Meclizine Hydrochloride

1 INDICATIONS AND USAGE Meclizine hydrochloride tablets, USP are indicated for the treatment of vertigo associated with diseases affecting the vestibular system in adults. Meclizine hydrochloride tablets, USP are indicated for the treatment of vertigo associated with diseases affecting the vestibular system in adults (1).

Purpose Antiemetic

2 DOSAGE AND ADMINISTRATION • Recommended dosage: 25 mg to 100 mg daily, in divided doses ( 2.1 ). • Tablets: Swallow whole ( 2.2 ). • Chewable Tablets: Must be chewed or crushed before swallowing; do not swallow whole ( 2.2 ). 2.1 Recommended Dosage The recommended dosage is 25 mg to 100 mg daily administered orally, in divided doses, depending upon clinical response. 2.2 Administration Instructions Tablets Meclizine hydrochloride tablets must be swallowed whole. Chewable Tablets Meclizine hydrochloride chewable tablets must be chewed or crushed completely before swallowing. Do not swallow chewable tablets whole.

3 DOSAGE FORMS AND STRENGTHS Meclizine Hydrochloride Tablets, USP are available containing 12.5 mg, 25 mg or 50 mg of meclizine dihydrochloride equivalent to 10.53 mg, 21.07 mg or 42.14 mg of meclizine free base, respectively. • The 12.5 mg tablets are a white to off-white 7.14 mm round, biconvex, beveled edge tablets debossed with 12 on one side of tablet and C on the other side of tablet. • The 25 mg tablets are a white to off-white 8.73 mm round, biconvex, beveled edge tablets debossed with 25 on one side of tablet and C on the other side of tablet. • The 50 mg tablets are a white to off-white 10.32 mm round, biconvex, beveled edge tablets debossed with C above the score on one side of tablet and 50 on the other side of tablet. • Tablets: 12.5 mg, 25 mg and 50 mg ( 3 ).

4 CONTRAINDICATIONS Meclizine hydrochloride tablets, USP are contraindicated in patients with a hypersensitivity to meclizine or any of the inactive ingredients [see Adverse Reactions (6) and Description (11)]. Meclizine hydrochloride tablets, USP are contraindicated in patients with hypersensitivity to meclizine or any of the inactive ingredients (4).

Do not give to children under 12 years of age unless directed by a doctor.

Ask a doctor before use if you have ■ a breathing problem such as emphysema or chronic bronchitis ■ glaucoma ■ trouble urinating due to an enlarged prostate gland

6 ADVERSE REACTIONS The following adverse reactions associated with the use of meclizine hydrochloride were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Anaphylactic reaction, drowsiness, dry mouth, headache, fatigue, and vomiting. On rare occasions blurred vision has been reported. Common adverse reactions are anaphylactic reaction, drowsiness, dry mouth, headache, fatigue, and vomiting. On rare occasions blurred vision has been reported ( 6 ). 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.

7 DRUG INTERACTIONS • Coadministration of meclizine hydrochloride tablets with other CNS depressants, including alcohol, may result in increased CNS depression ( 7.1 ). • CYP2D6 inhibitors: As meclizine is metabolized by CYP2D6, there is a potential for drug-drug interactions between meclizine hydrochloride tablets and CYP2D6 inhibitors ( 7.2 ). 7.1 CNS Depressants There may be increased CNS depression when meclizine hydrochloride tablets are administered concurrently with other CNS depressants, including alcohol [see Warnings and Precautions (5.1) ]. 7.2 CYP2D6 Inhibitors Based on in-vitro evaluation, meclizine is metabolized by CYP2D6. Therefore, there is a possibility for a drug interaction between meclizine hydrochloride tablets and CYP2D6 inhibitors. Therefore, monitor for adverse reactions and clinical effect accordingly.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Data from epidemiological studies have not generally indicated a drug-associated risk of major birth defects with meclizine during pregnancy. However, in a published study, an increased incidence of fetal malformations was observed following oral administration of meclizine to pregnant rats during the period of organogenesis, at doses similar to those used clinically. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Human Data Epidemiological studies reporting on pregnancies exposed to meclizine have not identified an association between the use of meclizine during pregnancy and an increased risk of major birth defects. Animal Data In a published study, oral administration of meclizine (25 to 250 mg/kg) to pregnant rats during the period of organogenesis resulted in a high incidence of fetal malformations. These effects occurred at doses as low as 25 mg/kg, which is approximately 2 times the maximum recommended human dose (100 mg) on a body surface area (mg/m 2 ) basis. 8.2 Lactation Risk Summary There are no data on the presence of meclizine in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for meclizine hydrochloride tablets and any potential adverse effects on the breastfed infant from meclizine hydrochloride tablets or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use 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. 8.6 Hepatic Impairment The effect of hepatic impairment on the pharmacokinetics of meclizine has not been evaluated. As meclizine hydrochloride tablets undergo metabolism, hepatic impairment may result in increased systemic exposure of meclizine. Treatment with meclizine hydrochloride tablets should be administered with caution in patients with hepatic impairment. 8.7 Renal Impairment The effect of renal impairment on the pharmacokinetics of meclizine has not been evaluated. Because of a potential for drug/metabolite accumulation, meclizine hydrochloride tablets should be administered with caution in patients with renal impairment and in the elderly, as renal function generally declines with age. 8.8 Genetic CYP2D6 Polymorphism The genetic polymorphism of CYP2D6 that results in poor-, intermediate-, extensive-, and ultrarapid metabolizer phenotypes could contribute to large inter-individual variability in meclizine exposure. Therefore, when meclizine hydrochloride tablets are administered to patients with CYP2D6 polymorphism, monitor for adverse reactions and clinical effect accordingly.

