ADVERSE REACTIONS SECTION.

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 Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CLINICAL PHARMACOLOGY SECTION.

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 marked effect in blocking the vasodepressor response to histamine, but only slight blocking action against acetylcholine. Its activity is relatively weak in inhibiting the spasmogenic action of histamine on isolated guinea pig ileum.PharmacokineticsThe available pharmacokinetic information for meclizine following oral administration has been summarized from published literature.AbsorptionMeclizine 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.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 ultrarapid metabolizer phenotypes could contribute to large inter-individual variability in meclizine exposure.EliminationMeclizine has plasma elimination half-life of about to hours in humans.

DESCRIPTION SECTION.

DESCRIPTION. Meclizine hydrochloride, USP, an oral antiemetic, is white or slightly yellowish, crystalline powder. It has the following structural formula:Chemically, meclizine hydrochloride, USP is 1-(p-chloro--phenylbenzyl)-4-(m-methylbenzyl) piperazine dihydrochloride monohydrate.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.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.. c89547bf-figure-01.

HOW SUPPLIED SECTION.

HOW SUPPLIED. 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.They are available as follows:Blistercards of 30: NDC 0615-8303-39Meclizine 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.Meclizine Hydrochloride Tablets, USP 50 mg, are supplied as white, oval shaped, partially bisected tablets with AN 444 debossed on one side and plain on the other side.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.Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807Rev. 02-2019-03.

PRECAUTIONS SECTION.

PRECAUTIONS. Pediatric UseClinical studies establishing safety and effectiveness in children have not been done; therefore, usage is not recommended in children under 12 years of age.PregnancyTeratogenic EffectsPregnancy Category BReproduction studies in rats have shown cleft palates at 25 to 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 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 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 InteractionsThere 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 possibility for drug interaction between meclizine and CYP2D6 inhibitors.

WARNINGS SECTION.

WARNINGS. Since drowsiness may, on occasion, occur with use of this drug, patients should be warned of this possibility and cautioned against driving 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.