Pronunciation(dye fen HYE dra meen)
U.S. Brand NamesAler-Cap [OTC]; Aler-Dryl [OTC]; Aler-Tab [OTC]; AllerMax® [OTC]; Banophen® [OTC]; Benadryl® Allergy [OTC]; Benadryl® Children's Allergy [OTC]; Benadryl® Children's Allergy Fastmelt® [OTC]; Benadryl® Dye-Free Allergy [OTC]; Benadryl® Injection; Benadryl® Itch Stopping [OTC]; Benadryl® Itch Stopping Extra Strength [OTC]; Compoz® Nighttime Sleep Aid [OTC]; Diphen® [OTC]; Diphen® AF [OTC]; Diphenhist [OTC]; Dynatan™; Genahist® [OTC]; Hydramine® [OTC]; Nytol® Quick Caps [OTC]; Nytol® Quick Gels [OTC]; Siladryl® Allergy [OTC]; Siladryl® DAS [OTC]; Silphen® [OTC]; Simply Sleep® [OTC]; Sleepinal® [OTC]; Sominex® [OTC]; Sominex® Maximum Strength [OTC]; Triaminic® Thin Strips™ Cough and Runny Nose [OTC]; Twilite® [OTC]; Unisom® Maximum Strength SleepGels® [OTC]
SynonymsDiphenhydramine Citrate; Diphenhydramine Hydrochloride; Diphenhydramine Tannate
Generic AvailableYes: Excludes chewable tablet, orally-disintegrating tablet, suspension, stick, strip, topical spray
Canadian Brand NamesAllerdryl®; Allernix; Benadryl®; Nytol®; Nytol® Extra Strength; PMS-Diphenhydramine; Simply Sleep®
UseSymptomatic relief of allergic symptoms caused by histamine release which include nasal allergies and allergic dermatosis; can be used for mild nighttime sedation; prevention of motion sickness and as an antitussive; has antinauseant and topical anesthetic properties; treatment of antipsychotic-induced extrapyramidal symptoms
Use - DentalSymptomatic relief of nasal mucosal congestion
Pregnancy Risk FactorB
LactationEnters breast milk/contraindicated
ContraindicationsHypersensitivity to diphenhydramine or any component of the formulation; acute asthma; not for use in neonates
Warnings/PrecautionsCauses sedation, caution must be used in performing tasks which require alertness (eg, operating machinery or driving). Sedative effects of CNS depressants or ethanol are potentiated. Use with caution in patients with angle-closure glaucoma, pyloroduodenal obstruction (including stenotic peptic ulcer), urinary tract obstruction (including bladder neck obstruction and symptomatic prostatic hyperplasia), hyperthyroidism, increased intraocular pressure, and cardiovascular disease (including hypertension and tachycardia). Diphenhydramine has high sedative and anticholinergic properties, so it may not be considered the antihistamine of choice for prolonged use in the elderly. May cause paradoxical excitation in pediatric patients, and can result in hallucinations, coma, and death in overdose. Some preparations contain sodium bisulfite; syrup formulations may contain alcohol. Some preparations contain soy protein; patients with soy protein or peanut allergies should avoid.
Adverse ReactionsFrequency not defined.Cardiovascular: Hypotension, palpitation, tachycardia Central nervous system: Sedation, sleepiness, dizziness, disturbed coordination, headache, fatigue, nervousness, paradoxical excitement, insomnia, euphoria, confusion Dermatologic: Photosensitivity, rash, angioedema, urticaria Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain, xerostomia, appetite increase, weight gain, dry mucous membranes, anorexia Genitourinary: Urinary retention, urinary frequency, difficult urination Hematologic: Hemolytic anemia, thrombocytopenia, agranulocytosis Neuromuscular & skeletal: Tremor, paresthesia Ocular: blurred vision Respiratory: Thickening of bronchial secretions
Overdosage/ToxicologySymptoms of overdose include CNS stimulation or depression; overdose may result in death in infants and children. There is no specific treatment for antihistamine overdose. Clinical toxicity is due to blockade of cholinergic receptors. For anticholinergic overdose with life-threatening symptoms, physostigmine 1-2 mg SubQ or I.V. slowly may be given to reverse these effects.
