diphenhydramine hydrochloride
Allergy DM, AllerMax, Banophen, Benadryl, Benadryl Allergy, Benylin, Compoz, Diphen AF, Diphen Cough, Diphenadryl, Diphenhist, Dormin, Genahist, Midol PM, Miles Nervine Nighttime Sleep-Aid, Nytol, Siladryl, Sleep-Eze 3, Snooze-Fast, Sominex, Twilite, 40 Winks

Pharmacologic classification: ethanolamine-derivative antihistamine (first generation)
Therapeutic classification: antihistamine (H1-receptor antagonist), antiemetic, antivertigo, antitussive, sedative-hypnotic, topical anesthetic, antidyskinetic (anticholinergic)
Pregnancy risk category B

Available forms
Available with or without a prescription
Capsules: 25 mg, 50 mg
Capsules (liquid-filled): 25 mg, 50 mg
Cream (topical): 1%, 2%
Elixir: 12.5 mg/5 ml
Gel (topical): 1%, 2%
Injection: 10 mg/ml, 50 mg/ml
Liquid: 12.5 mg/5 ml
Solution: 12.5 mg/5 ml
Solution (topical): 1%, 2%
Spray: 1%, 2%
Stick (topical): 2%
Syrup: 12.5 mg/5 ml
Tablets: 25 mg, 50 mg
Tablets (chewable): 12.5 mg
Tablets (film-coated): 25 mg, 50 mg

Indications and dosages
 Rhinitis, allergy symptoms, motion sickness, Parkinson’s disease. Adults and children age 12 and older: 25 to 50 mg P.O. t.i.d. or q.i.d. Or, 10 to 50 mg I.V. or deep I.M. Maximum I.M. or I.V. dose is 400 mg daily.
Children younger than age 12 who weigh more than 10 kg: 12.5 to 25 mg P.O. t.i.d. or q.i.d. Or, 5 mg/kg daily P.O., deep I.M., or I.V. in divided doses q.i.d. Maximum dose is 300 mg daily.
 Nonproductive cough. Adults and children age 12 and older: 25 mg P.O. q 4 to 6 hours. Maximum dose is 150 mg daily.
Children ages 6 to 12: 12.5 mg P.O. q 4 to 6 hours. Maximum dose is 75 mg daily.
Children ages 2 to 6: 6.25 mg P.O. q 4 to 6 hours. Maximum dose is 25 mg daily.
 Insomnia. Adults: 50 mg P.O. h.s.
 Sedation. Adults: 25 to 50 mg P.O., or deep I.M., p.r.n.

Antihistamine action: Antihistamines compete for H1-receptor sites on the smooth muscle of the bronchi, GI tract, uterus, and large blood vessels; by binding to cellular receptors, they prevent access of histamine and suppress histamine-induced allergic symptoms, even though they don’t prevent its release.
Antivertigo, antiemetic, and antidyskinetic actions: Central antimuscarinic actions of antihistamines probably are responsible for these effects of diphenhydramine.
Antitussive action: Drug suppresses the cough reflex by a direct effect on the cough center.
Sedative action: Mechanism of the CNS depressant effects of diphenhydramine is unknown.
Anesthetic action: Drug is structurally related to local anesthetics, which prevent initiation and transmission of nerve impulses; this is the probable source of its topical and local anesthetic effects.

Absorption: Well absorbed from the GI tract.
Distribution: Distributed widely throughout the body, including the CNS; drug crosses the placental barrier and appears in breast milk. Drug is about 82% protein-bound.
Metabolism: About 50% to 60% of an oral dose of diphenhydramine is metabolized by the liver before reaching the systemic circulation (first-pass effect); virtually all available drug is metabolized by the liver within 24 to 48 hours.
Excretion: Plasma elimination half-life of drug is about 21/2 to 9 hours; drug and metabolites are excreted primarily in urine.

