Allerdryl , Benadryl, Benadryl Dye-Free, Sleep-Eze 3, Sominex Formula 2, Tusstat, Twilite, Valdrene
Classifications: antihistamine; h1-receptor antagonist;
Therapeutic: antihistamine
; h1-receptor antagonist; antivertigo; antiemetic; sedative-hypnotic; antiparkinson; antidyskinetic
Pregnancy Category: C


25 mg, 50 mg capsules, tablets; 6.25 mg/5 mL, 12.5 mg/5 mL syrup; 50 mg/mL injection


Diphenhydramine is an H1-receptor antagonist and antihistamine with significant anticholinergic activity. Competes for H1-receptor sites on effector cells, thus blocking histamine release. Effects in parkinsonism and drug-induced extrapyramidal symptoms are apparently related to its ability to suppress central cholinergic activity and to prolong action of dopamine by inhibiting its reuptake and storage.

Therapeutic Effect

Has antihistamine, antivertigo, antiemetic, antianaphylactic, antitussive, antidyskinetic, and sedative-hypnotic effects.


Temporary symptomatic relief of various allergic conditions and to treat or prevent motion sickness, vertigo, and reactions to blood or plasma in susceptible patients. Also used in anaphylaxis as adjunct to epinephrine and other standard measures after acute symptoms have been controlled; in treatment of parkinsonism and drug-induced extrapyramidal reactions; as a nonnarcotic cough suppressant; as a sedative-hypnotic; and for treatment of intractable insomnia.


Hypersensitivity to antihistamines of similar structure; lower respiratory tract symptoms (including acute asthma); narrow-angle glaucoma; prostatic hypertrophy, bladder neck obstruction; GI obstruction or stenosis; pregnancy (category C), lactation, premature neonates, and neonates; use as nighttime sleep aid in children <2 y.

Cautious Use

History of asthma; COPD; convulsive disorders; increased IOP; hyperthyroidism; hypertension, cardiovascular disease; hepatic disease; diabetes mellitus; older adults, infants, and young children.

Route & Dosage

Allergy Symptoms, Antiparkinsonism, Motion Sickness, Nighttime Sedation
Adult: PO 25–50 mg t.i.d. or q.i.d. (max: 300 mg/d) IV/IM 10–50 mg q4–6h (max: 400 mg/d)
Child: PO 2–6 y, 6.25 mg q4–6h (max: 300 mg/24 h); 6–12 y, 12.5–25 mg q4–6h (max: 300 mg/24 h) IV/IM 5 mg/kg/d divided into 4 doses (max: 300 mg/d)

Nonproductive Cough
Adult: PO 25 mg q4–6h (max: 100 mg/d)
Child: PO 2–6 y, 6.25 mg q4–6h (max: 25 mg/24 h); 6–12 y, 12.5 mg q4–6h (max: 50 mg/24 h)


  • Give with food or milk to lessen GI adverse effects.
  • For motion sickness: Give the first dose 30 min before exposure to motion; give remaining doses before meals and at bedtime.
  • Give IM injection deep into large muscle mass; alternate injection sites. Avoid perivascular or SC injections because of its irritating effects.
  • Note: Hypersensitivity reactions (including anaphylactic shock) are more likely to occur with parenteral than PO administration.

PREPARE: Direct: Give undiluted.  

ADMINISTER: Direct: Give at a rate of 25 mg or a fraction thereof over 1 min.  

INCOMPATIBILITIES Solution/additive: Amphotericin B, dexamethasone, iodipamide, methylprednisolone, pentobarbital, phenobarbital, phenytoin, thiopental. Y-site: Allopurinol, amphotericin B cholesteryl complex, cefmetazole, foscarnet, furosemide.

  • Store in tightly covered containers at 15°–30° C (59°–86° F) unless otherwise directed by manufacturer. Keep injection and elixir formulations in light-resistant containers.

Adverse Effects (≥1%)

CNS: Drowsiness, dizziness, headache, fatigue, disturbed coordination, tingling, heaviness and weakness of hands, tremors, euphoria, nervousness, restlessness, insomnia; confusion; (especially in children): excitement, fever. CV: Palpitation, tachycardia, mild hypotension or hypertension, cardiovascular collapse. Special Senses: Tinnitus, vertigo, dry nose, throat, nasal stuffiness; blurred vision, diplopia, photosensitivity, dry eyes. GI: Dry mouth, nausea, epigastric distress, anorexia, vomiting, constipation, or diarrhea. Urogenital: Urinary frequency or retention, dysuria. Body as a Whole: Hypersensitivity (skin rash, urticaria, photosensitivity, anaphylactic shock). Respiratory: Thickened bronchial secretions, wheezing, sensation of chest tightness.

Diagnostic Test Interference

Diphenhydramine should be discontinued 4 d prior to skin testing procedures for allergy because it may obscure otherwise positive reactions.


Drug: Alcohol and other cns depressants, mao inhibitors compound CNS depression.


Absorption: Readily absorbed from GI tract but only 40–60% reaches systemic circulation. Onset: 15–30 min. Peak: 1–4 h. Duration: 4–7 h. Distribution: Crosses placenta; distributed into breast milk. Metabolism: In liver; some degradation in lung and kidney. Elimination: Mostly in urine within 24 h.

Nursing Implications

Assessment & Drug Effects

  • Monitor cardiovascular status especially with preexisting cardiovascular disease.
  • Monitor for adverse effects especially in children and the older adult.
  • Supervise ambulation and use side-rails as necessary. Drowsiness is most prominent during the first few days of therapy and often disappears with continued therapy. Older adults are especially likely to manifest dizziness, sedation, and hypotension.

Patient & Family Education

  • Do not use alcohol and other CNS depressants because of the possible additive CNS depressant effects with concurrent use.
  • Do not drive or engage in other potentially hazardous activities until the response to drug is known.
  • Increase fluid intake, if not contraindicated; drug has an atropine-like drying effect (thickens bronchial secretions) that may make expectoration difficult.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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