenhydramine hydrochloride) or 76 mg (as diphenhydramine citrate) at bedtime as needed, or as directed by a clinician.tt Higher dosages do not produce substantially greater benefit but may be associated with a higher incidence of adverse (e.g., anticholinergic) effects.tt

Use not recommended for ≥7–10 nights.104

Motion Sickness
Oral

Children 2–5 years of age† [off-label]: 6.25 mg (as diphenhydramine hydrochloride) 30–60 minutes before travel and every 4–6 hours during travel; do not exceed 37.5 mg in 24 hours.105

Self-medication in children 6–11 years of age: 12.5–25 mg (as diphenhydramine hydrochloride) 30–60 minutes before travel and every 4–6 hours during travel; do not exceed 150 mg in 24 hours.105 hh

Self-medication in children ≥12 years of age: 25–50 mg (as diphenhydramine hydrochloride) 30 minutes before exposure to motion and then every 4–6 hours (before meals and at bedtime) for duration of exposure; do not exceed 300 mg in 24 hours.hh

IV or IM

Children >1 month of age: 5 mg/kg daily or 150 mg/m2 daily (up to a maximum of 300 mg daily) divided in 4 doses.vv

Parkinsonian Syndrome
IV or IM

Children >1 month of age: 5 mg/kg daily or 150 mg/m2 daily (up to a maximum of 300 mg daily) divided in 4 doses.vv

Adults

Allergic Conditions and the Common Cold
Acute Allergic Reactions
IV or IM

10–50 mg; in a few patients, up to 100 mg may be required.vv

Alternatively, 25–50 mg recommended by some experts.102 103

Allergic Rhinitis and the Common Cold
Oral

Self-medication: 25–50 mg every 4–6 hours (as diphenhydramine hydrochloride)q s ww or 38 mg every 4 hours (as diphenhydramine citrate);yy aaa do not exceed 300 mg (as diphenhydramine hydrochloride) or 152 mg (as diphenhydramine citrate) in 24 hours.q s ww yy aaa

Insomnia
Oral

Self-medication: 50 mg (as diphenhydramine hydrochloride) or 76 mg (as diphenhydramine citrate) at bedtime as needed, or as directed by a clinician.tt Higher dosages do not produce substantially greater benefit but may be associated with a higher incidence of adverse (e.g., anticholinergic) effects.tt

Use not recommended for ≥7–10 nights.104

Motion Sickness
Oral

Self-medication: 25–50 mg (as diphenhydramine hydrochloride) 30 minutes before exposure to motion and then every 4–6 hours (before meals and at bedtime) for duration of exposure; do not exceed 300 mg in 24 hours.hh

IV or IM

10–50 mg; in a few patients, up to 100 mg may be required.vv

Parkinsonian Syndrome
Oral

Initially, 25 mg 3 times daily (as diphenhydramine hydrochloride).a If necessary, gradually increase dosage to 50 mg 4 times daily.a

IV or IM

10–50 mg; in a few patients, up to 100 mg may be required.vv

Prescribing Limits

Pediatric Patients

Oral

Children 2–5 years of age: Maximum 37.5 mg (as diphenhydramine hydrochloride) or 57 mg (as diphenhydramine citrate) in 24 hours.q ww yy (See Pediatric Use under Cautions.)

Children 6–11 years of age: Maximum 150 mg (as diphenhydramine hydrochloride) or 76 mg (as diphenhydramine citrate) in 24 hours.q s ww

Children ≥12 years of age: Maximum 300 mg (as diphenhydramine hydrochloride) or 152 mg (as diphenhydramine citrate) in 24 hours.q s ww yy aaa

IV or IM

Children >1 month: Maximum 300 mg daily.101

Adults

Oral

Maximum 300 mg in 24 hours.q s ww

IV or IM

Maximum 400 mg daily.101

Detailed Diphenhydramine dosage information

Cautions for diphenhydrAMINE

Contraindications

Warnings/Precautions

Warnings

Concomitant Diseases

Patients with glaucoma, respiratory conditions (e.g., emphysema, chronic bronchitis), or difficulty urinating due to prostatic hypertrophy should consult a clinician before initiating therapy with diphenhydramine.s

