Metoclopramide Orally DisintegratingTablets

Name: Metoclopramide Orally DisintegratingTablets

Indications and Usage for Metoclopramide Orally DisintegratingTablets

Symptomatic Gastroesophageal Reflux Disease

Metoclopramide Hydrochloride Orally Disintegrating Tablets are indicated as short-term (4 to 12 weeks) therapy for adults with symptomatic, documented gastroesophageal reflux disease (GERD) who fail to respond to conventional therapy.

Diabetic Gastroparesis (Diabetic Gastric Stasis)

Metoclopramide Hydrochloride Orally Disintegrating Tablets are indicated for the relief of symptoms associated with acute and recurrent diabetic gastroparesis (gastric stasis) in adults.

Important Limitations

Metoclopramide Hydrochloride Orally Disintegrating Tablets are indicated for adults only. Therapy should not exceed 12 weeks in duration. The safety and effectiveness in pediatric patients have not been established.

Dosage forms & strengths

5 mg Tablets: Metoclopramide Hydrochloride Orally Disintegrating Tablets are round, white to off-white, flat faced beveled edge tablet, debossed with 'N' on one side and "581" on the other side.

10 mg Tablets: Metoclopramide Hydrochloride Orally Disintegrating Tablets are round, white to off-white, flat faced beveled edge tablet, debossed with 'N' on one side and "580" on the other side.

Contraindications

Intestinal Obstruction, Hemorrhage, or Perforation

Do not use metoclopramide whenever stimulation of gastrointestinal motility may be dangerous such as in the presence of gastrointestinal hemorrhage, mechanical obstruction, or perforation.

Pheochromocytoma

Metoclopramide is contraindicated in patients with pheochromocytoma because the drug may precipitate a hypertensive crisis, most likely due to release of catecholamines from the tumor. Such hypertensive crises may be controlled by phentolamine.

Known Sensitivity or Intolerance

Metoclopramide is contraindicated in patients with known sensitivity or intolerance to the drug.

Epilepsy

Do not use metoclopramide in patients with epilepsy since the frequency and severity of seizures may be increased.

Concomitant Medications with Extrapyramidal Reactions

Do not use metoclopramide in patients receiving other drugs which are likely to cause extrapyramidal reactions, since the frequency and severity of extrapyramidal reactions may be increased [see Warnings and Precautions (5.2), Adverse Reactions (6.2) and Drug Interactions (7.5)].

Warnings and Precautions

Tardive Dyskinesia

[see Boxed Warning]

Treatment with metoclopramide can cause tardive dyskinesia (TD), a potentially irreversible and disfiguring disorder characterized by involuntary movements of the face, tongue, or extremities. The risk of developing tardive dyskinesia increases with the duration of treatment and the total cumulative dose. An analysis of utilization patterns showed that about 20% of patients who used metoclopramide took it for longer than 12 weeks. Treatment with metoclopramide for longer than the recommended 12 weeks should be avoided in all but rare cases where therapeutic benefit is thought to outweigh the risk of developing TD.

Although the risk of developing TD in the general population may be increased among the elderly, women, and diabetics, it is not possible to predict which patients will develop metoclopramide-induced TD. Both the risk of developing TD and the likelihood that TD will become irreversible increase with duration of treatment and total cumulative dose.

Metoclopramide should be discontinued in patients who develop signs or 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 is withdrawn.

Metoclopramide 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. Therefore, metoclopramide should not be used for the symptomatic control of TD.

Acute Dystonic Reactions, Drug-induced Parkinsonism, and Other Extrapyramidal Symptoms

Extrapyramidal symptoms (EPS), manifested primarily as acute dystonic reactions, occur in approximately 1 in 500 patients treated with the usual adult dosages of 30 to 40 mg/day of metoclopramide. These usually are seen during the first 24 to 48 hours of treatment with metoclopramide, occur more frequently in pediatric patients and adult patients less than 30 years of age and are even more frequent at higher doses. These symptoms may include 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 may present as stridor and dyspnea, possibly due to laryngospasm. If these symptoms occur, inject 50 mg diphenhydramine hydrochloride intramuscularly. Benztropine mesylate, 1 to 2 mg intramuscularly, may also be used to reverse these reactions.

