Meclizine Hydrochloride

1 INDICATIONS AND USAGE Meclizine hydrochloride tablet is indicated for the treatment of vertigo associated with diseases affecting the vestibular system in adults. Meclizine hydrochloride tablet is indicated for the treatment of vertigo associated with diseases affecting the vestibular system in adults ( 1 ).

2 DOSAGE AND ADMINISTRATION Recommended dosage: 25 mg to 100 mg daily, in divided doses ( 2.1 ). Tablets: 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.

3 DOSAGE FORMS AND STRENGTHS Tablets 12.5 mg: White to off-white, oval shaped, film-coated tablets, debossed with “ CE ” on one side and “ 256 ” on the other side. 25 mg: White to off-white, oval shaped, film-coated tablets, debossed with “ CE ” on one side and “ 257 ” on the other side. 50 mg: White to off-white, oval shaped, film-coated scored tablets, debossed with “ C ” breakline “ E ” on one side and “ 258 ” on the other side. Tablets: 12.5 mg, 25 mg, and 50 mg ( 3 ).

4 CONTRAINDICATIONS Meclizine hydrochloride tablets 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 are contraindicated in patients with hypersensitivity to meclizine or any of the inactive ingredients ( 4 ).

6 ADVERSE REACTIONS The following adverse reactions associated with the use of meclizine hydrochloride tablets 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 Chartwell RX, LLC at 1-845-232-1683, 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 and any potential adverse effects on the breastfed infant from meclizine hydrochloride 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 undergoes 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.

11 DESCRIPTION Meclizine Hydrochloride, USP, a histamine (H1) receptor antagonist, is a white or slightly yellowish crystalline powder. It has the following structural formula: Molecular Weight - 481.88 Chemically, meclizine hydrochloride is 1-( p -chloro-α-phenylbenzyl)-4-( m -methylbenzyl) piperazine dihydrochloride monohydrate. Tablets Inactive ingredients for the tablets are: colloidal silicon dioxide, corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, sodium starch glycolate, stearic acid, talc and titanium dioxide. Meclizine hydrochloride tablets, USP are available in three strengths, 12.5 mg, 25 mg and 50 mg. Each meclizine hydrochloride, USP 12.5 mg tablet contains 12.5 mg of meclizine dihydrochloride equivalent to 10.53 mg of meclizine free base. Each meclizine hydrochloride, USP 25 mg tablet contains 25 mg of meclizine dihydrochloride equivalent to 21.07 mg of meclizine free base. Each meclizine hydrochloride, USP 50 mg tablet contains 50 mg of meclizine dihydrochloride equivalent to 42.14 mg of meclizine free base. "Image Description"

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Tablets Meclizine Hydrochloride Tablets, USP, 12.5 mg are white to off-white, oval shaped, film-coated tablets, debossed with “ CE ” on one side and “ 256 ” on the other side. They are supplied as follows: Bottle of 90 NDC # 62135-952-90 Meclizine Hydrochloride Tablets, USP, 25 mg are white to off-white, oval shaped, film-coated tablets, debossed with “ CE ” on one side and “ 257 ” on the other side. They are supplied as follows: Bottle of 90 NDC # 62135-953-90 Meclizine Hydrochloride Tablets, USP, 50 mg are white to off-white, oval shaped, film-coated scored tablets, debossed with “ C ” breakline “ E ” on one side and “ 258 ” on the other side. They are supplied as follows: Bottle of 60 NDC # 62135-954-60 16.2 Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container, as defined in the USP with a child-resistant closure, as required.