Drug InteractionsInhibits CYP2D6 (moderate)Amantadine, rimantadine: Central and/or peripheral anticholinergic syndrome can occur when administered with amantadine or rimantadine Anticholinergic agents: Central and/or peripheral anticholinergic syndrome can occur when administered with narcotic analgesics, phenothiazines and other antipsychotics (especially with high anticholinergic activity), tricyclic antidepressants, quinidine and some other antiarrhythmics, and antihistamines Atenolol: Drugs with high anticholinergic activity may increase the bioavailability of atenolol (and possibly other beta-blockers); monitor for increased effect Cholinergic agents: Drugs with high anticholinergic activity may antagonize the therapeutic effect of cholinergic agents; includes donepezil, rivastigmine, and tacrine CNS depressants: Sedative effects may be additive with CNS depressants; includes ethanol, benzodiazepines, barbiturates, narcotic analgesics, and other sedative agents; monitor for increased effect CYP2D6 substrates: Diphenhydramine may increase the levels/effects of CYP2D6 substrates. Example substrates include amphetamines, selected beta-blockers, dextromethorphan, fluoxetine, lidocaine, mirtazapine, nefazodone, paroxetine, risperidone, ritonavir, thioridazine, tricyclic antidepressants, and venlafaxine. CYP2D6 prodrug substrates: Diphenhydramine may decrease the levels/effects of CYP2D6 prodrug substrates. Example prodrug substrates include codeine, hydrocodone, oxycodone, and tramadol. Digoxin: Drugs with high anticholinergic activity may decrease gastric degradation and increase the amount of digoxin absorbed by delaying gastric emptying Ethanol: Syrup should not be given to patients taking drugs that can cause disulfiram reactions (ie, metronidazole, chlorpropamide) due to high alcohol content Levodopa: Drugs with high anticholinergic activity may increase gastric degradation and decrease the amount of levodopa absorbed by delaying gastric emptying Neuroleptics: Drugs with high anticholinergic activity may antagonize the therapeutic effects of neuroleptics
Ethanol/Nutrition/Herb InteractionsEthanol: Avoid ethanol (may increase CNS depression). Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
StabilityProtect injection from light.
CompatibilityStable in dextran 6% in dextrose, dextran 6% in NS, D5LR, D51/4NS, D51/2NS, D5NS, D5W, D10W, fat emulsion 10%, LR, 1/2NS, NSY-site administration: Compatible: Acyclovir, aldesleukin, amifostine, amsacrine, aztreonam, ciprofloxacin, cisatracurium, cisplatin, cladribine, cyclophosphamide, cytarabine, docetaxel, doxorubicin, doxorubicin liposome, etoposide phosphate, famotidine, filgrastim, fluconazole, fludarabine, gatifloxacin, gemcitabine, granisetron, heparin, hydrocortisone sodium succinate, idarubicin, linezolid, melphalan, meperidine, meropenem, methotrexate, ondansetron, paclitaxel, piperacillin/tazobactam, potassium chloride, propofol, remifentanil, sargramostim, sufentanil, tacrolimus, teniposide, thiotepa, vinorelbine, vitamin B complex with C. Incompatible: Allopurinol, amphotericin B cholesteryl sulfate complex, cefepime, foscarnet Compatibility in syringe: Compatible: Atropine, butorphanol, chlorpromazine, cimetidine, diatrizoate meglumine, diatrizoate meglumine 34.3% and diatrizoate sodium 35%, diatrizoate sodium, diatrizoate sodium 75%, dimenhydrinate, droperidol, fentanyl, fluphenazine, glycopyrrolate, hydromorphone, hydroxyzine, iohexol, iopamidol, iothalamate meglumine, iothalamate meglumine 60%, iothalamate sodium 80%, meperidine, metoclopramide, midazolam, morphine, nalbuphine, pentazocine, perphenazine, prochlorperazine edisylate, promazine, promethazine, ranitidine, scopolamine, sufentanil. Incompatible: Diatrizoate meglumine 52% and diatrizoate sodium 8%, diatrizoate sodium 60%, haloperidol, iodipamide meglumine, iodipamide meglumine 52%, ioxaglate meglumine 39.3% and ioxaglate sodium 19.6%, pentobarbital, thiopental. Variable (consult detailed reference): Dexamethasone sodium phosphate, diatrizoate meglumine 52% and diatrizoate sodium 8% Compatibility when admixed: Compatible: Amikacin, aminophylline, ascorbic acid injection, bleomycin, buprenorphine, colistimethate, erythromycin lactobionate, hydrocortisone sodium succinate, lidocaine, methyldopate, nafcillin, netilmicin, penicillin G potassium , penicillin G sodium, polymyxin B, vitamin B complex with C. Incompatible: Amobarbital, amphotericin B, dexamethasone sodium phosphate with lorazepam and metoclopramide, iodipamide meglumine, phenytoin, phenobarbital, thiopental. Variable (consult detailed reference): Heparin in solution
