Pronunciation:

(dye fen HYE dra meen)

U.S. Brand Names:

Synonyms:

Generic Available:

Canadian Brand Names:

Use:

Use - Dental:

Pregnancy Risk Factor:

Lactation:

Contraindications:

Warnings/Precautions:

Adverse Reactions:

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/Toxicology:

Drug Interactions:

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 Interactions:

Ethanol: Avoid ethanol (may increase CNS depression).

Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).

Stability:

Compatibility:

Y-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 Action:

Pharmacodynamics/Kinetics:

Onset 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)

Dosage:

Children:

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

12 years: 25-50 mg every 4-6 hours; maximum: 300 mg/day

Night-time sleep aid: 30 minutes before bedtime:

2 to <12 years: 1 mg/kg/dose; maximum: 50 mg/dose

12 years: 50 mg

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

12 years: 25 mg every 4 hours; maximum 150 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 Parameters:

Reference Range:

Antihistamine 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 Interactions:

Dietary Considerations:

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 Education:

Nursing Implications:

Additional Information:

Anesthesia and Critical Care Concerns/Other Considerations:

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Dental Comment:

Dosage Forms:

Caplet, 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]

International Brand Names: