ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following adverse reactions associated with the use of meclizine hydrochloride were identified in clinical studies or post-marketing reports. Because some of these reactions were reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish 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 Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment ofFertility. CarcinogenesisAnimal 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.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 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 median Tmax value of hours post-dose (range: 1.5 to hours) for the tablet dosage form.DistributionDrug distribution characteristics for meclizine in humans are unknown. EliminationMeclizine has plasma elimination half-life of about to hours in humans.Metabolism 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.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. Meclizine hydrochloride tablets are contraindicated in patients with 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).

DESCRIPTION SECTION.

11 DESCRIPTION. Meclizine hydrochloride, histamine (H1) receptor antagonist, is white or slightly yellowish, crystalline powder. Its molecular formula is C25H27ClN2.2HCl.H2O and its molecular weight is 481.88. It has the following structural formula:Chemically, meclizine hydrochloride is 1-(p-chloro--phenylbenzyl)-4-(m-methylbenzyl) piperazine dihydrochloride monohydrate. 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. Inactive ingredients for the tablets are: colloidal silicon dioxide, lactose monohydrate, magnesium stearate, microcrystalline cellulose, sodium starch glycolate and talc. The 12.5 mg tablets also contain FD&C Blue Aluminum Lake. The 25 mg tablets also contain D&C Yellow 10 Aluminum Lake. 1.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Recommended dosage: 25 mg to 100 mg daily, in divided doses (2.1).Tablets: Swallow whole (2.2). Recommended dosage: 25 mg to 100 mg daily, in divided doses (2.1).. Tablets: Swallow whole (2.2). 2.1 RecommendedDosage. The recommended dosage is 25 mg to 100 mg daily administered orally, in divided doses, depending upon clinical response.. 2.2 Administration Instructions. TabletsMeclizine hydrochloride tablets must be swallowed whole.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Meclizine hydrochloride tablets USP, 12.5 mg are light blue colored, oval shaped tablets with AN 441 debossed on one side and plain on the other side. Meclizine hydrochloride tablets USP, 25 mg are light yellow colored, oval shaped tablets with AN 442 debossed on one side and plain on the other side. Meclizine hydrochloride tablets USP, 12.5 mg are light blue colored, oval shaped tablets with AN 441 debossed on one side and plain on the other side. Meclizine hydrochloride tablets USP, 25 mg are light yellow colored, oval shaped tablets with AN 442 debossed on one side and plain on the other side. Tablets: 12.5 mg and 25 mg (3).. Tablets: 12.5 mg and 25 mg (3).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. Co-administration of meclizine hydrochloride with other CNS depressants, including alcohol, may result in increased CNS depression (7.1). CYP2D6 inhibitors: As meclizine is metabolized by CYP2D6, there is potential for drug-drug interactions between meclizine hydrochloride and CYP2D6 inhibitors (7.2).. Co-administration of meclizine hydrochloride with other CNS depressants, including alcohol, may result in increased CNS depression (7.1). CYP2D6 inhibitors: As meclizine is metabolized by CYP2D6, there is potential for drug-drug interactions between meclizine hydrochloride and CYP2D6 inhibitors (7.2).. 7.1 CNSDepressants. There may be increased CNS depression when meclizine hydrochloride is 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 possibility for drug interaction between meclizine hydrochloride and CYP2D6 inhibitors. Therefore, monitor for adverse reactions and clinical effect accordingly.

GERIATRIC USE SECTION.

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.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. 16.1 HowSupplied. Meclizine Hydrochloride Tablets USP, 12.5 mg are supplied as light blue colored, oval shaped tablets with AN 441 debossed on one side and plain on the other side.Meclizine Hydrochloride Tablets USP, 25 mg are supplied as light yellow colored, oval shaped tablets with AN 442 debossed on one side and plain on the other side. They are available as follows:Blistercards of 30: NDC 0615-8462-39 16.2 Storage and Handling. Store at 20 to 25C (68 to 77F); excursions permitted between 15 to 30C (59 to 86F) [see USP Controlled Room Temperature].Dispense in tight, light-resistant container as defined in the USP.Keep this and all medication out of the reach of children.

INDICATIONS & USAGE SECTION.

