ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following adverse reactions are described, or described in greater detail, in other sections of the labeling:Tardive dyskinesia [see Boxed Warning and Warnings and Precautions (5.1)] Other extrapyramidal symptoms [see Warnings and Precautions (5.2)] Neuroleptic malignant syndrome [see Warnings and Precautions (5.3)] Depression [see Warnings and Precautions (5.4)] Hypertension [see Warnings and Precautions (5.5)] Fluid retention [see Warnings and Precautions (5.6)] Hyperprolactinemia [see Warnings and Precautions (5.7)] Effects on the ability to drive and operate machinery [see Warnings and Precautions (5.8)] The following adverse reactions have been identified from clinical studies or postmarketing reports of metoclopramide. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.The most common adverse reactions (in approximately 10% of patients receiving 10 mg of metoclopramide four times daily) were restlessness, drowsiness, fatigue, and lassitude. In general, the incidence of adverse reactions correlated with the dosage and duration of metoclopramide administration.Adverse reactions, especially those involving the nervous system, occurred after stopping metoclopramide including dizziness, nervousness, and headaches.Central Nervous System DisordersTardive dyskinesia, acute dystonic reactions, drug-induced parkinsonism, akathisia, and other extrapyramidal symptomsConvulsive seizuresHallucinationsRestlessness, drowsiness, fatigue, and lassitude occurred in approximately 10% of patients who received 10 mg four times daily. Insomnia, headache, confusion, dizziness, or depression with suicidal ideation occurred less frequently.Neuroleptic malignant syndrome, serotonin syndrome (in combination with serotonergic agents).Endocrine Disorders: Fluid retention secondary to transient elevation of aldosterone. Galactorrhea, amenorrhea, gynecomastia, impotence secondary to hyperprolactinemiaCardiovascular Disorders: Acute congestive heart failure, possible atrioventricular block, hypotension, hypertension, supraventricular tachycardia, bradycardia, fluid retentionGastrointestinal Disorders: Nausea, bowel disturbances (primarily diarrhea)Hepatic Disorders: Hepatotoxicity, characterized by, e.g., jaundice and altered liver function tests, when metoclopramide was administered with other drugs with known hepatotoxic potentialRenal and Urinary Disorders: Urinary frequency, urinary incontinenceHematologic Disorders: Agranulocytosis, neutropenia, leukopenia, methemoglobinemia, sulfhemoglobinemiaHypersensitivity Reactions: Bronchospasm (especially in patients with history of asthma), urticaria; rash; angioedema, including glossal or laryngeal edemaEye Disorders: Visual disturbancesMetabolism Disorders: Porphyria. Tardive dyskinesia [see Boxed Warning and Warnings and Precautions (5.1)] Other extrapyramidal symptoms [see Warnings and Precautions (5.2)] Neuroleptic malignant syndrome [see Warnings and Precautions (5.3)] Depression [see Warnings and Precautions (5.4)] Hypertension [see Warnings and Precautions (5.5)] Fluid retention [see Warnings and Precautions (5.6)] Hyperprolactinemia [see Warnings and Precautions (5.7)] Effects on the ability to drive and operate machinery [see Warnings and Precautions (5.8)] Tardive dyskinesia, acute dystonic reactions, drug-induced parkinsonism, akathisia, and other extrapyramidal symptoms. Convulsive seizures. Hallucinations. Restlessness, drowsiness, fatigue, and lassitude occurred in approximately 10% of patients who received 10 mg four times daily. Insomnia, headache, confusion, dizziness, or depression with suicidal ideation occurred less frequently.. Neuroleptic malignant syndrome, serotonin syndrome (in combination with serotonergic agents).. Most common adverse reactions (> 10%) are restlessness, drowsiness, fatigue, and lassitude. (6)To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. Most common adverse reactions (> 10%) are restlessness, drowsiness, fatigue, and lassitude. (6).

BOXED WARNING SECTION.

WARNING: TARDIVE DYSKINESIA. Metoclopramide, including metoclopramide tablets, can cause tardive dyskinesia (TD), potentially irreversible serious movement disorder. In patients treated with metoclopramide, including metoclopramide tablets, the risk of developing TD increases with duration of treatment and total cumulative dosage see Warnings and Precautions (5.1)].Metoclopramide is contraindicated in patients with history of TD. Use metoclopramide tablets for the shortest duration of treatment and periodically reassess the need for continued treatment. Immediately discontinue metoclopramide in patients who develop signs or symptoms of TD see Warnings and Precautions (5.1)].In patients with symptomatic, documented gastroesophageal reflux, the maximum duration of metoclopramide tablets treatment is 12 weeks see Dosage and Administration (2.1) and Warnings and Precautions (5.1)].In patients with diabetic gastroparesis, avoid total duration of treatment with metoclopramide products, including metoclopramide tablets, for longer than 12 weeks. If longer term use is unavoidable, routinely monitor for signs and symptoms of TD see Warnings and Precautions (5.1)].. Metoclopramide, including metoclopramide tablets, can cause tardive dyskinesia (TD), potentially irreversible serious movement disorder. In patients treated with metoclopramide, including metoclopramide tablets, the risk of developing TD increases with duration of treatment and total cumulative dosage see Warnings and Precautions (5.1)].. Metoclopramide is contraindicated in patients with history of TD. Use metoclopramide tablets for the shortest duration of treatment and periodically reassess the need for continued treatment. Immediately discontinue metoclopramide in patients who develop signs or symptoms of TD see Warnings and Precautions (5.1)].. In patients with symptomatic, documented gastroesophageal reflux, the maximum duration of metoclopramide tablets treatment is 12 weeks see Dosage and Administration (2.1) and Warnings and Precautions (5.1)].. In patients with diabetic gastroparesis, avoid total duration of treatment with metoclopramide products, including metoclopramide tablets, for longer than 12 weeks. If longer term use is unavoidable, routinely monitor for signs and symptoms of TD see Warnings and Precautions (5.1)].. WARNING: TARDIVE DYSKINESIA See full prescribing information for complete boxed warning.Metoclopramide, including metoclopramide tablets, can cause tardive dyskinesia (TD), potentially irreversible serious movement disorder. In patients treated with metoclopramide, including metoclopramide tablets, the risk of developing TD increases with duration of metoclopramide treatment and total cumulative metoclopramide dosage. (5.1) Metoclopramide is contraindicated in patients with history of TD. (4) Use metoclopramide for the shortest duration of treatment and periodically reassess the need for continued treatment. (2.1, 2.2, 5.1) Immediately discontinue metoclopramide in patients who develop signs or symptoms of TD. (5.1)In patients with symptomatic, documented gastroesophageal reflux, the maximum duration of treatment is 12 weeks. (2.1, 5.1) In patients with diabetic gastroparesis, avoid total duration of treatment with metoclopramide products, including metoclopramide tablets, for longer than 12 weeks. If longer-term use is unavoidable, routinely monitor for signs and symptoms of TD. (5.1). Metoclopramide, including metoclopramide tablets, can cause tardive dyskinesia (TD), potentially irreversible serious movement disorder. In patients treated with metoclopramide, including metoclopramide tablets, the risk of developing TD increases with duration of metoclopramide treatment and total cumulative metoclopramide dosage. (5.1). Metoclopramide is contraindicated in patients with history of TD. (4) Use metoclopramide for the shortest duration of treatment and periodically reassess the need for continued treatment. (2.1, 2.2, 5.1) Immediately discontinue metoclopramide in patients who develop signs or symptoms of TD. (5.1). In patients with symptomatic, documented gastroesophageal reflux, the maximum duration of treatment is 12 weeks. (2.1, 5.1) In patients with diabetic gastroparesis, avoid total duration of treatment with metoclopramide products, including metoclopramide tablets, for longer than 12 weeks. If longer-term use is unavoidable, routinely monitor for signs and symptoms of TD. (5.1).