Mechanism of ActionCompetes with histamine for H1-receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract; anticholinergic and sedative effects are also seen
Pharmacodynamics/KineticsOnset of action: Maximum sedative effect: 1-3 hours Duration: 4-7 hours Protein binding: 78% Metabolism: Extensively hepatic; smaller degrees in pulmonary and renal systems; significant first-pass effect Bioavailability: Oral: 40% to 60% Half-life elimination: 2-8 hours; Elderly: 13.5 hours Time to peak, serum: 2-4 hours Excretion: Urine (as unchanged drug)
DosageChildren: Oral, I.M., I.V.: Treatment of moderate to severe allergic reactions: 5 mg/kg/day or 150 mg/m2/day in divided doses every 6-8 hours, not to exceed 300 mg/day Minor allergic rhinitis or motion sickness: 2 to <6 years: 6.25 mg every 4-6 hours; maximum: 37.5 mg/day 6 to <12 years: 12.5-25 mg every 4-6 hours; maximum: 150 mg/day
Night-time sleep aid: 30 minutes before bedtime: 2 to <12 years: 1 mg/kg/dose; maximum: 50 mg/dose
Oral: Antitussive: 2 to <6 years: 6.25 mg every 4 hours; maximum 37.5 mg/day 6 to <12 years: 12.5 mg every 4 hours; maximum 75 mg/day
I.M., I.V.: Treatment of dystonic reactions: 0.5-1 mg/kg/dose Adults: Oral: 25-50 mg every 6-8 hours Minor allergic rhinitis or motion sickness: 25-50 mg every 4-6 hours; maximum: 300 mg/day Moderate to severe allergic reactions: 25-50 mg every 4 hours, not to exceed 400 mg/day Nighttime sleep aid: 50 mg at bedtime I.M., I.V.: 10-50 mg in a single dose every 2-4 hours, not to exceed 400 mg/day Dystonic reaction: 50 mg in a single dose; may repeat in 20-30 minutes if necessary Topical: For external application, not longer than 7 days
Monitoring ParametersRelief of symptoms, mental alertness
Reference RangeAntihistamine effects at levels >25 ng/mL Drowsiness at levels 30-40 ng/mL Mental impairment at levels >60 ng/mL Therapeutic: Not established Toxic: >0.1 mcg/mL
Test InteractionsMay suppress the wheal and flare reactions to skin test antigens
Dietary ConsiderationsTablet:Chewable, as hydrochloride: Contains phenylalanine 4.2 mg per 12.5 mg tablet Chewable, as tannate: Contains phenylalanine 1.5 mg per 25 mg tablet Orally-disintegrating, as citrate: Contains phenylalanine 4.5 mg per 19 mg [equivalent to diphenhydramine hydrochloride 12.5 mg] tablet; contains soy protein isolate (contraindicated in patients with soy protein allergies; use caution in peanut allergic individuals, ~10% are estimated to also have soy protein allergies)
Patient EducationTake as directed; do not exceed recommended dose. Avoid use of other depressants, alcohol, or sleep-inducing medications unless approved by prescriber. You may experience drowsiness or dizziness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); or dry mouth, nausea, or vomiting (small, frequent meals, frequent mouth care, chewing gum, or sucking hard candy may help). Report persistent sedation, confusion, or agitation; changes in urinary pattern; blurred vision; sore throat, respiratory difficulty, or expectorating (thick secretions); or lack of improvement or worsening or condition. Breast-feeding precaution: Do not breast-feed.
Nursing ImplicationsRaise bed rails, institute safety measures, assist with ambulation
Additional InformationIts use as a sleep aid is discouraged due to its anticholinergic effects.
Anesthesia and Critical Care Concerns/Other ConsiderationsDiphenhydramine's use as a sleep aid is discouraged due to its anticholinergic effects.
Dental Health: Effects on Dental TreatmentKey adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation) and dry mucous membranes. Chronic use of antihistamines will inhibit salivary flow, particularly in elderly patients; may contribute to periodontal disease and oral discomfort.
Dental Health: Vasoconstrictor/Local Anesthetic PrecautionsNo information available to require special precautions
Dental Comment25-50 mg of diphenhydramine orally every 4-6 hours can be used to treat mild dermatologic manifestations of allergic reactions to penicillin and other antibiotics. Diphenhydramine is not recommended as local anesthetic for either infiltration route or nerve block since the vehicle has caused local necrosis upon injection. A 50:50 mixture of diphenhydramine liquid (12.5 mg/5 mL) in Kaopectate® or Maalox® is used as a local application for recurrent aphthous ulcers; swish 1 tablespoonful for 2 minutes 4 times/day.
