DRUGS & SUPPLEMENTS
Active ingredient: Metoclopramide Hydrochloride
Metoclopramide Hydrochloride uses
1 INDICATIONS AND USAGE
Metoclopramide Hydrochloride tablets are indicated for the:
Metoclopramide Hydrochloride 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 Hydrochloride tablets are indicated for the:
Limitations of Use:
Metoclopramide Hydrochloride 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)
2 DOSAGE AND ADMINISTRATION
Acute and Recurrent Diabetic Gastroparesis (2.3)
Dosage Adjustment in Specific Populations (2.2, 2.3)
2.1 Important Administration Instructions
Avoid treatment with Metoclopramide Hydrochloride for longer than 12 weeks because of the increased risk of developing TD with longer-term use [see Dosage and Administration (2.2, 2.3), Warnings and Precautions (5.1)].
2.2 Dosage for Gastroesophageal Reflux
Metoclopramide Hydrochloride tablets may be administered continuously or intermittently in patients with symptomatic gastroesophageal reflux who fail to respond to conventional therapy:
The recommended adult dosage of Metoclopramide Hydrochloride is 10 to 15 mg four times daily for 4 to 12 weeks. The treatment duration is determined by endoscopic response. Administer the dosage thirty minutes before each meal and at bedtime. The maximum recommended daily dosage is 60 mg.
Table 1 displays the recommended daily dosage and maximum daily dosage for adults and dosage adjustments for patients with moderate or severe hepatic impairment, 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 symptoms only occur intermittently or at specific times of the day, administer Metoclopramide Hydrochloride in single dose up to 20 mg prior to the provoking situation. Consider dosage reductions for the populations and situations in Table 1.
2.3 Dosage for Acute and Recurrent Diabetic Gastroparesis
The recommended adult dosage for the treatment of acute and recurrent diabetic gastroparesis is 10 mg four times daily for 2 to 8 weeks, depending on symptomatic response. Avoid Metoclopramide Hydrochloride treatment for greater than 12 weeks [see Warnings and Precautions (5.1)]. Administer the dosage thirty minutes before each meal and at bedtime. The maximum recommended daily dosage is 40 mg.
Table 2 displays the recommended daily dosage and maximum daily dosage for adults and dosage adjustments for patients with moderate or severe hepatic impairment (Child-Pugh B 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 Hydrochloride tablets, consider starting therapy with Metoclopramide Hydrochloride injection given intramuscularly or intravenously for up to 10 days. After patients are able to take oral therapy, switch to Metoclopramide Hydrochloride tablets.
3 DOSAGE FORMS AND STRENGTHS
Tablets: 5 mg and 10 mg Metoclopramide Hydrochloride (3)
Metoclopramide Hydrochloride is contraindicated:
5 WARNINGS AND PRECAUTIONS
5.1 Tardive Dyskinesia
Metoclopramide Hydrochloride can cause tardive dyskinesia (TD), a syndrome of potentially irreversible and disfiguring involuntary movements of the face or tongue, and sometimes of the trunk and/or extremities. Movements may be choreoathetotic in appearance. 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 among the elderly, especially elderly women [see Use in Specific Populations (8.5)], and in patients with diabetes mellitus. Due to the risk of developing TD, avoid treatment with Metoclopramide Hydrochloride for longer than 12 weeks and reduce the dosage in elderly patients [see Dosage and Administration (2.2, 2.3)].
Discontinue Metoclopramide Hydrochloride immediately in patients who develop signs and symptoms of TD. There is no known effective treatment for established cases of TD, although in some patients TD may remit, partially or completely, within several weeks to months after Metoclopramide Hydrochloride is withdrawn.
Metoclopramide Hydrochloride itself may suppress, or partially suppress, the signs of TD, thereby masking the underlying disease process. The effect of this symptomatic suppression upon the long-term course of TD is unknown. Metoclopramide Hydrochloride is contraindicated in patients with a history of TD [see Contraindications (4)]. Avoid Metoclopramide Hydrochloride in patients receiving other drugs that are likely to cause TD (e.g., antipsychotics).
