diphenhydramine

Antagonizes the effects of histamine at H₁-receptor sites; does not bind to or inactivate histamine.
Significant CNS depressant and anticholinergic properties.

Therapeutic effects:

Decreased symptoms of histamine excess (sneezing, rhinorrhea, nasal and ocular pruritus, ocular tearing and redness, urticaria).
Relief of acute dystonic reactions.
Prevention of motion sickness.
Suppression of cough.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed after oral or IM administration but 40–60% of an oral dose reaches systemic circulation due to first-pass metabolism.

Distribution: Widely distributed. Crosses the placenta; enters breast milk.

Metabolism/Excretion: 95% metabolized by the liver.

Half-Life: 2.4–7 hr.

Time/Action Profile ⬆ ⬇

(antihistaminic effects)

ROUTE	ONSET	PEAK	DURATION
PO	15–60 min	2–4 hr	4–8 hr
IM	20–30 min	2–4 hr	4–8 hr
IV	rapid	unknown	4–8 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Acute attacks of asthma;
Known alcohol intolerance (some liquid products);
Lactation: Lactation.

Use Cautiously in:

Severe liver disease;
Angle-closure glaucoma;
Seizure disorders;
Prostatic hyperplasia;
Peptic ulcer;
May cause paradoxical excitation in young children;
Hyperthyroidism;
OB: Safety not established in pregnancy;
Geri: Appears on Beers list. risk of anticholinergic adverse reactions in older adults, including falls, delirium, and dementia. Avoid use of oral formulations in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, palpitations

Derm: photosensitivity

EENT: blurred vision, tinnitus

GI: anorexia, dry mouth, constipation, nausea

GU: dysuria, urinary frequency, urinary retention

Local: pain at IM site

Neuro: drowsiness, dizziness, headache, paradoxical excitation (↑ in children)

Resp: chest tightness, thickened bronchial secretions, wheezing

Interactions ⬆ ⬇

Drug-drug:

↑risk of CNS depression with other antihistamines, alcohol, opioid analgesics, and sedative/hypnotics.
↑anticholinergic effects with tricyclic antidepressants, quinidine, or disopyramide.
MAO inhibitors intensify and prolong the anticholinergic effects of antihistamines.

Drug-Natural Products:

Concomitant use of kava-kava, valerian, or chamomile can ↑ CNS depression.

Route/Dosage ⬆ ⬇

PO (Adults and Children >12 yr): Antihistaminic/antiemetic/antivertiginic: 25–50 mg every 4–6 hr, not to exceed 300 mg/day. Antitussive: 25 mg every 4 hr as needed, not to exceed 150 mg/day. Antidyskinetic: 25–50 mg every 4 hr (not to exceed 400 mg/day). Sedative/hypnotic: 50 mg 20–30 min before bedtime.
PO (Children 6–12 yr): Antihistaminic/antiemetic/antivertiginic: 12.5–25 mg every 4–6 hr (not to exceed 150 mg/day). Antidyskinetic: 1–1.5 mg/kg every 6–8 hr as needed (not to exceed 300 mg/day). Antitussive: 12.5 mg every 4 hr (not to exceed 75 mg/day). Sedative/hypnotic: 1 mg/kg/dose 20–30 min before bedtime (not to exceed 50 mg).
PO (Children 2–6 yr): Antihistaminic/antiemetic/antivertiginic: 6.25–12.5 mg every 4–6 hr (not to exceed 37.5 mg/day). Antidyskinetic: 1–1.5 mg/kg every 4–6 hr as needed (not to exceed 300 mg/day). Antitussive: 6.25 mg every 4 hr (not to exceed 37.5 mg/24 hr). Sedative/hypnotic: 1 mg/kg/dose 20–30 min before bedtime (not to exceed 50 mg).
IM IV (Adults ): 25–50 mg every 4 hr as needed (may need up to 100-mg dose, not to exceed 400 mg/day).
IM IV (Children ): 1.25 mg/kg (37.5 mg/m²) 4 times daily (not to exceed 300 mg/day).
(Adults and Children ≥2 yr): Apply to affected area up to 3–4 times daily.

Availability ⬆ ⬇

(Generic available)

Capsules: 25 mg^{Rx, OTC}; 50 mg^{Rx, OTC}
Tablets: 12.5 mg^{Rx, OTC}; 25 mg^{Rx, OTC}; 50 mg^{Rx, OTC}
Chewable tabletsgrape flavor: 25 mg^{Rx, OTC}
Orally disintegrating stripscherry and grape flavor: 12.5 mg^{Rx, OTC}; 25 mg^OTC
Orally disintegrating tablets: 12.5 mg^OTC; 25 mg^OTC; 50 mg^{Rx, OTC}
Elixircherry and other flavors: 12.5 mg/5 mL^{Rx, OTC}
Syrupcherry and raspberry flavor: 6.25 mg/5 mL^{Rx, OTC}; 12.5 mg/5 mL^{Rx, OTC}
Cream: 1%^{Rx, OTC}; 2%^{Rx, OTC}
Topical gel: 2%^OTC
Topical spray: 2%^OTC
Topical stick: 2%^OTC
Solution for injection: 50 mg/mL
In combination with: analgesics, decongestants, and expectorants, in OTC pain, sleep, cough, and cold preparations. See Appendix [not included in this PDA edition].