Dosage FormsCaplet, as hydrochloride: 25 mg, 50 mg Aler-Dryl, Sominex® Maximum Strength, Twilite®: 50 mg Simply Sleep®, Nytol® Quick Caps: 25 mg Capsule, as hydrochloride: 25 mg, 50 mg Aler-Cap, Banophen®, Benadryl® Allergy, Diphen®, Diphenhist®, Genahist®: 25 mg Sleepinal®: 50 mg Capsule, softgel, as hydrochloride: Benadryl® Dye-Free Allergy: 25 mg [dye-free] Compoz® Nighttime Sleep Aid, Nytol® Quick Gels, Unisom® Maximum Strength SleepGels®: 50 mg Cream, as hydrochloride: 2% (30 g) Benadryl® Itch Stopping: 1% (30 g) [contains zinc acetate 0.1%] Benadryl® Itch Stopping Extra Strength: 2% (30 g) [contains zinc acetate 0.1%] Elixir, as hydrochloride: 12.5 mg/5 mL (480 mL) Banophen®: 12.5 mg/5 mL (120 mL) Diphen AF: 12.5 mg/5 mL (120 mL, 240 mL, 480 mL) [alcohol free; cherry flavor] Gel, topical, as hydrochloride (Benadryl® Itch Stopping Extra Strength): 2% (120 mL) Injection, solution, as hydrochloride: 50 mg/mL (1 mL) Benadryl®: 50 mg/mL (1 mL, 10 mL) Liquid, as hydrochloride: 12.5 mg/5 mL (120 mL) Benadryl® Allergy: 12.5 mg/5 mL (120 mL, 240 mL) [alcohol free; contains sodium benzoate; cherry flavor] Benadryl® Dye-Free Allergy: 12.5 mg/5 mL (120 mL) [alcohol free, dye free, sugar free; contains sodium benzoate; bubble gum flavor] Genahist®: 12.5 mg/5 mL (120 mL) [alcohol free, sugar free; contains sodium benzoate; cherry flavor] Hydramine®: 12.5 mg/5 mL (120 mL, 480 mL) [alcohol free] Siladryl® Allergy: 12.5 mg/5 mL (120 mL, 240 mL, 480 mL) [alcohol free, sugar free; black cherry flavor] Siladryl® DAS: 12.5 mg/5 mL (120 mL) [alcohol free, dye free, sugar free; black cherry flavor] Solution, oral, as hydrochloride: AllerMax®: 12.5 mg/5 mL (120 mL) Banophen®: 12.5 mg/5mL (480 mL, 3840 mL) [sugar free] Diphenhist®: 12.5 mg/5 mL (120 mL, 480 mL) [contains sodium benzoate] Solution, topical, as hydrochloride [spray] (Benadryl® Itch Stopping Extra Strength): 2% (60 mL) [contains zinc acetate 0.1%] Stick, topical, as hydrochloride (Benadryl® Itch Stopping Extra Strength): 2% (14 mL) [contains zinc acetate 0.1%] Strips, oral, as hydrochloride (Triaminic® Thin Strips™ Cough and Runny Nose): 12. 5 mg (16s) [grape flavor] Suspension, as tannate (Dynatan™): 25 mg/5 mL (120 mL) [strawberry flavor] Syrup, as hydrochloride (Silphen® Cough): 12.5 mg/5 mL (120 mL, 240 mL, 480 mL) [contains alcohol; 5%; strawberry flavor] Tablet, as hydrochloride: 25 mg, 50 mg Aler-Tab, AllerMax®, Compoz® Nighttime Sleep Aid: 50 mg Benadryl® Allergy, Genahist®, Sominex®: 25 mg Tablet, chewable, as hydrochloride (Benadryl® Children's Allergy): 12.5 mg [contains phenylalanine 4.2 mg/tablet; grape flavor] Tablet, chewable, as tannate (Dynatan™): 25 mg [contains phenylalanine 1.5 mg/tablet; strawberry flavor] Tablet, orally-disintegrating, as citrate (Benadryl® Children's Allergy Fastmelt®): 19 mg [equivalent to diphenhydramine hydrochloride 12.5 mg; contains phenylalanine 4.5 mg/tablet and soy protein isolate; cherry flavor]