5.2 Other Extrapyramidal Symptoms
In addition to TD, Metoclopramide Hydrochloride may cause other extrapyramidal symptoms, parkinsonian symptoms, and motor restlessness. Advise patients to seek immediate medical attention if such symptoms occur and to discontinue Metoclopramide Hydrochloride.
5.3 Neuroleptic Malignant Syndrome
Metoclopramide Hydrochloride may cause a potentially fatal symptom complex called neuroleptic malignant syndrome (NMS). NMS has been reported in association with Metoclopramide Hydrochloride overdosage and concomitant treatment with another drug associated with NMS. Avoid Metoclopramide Hydrochloride 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:
Depression has occurred in metoclopramide-treated patients with and without a history of depression. Symptoms have included suicidal ideation and suicide. Avoid Metoclopramide Hydrochloride use in patients with a history of depression.
Metoclopramide Hydrochloride may elevate blood pressure. In one study in hypertensive patients, intravenously administered Metoclopramide Hydrochloride was shown to release catecholamines; hence, avoid use in patients with hypertension or in patients taking monoamine oxidase inhibitors [see Drug Interactions ].
There are also clinical reports of hypertensive crises in patients with undiagnosed pheochromocytoma. Metoclopramide Hydrochloride is contraindicated in patients with pheochromocytoma or other catecholamine-releasing paragangliomas [see Contraindications (4)]. Discontinue Metoclopramide Hydrochloride in any patient with a rapid rise in blood pressure.
5.6 Fluid Retention
Because Metoclopramide Hydrochloride produces a 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 Hydrochloride if any of these adverse reactions occur.
As with other dopamine D2 receptor antagonists, Metoclopramide Hydrochloride 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 Hydrochloride.
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 ].
5.8 Effects of the Ability to Drive and Operate Machinery
Metoclopramide Hydrochloride may impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a 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 Hydrochloride or the interacting drug, depending on the importance of the drug to the patient [see Drug Interactions (7.1)].
6 ADVERSE REACTIONS
The following adverse reactions are described, or described in greater detail, in other sections of the labeling:
The following adverse reactions have been identified from clinical studies or postmarketing reports of Metoclopramide Hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The most common adverse reactions (in approximately 10% of patients receiving 10 mg of Metoclopramide Hydrochloride four times daily) were restlessness, drowsiness, fatigue, and lassitude. In general, the incidence of adverse reactions correlated with the dosage and duration of Metoclopramide Hydrochloride administration.
Adverse reactions, especially those involving the nervous system, occurred after stopping Metoclopramide Hydrochloride including dizziness, nervousness, and headaches.
Central Nervous System Disorders
Endocrine Disorders: Fluid retention secondary to transient elevation of aldosterone. Galactorrhea, amenorrhea, gynecomastia, impotence secondary to hyperprolactinemia
Cardiovascular Disorders: Acute congestive heart failure, possible atrioventricular block, hypotension, hypertension, supraventricular tachycardia, bradycardia, fluid retention
Gastrointestinal Disorders: Nausea, bowel disturbances (primarily diarrhea)
Hepatic Disorders: Hepatotoxicity, characterized by, e.g., jaundice and altered liver function tests, when Metoclopramide Hydrochloride was administered with other drugs with known hepatotoxic potential
Renal and Urinary Disorders: Urinary frequency, urinary incontinence
Hematologic Disorders: Agranulocytosis, neutropenia, leukopenia, methemoglobinemia, sulfhemoglobinemia
Hypersensitivity Reactions: Bronchospasm (especially in patients with a history of asthma), urticaria; rash; angioedema, including glossal or laryngeal edema
Eye Disorders: Visual disturbances
Metabolism Disorders: Porphyria
To report SUSPECTED ADVERSE REACTIONS, contact TEVA USA, PHARMACOVIGILANCE at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
7 DRUG INTERACTIONS
7.1 Effects of Other Drugs on Metoclopramide Hydrochloride
Table 3 displays the effects of other drugs on Metoclopramide Hydrochloride.