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. CarcinogenesisA 77-week study was conducted in rats with oral metoclopramide doses up to 40 mg/kg/day (about six times the maximum recommended human dose on body surface area basis). Metoclopramide elevated prolactin levels and the elevation persisted during chronic administration. An increase in mammary neoplasms was found in rodents after chronic administration of metoclopramide [see Warnings and Precautions (5.7)]. In rat model for assessing the tumor promotion potential, 2-week oral treatment with metoclopramide at dose of 260 mg/kg/day (about 35 times the maximum recommended human dose based on body surface area) enhanced the tumorigenic effect of N-nitrosodiethylamine.MutagenesisMetoclopramide was positive in the in vitro Chinese hamster lung cell/HGPRT forward mutation assay for mutagenic effects and in the in vitro human lymphocyte chromosome aberration assay for clastogenic effects. It was negative in the in vitro Ames mutation assay, the in vitro unscheduled DNA synthesis assay with rat and human hepatocytes, and the in vivo rat micronucleus assay.Impairment of FertilityMetoclopramide at intramuscular doses up to 20 mg/kg/day (about three times the maximum recommended human dose based on body surface area) was found to have no effect on fertility and reproductive performance of male and female rats.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Metoclopramide stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. The exact mechanism of action of metoclopramide in the treatment of gastroesophageal reflux and acute and recurrent diabetic gastroparesis has not been fully established. It seems to sensitize tissues to the action of acetylcholine. The effect of metoclopramide on motility is not dependent on intact vagal innervation, but it can be abolished by anticholinergic drugs.Metoclopramide increases the tone and amplitude of gastric (especially antral) contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower esophageal sphincter. It has little, if any, effect on the motility of the colon or gallbladder.. 12.2 Pharmacodynamics. Gastroesophageal RefluxIn patients with gastroesophageal reflux and low lower esophageal sphincter pressure (LESP), single oral doses of metoclopramide produced dose-related increases in LESP. Effects began at about mg and increased through 20 mg. The increase in LESP from 5 mg dose lasted about 45 minutes and that of 20 mg lasted between and hours. Increased rate of stomach emptying was observed with single oral doses of 10 mg.. 12.3 Pharmacokinetics. AbsorptionRelative to an intravenous dose of 20 mg, the absolute bioavailability of oral metoclopramide is 80% +- 15.5% as demonstrated in crossover study of 18 subjects. Peak plasma concentrations occurred at about to hours after single oral dose. Similar time to peak was observed after individual doses at steady state.In single dose study of 12 subjects, the area under the drug concentration-time curve increased linearly with doses from 20 to 100 mg (5 times the maximum recommended single dose). Peak concentrations increased linearly with dose; time to peak concentrations remained the same; whole body clearance was unchanged; and the elimination rate remained the same. The mean elimination half-life in subjects with normal renal function was to hours. Linear kinetic processes adequately describe the absorption and elimination of metoclopramide.DistributionMetoclopramide is not extensively bound to plasma proteins (about 30%). The whole body volume of distribution is high (about 3.5 L/kg), which suggests extensive distribution of drug to the tissues.EliminationMetabolism: Metoclopramide undergoes enzymatic metabolism via oxidation as well as glucuronide and sulfate conjugation reactions in the liver. Monodeethylmetoclopramide, major oxidative metabolite, is formed primarily by CYP2D6, an enzyme subject to genetic variability [see Dosage and Administration (2.1 2.2), Use in Specific Populations (8.9)].Excretion: Approximately 85% of the radioactivity of an orally administered dose appeared in the urine within 72 hours. After oral administration of 10 or 20 mg, mean of 18% and 22% of the dose, respectively, was recovered as free metoclopramide in urine within 36 hours.Specific PopulationsPatients with Renal Impairment: In study of 24 patients with varying degrees of renal impairment (moderate, severe, and end-stage renal disease (ESRD) requiring dialysis), the systemic exposure (AUC) of metoclopramide in patients with moderate to severe renal impairment was about 2-fold the AUC in subjects with normal renal function. The AUC of metoclopramide in patients with ESRD on dialysis was about 3.5-fold the AUC in subjects with normal renal function [see Dosage and Administration (2.1 2.2) and Use in Specific Populations (8.6)].Patients with Hepatic Impairment: In group of patients with severe hepatic impairment (Child-Pugh C), the average metoclopramide clearance was reduced by approximately 50% compared to patients with normal hepatic function [see Dosage and Administration (2.1 2.2) and Use in Specific Populations (8.7)].Drug Interaction StudiesEffect of Metoclopramide on CYP2D6 Substrates Although in vitro studies suggest that metoclopramide can inhibit CYP2D6, metoclopramide is unlikely to interact with CYP2D6 substrates in vivo at therapeutically relevant concentrations.Effect of CYP2D6 Inhibitors on Metoclopramide In healthy subjects, 20 mg of metoclopramide and 60 mg of fluoxetine (a strong CYP2D6 inhibitor) were administered, following prior exposure to 60 mg fluoxetine orally for days. The patients who received concomitant metoclopramide and fluoxetine had 40% and 90% increase in metoclopramide Cmax and AUC0-, respectively, compared to patients who received metoclopramide alone (see Table 5) [see Drug Interactions (7.1)].Table 5. Metoclopramide Pharmacokinetic Parameters in Healthy Subjects with and without FluoxetineParameterMetoclopramide alone (mean +- SD)Metoclopramide with fluoxetine (mean +- SD)Cmax (ng/mL)44 +- 1562.7 +- 9.2AUC0- (ngh/mL)313 +- 113591 +- 140t1/2 (h)5.5 +- 1.18.5 +- 2.2.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. Metoclopramide is contraindicated:In patients with history of tardive dyskinesia (TD) or dystonic reaction to metoclopramide [see Warnings and Precautions 5.1, 5.2)].When stimulation of gastrointestinal motility might be dangerous (e.g., in the presence of gastrointestinal hemorrhage, mechanical obstruction, or perforation).In patients with pheochromocytoma or other catecholamine-releasing paragangliomas. Metoclopramide may cause hypertensive/pheochromocytoma crisis, probably due to release of catecholamines from the tumor [see Warnings and Precautions (5.5)].In patients with epilepsy. Metoclopramide may increase the frequency and severity of seizures [see Adverse Reactions (6)].In patients with hypersensitivity to metoclopramide. Reactions have included laryngeal and glossal angioedema and bronchospasm [see Adverse Reactions (6)].. In patients with history of tardive dyskinesia (TD) or dystonic reaction to metoclopramide [see Warnings and Precautions 5.1, 5.2)].. When stimulation of gastrointestinal motility might be dangerous (e.g., in the presence of gastrointestinal hemorrhage, mechanical obstruction, or perforation).. In patients with pheochromocytoma or other catecholamine-releasing paragangliomas. Metoclopramide may cause hypertensive/pheochromocytoma crisis, probably due to release of catecholamines from the tumor [see Warnings and Precautions (5.5)].. In patients with epilepsy. Metoclopramide may increase the frequency and severity of seizures [see Adverse Reactions (6)].. In patients with hypersensitivity to metoclopramide. Reactions have included laryngeal and glossal angioedema and bronchospasm [see Adverse Reactions (6)].. History of TD or dystonic reaction to metoclopramide (4)When stimulation of gastrointestinal motility might be dangerous (4)Pheochromocytoma, catecholamine-releasing paragangliomas (4)Epilepsy (4)Hypersensitivity to metoclopramide (4). History of TD or dystonic reaction to metoclopramide (4). When stimulation of gastrointestinal motility might be dangerous (4). Pheochromocytoma, catecholamine-releasing paragangliomas (4). Epilepsy (4). Hypersensitivity to metoclopramide (4).

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Metoclopramide stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. The exact mechanism of action of metoclopramide in the treatment of gastroesophageal reflux and acute and recurrent diabetic gastroparesis has not been fully established. It seems to sensitize tissues to the action of acetylcholine. The effect of metoclopramide on motility is not dependent on intact vagal innervation, but it can be abolished by anticholinergic drugs.Metoclopramide increases the tone and amplitude of gastric (especially antral) contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower esophageal sphincter. It has little, if any, effect on the motility of the colon or gallbladder.

DESCRIPTION SECTION.

