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.

5.1 Drowsiness

Since drowsiness may occur with use of meclizine hydrochloride tablets, patients should be warned of this possibility and cautioned against driving a car or operating dangerous machinery.

Patients should avoid alcoholic beverages while taking meclizine hydrochloride tablets [see DRUG INTERACTIONS (7.1)].

5.2 Concurrent Medical Conditions

Because of its potential anticholinergic action, meclizine hydrochloride tablets should be used with caution in patients with asthma, glaucoma, or enlargement of the prostate gland.

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-vitroevaluation, 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.

8.1 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.

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 H1 receptor.

12.2 Pharmacodynamics

There are no relevant pharmacodynamic data regarding meclizine.

12.3 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 maxvalue 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.

Elimination

Meclizine has a plasma elimination half-life of about 5 to 6 hours in humans.

Metabolism:

In an in vitrometabolic study using human hepatic microsome and recombinant CYP enzyme, CYP2D6 was found to be the dominant enzyme for metabolism of meclizine.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Animal studies to assess the carcinogenic potential of meclizine have not been conducted.

Mutagenesis

Genetic toxicology studies of meclizine have not been conducted.

Impairment of Fertility

Animal studies to assess the effects of meclizine on fertility and early embryonic development have not been conducted.

16.1 How Supplied

Tablets

Meclizine Hydrochloride Tablets, USP, 12.5 mgare 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 mgare 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 mgare 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.