7.2 Effects of Metoclopramide Hydrochloride on Other Drugs
Table 4 displays the effects of Metoclopramide Hydrochloride on other drugs.
8 USE IN SPECIFIC POPULATIONS
Published 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 Hydrochloride during pregnancy.
There are potential risks to the neonate following exposure in utero to Metoclopramide Hydrochloride during delivery [see Clinical Considerations]. In animal reproduction studies, no adverse developmental effects were observed with oral administration of Metoclopramide Hydrochloride to pregnant rats and rabbits at exposures about 6 and 12 times the maximum recommended human dose [see Data].
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a 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 2 to 4% and 15 to 20%, respectively.
Fetal/Neonatal Adverse Reactions
Metoclopramide Hydrochloride 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)].
Reproduction studies have been performed following administration of oral Metoclopramide Hydrochloride during organogenesis in pregnant rats at about 6 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 Hydrochloride were observed.
Limited published data report the presence of Metoclopramide Hydrochloride in human milk in variable amounts. Breastfed infants exposed to Metoclopramide Hydrochloride have experienced gastrointestinal adverse reactions, including intestinal discomfort and increased intestinal gas formation [see Data]. Metoclopramide Hydrochloride 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 mother’s clinical need for Metoclopramide Hydrochloride and any potential adverse effects on the breastfed child from Metoclopramide Hydrochloride or from the underlying maternal condition.
Monitor breastfeeding neonates because Metoclopramide Hydrochloride may cause extrapyramidal signs (dystonias) and methemoglobinemia [see Warnings and Precautions (5.1, 5.2), Use in Specific Populations (8.4)].
In published clinical studies, the estimated amount of Metoclopramide Hydrochloride received by the breastfed infant was less than 10% of the maternal weight-adjusted dose. In one study, the estimated daily amount of Metoclopramide Hydrochloride received by infants from breast milk ranged from 6 to 24 mcg/kg/day in early puerperium (3 to 9 days postpartum) and from 1 to 13 mcg/kg/day at 8 to 12 weeks postpartum.
8.4 Pediatric Use
Metoclopramide Hydrochloride is not recommended for use in pediatric patients due to the risk of tardive dyskinesia and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates. The safety and effectiveness of Metoclopramide Hydrochloride in pediatric patients have not been established.
Dystonias and other extrapyramidal symptoms associated with Metoclopramide Hydrochloride 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, a possible adverse reaction of Metoclopramide Hydrochloride use in neonates [see Use in Specific Populations (8.8)].
8.5 Geriatric Use
Metoclopramide Hydrochloride 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 Hydrochloride; therefore, consider a reduced dosage of Metoclopramide Hydrochloride in elderly patients [see Boxed Warning, Dosage and Administration (2.2, 2.3), Warnings and Precautions (5.1)].
8.6 Renal Impairment
The clearance of Metoclopramide Hydrochloride 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 Hydrochloride dosage in patients with moderate and severe renal impairment, including those receiving hemodialysis and continuous ambulatory peritoneal dialysis [see Dosage and Administration (2.2, 2.3), Clinical Pharmacology (12.3)].
8.7 Hepatic Impairment
Patients with severe hepatic impairment (Child-Pugh C) have reduced systemic Metoclopramide Hydrochloride clearance (by approximately 50%) compared to patients with normal hepatic function. The resulting increase in Metoclopramide Hydrochloride blood concentrations increases the risk of adverse reactions. There is no pharmacokinetic data in patients with moderate hepatic impairment (Child-Pugh B). Reduce Metoclopramide Hydrochloride dosage in patients with moderate or severe (Child-Pugh B or C) hepatic impairment [see Dosage and Administration (2.2, 2.3)]. There is no dosage adjustment required for patients with mild hepatic impairment (Child-Pugh A).