11 DESCRIPTION. Metoclopramide hydrochloride, USP, the active ingredient of metoclopramide tablets, USP is dopamine-2 receptor antagonist. Metoclopramide hydrochloride (metoclopramide monohydrochloride monohydrate) is white or practically white, crystalline, odorless or practically odorless powder. It is very soluble in water, freely soluble in alcohol, sparingly soluble in chloroform and practically insoluble in ether. Chemically, it is 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxy benzamide monohydrochloride monohydrate. Its structural formula is as follows:C14H22ClN3O2oHCloH2O M.W. 354.3Metoclopramide tablets, USP are for oral administration. Metoclopramide tablets, USP are available in mg and 10 mg tablets.Each metoclopramide tablet USP, mg contains mg metoclopramide (equivalent to 5.91 mg of metoclopramide hydrochloride, USP).Each metoclopramide tablet USP, 10 mg contains 10 mg metoclopramide (equivalent to 11.82 mg of metoclopramide hydrochloride, USP).Inactive IngredientsCorn starch, dibasic calcium phosphate anhydrous, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate.. Each metoclopramide tablet USP, mg contains mg metoclopramide (equivalent to 5.91 mg of metoclopramide hydrochloride, USP).. Each metoclopramide tablet USP, 10 mg contains 10 mg metoclopramide (equivalent to 11.82 mg of metoclopramide hydrochloride, USP).. \\Client\X\Products\Metoclopramide Tablets USP, 10 mg (ANDA 070184)\Submissions\2017-08-30 CBE-0 AJK\Working\INSERT\Images\metoclopramide-sf1.jpg.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Symptomatic, Documented Gastroesophageal Reflux in Adults Who Fail Conventional Therapy (2.1)Administer metoclopramide continuously or intermittently: Continuous: The recommended dosage is 10 to 15 mg orally, 30 minutes before each meal and at bedtime (maximum of 60 mg per day) for to 12 weeks, as determined by endoscopic response.Intermittent: Single doses up to 20 mg prior to provoking situation. Acute and Recurrent Diabetic Gastroparesis in Adults (2.2)The recommended dosage is 10 mg orally, 30 minutes before each meal and at bedtime (maximum of 40 mg per day).Dosage Adjustment in Specific Populations (2.1, 2.2)For symptomatic, documented gastroesophageal reflux and acute and recurrent diabetic gastroparesis, see Full Prescribing Information for recommended dosage reductions for elderly patients, in patients with moderate or severe hepatic or renal impairment, and cytochrome P450 2D6 (CYP2D6) poor metabolizers.. Administer metoclopramide continuously or intermittently: Continuous: The recommended dosage is 10 to 15 mg orally, 30 minutes before each meal and at bedtime (maximum of 60 mg per day) for to 12 weeks, as determined by endoscopic response.Intermittent: Single doses up to 20 mg prior to provoking situation. Continuous: The recommended dosage is 10 to 15 mg orally, 30 minutes before each meal and at bedtime (maximum of 60 mg per day) for to 12 weeks, as determined by endoscopic response.. Intermittent: Single doses up to 20 mg prior to provoking situation.. The recommended dosage is 10 mg orally, 30 minutes before each meal and at bedtime (maximum of 40 mg per day).. For symptomatic, documented gastroesophageal reflux and acute and recurrent diabetic gastroparesis, see Full Prescribing Information for recommended dosage reductions for elderly patients, in patients with moderate or severe hepatic or renal impairment, and cytochrome P450 2D6 (CYP2D6) poor metabolizers.. 2.1 Recommended Dosage for Symptomatic, Documented GastroesophagealReflux inAdults Who Fail Conventional Therapy. Metoclopramide tablets may be administered continuously or intermittently in patients with symptomatic, documented gastroesophageal reflux who fail to respond to conventional therapy:Continuous DosingThe recommended dosage of metoclopramide tablets is 10 to 15 mg orally four times daily. The maximum recommended daily oral dosage is 60 mg.Administer each dose thirty minutes before meal and at bedtime. The recommended treatment duration is to 12 weeks, as determined by endoscopic response. Use metoclopramide tablets for the shortest duration of treatment and periodically reassess the need for continued treatment. The maximum recommended duration of treatment is 12 weeks [see Warnings and Precautions (5.1)].Table displays the recommended daily dosage and maximum daily dosage for adults and dosage adjustments for patients with moderate or severe hepatic impairment (Child-Pugh or C), in patients with creatinine clearance less than 60 mL/minute, in cytochrome P450 2D6 (CYP2D6) poor metabolizers, and with concomitant use with strong CYP2D6 inhibitors.Intermittent DosingIf symptoms only occur intermittently or at specific times of the day, administer metoclopramide as single dose up to 20 mg prior to the provoking situation. Consider dosage reductions for the populations and situations in Table 1.Table 1. Recommended Dosage of Metoclopramide Tablet for Symptomatic, Documented Gastroesophageal Reflux in Adults Who Fail Conventional TherapyRecommended DosageMaximum Recommended Daily DosageAdult patients10 to 15 mg four times daily (thirty minutes before each meal and at bedtime)60 mgMild hepatic impairment (Child-Pugh A)Elderly patients [see Use in Specific Populations (8.5)] mg1four times daily (thirty minutes before each meal and at bedtime)Moderate or severe hepatic impairment (Child-Pugh or C) [see Use in Specific Populations (8.7)] mg four times daily (thirty minutes before each meal and at bedtime), or10 mg taken three times daily30 mgCYP2D6 poor metabolizers [see Use in Specific Populations (8.9)] Concomitant use with strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine) [see Drug Interactions (7.1)] Moderate or severe renal impairment (creatinine clearance less than or equal to 60 mL/minute) [see Use in Specific Populations (8.6)] Patients with End-Stage Renal Disease (ESRD) including those treated with hemodialysis and continuous ambulatory peritoneal dialysis [see Use in Specific Populations (8.6)] mg four times daily (thirty minutes before each meal and at bedtime) or 10 mg twice daily20 mg 1Elderly patients may be more sensitive to the therapeutic or adverse effects of metoclopramide; therefore, consider lower starting dosage of mg four times daily with titration to the recommended adult dosage of 10 to 15 mg four times daily based upon response and tolerability.. The recommended dosage of metoclopramide tablets is 10 to 15 mg orally four times daily. The maximum recommended daily oral dosage is 60 mg.. Administer each dose thirty minutes before meal and at bedtime. The recommended treatment duration is to 12 weeks, as determined by endoscopic response. Use metoclopramide tablets for the shortest duration of treatment and periodically reassess the need for continued treatment. The maximum recommended duration of treatment is 12 weeks [see Warnings and Precautions (5.1)].. 2.2 RecommendedDosage for Acute and Recurrent Diabetic Gastroparesis in Adults. The recommended oral dosage of metoclopramide tablets for the relief of symptoms in adults with acute and recurrent diabetic gastroparesis is 10 mg four times daily. The maximum recommended daily dosage is 40 mg.Administer each dose thirty minutes before each meal and at bedtime. Use metoclopramide for the shortest duration of treatment and periodically reassess the need for continued treatment. Avoid treatment with metoclopramide, including metoclopramide tablets, for longer than 12 weeks. If longer-term use is unavoidable, routinely monitor for signs and symptoms of TD [see Warnings and Precautions (5.1)].Table displays the recommended daily dosage and maximum daily dosage for adults and dosage adjustments for patients with moderate or severe hepatic impairment (Child-Pugh or C), in patients with creatinine clearance less than 60 mL/minute, in cytochrome P450 2D6 (CYP2D6) poor metabolizers, and with concomitant use with strong CYP2D6 inhibitors.If patients with diabetic gastroparesis have severe nausea or vomiting and are unable to take oral metoclopramide tablets, consider starting therapy with metoclopramide injection given intramuscularly or intravenously for up to 10 days (see the prescribing information for metoclopramide injection). After patients are able to take oral therapy, switch to metoclopramide tablets.Table 2. Recommended Metoclopramide Tablet Dosage in Adult Patients with Acute and Recurrent Diabetic GastroparesisRecommended DosageMaximum Recommended Daily DosageAdult Patients10 mg four times daily (30 minutes before each meal and at bedtime)40 mgMild hepatic impairment (Child-Pugh A)Elderly patients [see Use in Specific Populations (8.5)] mg1 four times daily (30 minutes before each meal and at bedtime)Moderate or severe hepatic impairment (Child-Pugh or C) [see Use in Specific Populations (8.7)] mg four times daily (30 minutes before each meal and at bedtime)20 mgCYP2D6 poor metabolizers [see Use in Specific Populations (8.9)] Concomitant use with strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine) [see Drug Interactions (7.1)] Moderate or severe renal impairment (creatinine clearance less than 60 mL/minute) [see Use in Specific Populations (8.6)] Patients with End-Stage Renal Disease (ESRD) including those treated with hemodialysis and continuous ambulatory peritoneal dialysis [see Use in Specific Populations (8.6)] mg twice daily10 mg 1Elderly patients may be more sensitive to the therapeutic or adverse effects of metoclopramide; therefore, consider lower dosage of mg four times daily with titration to the recommended adult dosage of 10 mg four times daily based upon response and tolerability.. The recommended oral dosage of metoclopramide tablets for the relief of symptoms in adults with acute and recurrent diabetic gastroparesis is 10 mg four times daily. The maximum recommended daily dosage is 40 mg.. Administer each dose thirty minutes before each meal and at bedtime. Use metoclopramide for the shortest duration of treatment and periodically reassess the need for continued treatment. Avoid treatment with metoclopramide, including metoclopramide tablets, for longer than 12 weeks. If longer-term use is unavoidable, routinely monitor for signs and symptoms of TD [see Warnings and Precautions (5.1)].

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Tablets:5 mg metoclopramide, USP: white, round, unscored, debossed TV on one side and 2204 on the other side.10 mg metoclopramide, USP: white, round, scored, debossed TEVA on one side and 2203 above the score on the other side.. mg metoclopramide, USP: white, round, unscored, debossed TV on one side and 2204 on the other side.. 10 mg metoclopramide, USP: white, round, scored, debossed TEVA on one side and 2203 above the score on the other side.. Tablets: mg and 10 mg metoclopramide (3).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. Antipsychotics: Potential for additive effects, including TD, EPS, and NMS; avoid concomitant use. (7.1)Central Nervous System (CNS) depressants: Increased risk of CNS depression. Avoid concomitant use and monitor for adverse reactions. (7.1)Strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine): See Full Prescribing Information for recommended dosage reductions. (2.1, 2.3, 7.1)Monoamine oxidase (MAO) inhibitors: Increased risk of hypertension; avoid concomitant use. (5.5, 7.1)Additional drug interactions: See Full Prescribing Information. (7.1, 7.2). Antipsychotics: Potential for additive effects, including TD, EPS, and NMS; avoid concomitant use. (7.1). Central Nervous System (CNS) depressants: Increased risk of CNS depression. Avoid concomitant use and monitor for adverse reactions. (7.1). Strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine): See Full Prescribing Information for recommended dosage reductions. (2.1, 2.3, 7.1). Monoamine oxidase (MAO) inhibitors: Increased risk of hypertension; avoid concomitant use. (5.5, 7.1). Additional drug interactions: See Full Prescribing Information. (7.1, 7.2). 7.1 Effects of Other Drugs on Metoclopramide. Table displays the effects of other drugs on metoclopramide.Table 3. Effects of Other Drugs on MetoclopramideAntipsychoticsClinical ImpactPotential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS).InterventionAvoid concomitant use [see Warnings and Precautions (5.1, 5.2, 5.3)].Strong CYP2D6 Inhibitors, not Included in Antipsychotic Category AboveClinical ImpactIncreased plasma concentrations of metoclopramide; risk of exacerbation of extrapyramidal symptoms [see Clinical Pharmacology (12.3)].InterventionReduce the metoclopramide dosage [see Dosage and Administration (2.1, 2.2)].Examplesquinidine, bupropion, fluoxetine, and paroxetineMonoamine Oxidase InhibitorsClinical ImpactIncreased risk of hypertension [see Warnings and Precautions (5.5)].InterventionAvoid concomitant use.Central Nervous System (CNS) DepressantsClinical ImpactIncreased risk of CNS depression [see Warnings and Precautions (5.8)].InterventionAvoid metoclopramide or the interacting drug, depending on the importance of the drug to the patient.Examplesalcohol, sedatives, hypnotics, opiates and anxiolyticsDrugs that Impair Gastrointestinal MotilityClinical ImpactDecreased systemic absorption of metoclopramide.InterventionMonitor for reduced therapeutic effect.Examplesantiperistaltic antidiarrheal drugs, anticholinergic drugs, and opiatesDopaminergic Agonists and Other Drugs that Increase Dopamine ConcentrationsClinical ImpactDecreased therapeutic effect of metoclopramide due to opposing effects on dopamine.InterventionMonitor for reduced therapeutic effect.Examplesapomorphine, bromocriptine, cabergoline, levodopa, pramipexole, ropinirole, and rotigotine. 7.2 Effects of Metoclopramide on Other Drugs. Table displays the effects of metoclopramide on other drugs.Table 4. Effects of Metoclopramide on Other DrugsDopaminergic Agonists and Drugs Increasing Dopamine ConcentrationsClinical ImpactOpposing effects of metoclopramide and the interacting drug on dopamine. Potential exacerbation of symptoms (e.g., parkinsonian symptoms).InterventionAvoid concomitant use [see Warnings and Precautions (5.2)].ExamplesApomorphine, bromocriptine, cabergoline, levodopa, pramipexole, ropinirole, rotigotineSuccinylcholine, MivacuriumClinical ImpactMetoclopramide inhibits plasma cholinesterase leading to enhanced neuromuscular blockade.InterventionMonitor for signs and symptoms of prolonged neuromuscular blockadeDrugs with Absorption Altered due to Increased Gastrointestinal MotilityClinical ImpactThe effect of metoclopramide on other drugs is variable. Increased gastrointestinal (GI) motility by metoclopramide may impact absorption of other drugs leading to decreased or increased drug exposure.InterventionDrugs with Decreased Absorption (e.g., digoxin, atovaquone, posaconazole oral suspensionInteraction does not apply to posaconazole delayed-release tablets, fosfomycin): Monitor for reduced therapeutic effect of the interacting drug. For digoxin monitor therapeutic drug concentrations and increase the digoxin dose as needed (see prescribing information for digoxin).Drugs with Increased Absorption (e.g., sirolimus, tacrolimus, cyclosporine): Monitor therapeutic drug concentrations and adjust the dose as needed. See prescribing information for the interacting drug.InsulinClinical ImpactIncreased GI motility by metoclopramide may increase delivery of food to the intestines and increase blood glucose.InterventionMonitor blood glucose and adjust insulin dosage regimen as needed.