Assessment ⬆ ⬇

Diphenhydramine has multiple uses. Determine why the medication was ordered and assess symptoms that apply to the individual patient. Geri: Appears in the Beers list. May cause sedation and confusion due to increased sensitivity to anticholinergic effects. Monitor carefully, assess for confusion, delirium, other anticholinergic side effects and fall risk. Institute measures to prevent falls.
Prevention and Treatment of Anaphylaxis: Assess for urticaria and for patency of airway.
Allergic Rhinitis: Assess degree of nasal stuffiness, rhinorrhea, and sneezing.
Parkinsonism and Extrapyramidal Reactions: Assess movement disorder before and after administration.
Insomnia: Assess sleep patterns.
Motion Sickness: Assess nausea, vomiting, bowel sounds, and abdominal pain.
Cough Suppressant: Assess frequency and nature of cough, lung sounds, and amount and type of sputum produced. Unless contraindicated, maintain fluid intake of 1500–2000 mL daily to decrease viscosity of bronchial secretions.
Pruritus: Assess degree of itching, skin rash, and inflammation.

Lab Test Considerations:

May ↓ skin response to allergy tests. Discontinue 4 days before skin testing.

Implementation ⬆ ⬇

Do not confuse Benadryl with benazepril. Do not confuse diphenhydramine with dimenhydrinate.
- When used for insomnia, administer 20–30 min before bedtime and schedule activities to minimize interruption of sleep.
- When used for prophylaxis of motion sickness, administer at least 30 min and preferably 1–2 hr before exposure to conditions that may precipitate motion sickness.
PO: Administer with meals or milk to minimize GI irritation. Capsule may be emptied and contents taken with water or food.
- Orally disintegrating tablets and strips should be left in the package until use. Remove from the blister pouch. Do not push tablet through the blister; peel open the blister pack with dry hands and place tablet on tongue. Tablet will dissolve rapidly and be swallowed with saliva. No liquid is needed to take the orally disintegrating tablet.
IM: Administer 50 mg/mL into well-developed muscle. Avoid SUBQ injections.
Apply a thin coat and rub gently until absorbed. Only for topical use; avoid ingestion.

IV Administration:

Diluent: May be further diluted in 0.9% NaCl, 0.45% NaCl, D5W, D10W, dextrose/saline combinations, Ringer’s solution, LR, and dextrose/Ringer’s combinations.Concentration: 25 mg/mL.
Rate: Infuse at a rate not to exceed 25 mg/min. For pediatric patients, may further dilute as an intermittent infusion over 10 to 15 min.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed; do not exceed recommended amount. Caution patient not to use oral OTC diphenhydramine products with any other product containing diphenhydramine, including products used topically.
- May cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to drug is known.
- May cause dry mouth. Inform patient that frequent oral rinses, good oral hygiene, and sugarless gum or candy may minimize this effect. Notify health care professional if dry mouth persists for more than 2 wk.
- Teach sleep hygiene techniques (dark room, quiet, bedtime ritual, limit daytime napping, avoidance of nicotine and caffeine) to patients taking diphenhydramine to aid sleep.
- Advise patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
- Caution patient to avoid use of alcohol and other CNS depressants, including opioids, concurrently with this medication.
- Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Monitor infants exposed to diphenhydramine through breast milk for irritability and drowsiness.
- Can cause excitation in children. Caution parents or caregivers about proper dose calculation; overdose, especially in infants and children, can cause hallucinations, seizures, or death. Caution parents to avoid OTC cough and cold products while breastfeeding or to children <4 yr.
- Instruct older adults to avoid OTC products that contain diphenhydramine due to increased sensitivity to anticholinergic effects and potential for adverse reactions related to these effects.
- Advise patients taking diphenhydramine in OTC preparations to notify health care professional if symptoms worsen or persist for more than 7 days.

Evaluation/Desired Outcomes ⬆ ⬇

Prevention of, or decreased urticaria in, anaphylaxis or other allergic reactions.
Decreased dyskinesia in parkinsonism and extrapyramidal reactions.
Sedation when used as a sedative/hypnotic.
Prevention of or decrease in nausea and vomiting caused by motion sickness.
Decrease in frequency and intensity of cough without eliminating cough reflex.

US Brand Names ⬆ ⬇

AllerMax, Banophen, Benadryl Dye-Free Allergy, Benadryl Allergy, Benadryl, Compoz, Compoz Nighttime Sleep Aid, Diphen AF, Diphen Cough, Genahist, 40 Winks, Hyrexin-50, Maximum Strength Nytol, Maximum Strength Sleepinal, Midol PM, Miles Nervine, Nighttime Sleep Aid, Nytol, Scot-Tussin Allergy DM, Siladril, Silphen, Sleep-Eze 3, Sleepwell 2-night, Sominex, Snooze Fast, Sominex, Tusstat, Twilite, Unisom Nighttime Sleep-Aid

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