Validol (Hydroxyzine)

Uses

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 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. Validol (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.

Validol (Hydroxyzine) is also used to associated treatment for these conditions: Anxiety, Nausea and vomiting, Pruritus

How Validol (Hydroxyzine) works

The H₁ histamine receptor is responsible for mediating hypersensitivity and allergic reactions. Exposure to an allergen results in degranulation of mast cells and basophils, which then release histamine and other inflammatory mediators. Histamine binds to, and activates, H₁ receptors, which results in the further release of pro-inflammatory cytokines, such as interleukins, from basophils and mast cells. These downstream effects of histamine binding are responsible for a wide variety of allergic symptoms, such as pruritus, rhinorrhea, and watery eyes.

Validol (Hydroxyzine) is a potent inverse agonist of histamine H₁-receptors - inverse agonists are agents that are considered to have a "negative efficacy", so rather than simply blocking activity at a receptor they actively dampen its activity. Inverse agonism at these receptors is responsible for hydroxyzine's efficacy in the treatment of histaminic edema, flare, and pruritus.

Validol (Hydroxyzine) is not a cortical depressant, so its sedative properties likely occur at the subcortical level of the CNS. These sedative properties allow activity as an anxiolytic. Antiemetic efficacy is likely secondary to activity at off-targets.

Dosage

Validol (Hydroxyzine) dosage

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

• Adults: 50-100 mg q.i.d.
• Children under 6 years: 50 mg daily in divided doses
• Over 6 years: 50-100 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:

• Adults: 25 mg t.i.d. or q.i.d.
• Children under 6 years: 50 mg daily in divided doses
• Over 6 years: 50-100 mg daily in divided doses

As a sedative when used as a premedication and following general anesthesia:

• Adults: 50-100 mg
• Children: 0.6 mg/kg of body weight

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.

May be taken with or without food.

Side Effects

Side effects reported with the administration of hydroxyzine hydrochloride are usually mild and transitory in nature.

Anticholinergic: Dry mouth.

Central Nervous System: Drowsiness is usually transitory and may disappear in a few days of continued therapy or upon reduction of the dose. Involuntary motor activity including rare instances of tremor and convulsions have been reported, usually with doses considerably higher than those recommended. Clinically significant respiratory depression has not been reported at recommended doses.

Toxicity

The oral LD₅₀ 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.

Precaution

Patient with porphyria, suffering from glaucoma, bladder outflow obstruction, decreased GI motility, myasthenia gravis, or dementia; with known predisposing factor to cardiac arrhythmia, including electrolyte imbalance, increased potential for convulsions, and pre-existing heart disease. Do not admin via SC, IV, or intra-arterial inj. Renal and hepatic impairment.

Interaction

Additive or may potentiate CNS depressant effects of opiates or other analgesics, barbiturates or other sedatives, and anaesth. MAOIs and TCAs potentiate antimuscarinic effects.

Food Interaction

• Avoid alcohol. Co-administration with alcohol may potentiate the CNS adverse effects of hydroxyzine.
• Avoid grapefruit products. Co-administration with grapefruit inhibits hydroxyzine metabolism and can result in elevated serum concentrations.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Validol (Hydroxyzine) Drug Interaction

Major: escitalopram, escitalopramModerate: diphenhydramine, diphenhydramine, duloxetine, duloxetine, pregabalin, pregabalin, alprazolam, alprazolam, sertraline, sertraline, cetirizine, cetirizineUnknown: acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol

Validol (Hydroxyzine) Disease Interaction

Major: depression, QT prolongationModerate: anticholinergic effects, asthma/COPD, cardiovascular, renal/liver disease, glaucoma, liver disease, renal/liver disease

Volume of Distribution

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

Elimination Route

The absolute bioavailability of hydroxyzine has not been ascertained, as intravenous formulations are unavailable due to a risk of hemolysis. Validol (Hydroxyzine) is rapidly absorbed from the gastrointestinal tract upon oral administration, reaching its maximum plasma concentration (T_max) approximately 2 hours following administration.

Half Life

The half-life of hydroxyzine is reportedly 14-25 hours, 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, and is likely to be similarly prolonged in patients with renal or hepatic impairment.

Clearance

Clearance 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.

Elimination Route

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.

Pregnancy & Breastfeeding use

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Nursing mothers: 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.

Contraindication

Validol (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. Validol (Hydroxyzine) is contraindicated for patients who have shown a previous hypersensitivity to it.

Special Warning

Renal Impairment: Moderate to severe: Reduce dose by 50%.

Hepatic Impairment: Oral: Reduce total daily dose by 33%.

Geriatric use: A determination has not been made whether controlled clinical studies of hydroxyzine included sufficient numbers of subjects aged 65 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 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 and observed closely.

Acute Overdose

Symptoms: Excessive sedation, hypotension (rare).

Management: Symptomatic and supportive treatment. Empty stomach immediately by inducing emesis or by gastric lavage. Admin IV fluids and norepinephrine or metaraminol if hypotension occurs.

Storage Condition

Store between 15-30° C. Protect from light.

Innovators Monograph

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