GERIATRIC USE SECTION.

8.5 Geriatric Use. Metoclopramide is known to be substantially excreted by the kidney, and the risk of adverse reactions, including tardive dyskinesia (TD), may be greater in patients with impaired renal function [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)]. Elderly patients are more likely to have decreased renal function and may be more sensitive to the therapeutic or adverse effects of metoclopramide; therefore, consider reduced dosage of metoclopramide in elderly patients [see Boxed Warning, Dosage and Administration (2.1, 2.2), Warnings and Precautions (5.1)].

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. Each white, round, unscored, debossed TV on one side and 2204 on the other side, compressed metoclopramide tablet, USP contains metoclopramide hydrochloride, USP equivalent to mg metoclopramide. Available in bottles of 100 (NDC 0093-2204-01) and 500 (NDC 0093-2204-05).Each white, round, scored, debossed TEVA on one side and 2203 above the score on the other side, compressed metoclopramide tablet, USP contains metoclopramide hydrochloride, USP equivalent to 10 mg metoclopramide. Available in bottles of 100 (NDC 0093-2203-01), 500 (NDC 0093-2203-05), and 1,000 (NDC 0093-2203-10).Store at 20 to 25C (68 to 77F) [See USP Controlled Room Temperature]. PROTECT FROM LIGHT. This product is light sensitive. It should be inspected before use and discarded if either color or particulate is observed.Dispense in tight, light-resistant container. KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. Metoclopramide tablets are indicated for the:Treatment for to 12 weeks of symptomatic, documented gastroesophageal reflux in adults who fail to respond to conventional therapy.Relief of symptoms in adults with acute and recurrent diabetic gastroparesis.Limitations of Use:Metoclopramide tablets have not been shown to be safe and effective for the treatment of symptomatic, documented gastroesophageal reflux for longer than 12 weeks [see Warnings and Precautions (5.1)]. Metoclopramide tablets are not recommended for use in pediatric patients due to the risk of developing tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates [see Use in Specific Populations (8.4)].. Treatment for to 12 weeks of symptomatic, documented gastroesophageal reflux in adults who fail to respond to conventional therapy.. Relief of symptoms in adults with acute and recurrent diabetic gastroparesis.. Metoclopramide tablets have not been shown to be safe and effective for the treatment of symptomatic, documented gastroesophageal reflux for longer than 12 weeks [see Warnings and Precautions (5.1)]. Metoclopramide tablets are not recommended for use in pediatric patients due to the risk of developing tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates [see Use in Specific Populations (8.4)].. Metoclopramide tablets are indicated for the:Treatment for to 12 weeks of symptomatic, documented gastroesophageal reflux in adults who fail to respond to conventional therapy. (1)Relief of symptoms in adults with acute and recurrent diabetic gastroparesis. (1)Limitations of Use:Metoclopramide tablets have not been shown to be safe and effective for the treatment of gastroesophageal reflux for longer than 12 weeks. (1, 5.1)Metoclopramide tablets are not recommended for use in pediatric patients due to the risk of tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates. (1, 8.4). Treatment for to 12 weeks of symptomatic, documented gastroesophageal reflux in adults who fail to respond to conventional therapy. (1). Relief of symptoms in adults with acute and recurrent diabetic gastroparesis. (1). Metoclopramide tablets have not been shown to be safe and effective for the treatment of gastroesophageal reflux for longer than 12 weeks. (1, 5.1). Metoclopramide tablets are not recommended for use in pediatric patients due to the risk of tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates. (1, 8.4).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Advise the patient to read the FDA-approved patient labeling (Medication Guide).Tardive Dyskinesia and/or other Extrapyramidal ReactionsInform patients that metoclopramide tablets may cause tardive dyskinesia or other extrapyramidal symptoms, parkinsonian symptoms, and motor restlessness. Instruct patients to immediately discontinue metoclopramide tablets and contact their healthcare provider if symptoms occur see Warnings and Precautions (5.1, 5.2)].Neuroleptic Malignant SyndromeInform patients that serious neuroleptic malignant syndrome (NMS) has been reported in association with concomitant treatment with another drug associated with NMS. Advise patients to report all prescription and over-the-counter medications to the healthcare provider. Instruct patients to immediately discontinue metoclopramide tablets and seek medical attention if symptoms occur see Warnings and Precautions (5.3)].Depression and/or Possible Suicidal IdeationInform patients that symptoms of new onset or worsening depression as well as suicidal ideation have been reported in patients taking metoclopramide. Instruct patients to immediately discontinue metoclopramide tablets and contact their healthcare provider if any of these symptoms occur see Warnings and Precautions (5.4)].Drug InteractionsInform patients or their caregivers that concomitant treatment with numerous other medications can precipitate or worsen serious adverse reactions such as tardive dyskinesia or other extrapyramidal reactions, neuroleptic malignant syndrome, and CNS depression see Drug Interactions (7.1, 7.2)]. Explain that the prescriber of any other medication must be made aware that the patient is taking metoclopramide tablets.Effects on the Ability to Drive and Operate MachineryInform patients or their caregivers that metoclopramide tablets can cause drowsiness or dizziness, or otherwise impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving motor vehicle see Warnings and Precautions (5.8)].Manufactured In Croatia By: Pliva Hrvatska d.o.o. Zagreb, CroatiaManufactured For: Teva Pharmaceuticals Parsippany, NJ 07054Rev. 3/2026.

LACTATION SECTION.

8.2 Lactation. Risk SummaryLimited published data report the presence of metoclopramide in human milk in variable amounts (see Data). Breastfed infants exposed to metoclopramide have experienced gastrointestinal adverse reactions, including intestinal discomfort and increased intestinal gas formation (see Clinical Considerations). Metoclopramide elevates prolactin levels see Warnings and Precautions (5.7)]; however, the published data are not adequate to support drug effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for metoclopramide and any potential adverse effects on the breastfed child from metoclopramide or from the underlying maternal condition.Clinical ConsiderationsMonitor breastfeeding neonates because metoclopramide may cause extrapyramidal signs (dystonias) and methemoglobinemia [see Warnings and Precautions (5.1, 5.2), Use in Specific Populations (8.4)].DataIn published clinical studies, the estimated amount of metoclopramide received by the breastfed infant was less than 10% of the maternal weight-adjusted dose. In one study, the estimated daily amount of metoclopramide received by infants from breast milk ranged from to 24 mcg/kg/day in early puerperium (3 to days postpartum) and from to 13 mcg/kg/day at to 12 weeks postpartum.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. CarcinogenesisA 77-week study was conducted in rats with oral metoclopramide doses up to 40 mg/kg/day (about six times the maximum recommended human dose on body surface area basis). Metoclopramide elevated prolactin levels and the elevation persisted during chronic administration. An increase in mammary neoplasms was found in rodents after chronic administration of metoclopramide [see Warnings and Precautions (5.7)]. In rat model for assessing the tumor promotion potential, 2-week oral treatment with metoclopramide at dose of 260 mg/kg/day (about 35 times the maximum recommended human dose based on body surface area) enhanced the tumorigenic effect of N-nitrosodiethylamine.MutagenesisMetoclopramide was positive in the in vitro Chinese hamster lung cell/HGPRT forward mutation assay for mutagenic effects and in the in vitro human lymphocyte chromosome aberration assay for clastogenic effects. It was negative in the in vitro Ames mutation assay, the in vitro unscheduled DNA synthesis assay with rat and human hepatocytes, and the in vivo rat micronucleus assay.Impairment of FertilityMetoclopramide at intramuscular doses up to 20 mg/kg/day (about three times the maximum recommended human dose based on body surface area) was found to have no effect on fertility and reproductive performance of male and female rats.

OVERDOSAGE SECTION.

10 OVERDOSAGE. Manifestations of metoclopramide overdosage included drowsiness, disorientation, extrapyramidal reactions, other adverse reactions associated with metoclopramide use (including, e.g., methemoglobinemia), and sometimes death. Neuroleptic malignant syndrome (NMS) has been reported in association with metoclopramide overdose and concomitant treatment with another drug associated with NMS [see Warnings and Precautions (5.1, 5.2, 5.3)].There are no specific antidotes for metoclopramide overdosage. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.Methemoglobinemia can be reversed by the intravenous administration of methylene blue. However, methylene blue may cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, which may be fatal.Hemodialysis and continuous ambulatory peritoneal dialysis do not remove significant amounts of metoclopramide.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

Package/Label Display Panel. NDC 0093-2204-01Metoclopramide Tablets, USP mgPHARMACIST: Dispense the accompanying Medication Guide to each patient.Rx only100 Tablets. 5mg 100s 8/2021.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. Metoclopramide is not recommended for use in pediatric patients due to the risk of tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates. The safety and effectiveness of metoclopramide tablets in pediatric patients have not been established.Dystonias and other extrapyramidal symptoms associated with metoclopramide are more common in pediatric patients than in adults [see Warnings and Precautions (5.1, 5.2)]. In addition, neonates have reduced levels of NADH-cytochrome b5 reductase, making them more susceptible to methemoglobinemia, possible adverse reaction of metoclopramide use in neonates [see Use in Specific Populations (8.8)].