12.1 Mechanism of Action The precise mechanism by which meclizine exerts its therapeutic effect is unknown but is presumed to involve antagonism of the histamine H 1 receptor.

11 DESCRIPTION Meclizine hydrochloride, a histamine (H1) receptor antagonist, is a white or slightly yellowish, crystalline powder. It has the following structural formula: Chemically, meclizine hydrochloride is 1-(p-chloro-α-phenylbenzyl)-4-(m-methylbenzyl) piperazine dihydrochloride monohydrate. Tablets Inactive ingredients for the tablets are: corn starch; dibasic calcium phosphate; magnesium stearate; polyethylene glycol; sucrose. The 12.5 mg tablets also contain: FD&C Blue # 1. The 25 mg tablets also contain: FD&C Yellow # 6 and D&C Yellow # 10. The 50 mg tablets also contain: FD&C Blue # 1, FD&C Yellow # 6 and D&C Yellow # 10. Each meclizine hydrochloride 12.5 mg tablet contains 12.5 mg of meclizine dihydrochloride equivalent to 10.53 mg of meclizine free base. Each meclizine hydrochloride 25 mg tablet contains 25 mg of meclizine dihydrochloride equivalent to 21.07 mg of meclizine free base. Each meclizine hydrochloride 50 mg tablet contains 50 mg of meclizine dihydrochloride equivalent to 42.14 mg of meclizine free base. Chewable Tablets Inactive ingredients for the chewable tablets are: corn starch, colloidal silicon dioxide, FD&C Red # 40, lactose monohydrate, magnesium stearate, raspberry flavor, saccharin sodium, and talc. Each meclizine hydrochloride 25 mg chewable tablet contains 25 mg of meclizine dihydrochloride equivalent to 21.07 mg of meclizine free base. struct-1.jpg

Active Ingredient (in each tablet) 12.5mg tablet: Meclizine HCL.... 12.5 mg 25mg tablet : Meclizine HCL .....25 mg

In case of overdose, get medical help or contact a Poison Control Center (1-800-222-1222) right away.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Meclizine Hydrochloride Tablets USP, 12.5 mg are light blue to blue colored, spotted, oval shaped, biconvex uncoated tablet, debossed with '1161' on one side and plain on the other side and are supplied as follows: NDC 70710-1161-3 in bottles of 30 tablets with child-resistance closure NDC 70710-1161-9 in bottles of 90 tablets with child-resistance closure NDC 70710-1161-1 in bottles of 100 tablets with child-resistance closure NDC 70710-1161-0 in bottles of 1000 tablets with non-child-resistance closure NDC 70710-1161-4 in unit-dose blister cartons of 100 tablets (10 X 10 Unit-dose) Meclizine Hydrochloride Tablets USP, 25 mg are light yellow to yellow colored, spotted, oval shaped, biconvex uncoated tablets debossed with '1162' on one side and plain on the other side and are supplied as follows: NDC 70710-1162-3 in bottles of 30 tablets with child-resistance closure NDC 70710-1162-9 in bottles of 90 tablets with child-resistance closure NDC 70710-1162-1 in bottles of 100 tablets with child-resistance closure NDC 70710-1162-0 in bottles of 1000 tablets with non-child-resistance closure NDC 70710-1162-4 in unit-dose blister cartons of 100 tablets (10 X 10 Unit-dose) 16.2 Storage and Handling Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container (USP).

16.1 How Supplied Meclizine Hydrochloride Tablets USP, 12.5 mg are light blue to blue colored, spotted, oval shaped, biconvex uncoated tablet, debossed with '1161' on one side and plain on the other side and are supplied as follows: NDC 70710-1161-3 in bottles of 30 tablets with child-resistance closure NDC 70710-1161-9 in bottles of 90 tablets with child-resistance closure NDC 70710-1161-1 in bottles of 100 tablets with child-resistance closure NDC 70710-1161-0 in bottles of 1000 tablets with non-child-resistance closure NDC 70710-1161-4 in unit-dose blister cartons of 100 tablets (10 X 10 Unit-dose) Meclizine Hydrochloride Tablets USP, 25 mg are light yellow to yellow colored, spotted, oval shaped, biconvex uncoated tablets debossed with '1162' on one side and plain on the other side and are supplied as follows: NDC 70710-1162-3 in bottles of 30 tablets with child-resistance closure NDC 70710-1162-9 in bottles of 90 tablets with child-resistance closure NDC 70710-1162-1 in bottles of 100 tablets with child-resistance closure NDC 70710-1162-0 in bottles of 1000 tablets with non-child-resistance closure NDC 70710-1162-4 in unit-dose blister cartons of 100 tablets (10 X 10 Unit-dose)