Diphenhydramine

• Injectable diphenhydramine is used for its antiallergic, antiemetic, and antispasmodic effects when, in the physician's judgment, a prompt effect is needed and oral therapy would not be adequate.
• Higher doses may be used for acute generalized or chronic hives (urticaria), allergic eczema, bronchial asthma, and status asthmaticus, as part of broader treatment of the allergic component of these conditions.
• Diphenhydramine injection is also well established in clinical practice for the prompt treatment of acute drug-induced dystonic (muscle spasm) reactions, when rapid relief is required.

• The safe use of diphenhydramine injection during pregnancy has not been established.
• Its use during pregnancy should involve careful consideration of the expected benefits against the possible risks to the mother and fetus.

• The safe use of diphenhydramine injection during breastfeeding has not been established.
• Diphenhydramine is known to pass into breast milk in small amounts, and because of its sedating and anticholinergic effects, it may cause drowsiness or reduce milk supply in a nursing infant; caution and a discussion with a doctor are advised.

• This product monograph does not include separate dosing guidance for older adults, but diphenhydramine's anticholinergic and sedative effects are generally more pronounced in this age group.
• Older adults are at higher risk of confusion, urinary retention, dizziness, and falls with diphenhydramine, so cautious use and close monitoring are advised.

• The pediatric dose is based on body weight or body surface area, divided into four doses given intravenously or by deep intramuscular injection.
• Caution is advised in neonates and premature infants, who are generally more susceptible to the anticholinergic and central nervous system effects of antihistamines.

• The usual adult dose is 10 to 50 mg given intravenously or by deep intramuscular injection.
• A higher daily dosage of 300 to 400 mg may be required for acute generalized or chronic urticaria, allergic eczema, bronchial asthma, or status asthmaticus.
• The pediatric dose is 5 mg/kg over 24 hours, or 150 mg/m2 of body surface area over 24 hours, up to a maximum of 300 mg per day, divided into four doses given intravenously or by deep intramuscular injection.
• A single parenteral dose greater than 100 mg should be avoided, particularly in patients with hypertension or cardiac disease.
• Subcutaneous or perivascular injection should be avoided, since it can cause tissue irritation.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• Diphenhydramine overdose typically produces anticholinergic effects, such as dry mucous membranes, flushed and hot skin, dilated pupils, reduced bowel sounds, and urinary retention.
• More severe overdose can cause hallucinations, delirium, seizures, or coma.
• Death has been reported from seizures or from cardiac arrhythmias caused by sodium-channel blockade, similar to Class Ia antiarrhythmic drugs.
• Rhabdomyolysis (muscle breakdown) has occurred even without severe toxicity.
• Management is primarily supportive, and may include emptying the stomach (induced vomiting in alert patients or gastric lavage) and activated charcoal if given within about 2 hours of ingestion.
• Overdose during pregnancy has been reported to cause oxytocin-like uterine contractions, which can be treated with intravenous magnesium.

• Drowsiness is common.
• Dizziness is common.
• Dryness of the mouth is common.
• Nausea may occur.
• Nervousness may occur.
• Vertigo may occur.
• Palpitations may occur.
• Blurring of vision may occur.
• Headache may occur.
• Restlessness may occur.
• Insomnia may occur.
• Thickening of bronchial secretions may occur.
• Diarrhea may occur.
• Vomiting may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Allergic reactions to diphenhydramine itself, including severe hypersensitivity reactions, can occur even though the drug is used to treat allergic symptoms.
• Excitation, including paradoxical agitation or overstimulation, may occur, particularly in children.
• Anticholinergic toxicity, including confusion, disorientation, or hallucinations, can occur, particularly in older adults, in overdose, or when combined with other anticholinergic drugs.
• Seizures can occur with significant overdose.
• Severe drowsiness progressing to difficulty waking, slowed breathing, or respiratory depression can occur with overdose or when combined with other central nervous system depressants.
• Rapid intravenous administration or doses above 100 mg can increase the risk of a drop in blood pressure or an abnormal heart rhythm, particularly in patients with hypertension or cardiac disease.
• Tissue irritation or damage can occur if the injection is given subcutaneously or leaks outside the vein (perivascularly) rather than by the intended intravenous or deep intramuscular route.
• Seek urgent medical attention for signs of a severe allergic reaction, a seizure, an irregular or racing heartbeat, or severe drowsiness that is difficult to rouse from.

• Use with caution in patients with a history of asthma, since diphenhydramine's atropine-like effect can thicken bronchial secretions.
• Use with caution in patients with hypertension or cardiac disease, and avoid single doses greater than 100 mg in these patients.
• Patients should be cautioned not to operate a vehicle or hazardous machinery until they know how this medication affects them.
• Use with caution together with alcohol or other central nervous system depressants, such as hypnotics, sedatives, and tranquilizers, because of additive sedative effects.
• Avoid subcutaneous or perivascular injection.
• Use with caution in older adults, who are generally more sensitive to diphenhydramine's anticholinergic and sedating effects.
• Use with caution in patients with narrow-angle glaucoma or urinary retention, including men with an enlarged prostate, since diphenhydramine's anticholinergic effect can worsen these conditions.

• Contraindicated in patients with known hypersensitivity to diphenhydramine hydrochloride or to any ingredient in the formulation.
• Not recommended for use in neonates or premature infants, given the increased risk of anticholinergic and central nervous system effects, including seizures, in this age group.

• Alcohol and other central nervous system depressants, including hypnotics, sedatives, and tranquilizers, have additive sedative effects with diphenhydramine.
• Monoamine oxidase (MAO) inhibitors may prolong and intensify the anticholinergic effects of diphenhydramine.
• Other drugs with anticholinergic activity, such as tricyclic antidepressants and atropine-like agents, can add to diphenhydramine's dry mouth, constipation, urinary retention, and confusion effects.
• Diphenhydramine's antiemetic and antivertigo effects can mask the early warning signs of hearing damage (ototoxicity) from other drugs, such as certain antibiotics, so caution is needed when it is given together with a potentially ototoxic drug.

• Food interactions do not apply to this product, since it is given by injection by a health professional rather than taken by mouth.

• Given by intravenous or deep intramuscular injection by a health professional when a prompt effect is needed; because it is not self-administered by mouth, food timing does not apply.

• Store vials at room temperature, between 15°C and 30°C, and protect from freezing and light.
• This product is preservative-free and supplied in single-use vials; discard any unused portion after use.

• Injectable diphenhydramine is a fast-acting antihistamine given by a health professional when prompt antiallergic, antiemetic, or antispasmodic relief is needed.
• Drowsiness, dizziness, and dry mouth are common; avoid driving or hazardous activities until you know how it affects you.
• Avoid alcohol and other sedating medications, since their effects can add together.
• Single doses above 100 mg are avoided, particularly in patients with high blood pressure or heart disease.
• Seek urgent medical attention for a severe allergic reaction, a seizure, an irregular heartbeat, or extreme drowsiness.