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. Gastroesophageal RefluxIn patients with gastroesophageal reflux and low lower esophageal sphincter pressure (LESP), single oral doses of metoclopramide produced dose-related increases in LESP. Effects began at about mg and increased through 20 mg. The increase in LESP from 5 mg dose lasted about 45 minutes and that of 20 mg lasted between and hours. Increased rate of stomach emptying was observed with single oral doses of 10 mg.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. AbsorptionRelative to an intravenous dose of 20 mg, the absolute bioavailability of oral metoclopramide is 80% +- 15.5% as demonstrated in crossover study of 18 subjects. Peak plasma concentrations occurred at about to hours after single oral dose. Similar time to peak was observed after individual doses at steady state.In single dose study of 12 subjects, the area under the drug concentration-time curve increased linearly with doses from 20 to 100 mg (5 times the maximum recommended single dose). Peak concentrations increased linearly with dose; time to peak concentrations remained the same; whole body clearance was unchanged; and the elimination rate remained the same. The mean elimination half-life in subjects with normal renal function was to hours. Linear kinetic processes adequately describe the absorption and elimination of metoclopramide.DistributionMetoclopramide is not extensively bound to plasma proteins (about 30%). The whole body volume of distribution is high (about 3.5 L/kg), which suggests extensive distribution of drug to the tissues.EliminationMetabolism: Metoclopramide undergoes enzymatic metabolism via oxidation as well as glucuronide and sulfate conjugation reactions in the liver. Monodeethylmetoclopramide, major oxidative metabolite, is formed primarily by CYP2D6, an enzyme subject to genetic variability [see Dosage and Administration (2.1 2.2), Use in Specific Populations (8.9)].Excretion: Approximately 85% of the radioactivity of an orally administered dose appeared in the urine within 72 hours. After oral administration of 10 or 20 mg, mean of 18% and 22% of the dose, respectively, was recovered as free metoclopramide in urine within 36 hours.Specific PopulationsPatients with Renal Impairment: In study of 24 patients with varying degrees of renal impairment (moderate, severe, and end-stage renal disease (ESRD) requiring dialysis), the systemic exposure (AUC) of metoclopramide in patients with moderate to severe renal impairment was about 2-fold the AUC in subjects with normal renal function. The AUC of metoclopramide in patients with ESRD on dialysis was about 3.5-fold the AUC in subjects with normal renal function [see Dosage and Administration (2.1 2.2) and Use in Specific Populations (8.6)].Patients with Hepatic Impairment: In group of patients with severe hepatic impairment (Child-Pugh C), the average metoclopramide clearance was reduced by approximately 50% compared to patients with normal hepatic function [see Dosage and Administration (2.1 2.2) and Use in Specific Populations (8.7)].Drug Interaction StudiesEffect of Metoclopramide on CYP2D6 Substrates Although in vitro studies suggest that metoclopramide can inhibit CYP2D6, metoclopramide is unlikely to interact with CYP2D6 substrates in vivo at therapeutically relevant concentrations.Effect of CYP2D6 Inhibitors on Metoclopramide In healthy subjects, 20 mg of metoclopramide and 60 mg of fluoxetine (a strong CYP2D6 inhibitor) were administered, following prior exposure to 60 mg fluoxetine orally for days. The patients who received concomitant metoclopramide and fluoxetine had 40% and 90% increase in metoclopramide Cmax and AUC0-, respectively, compared to patients who received metoclopramide alone (see Table 5) [see Drug Interactions (7.1)].Table 5. Metoclopramide Pharmacokinetic Parameters in Healthy Subjects with and without FluoxetineParameterMetoclopramide alone (mean +- SD)Metoclopramide with fluoxetine (mean +- SD)Cmax (ng/mL)44 +- 1562.7 +- 9.2AUC0- (ngh/mL)313 +- 113591 +- 140t1/2 (h)5.5 +- 1.18.5 +- 2.2.

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryPublished studies, including retrospective cohort studies, national registry studies, and meta-analyses, do not report an increased risk of adverse pregnancy-related outcomes with use of metoclopramide during pregnancy.There are potential risks to the neonate following exposure in utero to metoclopramide during delivery (see Clinical Considerations). In animal reproduction studies, no adverse developmental effects were observed with oral administration of metoclopramide to pregnant rats and rabbits at exposures about and 12 times the maximum recommended human dose (MRHD) (see Data).The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have background risk of birth defects, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is to 4% and 15 to 20%, respectively.Clinical ConsiderationsFetal/Neonatal Adverse ReactionsMetoclopramide crosses the placental barrier and may cause extrapyramidal signs and methemoglobinemia in neonates with maternal administration during delivery. Monitor neonates for extrapyramidal signs [see Warnings and Precautions (5.1, 5.2), Use in Specific Populations (8.4)].DataAnimal DataReproduction studies have been performed following administration of oral metoclopramide during organogenesis in pregnant rats at about times the MRHD calculated on body surface area and in pregnant rabbits at about 12 times the MRHD calculated on body surface area. No evidence of adverse developmental effects due to metoclopramide were observed.

RECENT MAJOR CHANGES SECTION.

Boxed Warning 02/2026 Indications and Usage (1) 02/2026 Dosage and Administration (2.1, 2.2) 02/2026 Warnings and Precautions, Tardive Dyskinesia (5.1) 02/2026 Warnings and Precautions, Other Extrapyramidal Symptoms (5.2) 02/2026.

SPL MEDGUIDE SECTION.