Drug-induced Parkinsonism can occur during metoclopramide therapy, more commonly within the first 6 months after beginning treatment, but also after longer periods. Parkinsonian symptoms generally subside within 2 to 3 months following discontinuation of metoclopramide. Patients with a history of Parkinson's disease should be given metoclopramide cautiously, if at all, since such patients can experience exacerbation of Parkinsonian symptoms when taking metoclopramide.

Neuroleptic Malignant Syndrome

There have been rare reports of an uncommon but potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) associated with metoclopramide. Clinical manifestations of NMS include hyperthermia, muscle rigidity, altered consciousness, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac arrhythmias). The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, malignant hyperthermia, drug fever and primary central nervous system (CNS) pathology. The management of NMS should include immediate discontinuation of metoclopramide and other drugs not essential to concurrent therapy; intensive symptomatic treatment and medical monitoring; and, treatment of any concomitant serious medical problems for which specific treatments are available. Bromocriptine and dantrolene sodium have been used in treatment of NMS, but their effectiveness has not been established [see Adverse Reactions (6)].

Depression

Depression associated with metoclopramide use has occurred in patients with and without a history of depression. Symptoms ranged from mild to severe and included suicidal ideation and suicide. For those patients with a prior history of depression, metoclopramide should only be given if the expected benefits outweigh the potential risks.

Hypertension

In one study in hypertensive patients, intravenously administered metoclopramide was shown to release catecholamines; hence, caution should be exercised when metoclopramide is used in patients with hypertension. There are also clinical reports of hypertensive crises in some patients with undiagnosed pheochromocytoma, thus any rapid rise in blood pressure associated with Metoclopramide Hydrochloride Orally Disintegrating Tablets use should result in immediate cessation of metoclopramide use in those patients [see Contraindications (4.2)].

Congestive Heart Failure and Ventricular Arrhythmia

Since metoclopramide 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. If these side effects occur at any time in any patients during metoclopramide therapy, the drug should be discontinued.

Withdrawal from Metoclopramide

Adverse reactions, especially those involving the nervous system, may occur after stopping the use of Metoclopramide Hydrochloride Orally Disintegrating Tablets. A small number of patients may experience withdrawal symptoms after stopping that could include dizziness, nervousness, and/or headaches.

Phenylketonurics:

Phenylalanine is a component of aspartame. Each 5 mg and 10 mg Metoclopramide Hydrochloride Orally Disintegrating Tablets contains 4.7 mg of phenylalanine.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

A 77-week study was conducted in rats with oral doses up to 40 mg/kg/day (about 5 times the maximum recommended human dose on surface area basis). Metoclopramide elevates prolactin levels and the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin-dependent in vitro, a factor of potential importance if the prescription of metoclopramide is contemplated in a patient with previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported with prolactin-elevating drugs, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of prolactin-stimulating neuroleptic drugs and metoclopramide. Neither clinical studies nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is too limited to be conclusive at this time.

In a rat model for assessing the tumor promotion potential, a two-week oral treatment with metoclopramide 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 was positive in the in vitro Chinese hamster lung cell / HGPRT forward mutation assay for mutagenic effects and 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 (UDS) assay with rat and human hepatocytes and the in vivo rat micronucleus assay.

Metoclopramide at intramuscular doses up to 20 mg/kg/day (about 3 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.

How Supplied/Storage and Handling

Metoclopramide Hydrochloride Orally Disintegrating Tablets 5 mg strength are round, white to off-white, flat faced beveled edge tablet debossed with 'N' on one side and "581" on the other side; it is comprised of 5 mg metoclopramide (as 5.91 mg of metoclopramide hydrochloride). These are packaged in blister cards as follows:

Box of 10 (1x10)   NDC 43386-581-31

Metoclopramide Hydrochloride Orally Disintegrating Tablets 10 mg are round, white to off-white, flat faced beveled edge tablet debossed with 'N' on one side and "580" on the other side; it is comprised of 10 mg metoclopramide (as 11.82 mg of metoclopramide hydrochloride). These are packaged in blister cards as follows:

Box of 10 (1x10)   NDC 43386-580-31

Tablets should be stored at controlled room temperature, between 20°C and 25°C (68°F and 77°F).

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