ReferencesBecker DE, "Management of Immediate Allergic Reactions,"Dent Clin North Am, 1995, 39(3):577-86 Blyden GT, Greenblatt DJ, Scavone JM, et al, "Pharmacokinetics of Diphenhydramine and a Demethylated Metabolite Following Intravenous and Oral Administration,"J Clin Pharmacol, 1986, 26(7):529-33. Corre KA, Niemann JT, Bessen HA, et al, "Extended Therapy for Acute Dystonic Reactions,"Ann Emerg Med, 1984, 13(3):194:7. Doenecke AL and Heuermann RC, "Treatment of Haloperidol Abuse With Diphenhydramine,"Am J Psychiatry, 1980, 137(4):487-8. Eigenmann, PA, Burks, AW, Bannon GA, et al, "Identification of Unique Peanut and Soy Allergens in Sera Adsorbed With Cross-Reacting Antibodies,"J Allergy Clin Immunol, 1996, 98 (5 Pt 1):969-78. Garnett WR, "Diphenhydramine,"Am Pharm, 1986, NS26(2):35-40. Lindsay CA, Williams GD, and Levin DL, "Fatal Adult Respiratory Distress Syndrome After Diphenhydramine Toxicity in a Child: A Case Report,"Crit Care Med, 1995, 23(4):777-81. Simons KJ, Watson WT, Martin TJ, et al, "Diphenhydramine: Pharmacokinetics and Pharmacodynamics in Elderly Adults, Young Adults, and Children,"J Clin Pharmacol, 1990, 30(7):665-71. Sridhar KS and Donnelly E, "Combination Antiemetics for Cisplatin Chemotherapy,"Cancer, 1988, 61(8):1508-17. Stancavage M, Osterhoudt KC, and Henretig FM, "Caladryl Ingestion: A New Poisoning From a Common Household Product,"Clin Toxicol, 1995, 33(5):520. Tsavaris N, Zamanis N, Zinelis A, et al, "Diphenhydramine for Nausea and Vomiting Related to Cancer Chemotherapy With Cisplatin,"J Pain Symptom Manage, 1991, 6(8):461-5. Weston MV, "Lovelorn and Snakebite,"Hosp Pract (Off Ed), 1986, 21(3A):140-3.
International Brand NamesAlergil® (HN); Alledryl® (IL); Allerdryl® (CA); Allergan® (IT); Allerjin® (TR); Allernix (CA); Arcodryl® (ID); Azaron® (BE); Bedorma® (CH); Belarmin Expectorant® (CY); Benaderma® (PT); Benadryl® (AR, BR, CA, CO, ES, GB, HK, ID, IN, TH, TR); Benadryl N® (CH, CZ, DE); Benison® (TR); Benocten® (CH, CR, CY, JO, KW, LB, SG, SV); Benylan® (DK); Benylin antihistaminicum® (BE); Benzantine® (IL); Betadorm D® (DE); Betasleep® (ZA); Butix® (FR); Caladryl® (AR, EG, ES, NL, TR, ZA); Calmaben® (AT); Cathejell® (AT, DE, IL); Daslin® (IN); Dermodrin® (AT, PL); Desentol® (SE); Dibondrin® (AT); Difenhidramina Denver Farma® (AR); Difenhidramina Fada® (AR); Difenhidramina Richmond® (AR); Difenidramina® (BR); Difenidramina Cloridrato® (IT); Dimedrol® (RU); Dimidril® (HR, SI); Dimiril® (IN); Diphamine® (BE); Diphenhydramine-Asta Medica® (LU); Dolestan® (DE); Dormutil N® (DE); Dramina® (SI); Emesan® (DE); Fabolergic® (AR); Fenotral® (TR); Halbmond-Tabletten® (DE); Hemodorm® (DE); Hevert-Dorm® (DE); Histaler® (AR); Histam® (DO); Histaxin® (AT); Medinex® (GB); Mudantos H® (AR); Nautamine® (FR); Neo Respir® (AR); Neosayomol® (ES); nervo OPT® (DE); Noctor® (AT); Nuicalm® (BE); Nustasium® (BE); Nytol® (CA, ES, GB); Nytol® Extra Strength (CA); Nytol SM® (CH); Otede® (ID); Pasifen® (CL); Paxidorm® (SG); Pedeamin® (BD); Phenadryl® (BD); PMS-Diphenhydramine (CA); Prurex® (AT); Psilo® (BG); Purigel® (BE); ratioAllerg® (DE); R-Calm® (BE); S.8® (DE); Schlaftabletten N® (DE); Schlaftabletten S® (CH); Sedativum-Hevert® (DE); Sediat® (DE); Sedopretten® (DE); Sidiadryl® (ID); Simply Sleep® (CA); Sleepeze-PM® (ZA); Sleepia® (CH, DE); Somol® (CL); Sonodor® (ES); Tzoali® (MX); Unisom Sleepgels® (AU); Vivinox® (DE)
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12 years: 25-50 mg every 4-6 hours; maximum: 300 mg/day