MEDICATION GUIDE. Metoclopramide (met oh kloe pra mide) Tablets Read this Medication Guide before you start taking metoclopramide tablets and each time you get refill. There may be new information. If you take another product that contains metoclopramide (such as metoclopramide injection, metoclopramide orally disintegrating tablets, or metoclopramide oral solution), you should read the Medication Guide that comes with that product. Some of the information may be different. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.What is the most important information should know about metoclopramide tabletsMetoclopramide tablets can cause potentially irreversible serious side effect called tardive dyskinesia (abnormal muscle movements).These movements happen mostly in the face or tongue, and sometimes in other body parts. You cannot control these movements. These symptoms may not go away even after stopping metoclopramide tablets. Your chances of getting tardive dyskinesia increase: the longer you take metoclopramide tablets and the more metoclopramide tablets you take. Use the lowest dose possible for the shortest time needed. People taking metoclopramide tablets to relieve heartburn symptoms with gastroesophageal reflux should not take metoclopramide tablets for more than 12 weeks.People taking metoclopramide tablets to relieve symptoms of slow stomach emptying due to diabetes, should not take metoclopramide tablets for more than 12 weeks. If you require treatment for longer than 12 weeks, your healthcare provider should frequently monitor you for signs and symptoms of tardive dyskinesia. if you are older, especially if you are an older woman.if you have diabetes.It is not possible for your healthcare provider to know if you will get tardive dyskinesia if you take metoclopramide tablets.Stop taking metoclopramide tablets and call your healthcare provider right away if you get movements you cannot stop or control, such as:lip smacking, chewing, or puckering up your mouthfrowning or scowlingsticking out your tongueblinking and moving your eyesshaking of your arms and legsYour healthcare provider may decide not to continue treatment with metoclopramide tablets if you develop signs or symptoms of tardive dyskinesia. See the section What are the possible side effects of metoclopramide tablets for more information about side effects.What are metoclopramide tabletsMetoclopramide tablets are prescription medicine used in adults:for to 12 weeks to relieve heartburn symptoms with gastroesophageal reflux when certain other treatments do not work.to relieve the symptoms of slow stomach emptying in people with diabetes. Metoclopramide tablets are not recommended for use in children or for longer than 12 weeks if you are being treated to relieve heart burn symptoms with gastroesophageal reflux.Do not take metoclopramide tablets if you:have history of tardive dyskinesia or have problem controlling your muscles and movements after taking metoclopramide tablets or medicine that works like metoclopramide tablets.have stomach or intestine problems that could get worse with metoclopramide tablets, such as bleeding, blockage or tear in the stomach or bowel wall.have type of tumor that can cause high blood pressure such as pheochromocytoma.have epilepsy (seizures). Metoclopramide tablets can increase your chance for seizures and make them worse.are allergic to metoclopramide. Metoclopramide tablets can cause serious allergic reactions. Stop taking metoclopramide tablets right away and get emergency help if you have any of these symptoms: swelling of your tongue, throat, lips, eyes or face.trouble swallowing or breathing.skin rash, hives, sores in your mouth, or skin blisters. Before taking metoclopramide tablets, tell your healthcare provider about all of your medical conditions, including if you:had problems controlling your muscle movements after taking any medicine.have Parkinsons disease.have or had depression or mental illness.have kidney or liver disease.have heart failure or heart rhythm problems.have high blood pressure.drink alcohol.have diabetes. Your dose of insulin may need to be changed.are pregnant or plan to become pregnant. Metoclopramide tablets may harm your unborn baby if taken during the end of pregnancy. Talk to your healthcare provider if you become pregnant while taking metoclopramide tablets.are breastfeeding or plan to breastfeed. Metoclopramide can pass into your breast milk and may harm your baby. You and your healthcare provider should decide if you will take metoclopramide tablets or breastfeed.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.Metoclopramide tablets may affect the way other medicines work, and other medicines may affect how metoclopramide tablets work.Tell your healthcare provider before you start or stop other medicines.Especially tell your healthcare provider if you take:another medicine that contains metoclopramide, such as metoclopramide injection, metoclopramide orally disintegrating tablets (ODT), metoclopramide oral solution, or Gimoti nasal sprayan anti-psychotic medicine, used to treat mental illness such as schizophreniaa medicine for Parkinsons diseasea medicine for depression, especially Monoamine Oxidase Inhibitor (MAOI)insulinmedicines that can make you sleepy, such as anti-anxiety medicines, sleep medicines, and narcoticsIf you are not sure if your medicine is one listed above, ask your healthcare provider or pharmacist.Know the medicines you take. Keep list of them to show your healthcare provider and pharmacist when you get new medicine.How should take metoclopramide tabletsTake metoclopramide tablets exactly as your healthcare provider tells you. Do not change your dose unless your healthcare provider tells you to.Metoclopramide comes as tablet you take by mouth.Take metoclopramide tablets at least 30 minutes before each meal and at bedtime.You should not take medicines containing metoclopramide (including metoclopramide tablets) for more than 12 weeks. If you are being treated with metoclopramide tablets to relieve the symptoms of slow stomach emptying due to diabetes and require treatment for longer than 12 weeks, your healthcare provider should frequently monitor you for signs and symptoms of tardive dyskinesia. If you take too much metoclopramide tablets, call your poison control center at 1-800-222-1222 or go to the nearest emergency room right away.Keep all follow-up visits with your healthcare provider as scheduled, so that your healthcare provider can see how you are responding to treatment with metoclopramide tablets.What should avoid while taking metoclopramide tabletsDo not drink alcohol while taking metoclopramide tablets. Alcohol may make some side effects of metoclopramide tablets worse, such as feeling sleepy.Do not drive, operate machinery, or do other dangerous activities until you know how metoclopramide tablets affect you. Metoclopramide tablets may cause sleepiness or dizziness.What are the possible side effects of metoclopramide tabletsTardive dyskinesia (abnormal muscle movements). See What is the most important information need to know about metoclopramide tabletsOther changes in muscle control and movement, such as:Uncontrolled spasms of your face and neck muscles, or muscles of your body, arms, and legs (dystonia). These muscle spasms can cause abnormal movements and body positions, and speech problems. These spasms usually start within the first days of treatment. Rarely, these muscle spasms may cause trouble breathing. These spasms happen more often in adults less than 30 years of age who took higher doses of metoclopramide tablets.Parkinsonism. Symptoms include slight shaking, body stiffness, trouble moving or keeping your balance. If you already have Parkinsons Disease, your symptoms may become worse while you are taking metoclopramide tablets.Being unable to sit still or feeling you need to move your hands, feet, or body (akathisia). Symptoms can include feeling jittery, anxious, irritated or unable to sleep (insomnia), feeling the need to walk around (pacing) and tapping your feet.Neuroleptic Malignant Syndrome (NMS). NMS is very rare but very serious condition that can happen with metoclopramide tablets. NMS can cause death and must be treated in hospital. Symptoms of NMS include: high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating.Depression, thoughts about suicide, and suicide. Some people who take metoclopramide tablets become depressed, even if they have no history of depression. You may have thoughts about hurting or killing yourself. Some people who have taken metoclopramide tablets have ended their own lives (suicide).High blood pressure. Metoclopramide tablets can cause your blood pressure to increase.Too much body water. People who have certain liver problems or heart failure and take metoclopramide tablets may hold too much water in their body (fluid retention). Tell your doctor right away if you have sudden weight gain, or swelling of your hands, legs, or feet.Increased prolactin. Tell your doctor if your menstrual periods stop, your breasts get larger and make milk, or you cannot have sex (impotence). These symptoms go away when you stop taking metoclopramide tablets.Stop taking metoclopramide tablets, call your healthcare provider and get medical help right away if you:feel depressed or have thoughts about hurting or killing yourselfhave high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweatinghave muscle movements you cannot stop or controlhave muscle movements that are new or unusualThe most common side effects of metoclopramide tablets include:restlessnessdrowsinesstirednesslack of energyYou may have more side effects the longer you take metoclopramide tablets and the more metoclopramide tablets you take.You may still have side effects after stopping metoclopramide tablets. You may have symptoms from stopping metoclopramide tablets such as headaches and feeling dizzy or nervous.Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of metoclopramide tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should store metoclopramide tabletsStore metoclopramide tablets at room temperature between 68F to 77F (20C to 25C).Keep metoclopramide tablets in the bottle it comes in and away from light. Keep the bottle closed tightly.Keep metoclopramide tablets and all medicines out of the reach of children.General information about the safe and effective use of metoclopramide tablets.Medicines are sometimes prescribed for purposes other than those listed in Medication Guide. Do not use metoclopramide tablets for condition for which they were not prescribed. Do not give metoclopramide tablets to other people, even if they have the same symptoms that you have. They may harm them.You can ask your pharmacist or healthcare provider for information about metoclopramide tablets that is written for health professionals. For more information, call 1-888-838-2872.What are the ingredients in metoclopramide tabletsActive ingredient: metoclopramide hydrochlorideInactive ingredients: corn starch, dibasic calcium phosphate anhydrous, magnesium stearate, microcrystalline cellulose, and sodium starch glycolateManufactured In Croatia By: Pliva Hrvatska d.o.o., Zagreb, Croatia Manufactured For: Teva Pharmaceuticals, Parsippany, NJ 07054This Medication Guide has been approved by the U.S. Food and Drug Administration. Rev. 3/2026. These movements happen mostly in the face or tongue, and sometimes in other body parts. You cannot control these movements. These symptoms may not go away even after stopping metoclopramide tablets. Your chances of getting tardive dyskinesia increase: the longer you take metoclopramide tablets and the more metoclopramide tablets you take. Use the lowest dose possible for the shortest time needed. People taking metoclopramide tablets to relieve heartburn symptoms with gastroesophageal reflux should not take metoclopramide tablets for more than 12 weeks.People taking metoclopramide tablets to relieve symptoms of slow stomach emptying due to diabetes, should not take metoclopramide tablets for more than 12 weeks. If you require treatment for longer than 12 weeks, your healthcare provider should frequently monitor you for signs and symptoms of tardive dyskinesia. Use the lowest dose possible for the shortest time needed. People taking metoclopramide tablets to relieve heartburn symptoms with gastroesophageal reflux should not take metoclopramide tablets for more than 12 weeks.. People taking metoclopramide tablets to relieve symptoms of slow stomach emptying due to diabetes, should not take metoclopramide tablets for more than 12 weeks. If you require treatment for longer than 12 weeks, your healthcare provider should frequently monitor you for signs and symptoms of tardive dyskinesia.. if you are older, especially if you are an older woman.. if you have diabetes.. lip smacking, chewing, or puckering up your mouth. frowning or scowling. sticking out your tongue. blinking and moving your eyes. shaking of your arms and legs. for to 12 weeks to relieve heartburn symptoms with gastroesophageal reflux when certain other treatments do not work.. to relieve the symptoms of slow stomach emptying in people with diabetes.. have history of tardive dyskinesia or have problem controlling your muscles and movements after taking metoclopramide tablets or medicine that works like metoclopramide tablets.. have stomach or intestine problems that could get worse with metoclopramide tablets, such as bleeding, blockage or tear in the stomach or bowel wall.. have type of tumor that can cause high blood pressure such as pheochromocytoma.. have epilepsy (seizures). Metoclopramide tablets can increase your chance for seizures and make them worse.. are allergic to metoclopramide. Metoclopramide tablets can cause serious allergic reactions. Stop taking metoclopramide tablets right away and get emergency help if you have any of these symptoms: swelling of your tongue, throat, lips, eyes or face.trouble swallowing or breathing.skin rash, hives, sores in your mouth, or skin blisters. swelling of your tongue, throat, lips, eyes or face.. trouble swallowing or breathing.. skin rash, hives, sores in your mouth, or skin blisters.. had problems controlling your muscle movements after taking any medicine.. have Parkinsons disease.. have or had depression or mental illness.. have kidney or liver disease.. have heart failure or heart rhythm problems.. have high blood pressure.. drink alcohol.. have diabetes. Your dose of insulin may need to be changed.. are pregnant or plan to become pregnant. Metoclopramide tablets may harm your unborn baby if taken during the end of pregnancy. Talk to your healthcare provider if you become pregnant while taking metoclopramide tablets.. are breastfeeding or plan to breastfeed. Metoclopramide can pass into your breast milk and may harm your baby. You and your healthcare provider should decide if you will take metoclopramide tablets or breastfeed.. another medicine that contains metoclopramide, such as metoclopramide injection, metoclopramide orally disintegrating tablets (ODT), metoclopramide oral solution, or Gimoti nasal spray. an anti-psychotic medicine, used to treat mental illness such as schizophrenia. medicine for Parkinsons disease. medicine for depression, especially Monoamine Oxidase Inhibitor (MAOI). insulin. medicines that can make you sleepy, such as anti-anxiety medicines, sleep medicines, and narcotics. Take metoclopramide tablets exactly as your healthcare provider tells you. Do not change your dose unless your healthcare provider tells you to.. Metoclopramide comes as tablet you take by mouth.. Take metoclopramide tablets at least 30 minutes before each meal and at bedtime.. You should not take medicines containing metoclopramide (including metoclopramide tablets) for more than 12 weeks. If you are being treated with metoclopramide tablets to relieve the symptoms of slow stomach emptying due to diabetes and require treatment for longer than 12 weeks, your healthcare provider should frequently monitor you for signs and symptoms of tardive dyskinesia. If you are being treated with metoclopramide tablets to relieve the symptoms of slow stomach emptying due to diabetes and require treatment for longer than 12 weeks, your healthcare provider should frequently monitor you for signs and symptoms of tardive dyskinesia.. If you take too much metoclopramide tablets, call your poison control center at 1-800-222-1222 or go to the nearest emergency room right away.. Keep all follow-up visits with your healthcare provider as scheduled, so that your healthcare provider can see how you are responding to treatment with metoclopramide tablets.. Do not drink alcohol while taking metoclopramide tablets. Alcohol may make some side effects of metoclopramide tablets worse, such as feeling sleepy.. Do not drive, operate machinery, or do other dangerous activities until you know how metoclopramide tablets affect you. Metoclopramide tablets may cause sleepiness or dizziness.. Tardive dyskinesia (abnormal muscle movements). See What is the most important information need to know about metoclopramide tablets. Other changes in muscle control and movement, such as:Uncontrolled spasms of your face and neck muscles, or muscles of your body, arms, and legs (dystonia). These muscle spasms can cause abnormal movements and body positions, and speech problems. These spasms usually start within the first days of treatment. Rarely, these muscle spasms may cause trouble breathing. These spasms happen more often in adults less than 30 years of age who took higher doses of metoclopramide tablets.Parkinsonism. Symptoms include slight shaking, body stiffness, trouble moving or keeping your balance. If you already have Parkinsons Disease, your symptoms may become worse while you are taking metoclopramide tablets.Being unable to sit still or feeling you need to move your hands, feet, or body (akathisia). Symptoms can include feeling jittery, anxious, irritated or unable to sleep (insomnia), feeling the need to walk around (pacing) and tapping your feet.. Uncontrolled spasms of your face and neck muscles, or muscles of your body, arms, and legs (dystonia). These muscle spasms can cause abnormal movements and body positions, and speech problems. These spasms usually start within the first days of treatment. Rarely, these muscle spasms may cause trouble breathing. These spasms happen more often in adults less than 30 years of age who took higher doses of metoclopramide tablets.. Parkinsonism. Symptoms include slight shaking, body stiffness, trouble moving or keeping your balance. If you already have Parkinsons Disease, your symptoms may become worse while you are taking metoclopramide tablets.. Being unable to sit still or feeling you need to move your hands, feet, or body (akathisia). Symptoms can include feeling jittery, anxious, irritated or unable to sleep (insomnia), feeling the need to walk around (pacing) and tapping your feet.. Neuroleptic Malignant Syndrome (NMS). NMS is very rare but very serious condition that can happen with metoclopramide tablets. NMS can cause death and must be treated in hospital. Symptoms of NMS include: high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating.. Depression, thoughts about suicide, and suicide. Some people who take metoclopramide tablets become depressed, even if they have no history of depression. You may have thoughts about hurting or killing yourself. Some people who have taken metoclopramide tablets have ended their own lives (suicide).. High blood pressure. Metoclopramide tablets can cause your blood pressure to increase.. Too much body water. People who have certain liver problems or heart failure and take metoclopramide tablets may hold too much water in their body (fluid retention). Tell your doctor right away if you have sudden weight gain, or swelling of your hands, legs, or feet.. Increased prolactin. Tell your doctor if your menstrual periods stop, your breasts get larger and make milk, or you cannot have sex (impotence). These symptoms go away when you stop taking metoclopramide tablets.. feel depressed or have thoughts about hurting or killing yourself. have high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating. have muscle movements you cannot stop or control. have muscle movements that are new or unusual. restlessness. drowsiness. tiredness. lack of energy. Store metoclopramide tablets at room temperature between 68F to 77F (20C to 25C).. Keep metoclopramide tablets in the bottle it comes in and away from light. Keep the bottle closed tightly.

