CROXIZINE

Hydroxyzine is a first-generation histamine

H 1 -receptor antagonist of the dephenylmethane and piperazine classes that exhibits sedative, anxiolytic, and antiemetic properties. 2, 12 It was first developed in and has since remained a relatively common treatment for allergic conditions such as pruritus, urticaria, dermatoses, and histamine-mediated pruritus.

The active metabolite of hydroxyzine, cetirizine, is also available as an active ingredient in allergic medications, and is responsible for much of its hydroxyzine's antihistaminic effect.

Hydroxyzine is also used for generalized anxiety disorder, tension caused by psychoneurosis, and other conditions with manifestations of anxiety.

Hydroxyzine is indicated for the symptomatic relief of anxiety and tension associated with psychoneuroses, and as an adjunct in organic disease states in which anxiety is manifested.

It is also indicated in the treatment of histamine-mediated pruritus and pruritus due to allergic conditions such as chronic urticaria.

Canadian labeling states that hydroxyzine is also indicated in adults and children as a premedication prior to medical procedures, such as dental surgery.

It is also used in the control of nausea and vomiting, excluding nausea and vomiting of pregnancy.

Hydroxyzine blocks the activity of histamine to relieve allergic symptoms such as pruritus.

Activity at off-targets also allows for its use as a sedative anxiolytic and an antiemetic in certain disease states.

Hydroxyzine is relatively fast-acting, with an onset of effect that occurs between and 60 minutes and a duration of action between 4-6 hours.

Hydroxyzine may potentiate the effects of central nervous system (CNS) depressants following general anesthesia.

• patients maintained on hydroxyzine should receive reduced doses of any CNS depressants required.

Hydroxyzine is reported to prolong the

QT/QTc interval based on postmarketing reports of rare events of Torsade de Pointes, cardiac arrest, and sudden death, and should be used with caution in patients with an increased baseline risk for QTc prolongation. 15, 10.

The absolute bioavailability of hydroxyzine has not been ascertained, as intravenous formulations are unavailable due to a risk of hemolysis.

Hydroxyzine is rapidly absorbed from the gastrointestinal tract upon oral administration, 18 reaching its maximum plasma concentration (T max ) approximately 2 hours following administration.

The mean volume of distribution is 16.0 ± 3.0 L/kg. Higher concentrations are found in the skin than in the plasma.

Hydroxyzine is metabolized in the liver by CYP3A4 and CYP3A5.

While the precise metabolic fate of hydroxyzine is unclear, its main and active metabolite (~45-60% of an Oral administered dose), 13 generated by oxidation of its alcohol moiety to a carboxylic acid, is the second-generation antihistamine cetirizine.

Hydroxyzine is likely broken down into several other metabolites, though specific structures and pathways have not been elucidated in humans.

Hover over products below to view reaction partners Hydroxyzine Cetirizine.

Approximately 70% of hydroxyzine's active metabolite, cetirizine, is excreted unchanged in the urine.

The precise extent of renal and fecal excretion in humans has not been determined.

The half-life of hydroxyzine is reportedly 14-25 hours, 2 and appears to be, on average, shorter in children (~7.1 hours) than in adults (~20 hours).

Elimination half-life is prolonged in the elderly, averaging approximately 29 hours, 3 and is likely to be similarly prolonged in patients with renal or hepatic impairment.

of hydroxyzine has been reported to be 31.1 ± 11.1 mL/min/kg in children and 9.8 ± 3.3 mL/min/kg in adults.

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The oral

LD is 840 mg/kg in rats and 400 mg/kg in mice.

Overdose from hydroxyzine is most commonly characterized by hypersedation, but may also manifest as convulsions, stupor, nausea, and vomiting.

In cases of overdose, consider the induction of vomiting and the use of gastric lavage.

Other treatment should involve general symptomatic and supportive care.

Hypotension may be controlled by intravenous fluids and pressors, and caffeine and sodium benzoate injection may be used to counteract any observed CNS depressant effects.

Hemodialysis is unlikely to provide any benefit in the treatment hydroxyzine overdose.

It is not known whether this drug is excreted in human milk.

Since many drugs are so excreted, hydroxyzine should not be given to nursing mothers.

Hydroxyzine, when administered to the pregnant mouse, rat, and rabbit, induced fetal abnormalities in the rat and mouse at doses substantially above the human therapeutic range.

Clinical data in human beings are inadequate to establish safety in early pregnancy.

Until such data are available, hydroxyzine is contraindicated in early pregnancy.

Hydroxyzine is contraindicated in patients with a prolonged QT interval.

Hydroxyzine pamoate is contraindicated for patients who have shown a previous hypersensitivity to any component of this medication.

Hydroxyzine is contraindicated in patients with known hypersensitivity to hydroxyzine products, and in patients with known hypersensitivity to cetirizine hydrochloride or levocetirizine hydrochloride.

For symptomatic relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states in which anxiety is manifested: in adults, 50 mg to 100 mg q.i.d.; children under 6 years, 50 mg daily in divided doses; and over 6 years, 50 mg to 100 mg daily in divided doses.

For use in the management of pruritus due to allergic conditions such as chronic urticaria and atopic and contact dermatoses, and in histamine-mediated pruritus: in adults, 25 mg t.i.d. or q.i.d.; children under 6 years, 50 mg daily in divided doses; and over 6 years, 50 mg to 100 mg daily in divided doses.

As a sedative when used as a premedication and following general anesthesia: 50 mg to 100 mg in adults, and 0.6 mg/kg in children.

When treatment is initiated by the intramuscular route of administration, subsequent doses may be administered orally.

As with all medications, the dosage should be adjusted according to the patient’s response to therapy.

Capsules, USP, for oral administration, are available as 25 mg (equivalent to 25 mg hydroxyzine hydrochloride) are light green/dark green capsules imprinted “E 613” and supplied as: NDC: 63629-8874-1 bottles of 500 Storage Store at 20° to 25°C (68° to 77°F) .

Protect from moisture.

Dispense contents in a tight, light-resistant container as defined in the USP, with a child-resistant closure, as required.

Repackaged/Relabeled by: Bryant Ranch Prepack, Inc.

Burbank, CA 91504.

A determination has not been made whether controlled clinical studies of hydroxyzine pamoate included sufficient numbers of subjects aged and over to define a difference in response from younger subjects.

Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy.

The extent of renal excretion of hydroxyzine pamoate has not been determined.

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selections.

Sedating drugs may cause confusion and over sedation in the elderly; elderly patients generally should be started on low doses of hydroxyzine pamoate and observed closely.