ATADOZE

Hydroxyzine pamoate is a light yellow, practically odorless powder practically insoluble in water and methanol and freely soluble in dimethylformamide.

It is chemically designated as (±)-2-[2-[4-( p -Chloro-α-phenylbenzyl)-1-piperazinyl]ethoxy]ethanol 4,4’-methylenebis[3-hydroxy-2-naphthoate] (1:1) and can be structurally represented as follows: C 21 H 27 CIN 2 O 2 •C 23 H 16 O 6 M.W. 763.27 Each capsule, for oral administration, contains hydroxyzine pamoate equivalent to hydroxyzine hydrochloride 25 mg or 50 mg. In addition, each capsule contains the following inactive ingredients: colloidal silicon dioxide, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, sodium starch glycolate (potato), and sodium lauryl sulfate.

The capsule shell contains the following ingredients: D&C Yellow #10, FD&C Green #3, FD&C Yellow #6, gelatin, and titanium dioxide.

The edible imprinting ink contains the following ingredients: black iron oxide, D&C Yellow #10, FD&C Blue #1, FD&C Blue #2, FD&C Red #40, propylene glycol, and shellac glaze.

For symptomatic relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states in which anxiety is manifested.

Useful in the management of pruritus due to allergic conditions such as chronic urticaria and atopic and contact dermatoses, and in histamine-mediated pruritus.

As a sedative when used as premedication and following general anesthesia, hydroxyzine may potentiate meperidine (Demerol ® ) and barbiturates, so their use in pre-anesthetic adjunctive therapy should be modified on an individual basis.

Atropine and other belladonna alkaloids are not affected by the drug.

Hydroxyzine is not known to interfere with the action of digitalis in any way and it may be used concurrently with this agent.

The effectiveness of hydroxyzine as an antianxiety agent for long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies.

The physician should reassess periodically the usefulness of the drug for the individual patient.

Mental confusion Dementia

Child under 6 years of age Female likely to be pregnant Glaucoma Pregnancy Insomnia Severe hepatic impairment Renal impairment: 15 ml/min < creatinine clearance < 60 ml/min Digestive Motility (decrease) Severe myasthenia Newborn exposed in utero to the medicine Urinary retention Elderly Cognitive disorder.

Hydroxyzine pamoate is unrelated chemically to the phenothiazines, reserpine, meprobamate, or the benzodiazepines.

Hydroxyzine pamoate is not a cortical depressant, but its action may be due to a suppression of activity in certain key regions of the subcortical area of the central nervous system.

Primary skeletal muscle relaxation has been demonstrated experimentally.

Bronchodilator activity, and antihistaminic and analgesic effects have been demonstrated experimentally and confirmed clinically.

An antiemetic effect, both by the apomorphine test and the veriloid test, has been demonstrated.

Pharmacological and clinical studies indicate that hydroxyzine in therapeutic dosage does not increase gastric secretion or acidity and in most cases has mild antisecretory activity.

Hydroxyzine is rapidly absorbed from the gastrointestinal tract and hydroxyzine pamoate clinical effects are usually noted within to 30 minutes after oral administration.

Mechanism of action

Hydrazine is an anxiolytic derived from piperazine, not chemically related to phenothiazines and benzodiazepines.

It is also an antihistamine antagonist of central and peripheral H1 receptors with anticholinergic properties.

Hydrazine has shown its efficacy in humans in urticaria.

It has a sedative effect evidenced by EEG recordings in healthy volunteers.

Hydrazine has activity on minor symptoms of anxiety.

• Liver status (abnormality) (Rare)
• Alkaline phosphates (increase)
• Gamma GT (increase)
• Bilirubinaemia (increase)
• Transaminases (increase)
• Bully dermatosis (Very rare)
• Generalised acute exanthemous pusulosis (Very rare)
• Fixed pigmented Erythema (Very rare)
• Hypersudation (Very rare)
• Dermatitis (Rare)
• Papulous eruption (Rare)
• Pemphigoid Toxic epidermal necrolysis Stevens-Johnson Syndrome
• Pruritus Maculopapulous eruption Skin Erythema Eczema Lyell's syndrome Urticaria
• Polymorphic Erythema Asthenia Fatigue Fever Wearing Edema Thrombocytopenia Hepatitis
• Oedema of Quincke (Rare)
• Angioedema (Very rare)
• Anaphylactoid reaction (Rare)
• Anaphylactic shock (Very rare)
• Hypersensitivity Weight (increase)
• Blurty vision (Rare)
• Accommodation disorder Vertigo (Rare)
• Oral dryness Insomnia (Rare)
• Temporospatial disorientation (Rare)
• Hallucination (Rare)
• Agitation (Rare)
• Aggressiveness Depression Mental confusion Cardiac arrest (Rare)
• Ventricular fibrillation (Rare)
• Ventricular tachycardia (Rare)
• Sudden cardiac death
• Tachycardia QT space extension Torsades de pointes Ventricular arrhythmia Malaise
• Syncope Hypotension Vomiting Constipation Nausea Diarrhoea Sedation (Common)
• Loss of consciousness (Rare)
• Convulsions (Rare)
• Trembling (Rare)
• Dyskinesia (Rare)
• Paraesthesia Central nervous system depression
• Oculogy crisis Headache Paradoxic reaction Somnolence Psychomotor disorder Tics Central nervous system disorder
• Dystonia Ataxia Bronchospasm (Rare)
• Atropinic effect Urinary retention Dysuria Enuresis.

The most common manifestation of overdosage of hydroxyzine pamoate is hypersedation.

Other reported signs and symptoms were convulsions, stupor, nausea and vomiting.

As in the management of overdosage with any drug, it should be borne in mind that multiple agents may have been taken.

If vomiting has not occurred spontaneously, it should be induced.

Immediate gastric lavage is also recommended.

General supportive care, including frequent monitoring of the vital signs and close observation of the patient, is indicated.

Hypotension, though unlikely, may be controlled with intravenous fluids and vasopressors ( do not use epinephrine as hydroxyzine counteracts its pressor action ).

Injection, USP, may be used to counteract central nervous system depressant effects.

Hydroxyzine overdose may cause QT prolongation and Torsade de Pointes.

ECG monitoring is recommended in cases of hydroxyzine overdose.

There is no specific antidote.

It is doubtful that hemodialysis would be of any value in the treatment of overdosage with hydroxyzine.

However, if other agents such as barbiturates have been ingested concomitantly, hemodialysis may be indicated.

There is no practical method to quantitate hydroxyzine in body fluids or tissue after its ingestion or administration.

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.