SPL UNCLASSIFIED SECTION.

2.1 Recommended Dosage for Symptomatic, Documented GastroesophagealReflux inAdults Who Fail Conventional Therapy. Metoclopramide tablets may be administered continuously or intermittently in patients with symptomatic, documented gastroesophageal reflux who fail to respond to conventional therapy:Continuous DosingThe recommended dosage of metoclopramide tablets is 10 to 15 mg orally four times daily. The maximum recommended daily oral dosage is 60 mg.Administer each dose thirty minutes before meal and at bedtime. The recommended treatment duration is to 12 weeks, as determined by endoscopic response. Use metoclopramide tablets for the shortest duration of treatment and periodically reassess the need for continued treatment. The maximum recommended duration of treatment is 12 weeks [see Warnings and Precautions (5.1)].Table displays the recommended daily dosage and maximum daily dosage for adults and dosage adjustments for patients with moderate or severe hepatic impairment (Child-Pugh or C), in patients with creatinine clearance less than 60 mL/minute, in cytochrome P450 2D6 (CYP2D6) poor metabolizers, and with concomitant use with strong CYP2D6 inhibitors.Intermittent DosingIf symptoms only occur intermittently or at specific times of the day, administer metoclopramide as single dose up to 20 mg prior to the provoking situation. Consider dosage reductions for the populations and situations in Table 1.Table 1. Recommended Dosage of Metoclopramide Tablet for Symptomatic, Documented Gastroesophageal Reflux in Adults Who Fail Conventional TherapyRecommended DosageMaximum Recommended Daily DosageAdult patients10 to 15 mg four times daily (thirty minutes before each meal and at bedtime)60 mgMild hepatic impairment (Child-Pugh A)Elderly patients [see Use in Specific Populations (8.5)] mg1four times daily (thirty minutes before each meal and at bedtime)Moderate or severe hepatic impairment (Child-Pugh or C) [see Use in Specific Populations (8.7)] mg four times daily (thirty minutes before each meal and at bedtime), or10 mg taken three times daily30 mgCYP2D6 poor metabolizers [see Use in Specific Populations (8.9)] Concomitant use with strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine) [see Drug Interactions (7.1)] Moderate or severe renal impairment (creatinine clearance less than or equal to 60 mL/minute) [see Use in Specific Populations (8.6)] Patients with End-Stage Renal Disease (ESRD) including those treated with hemodialysis and continuous ambulatory peritoneal dialysis [see Use in Specific Populations (8.6)] mg four times daily (thirty minutes before each meal and at bedtime) or 10 mg twice daily20 mg 1Elderly patients may be more sensitive to the therapeutic or adverse effects of metoclopramide; therefore, consider lower starting dosage of mg four times daily with titration to the recommended adult dosage of 10 to 15 mg four times daily based upon response and tolerability.. The recommended dosage of metoclopramide tablets is 10 to 15 mg orally four times daily. The maximum recommended daily oral dosage is 60 mg.. Administer each dose thirty minutes before meal and at bedtime. The recommended treatment duration is to 12 weeks, as determined by endoscopic response. Use metoclopramide tablets for the shortest duration of treatment and periodically reassess the need for continued treatment. The maximum recommended duration of treatment is 12 weeks [see Warnings and Precautions (5.1)].

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk SummaryPublished studies, including retrospective cohort studies, national registry studies, and meta-analyses, do not report an increased risk of adverse pregnancy-related outcomes with use of metoclopramide during pregnancy.There are potential risks to the neonate following exposure in utero to metoclopramide during delivery (see Clinical Considerations). In animal reproduction studies, no adverse developmental effects were observed with oral administration of metoclopramide to pregnant rats and rabbits at exposures about and 12 times the maximum recommended human dose (MRHD) (see Data).The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have background risk of birth defects, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is to 4% and 15 to 20%, respectively.Clinical ConsiderationsFetal/Neonatal Adverse ReactionsMetoclopramide crosses the placental barrier and may cause extrapyramidal signs and methemoglobinemia in neonates with maternal administration during delivery. Monitor neonates for extrapyramidal signs [see Warnings and Precautions (5.1, 5.2), Use in Specific Populations (8.4)].DataAnimal DataReproduction studies have been performed following administration of oral metoclopramide during organogenesis in pregnant rats at about times the MRHD calculated on body surface area and in pregnant rabbits at about 12 times the MRHD calculated on body surface area. No evidence of adverse developmental effects due to metoclopramide were observed.. 8.2 Lactation. Risk SummaryLimited published data report the presence of metoclopramide in human milk in variable amounts (see Data). Breastfed infants exposed to metoclopramide have experienced gastrointestinal adverse reactions, including intestinal discomfort and increased intestinal gas formation (see Clinical Considerations). Metoclopramide elevates prolactin levels see Warnings and Precautions (5.7)]; however, the published data are not adequate to support drug effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for metoclopramide and any potential adverse effects on the breastfed child from metoclopramide or from the underlying maternal condition.Clinical ConsiderationsMonitor breastfeeding neonates because metoclopramide may cause extrapyramidal signs (dystonias) and methemoglobinemia [see Warnings and Precautions (5.1, 5.2), Use in Specific Populations (8.4)].DataIn published clinical studies, the estimated amount of metoclopramide received by the breastfed infant was less than 10% of the maternal weight-adjusted dose. In one study, the estimated daily amount of metoclopramide received by infants from breast milk ranged from to 24 mcg/kg/day in early puerperium (3 to days postpartum) and from to 13 mcg/kg/day at to 12 weeks postpartum.. 8.4 Pediatric Use. Metoclopramide is not recommended for use in pediatric patients due to the risk of tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates. The safety and effectiveness of metoclopramide tablets in pediatric patients have not been established.Dystonias and other extrapyramidal symptoms associated with metoclopramide are more common in pediatric patients than in adults [see Warnings and Precautions (5.1, 5.2)]. In addition, neonates have reduced levels of NADH-cytochrome b5 reductase, making them more susceptible to methemoglobinemia, possible adverse reaction of metoclopramide use in neonates [see Use in Specific Populations (8.8)].. 8.5 Geriatric Use. Metoclopramide is known to be substantially excreted by the kidney, and the risk of adverse reactions, including tardive dyskinesia (TD), may be greater in patients with impaired renal function [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)]. Elderly patients are more likely to have decreased renal function and may be more sensitive to the therapeutic or adverse effects of metoclopramide; therefore, consider reduced dosage of metoclopramide in elderly patients [see Boxed Warning, Dosage and Administration (2.1, 2.2), Warnings and Precautions (5.1)].. 8.6 Renal Impairment. The clearance of metoclopramide is decreased and the systemic exposure is increased in patients with moderate to severe renal impairment compared to patients with normal renal function, which may increase the risk of adverse reactions. Reduce the metoclopramide dosage in patients with moderate and severe renal impairment (creatinine clearance less than or equal to 60 mL/minute), including those receiving hemodialysis and continuous ambulatory peritoneal dialysis [see Dosage and Administration (2.1, 2.2), Clinical Pharmacology (12.3)].. 8.7 Hepatic Impairment. Patients with severe hepatic impairment (Child-Pugh C) have reduced systemic metoclopramide clearance (by approximately 50%) compared to patients with normal hepatic function. The resulting increase in metoclopramide blood concentrations increases the risk of adverse reactions. There is no pharmacokinetic data in patients with moderate hepatic impairment (Child-Pugh B). Reduce the metoclopramide dosage in patients with moderate or severe (Child-Pugh or C) hepatic impairment [see Dosage and Administration (2.1, 2.2)]. There is no dosage adjustment required for patients with mild hepatic impairment (Child-Pugh A).Metoclopramide, by producing transient increase in plasma aldosterone, may increase the risk of fluid retention in patients with hepatic impairment [see Warnings and Precautions (5.6)].Monitor patients with hepatic impairment for the occurrence of fluid retention and volume overload.. 8.8 NADH-Cytochrome b5 Reductase Deficiency. Metoclopramide-treated patients with NADH-cytochrome b5 reductase deficiency are at an increased risk of developing methemoglobinemia and/or sulfhemoglobinemia. For patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency with metoclopramide-induced methemoglobinemia, methylene blue treatment is not recommended. Methylene blue may cause hemolytic anemia in patients with G6PD deficiency, which may be fatal [see Overdosage (10)].. 8.9 CYP2D6 Poor Metabolizers. Metoclopramide is substrate of CYP2D6. The elimination of metoclopramide may be slowed in patients who are CYP2D6 poor metabolizers (compared to patients who are CYP2D6 intermediate, extensive, or ultra-rapid metabolizers); possibly increasing the risk of dystonic and other adverse reactions to metoclopramide [see Clinical Pharmacology (12.3)]. Reduce the metoclopramide dosage in patients who are poor CYP2D6 metabolizers [see Dosage and Administration (2.1, 2.2)].