In addition, Metoclopramide Hydrochloride, by producing a 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 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 Hydrochloride is a substrate of CYP2D6. The elimination of Metoclopramide Hydrochloride 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 Hydrochloride [see Clinical Pharmacology (12.3)]. Reduce the Metoclopramide Hydrochloride dosage in patients who are poor CYP2D6 metabolizers [see Dosage and Administration (2.2, 2.3)].
Manifestations of Metoclopramide Hydrochloride overdosage included drowsiness, disorientation, extrapyramidal reactions, other adverse reactions associated with Metoclopramide Hydrochloride use (including, e.g., methemoglobinemia), and sometimes death. Neuroleptic malignant syndrome (NMS) has been reported in association with Metoclopramide Hydrochloride 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 Hydrochloride 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 Hydrochloride.
Metoclopramide Hydrochloride hydrochloride, USP, the active ingredient of Metoclopramide Hydrochloride tablets, is a dopamine-2 receptor antagonist. Metoclopramide Hydrochloride hydrochloride (metoclopramide monohydrochloride monohydrate) is a 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:
C14H22ClN3O2-HCl-H2O M.W. 354.3
Metoclopramide Hydrochloride tablets are for oral administration. Metoclopramide Hydrochloride tablets are available in 5 mg and 10 mg tablets.
Corn starch, dibasic calcium phosphate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Metoclopramide Hydrochloride stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. The exact mechanism of action of Metoclopramide Hydrochloride 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 Hydrochloride on motility is not dependent on intact vagal innervation, but it can be abolished by anticholinergic drugs.
Metoclopramide Hydrochloride increases the tone and amplitude of gastric 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.
In patients with gastroesophageal reflux and low lower esophageal sphincter pressure (LESP), single oral doses of Metoclopramide Hydrochloride produced dose-related increases in LESP. Effects began at about 5 mg and increased through 20 mg. The increase in LESP from a 5 mg dose lasted about 45 minutes and that of 20 mg lasted between 2 and 3 hours. Increased rate of stomach emptying was observed with single oral doses of 10 mg.
Relative to an intravenous dose of 20 mg, the absolute bioavailability of oral Metoclopramide Hydrochloride is 80% ± 15.5% as demonstrated in a crossover study of 18 subjects. Peak plasma concentrations occurred at about 1 to 2 hours after a single oral dose. Similar time to peak was observed after individual doses at steady state.
In a 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 5 to 6 hours. Linear kinetic processes adequately describe the absorption and elimination of Metoclopramide Hydrochloride.
Metoclopramide Hydrochloride 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.
Metabolism: Metoclopramide Hydrochloride undergoes enzymatic metabolism via oxidation as well as glucuronide and sulfate conjugation reactions in the liver. Monodeethylmetoclopramide, a major oxidative metabolite, is formed primarily by CYP2D6, an enzyme subject to genetic variability [see Dosage and Administration (2.2, 2.3), 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, a mean of 18% and 22% of the dose, respectively, was recovered as free Metoclopramide Hydrochloride in urine within 36 hours.
Patients with Renal Impairment: In a 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 Hydrochloride in patients with moderate to severe renal impairment was about 2-fold the AUC in subjects with normal renal function. The AUC of Metoclopramide Hydrochloride in patients with ESRD on dialysis was about 3.5-fold the AUC in subjects with normal renal function [see Dosage and Administration (2.2, 2.3) and Use in Specific Populations (8.6)].
Patients with Hepatic Impairment: In a group of 8 patients with severe hepatic impairment (Child-Pugh C), the average Metoclopramide Hydrochloride clearance was reduced by approximately 50% compared to patients with normal hepatic function [see Dosage and Administration (2.2, 2.3) and Use in Specific Populations (8.7)].