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

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. May cause drowsiness: Use caution when driving car or operating dangerous machinery (5.1).Potential anticholinergic action: this drug should be prescribed with care to patients with history of asthma, glaucoma, or enlargement of the prostate gland (5.2).. May cause drowsiness: Use caution when driving car or operating dangerous machinery (5.1).. Potential anticholinergic action: this drug should be prescribed with care to patients with history of asthma, glaucoma, or enlargement of the prostate gland (5.2).. 5.1 Drowsiness. Since drowsiness may occur with use of meclizine hydrochloride, patients should be warned of this possibility and cautioned against driving car or operating dangerous machinery. Patients should avoid alcoholic beverages while taking meclizine hydrochloride [see Drug Interactions (7.1)]. 5.2 ConcurrentMedical Conditions. Because of its potential anticholinergic action, meclizine hydrochloride should be used with caution in patients with asthma, glaucoma, or enlargement of the prostate gland.

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Administration InstructionsAdvise patients that the tablets must be swallowed whole [see Dosage and Administration (2.1)]. Adverse ReactionsAdvise patients that meclizine hydrochloride may cause anaphylactic reaction, drowsiness, dry mouth, headache, fatigue, vomiting and, on rare occasions, blurred vision [see Warnings and Precautions (5.1), Adverse Reactions (6)]. Inform patients that meclizine hydrochloride may impair their ability to engage in potentially dangerous activities, such as operating machinery or vehicles. Concomitant Drug InteractionsAdvise patients regarding medications that should not be taken in combination with meclizine hydrochloride or that may necessitate increased monitoring [see Drug Interactions (7.1, 7.2)]. Inform patients that alcohol may increase adverse reactions. Concurrent Medical ConditionsAdvise patients to notify their healthcare provider about all of their medical conditions, including if they are pregnant or plan to become pregnant or if they are breastfeeding [see Warnings and Precautions (5.2), Use in Specific Populations (8.1, 8.2)]. Manufactured by: Amneal Pharmaceuticals Pvt. Ltd.Oral Solid Dosage UnitAhmedabad 382213, INDIADistributed by: Amneal Pharmaceuticals LLCBridgewater, NJ 08807Rev. 08-2021-00.

LABOR & DELIVERY SECTION.

8.2 Lactation. Risk SummaryThere 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 mothers clinical need for meclizine hydrochloride and any potential adverse effects on the breastfed infant from meclizine hydrochloride or from the underlying maternal condition.

MECHANISM OF ACTION SECTION.

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.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment ofFertility. CarcinogenesisAnimal 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.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL. Principal Display Panel.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. Safety and effectiveness in pediatric patients have not been established.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. There are no relevant pharmacodynamic data regarding meclizine.

PHARMACOKINETICS SECTION.

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 median Tmax value of hours post-dose (range: 1.5 to hours) for the tablet dosage form.DistributionDrug distribution characteristics for meclizine in humans are unknown. EliminationMeclizine has plasma elimination half-life of about to hours in humans.Metabolism 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.

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryData from epidemiological studies have not generally indicated drug-associated risk of major birth defects with meclizine during pregnancy. However, in 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. DataHuman 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 published study, oral administration of meclizine (25 mg/kg to 250 mg/kg) to pregnant rats during the period of organogenesis resulted in high incidence of fetal malformations. These effects occurred at doses as low as 25 mg/kg, which is approximately times the maximum recommended human dose (100 mg) on body surface area (mg/m2) basis.

SPL UNCLASSIFIED SECTION.

2.1 RecommendedDosage. The recommended dosage is 25 mg to 100 mg daily administered orally, in divided doses, depending upon clinical response.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk SummaryData from epidemiological studies have not generally indicated drug-associated risk of major birth defects with meclizine during pregnancy. However, in 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. DataHuman 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 published study, oral administration of meclizine (25 mg/kg to 250 mg/kg) to pregnant rats during the period of organogenesis resulted in high incidence of fetal malformations. These effects occurred at doses as low as 25 mg/kg, which is approximately times the maximum recommended human dose (100 mg) on body surface area (mg/m2) basis.. 8.2 Lactation. Risk SummaryThere 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 mothers 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 HepaticImpairment. The effect of hepatic impairment on the pharmacokinetics of meclizine has not been evaluated. As meclizine hydrochloride undergoes metabolism, hepatic impairment may result in increased systemic exposure of meclizine. Treatment with meclizine hydrochloride should be administered with caution in patients with hepatic impairment.. 8.7 RenalImpairment. The effect of renal impairment on the pharmacokinetics of meclizine has not been evaluated. Because of potential for drug/metabolite accumulation, meclizine hydrochloride should be administered with caution in patients with renal impairment and in the elderly, as renal function generally declines with age. 8.8 GeneticCYP2D6 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 is administered to patients with CYP2D6 polymorphism, monitor for adverse reactions and clinical effect accordingly.