MECLIZINE HYDROCHLORIDE

ADVERSE REACTIONS Anaphylactoid reaction, drowsiness, dry mouth, headache, fatigue, vomiting and, on rare occasions, blurred vision have been reported. To report SUSPECTED ADVERSE REACTIONS, contact Jubilant Cadista Pharmaceuticals Inc. at 1-800-313-4623 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CONTRAINDICATIONS Meclizine hydrochloride tablets are contraindicated in individuals who have shown a previous hypersensitivity to it.

DESCRIPTION Chemically, Meclizine HCl is 1-( p -chloro-α-phenylbenzyl)-4-( m -methylbenzyl) piperazine dihydrochloride monohydrate. C 25 H 27 ClN 2 • 2HCl • H 2 O Molecular Weight 481 . 88 Meclizine hydrochloride tablets, USP are available in two different strengths: 12.5 mg and 25 mg. In addition each tablet contains the following inactive ingredients: Colloidal Silicon Dioxide, Croscarmellose Sodium, Lactose Monohydrate, Magnesium Stearate, Microcrystalline Cellulose. Also, Meclizine hydrochloride tablets USP, 12.5 mg contains FD&C Blue #1 Aluminum Lake (11-13%) and Meclizine hydrochloride tablets USP, 25 mg contains D&C Yellow #10 Aluminum Lake (15-20%). Structure of Meclizine HCl

DOSAGE AND ADMINISTRATION For the treatment of vertigo associated with diseases affecting the vestibular system, the recommended dose is 25 to 100 mg daily, in divided dosage, depending upon clinical response.

INDICATIONS AND USAGE Meclizine hydrochloride tablets are indicated for the treatment of vertigo associated with diseases affecting the vestibular system.

WARNINGS Since drowsiness may, on occasion, occur with use of this drug, patients should be warned of this possibility and cautioned against driving a car or operating dangerous machinery. Patients should avoid alcoholic beverages while taking this drug. Due to its potential anticholinergic action, this drug should be used with caution in patients with asthma, glaucoma, or enlargement of the prostate gland.

CLINICAL PHARMACOLOGY Meclizine hydrochloride is an antihistamine that shows marked protective activity against nebulized histamine and lethal doses of intravenously injected histamine in guinea pigs. It has a marked effect in blocking the vasodepressor response to histamine, but only a slight blocking action against acetylcholine. Its activity is relatively weak in inhibiting the spasmogenic action of histamine on isolated guinea pig ileum. Pharmacokinetics The available pharmacokinetic information for meclizine following oral administration has been summarized from published literature. Absorption Meclizine is absorbed after oral administration with maximum plasma concentrations reaching at a median T max value of 3 hours post-dose (range: 1.5 to 6 hours) for the tablet dosage form. Distribution Drug distribution characteristics for meclizine in humans are unknown. Metabolism The metabolic fate of meclizine in humans is unknown. In an in vitro metabolic study using human hepatic microsome and recombinant CYP enzyme, CYP2D6 was found to be the dominant enzyme for metabolism of meclizine. The genetic polymorphism of CYP2D6 that results in extensive-, poor-, intermediate- and ultra-rapid metabolizer phenotypes could contribute to large inter-individual variability in meclizine exposure. Elimination Meclizine has a plasma elimination half-life of about 5-6 hours in humans.

Pharmacokinetics The available pharmacokinetic information for meclizine following oral administration has been summarized from published literature.

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MECLIZINE HYDROCHLORIDE Meclizine Hydrocloride SILICON DIOXIDE CROSCARMELLOSE SODIUM LACTOSE MONOHYDRATE MAGNESIUM STEARATE CELLULOSE, MICROCRYSTALLINE D&C YELLOW NO. 10 ALUMINUM OXIDE MECLIZINE HYDROCHLORIDE MECLIZINE TL121

ANDA040659

MECLIZINE HYDROCHLORIDE

Meclizine Hydrocloride

68071-4694

HUMAN PRESCRIPTION DRUG

ORAL

PRINCIPAL DISPLAY PANEL PDP

HOW SUPPLIED 25 mg (Yellow, oval shaped tablets, debossed with TL 121 with score on one side and plain on the other side.) NDC 68071-4694-4 BOTTLES OF 4 NDC 68071-4694-6 BOTTLES OF 6 Store at 20 to 25°C (68 to 77°F) [See USP Controlled Room Temperature]. Manufactured By: Jubilant Cadista Pharmaceuticals Inc. Salisbury, MD 21801, USA Revised 05/2018

PRECAUTIONS Pediatric Use Clinical studies establishing safety and effectiveness in children have not been done; therefore, usage is not recommended in children under 12 years of age. Pregnancy Pregnancy Category B. Reproduction studies in rats have shown cleft palates at 25-50 times the human dose. Epidemiological studies in pregnant women, however, do not indicate that meclizine increases the risk of abnormalities when administered during pregnancy. Despite the animal findings, it would appear that the possibility of fetal harm is remote. Nevertheless, meclizine, or any other medication, should be used during pregnancy only if clearly necessary. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when meclizine is administered to a nursing woman. Hepatic Impairment The effect of hepatic impairment on the pharmacokinetics of meclizine has not been evaluated. As meclizine undergoes metabolism, hepatic impairment may result in increased systemic exposure of the drug. Treatment with meclizine should be administered with caution in patients with hepatic impairment. Renal Impairment The effect of renal impairment on the pharmacokinetics of meclizine has not been evaluated. Due to a potential for drug/metabolite accumulation, meclizine should be administered with caution in patients with renal impairment and in the elderly as renal function generally declines with age. Drug Interactions There may be increased CNS depression when meclizine is administered concurrently with other CNS depressants, including alcohol, tranquilizers, and sedatives. ( see WARNINGS ). Based on in-vitro evaluation, meclizine is metabolized by CYP2D6. Therefore there is a possibility for a drug interaction between meclizine and CYP2D6 inhibitors.