Use with caution in patients with increased IOP, angle-closure glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, bladder-neck obstruction, symptomatic prostatic hypertrophy, active or a history of lower respiratory disease (e.g., bronchial asthma), hyperthyroidism, or cardiovascular disease (e.g., hypertension).vv

CNS Effects

Risk of marked drowsiness.s Among first generation antihistamines, ethanolamines (e.g., diphenhydramine) considered the most sedating106 c and alkylamines (e.g., brompheniramine, chlorpheniramine) considered the least sedating.106

Possible excitability (especially in children).s

Caution when driving a motor vehicle, operating machinery, or engaging in other potentially hazardous tasks.s c (See CNS Depressants under Interactions.)

Diphenhydramine Toxicity

Risk of toxicity.ddd (See Pediatric Use under Cautions.) Do not use more often than directed for any condition; do not concomitantly use more than one preparation containing diphenhydramine (e.g., avoid simultaneous use of oral and topical preparations).ddd jjj

Local Necrosis

Risk of local necrosis with subcutaneous or intradermal administration.vv Do not use diphenhydramine injection as a local anesthetic.vv

Sensitivity Reactions

Sulfite Sensitivity

Some formulations may contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.a

General Precautions

Duration of Therapy

When used for insomnia, avoid using for self-medication for longer than 7–10 nights,104 and consult a clinician if insomnia persists continuously for >2 weeks.v tt

Use of Fixed Combinations

When used in fixed combination with other agents (e.g., acetaminophen, phenylephrine), consider the cautions, precautions, and contraindications associated with the concomitant agent(s).107 108 109 110 111 112 113 114

Specific Populations

Pregnancy

Category B.vv

Lactation

Has been detected in milk.k l Discontinue nursing or the drug because of potential risk to nursing infants.s u vv

Pediatric Use

Risk of diminished mental alertness.vv Risk of excitation in young pediatric patients.vv

Risk of diphenhydramine toxicity (e.g., dilated pupils, flushed face, hallucinations, ataxic gait, urinary retention) when oral preparations used concomitantly with topical preparations of diphenhydramine.ddd (See Diphenhydramine Toxicity under Cautions.)

Potential for misuse and abuse following parenteral administration over a prolonged period of time.iii

Use with caution in infants and young children; should not be used in premature or full-term neonates.s u vv Children <6 years of age should receive oral diphenhydramine only under the direction of a physician.b q t hh

Safety and efficacy of diphenhydramine as a nighttime sleep aid in children <12 years of age have not been established.v tt Consider risk of possible CNS stimulation when used as nighttime sleep aids.v w

Risk of overdosage and toxicity (including death) in children <2 years of age receiving OTC preparations containing antihistamines, cough suppressants, expectorants, and nasal decongestants alone or in combination for relief of symptoms of upper respiratory tract infection.nnn ooo Limited evidence of efficacy for these preparations in this age group; appropriate dosages not established.nnn Therefore, FDA recommended not to use such preparations in children <2 years of age;ppp safety and efficacy in older children under evaluation.rr ttt Because children 2–3 years of age also are at increased risk of overdosage and toxicity, some manufacturers of oral nonprescription cough and cold preparations agreed to voluntarily revise the product labeling to state that such preparations should not be used in children <4 years of age.qqq rr sss ttt FDA recommends that parents and caregivers adhere to dosage instructions and warnings on the product labeling that accompanies the preparation and consult a clinician about any concerns.qqq rr sss Clinicians should ask caregivers about use of OTC cough/cold preparations to avoid overdosage.nnn

Geriatric Use

Possible increased risk of dizziness, sedation, and hypotension in patients ≥60 years of age.vv