Route Onset Peak Duration
P.O. 15-30 min 1-4 hr 4-8 hr
I.V. Immediate 1-4 hr 6-8 hr
I.M. Unknown 1-4 hr 6-8 hr
Topical Unknown Unknown Unknown

Contraindications and precautions
Contraindicated in patients hypersensitive to drug, patients having acute asthmatic attacks, and neonates, premature neonates, and breast-feeding women.
  Use with extreme caution in patients with angle-closure glaucoma, prostatic hyperplasia, pyloroduodenal and bladder neck obstruction, asthma or COPD, increased intraocular pressure, hyperthyroidism, CV disease, hypertension, and stenosing peptic ulcer.

Drug-drug. CNS depressants, such as anxiolytics, barbiturates, sleeping aids, and tranquilizers: Causes additive CNS depression. Use together cautiously.
Heparin: Partially counteracts anticoagulant effects of heparin. Monitor PT and INR.
MAO inhibitors: Increases anticholinergic effects. Don’t use together.
Sulfonylureas: May diminish effects of sulfonylureas. Monitor patient closely.
Drug-lifestyle. Alcohol use: May cause additive CNS depression. Discourage alcohol use.
Sun exposure: May cause photosensitivity reactions. Advise patient to take precautions.

Adverse reactions
CNS: drowsiness, confusion, insomnia, headache, vertigo, sedation, sleepiness, dizziness, incoordination, fatigue, restlessness, tremor, nervousness, seizures.
CV: palpitations, hypotension, tachycardia.
EENT: diplopia, blurred vision, tinnitus.
GI: nausea, vomiting, diarrhea, dry mouth, constipation, epigastric distress, anorexia.
GU: dysuria, urine retention, urinary frequency.
Hematologic: hemolytic anemia, thrombocytopenia, agranulocytosis.
Respiratory: nasal congestion, thickening of bronchial secretions.
Skin: urticaria, photosensitivity, rash.
Other: anaphylaxis.

Effects on lab test results
• May decrease hemoglobin and platelet and granulocyte counts.

Overdose and treatment
Drowsiness is the usual symptom of overdose. Seizures, coma, and respiratory depression may occur with profound overdose. Anticholinergic symptoms, such as dry mouth, flushed skin, fixed and dilated pupils, and GI symptoms, are common, especially in children.
 Treat overdose by inducing emesis with ipecac syrup (in conscious patient), followed by activated charcoal to reduce further drug absorption. Use gastric lavage if patient is unconscious or ipecac fails. Treat hypotension with vasopressors and control seizures with diazepam or phenytoin. Don’t give stimulants.

Special considerations
• Ask patient undergoing skin testing for allergies about current drug therapy.
• Stop drug 4 days before diagnostic skin tests; antihistamines can prevent, reduce, or mask positive skin test response.
• Diphenhydramine injection is compatible with most I.V. solutions but is incompatible with some drugs; check compatibility before mixing in the same I.V. line.
• Alternate injection sites to prevent irritation. Administer deep I.M. into large muscle.
• Drowsiness is the most common adverse effect during initial therapy but usually disappears with continued use of drug.
• Injectable and elixir solutions are light-sensitive; protect them from light.
• Monitor length of use for insomnia; reevaluate if used for longer than 2 weeks.
Breast-feeding patients
• Many antihistamines appear in breast milk, exposing the infant to risks of unusual excitability; premature infants are at particular risk for seizures. Avoid use of antihistamines during breast-feeding.
Pediatric patients
• Drug shouldn’t be used in premature infants or neonates. Infants and children, especially those younger than age 6, may experience paradoxical hyperexcitability.
Geriatric patients
• These patients are usually more sensitive to adverse effects of antihistamines than younger patients and are especially likely to experience a greater degree of dizziness, sedation, hyperexcitability, dry mouth, and urine retention. Symptoms usually respond to a decrease in dosage.

Patient education
• Advise patient that drowsiness is very common initially, but may be reduced with continued use of drug.
• Tell patients to take drug 30 minutes before exposure to motion for motion sickness and before meals and at bedtime during exposure.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use