Drug Interaction Studies
Effect of Metoclopramide Hydrochloride on CYP2D6 Substrates
Although in vitro studies suggest that Metoclopramide Hydrochloride can inhibit CYP2D6, Metoclopramide Hydrochloride is unlikely to interact with CYP2D6 substrates in vivo at therapeutically relevant concentrations.
Effect of CYP2D6 Inhibitors on Metoclopramide Hydrochloride
In healthy subjects, 20 mg of Metoclopramide Hydrochloride and 60 mg of fluoxetine (a strong CYP2D6 inhibitor) were administered, following prior exposure to 60 mg fluoxetine orally for 8 days. The patients who received concomitant Metoclopramide Hydrochloride and fluoxetine had a 40% and 90% increase in Metoclopramide Hydrochloride Cmax and AUC0-∞, respectively, compared to patients who received Metoclopramide Hydrochloride alone [see Drug Interactions (7.1)].
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
A 77-week study was conducted in rats with oral Metoclopramide Hydrochloride doses up to 40 mg/kg/day (about six times the maximum recommended human dose on body surface area basis). Metoclopramide Hydrochloride elevated prolactin levels and the elevation persisted during chronic administration. An increase in mammary neoplasms was found in rodents after chronic administration of Metoclopramide Hydrochloride [see Warnings and Precautions (5.7)]. In a rat model for assessing the tumor promotion potential, a 2-week oral treatment with Metoclopramide Hydrochloride at a 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.
Metoclopramide Hydrochloride 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 Fertility
Metoclopramide Hydrochloride 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.
16 HOW SUPPLIED/STORAGE AND HANDLING
Each white, round, unscored, debossed “TV” on one side and “2204” on the other side, compressed Metoclopramide Hydrochloride tablet, USP contains Metoclopramide Hydrochloride hydrochloride, USP equivalent to 5 mg Metoclopramide Hydrochloride. 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 Hydrochloride tablet, USP contains Metoclopramide Hydrochloride hydrochloride, USP equivalent to 10 mg Metoclopramide Hydrochloride. Available in bottles of 100 (NDC 0093-2203-01), 500 (NDC 0093-2203-05), and 1000 (NDC 0093-2203-10).
Dispense in a tight, light-resistant container. Store tablets at 20° to 25°C (68° to 77°F).
This product is light sensitive. It should be inspected before use and discarded if either color or particulate is observed.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Inform patients or their caregivers that Metoclopramide Hydrochloride can cause serious adverse reactions. Instruct patients to discontinue Metoclopramide Hydrochloride and contact a healthcare provider immediately if the following serious reactions occur:
Inform 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 Hydrochloride.
Inform patients or their caregivers that Metoclopramide Hydrochloride 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 a motor vehicle [see Warnings and Precautions (5.8)].
Manufactured In Croatia By:
Pliva Hrvatska d.o.o.
Teva Pharmaceuticals USA, Inc.
North Wales, PA 19454
Rev. Q 8/2017
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Manufactured In Croatia By:
Pliva Hrvatska d.o.o.
Teva Pharmaceuticals USA, Inc.
North Wales, PA 19454
Rev. D 8/2017
PHARMACIST: Dispense the accompanying
Medication Guide to each patient.
PHARMACIST: Dispense the accompanying
Medication Guide to each patient.
Metoclopramide Hydrochloride available forms, composition, doses:
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Frequently asked QuestionsCan i drive or operate heavy machine after consuming Metoclopramide Hydrochloride?
Depending on the reaction of the Metoclopramide Hydrochloride after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Metoclopramide Hydrochloride not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Metoclopramide Hydrochloride addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
Reviewsdrugs.com conducted a study on Metoclopramide Hydrochloride, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Metoclopramide Hydrochloride consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.
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The information was verified by Dr. Arunabha Ray, MD Pharmacology