Common Adverse Effects

Sedation, sleepiness, dizziness, disturbed coordination, epigastric distress, thickening of bronchial secretions.vv

Drug Interactions

CNS Depressants

Potential pharmacologic interaction (additive CNS depression) with alcohol and other CNS depressants (e.g., hypnotics, sedatives, tranquilizers).vv

Laboratory Test Interferences

Antihistamines may suppress inhalation-challenge testing with histamine or antigen as well as the wheal and flare reactions to antigen skin testing.x y z aa bb cc dd ee ff

Specific Drugs

Drug

Interaction

MAO inhibitors

MAO inhibitors prolong and intensify anticholinergic effects of antihistaminesvv
Diphenhydramine drug interactions (more detail)

diphenhydrAMINE Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration, but only about 40–60% of an oral dose reaches systemic circulation as unchanged drug.e f gg oo pp

Onset

Appears in plasma within 15 minutese following oral administration of a single dose; peak plasma concentrations are attained within 1–4 hours.e f g h

Antihistamine effect peaks within 1–3 hours and persists for up to 7 hours after administration of a single dose.f s

Sedative effects peak within 1–3 hours after administration of a single dose.e f oo pp

Distribution

Extent

Highest concentrations detected in the lungs, spleen, and brain in rats; small amounts detected in the heart, muscle, and liver.i

Crosses the placentaj and has been detected in milk, although the extent of distribution into milk has not been quantitated.k l

Plasma Protein Binding

Approximately 80–85%.e oo uuu

Special Populations

Larger volume of distribution in Asian adults (about 480 L) than in white adults (188–336 L).f oo pp oo

Less extensive protein binding reported in healthy Asian adultsoo and in adults with liver cirrhosis.uuu

Elimination

Metabolism

Rapidly and apparently almost completely metabolized.e f g m

Undergoes substantial first-pass metabolism in the liver following oral administration.e f gg

Elimination Route

Excreted in urine (50–75%) mainly as metabolites.m s

Half-Life

2.4–9.3 hours in healthy adults.e f g gg oo uuu pp

Special Populations

Terminal elimination half-life is prolonged in adults with liver cirrhosis.uuu

Stability

Storage

Oral

Capsules and Tablets

15–25°C.s Protect from heat, light, and moisture.vv

Parenteral

Injection

15–30°C.vv Protect from freezing and light.vv

Compatibility

Parenteral

Solution CompatibilityHID

Compatible

Dextrose–Ringer’s injection combinations

Dextrose–Ringer’s injection, lactated, combinations

Dextrose–saline combinations

Dextrose 2.5, 5, or 10% in water

Fat emulsion 10%, intravenous

Ionosol products

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Sodium lactate (1/6) M
Drug Compatibility
Admixture CompatibilityHID

Compatible

Amikacin sulfate

Aminophylline

Ascorbic acid injection

Bleomycin sulfate

Colistimethate sodium

Erythromycin lactobionate

Lidocaine HCl

Methyldopate HCl

Nafcillin sodium

Penicillin G potassium

Penicillin G sodium

Polymyxin B sulfate

Incompatible

Amphotericin B

Dexamethasone sodium phosphate with lorazepam and metoclopramide HCl

Iodipamide meglumine (% unspecified)
Y-Site CompatibilityHID

Compatible

Abciximab

Aldesleukin

Amifostine

Argatroban

Azithromycin

Aztreonam

Bivalirudin

Caspofungin acetate

Ceftaroline fosamil

Ciprofloxacin

Cisatracurium besylate

Cladribine

Dexmedetomidine HCl

Docetaxel

Doripenem

Doxorubicin HCl liposome injection

Etoposide phosphate

Famotidine

Fenoldopam mesylate

Fentanyl citrate

Filgrastim

Fluconazole

Fludarabine phosphate

Gallium nitrate

Gemcitabine HCl

Granisetron HCl

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Hydrocortisone sodium succinate