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Tardive Dyskinesia (TD), Other Extrapyramidal Symptoms (EPS), and Neuroleptic Malignant Syndrome (NMS): Avoid concomitant use of other drugs known to cause TD/EPS/NMS and avoid use in patients with Parkinsons Disease. If symptoms occur, discontinue metoclopramide and seek immediate medical attention. (5.1, 5.2, 5.3, 7.1, 7.2)Depression and suicidal ideation/suicide: Avoid use. (5.4). Tardive Dyskinesia (TD), Other Extrapyramidal Symptoms (EPS), and Neuroleptic Malignant Syndrome (NMS): Avoid concomitant use of other drugs known to cause TD/EPS/NMS and avoid use in patients with Parkinsons Disease. If symptoms occur, discontinue metoclopramide and seek immediate medical attention. (5.1, 5.2, 5.3, 7.1, 7.2). Depression and suicidal ideation/suicide: Avoid use. (5.4). 5.1 Tardive Dyskinesia. Metoclopramide, including metoclopramide tablets, can cause tardive dyskinesia (TD), syndrome of potentially irreversible and disfiguring involuntary movements of the face or tongue, and sometimes of the trunk and/or extremities. Metoclopramide, including metoclopramide tablets, may also suppress, or partially suppress, the signs of TD, and may delay the diagnosis of TD because it may mask the underlying disease process. The effect of this symptomatic suppression upon the long-term course of TD is unknown. TD may remit, partially or completely, if metoclopramide treatment is discontinued. In patients treated with metoclopramide, including metoclopramide tablets, the risk of developing TD and the likelihood that TD will become irreversible increases with duration of treatment and total cumulative dosage. Additionally, the risk of developing TD is increased in elderly patients, especially in elderly women see Use in Specific Populations (8.5)], and in patients with diabetes mellitus.Prevention, Mitigation, and Monitoring for TDMetoclopramide is contraindicated in patients with history of TD. Avoid use of metoclopramide in patients receiving concomitant antipsychotics due to the potential additive effects of TD [see Drug Interactions (7.1)]. Reduce the metoclopramide dosage in the elderly [see Dosage and Administration (2.1, 2.2)]. Use metoclopramide for the shortest duration of treatment and periodically reassess the need for continued treatment. Immediately discontinue metoclopramide in patients who develop signs and symptoms of TD. In patients with symptomatic, documented gastroesophageal reflux, the maximum duration of treatment is 12 weeks [see Dosage and Administration (2.2)]. In patients with diabetic gastroparesis, avoid total duration of treatment with metoclopramide products, including metoclopramide tablets, for longer than 12 weeks. If longer-term use is unavoidable, routinely monitor for signs and symptoms of TD. If patients have continued TD symptoms, consider TD treatment.. Metoclopramide is contraindicated in patients with history of TD. Avoid use of metoclopramide in patients receiving concomitant antipsychotics due to the potential additive effects of TD [see Drug Interactions (7.1)]. Reduce the metoclopramide dosage in the elderly [see Dosage and Administration (2.1, 2.2)]. Use metoclopramide for the shortest duration of treatment and periodically reassess the need for continued treatment. Immediately discontinue metoclopramide in patients who develop signs and symptoms of TD. In patients with symptomatic, documented gastroesophageal reflux, the maximum duration of treatment is 12 weeks [see Dosage and Administration (2.2)]. In patients with diabetic gastroparesis, avoid total duration of treatment with metoclopramide products, including metoclopramide tablets, for longer than 12 weeks. If longer-term use is unavoidable, routinely monitor for signs and symptoms of TD. If patients have continued TD symptoms, consider TD treatment.. 5.2 Other Extrapyramidal Symptoms. In addition to TD, metoclopramide may cause other extrapyramidal symptoms (EPS), parkinsonian symptoms, and motor restlessness. Advise patients to seek immediate medical attention if such symptoms occur and to discontinue metoclopramide.Extrapyramidal symptoms (EPS), such as acute dystonic reactions, occurred in patients treated with metoclopramide dosages of 30 mg to 40 mg daily. Such reactions occurred more frequently in adults less than 30 years of age and at higher than recommended dosages. EPS occurred more frequently in pediatric patients compared to adults (metoclopramide is not approved for use in pediatric patients). Symptoms can occur in the first 24 to 48 hours after starting metoclopramide. Symptoms included involuntary movements of limbs and facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of tongue, bulbar type of speech, trismus, or dystonic reactions resembling tetanus. Rarely, dystonic reactions were present as stridor and dyspnea, possibly due to laryngospasm. Diphenhydramine hydrochloride or benztropine mesylate may be used to treat these adverse reactions. Avoid metoclopramide in patients receiving other drugs that can cause EPS (e.g., antipsychotics).Parkinsonian symptoms (bradykinesia, tremor, cogwheel rigidity, mask-like facies) have occurred after starting metoclopramide, more commonly within the first months, but also after longer periods. Symptoms generally have subsided within to months after discontinuation of metoclopramide. Avoid metoclopramide in patients with Parkinsons disease and other patients being treated with antiparkinsonian drugs due to potential exacerbation of symptoms. If treatment is unavoidable, use metoclopramide tablets for the shortest duration of treatment and periodically reassess the need for continued treatment. Routinely monitor for signs and symptoms of Parkinsons disease see Dosage and Administration (2.1, 2.2)].Motor restlessness (akathisia) has developed and consisted of feelings of anxiety, agitation, jitteriness, and insomnia, as well as inability to sit still, pacing, and foot tapping. If symptoms resolve, consider restarting at lower dosage.. Extrapyramidal symptoms (EPS), such as acute dystonic reactions, occurred in patients treated with metoclopramide dosages of 30 mg to 40 mg daily. Such reactions occurred more frequently in adults less than 30 years of age and at higher than recommended dosages. EPS occurred more frequently in pediatric patients compared to adults (metoclopramide is not approved for use in pediatric patients). Symptoms can occur in the first 24 to 48 hours after starting metoclopramide. Symptoms included involuntary movements of limbs and facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of tongue, bulbar type of speech, trismus, or dystonic reactions resembling tetanus. Rarely, dystonic reactions were present as stridor and dyspnea, possibly due to laryngospasm. Diphenhydramine hydrochloride or benztropine mesylate may be used to treat these adverse reactions. Avoid metoclopramide in patients receiving other drugs that can cause EPS (e.g., antipsychotics).. Parkinsonian symptoms (bradykinesia, tremor, cogwheel rigidity, mask-like facies) have occurred after starting metoclopramide, more commonly within the first months, but also after longer periods. Symptoms generally have subsided within to months after discontinuation of metoclopramide. Avoid metoclopramide in patients with Parkinsons disease and other patients being treated with antiparkinsonian drugs due to potential exacerbation of symptoms. If treatment is unavoidable, use metoclopramide tablets for the shortest duration of treatment and periodically reassess the need for continued treatment. Routinely monitor for signs and symptoms of Parkinsons disease see Dosage and Administration (2.1, 2.2)].. Motor restlessness (akathisia) has developed and consisted of feelings of anxiety, agitation, jitteriness, and insomnia, as well as inability to sit still, pacing, and foot tapping. If symptoms resolve, consider restarting at lower dosage.. 5.3 Neuroleptic Malignant Syndrome. Metoclopramide may cause potentially fatal symptom complex called neuroleptic malignant syndrome (NMS). NMS has been reported in association with metoclopramide overdosage and concomitant treatment with another drug associated with NMS. Avoid metoclopramide in patients receiving other drugs associated with NMS, including typical and atypical antipsychotics.Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and manifestations of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac arrhythmias). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Patients with such symptoms should be evaluated immediately.In the diagnostic evaluation, consider the presence of other serious medical conditions (e.g., pneumonia, systemic infection) and untreated or inadequately treated extrapyramidal signs and symptoms. Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, malignant hyperthermia, drug fever, serotonin syndrome, and primary central nervous system pathology.Management of NMS includes:Immediate discontinuation of metoclopramide and other drugs not essential to concurrent therapy [see Drug Interactions (7.1)].Intensive symptomatic treatment and medical monitoring.Treatment of any concomitant serious medical problems for which specific treatments are available.. Immediate discontinuation of metoclopramide and other drugs not essential to concurrent therapy [see Drug Interactions (7.1)].. Intensive symptomatic treatment and medical monitoring.. Treatment of any concomitant serious medical problems for which specific treatments are available.. 5.4 Depression. Depression has occurred in metoclopramide-treated patients with and without history of depression. Symptoms have included suicidal ideation and suicide. Avoid metoclopramide use in patients with history of depression.. 5.5 Hypertension. Metoclopramide may elevate blood pressure. In one study in hypertensive patients, intravenously administered metoclopramide was shown to release catecholamines; hence, avoid use in patients with hypertension or in patients taking monoamine oxidase inhibitors [see Drug Interactions (7.1)].There are also clinical reports of hypertensive crises in patients with undiagnosed pheochromocytoma. Metoclopramide is contraindicated in patients with pheochromocytoma or other catecholamine-releasing paragangliomas [see Contraindications (4)]. Discontinue metoclopramide in any patient with rapid rise in blood pressure.. 5.6 Fluid Retention. Because metoclopramide produces transient increase in plasma aldosterone, patients with cirrhosis or congestive heart failure may be at risk of developing fluid retention and volume overload. Discontinue metoclopramide if any of these adverse reactions occur.. 5.7 Hyperprolactinemia. As with other dopamine D2 receptor antagonists, metoclopramide elevates prolactin levels.Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported with prolactin-elevating drugs, including metoclopramide.Hyperprolactinemia may potentially stimulate prolactin-dependent breast cancer. However, some clinical studies and epidemiology studies have not shown an association between administration of dopamine D2 receptor antagonists and tumorigenesis in humans [see Nonclinical Toxicology (13.1)].. 5.8 Effects on the Ability to Drive and Operate Machinery. Metoclopramide may impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving motor vehicle. Concomitant use of central nervous system (CNS) depressants or drugs associated with EPS may increase this effect (e.g., alcohol, sedatives, hypnotics, opiates, and anxiolytics). Avoid metoclopramide or the interacting drug, depending on the importance of the drug to the patient [see Drug Interactions (7.1)].