Hydromorphone HCl

Idarubicin HCl

Linezolid

Melphalan HCl

Meperidine HCl

Meropenem

Methadone HCl

Morphine sulfate

Ondansetron HCl

Oxaliplatin

Paclitaxel

Pemetrexed disodium

Piperacillin sodium–tazobactam sodium

Potassium chloride

Propofol

Remifentanil HCl

Sargramostim

Tacrolimus

Teniposide

Thiotepa

Vinorelbine tartrate

Incompatible

Allopurinol sodium

Amphotericin B cholesteryl sulfate complex

Foscarnet sodium

Variable

Acyclovir sodium

Actions

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

diphenhydrAMINE Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

25 mg*

Diphenhist

Rugby

Diphenhydramine Hydrochloride Capsules

50 mg*

Diphenhydramine Hydrochloride Capsules

Sleepinal Night-time Sleep Aid Capsules

Blairex

Capsules, liquid-filled

25 mg

Benadryl Allergy Dye-Free Liqui-Gels

McNeil Consumer

50 mg

Unisom SleepGels

Chattem

Elixir

12.5 mg/5 mL*

Diphenhydramine Hydrochloride Elixir

Hydramine Elixir

Goldline

Solution

12.5 mg/5 mL*

AllerMax

Pfeiffer

Diphenhist

Rugby

Diphenhydramine Solution

Tablets

25 mg*

Diphenhist Captabs

Rugby

diphenhydrAMINE Hydrochloride Tablets

Nytol QuickCaps Caplets

GlaxoSmithKline

Sominex Nighttime Sleep Aid

GlaxoSmithKline

50 mg

Compoz Nighttime Sleep Aid

Medtech

Nighttime Sleep Aid

Rugby

Sominex Nighttime Sleep Aid

GlaxoSmithKline

Twilite Caplets

Pfeiffer

Tablets, film-coated

25 mg

Benadryl Allergy Ultratab

McNeil Consumer

50 mg

AllerMax Caplets

Pfeiffer

Sominex Caplets Maximum Strength

GlaxoSmithKline

Parenteral

Injection

50 mg/mL*

Benadryl

Pfizer

diphenhydrAMINE Hydrochloride Injection
diphenhydrAMINE Citrate and Acetaminophen

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

For solution

38 mg/packet with 500 mg/packet Acetaminophen

Goody’s PM Powder

GlaxoSmithKline

Tablets, film-coated

38 mg with Acetaminophen 500 mg

Excedrin P.M. Caplets

Novartis

Excedrin P.M. Gelcaps

Novartis
Other diphenhydrAMINE Citrate Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

38 mg with Aspirin 500 mg

Bayer PM Extra Strength Caplets

Bayer
diphenhydrAMINE Hydrochloride Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

12.5 mg/5 mL with Acetaminophen 160 mg/5 mL, and Phenylephrine Hydrochloride 2.5 mg/5 mL

Children’s Tylenol Plus Cold and Allergy

McNeil

Tablets

25 mg with Acetaminophen 500 mg

Tylenol PM Caplets

McNeil

Tylenol PM Geltabs

McNeil

Tylenol PM Rapid Release Gels

McNeil

Tablets, film-coated

12.5 mg with Acetaminophen 325 mg and Phenylephrine Hydrochloride 5 mg

Sudafed PE Severe Cold Caplets

Pfizer

12.5 mg with Acetaminophen 500 mg

Percogesic Aspirin-Free Caplets Extra Strength

Medtech

Tylenol Severe Allergy Caplets

McNeil

25 mg with Acetaminophen 325 mg and Phenylephrine Hydrochloride 5 mg

Tylenol Allergy Multi-Symptom Nighttime Cool Burst Caplets

McNeil

25 mg with Acetaminophen 500 mg

Tylenol PM Caplets

McNeil

AHFS DI Essentials™. © Copyright 2024, Selected Revisions October 13, 2015. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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