INDICATIONS & USAGE Diabetic Gastroparesis (Diabetic Gastric Stasis) Metoclopramide is indicated for the relief of symptoms associated with acute and recurrent diabetic gastric stasis.

The Prevention of Nausea and Vomiting Associated with Emetogenic Cancer Chemotherapy Metoclopramide Injection, USP is indicated for the prophylaxis of vomiting associated with emetogenic cancer chemotherapy.

The Prevention of Postoperative Nausea and Vomiting Metoclopramide Injection, USP is indicated for the prophylaxis of postoperative nausea and vomiting in those circumstances where nasogastric suction is undesirable.

Small Bowel Intubation Metoclopramide Injection, USP may be used to facilitate small bowel intubation in adults and pediatric patients in whom the tube does not pass the pylorus with conventional maneuvers.

Radiological Examination Metoclopramide Injection, USP may be used to stimulate gastric emptying and intestinal transit of barium in cases where delayed emptying interferes with radiological examination of the stomach and/or small intestine.

WARNINGS Neuroleptic Malignant Syndrome (NMS) 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, etc.) 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 1) immediate discontinuation of metoclopramide and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) 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 have not been established (see ADVERSE REACTIONS ).

Extrapyramidal Symptoms (EPS) Acute Dystonic Reactions 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 the higher doses used in prophylaxis of vomiting due to cancer chemotherapy.

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 should occur, inject 50 mg Benadryl® (diphenhydramine hydrochloride) intramuscularly, and they usually will subside.

Cogentin® (benztropine mesylate), 1 to 2 mg intramuscularly, may also be used to reverse these reactions.

Tardive Dyskinesia (see BOXED WARNINGS ) 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 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 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.

Parkinsonian-like Symptoms Parkinsonian-like symptoms, including bradykinesia, tremor, cogwheel rigidity, or mask-like facies, have occurred, more commonly within the first 6 months after beginning treatment with metoclopramide, but occasionally after longer periods.

These symptoms generally subside within 2 to 3 months following discontinuance of metoclopramide.

Patients with pre-existing Parkinson's disease should be given metoclopramide cautiously, if at all, since such patients may experience exacerbation of parkinsonian symptoms when taking metoclopramide.

Depression Mental depression has occurred in patients with and without prior history of depression.

Symptoms have ranged from mild to severe and have included suicidal ideation and suicide.

Metoclopramide should be given to patients with a prior history of depression only if the expected benefits outweigh the potential risks.

ADVERSE REACTIOS In general, the incidence of adverse reactions correlates with the dose and duration of metoclopramide administration.

The following reactions have been reported, although in most instances, data do not permit an estimate of frequency.

CNS Effects Restlessness, drowsiness, fatigue and lassitude may occur in patients receiving the recommended prescribed dosage of metoclopramide injection.

Insomnia, headache, confusion, dizziness, or mental depression with suicidal ideation also may occur (see WARNINGS ).

In cancer chemotherapy patients being treated with 1 to 2 mg/kg per dose, incidence of drowsiness is about 70%.

There are isolated reports of convulsive seizures without a clear-cut relationship to metoclopramide.

Rarely, hallucinations have been reported.

Extrapyramidal Reactions (EPS) Acute dystonic reactions, the most common type of EPS associated with metoclopramide, occur in approximately 0.2% of patients (1 in 500) treated with 30 to 40 mg of metoclopramide per day.

In cancer chemotherapy patients receiving 1 to 2 mg/kg per dose, the incidence is 2% in patients over the ages of 30 to 35, and 25% or higher in pediatric patients and adult patients less than 30 years of age who have not had prophylactic administration of diphenhydramine.

Symptoms include involuntary movements of limbs, facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of tongue, bulbar type of speech, trismus, opisthotonus (tetanus-like reactions) and rarely, stridor and dyspnea, possibly due to laryngospasm; ordinarily these symptoms are readily reversed by diphenhydramine (see WARNINGS ).

Parkinsonian-like symptoms may include bradykinesia, tremor, cogwheel rigidity, mask-like facies (see WARNINGS ).

Tardive dyskinesia most frequently is characterized by involuntary movements of the tongue, face, mouth or jaw, and sometimes by involuntary movements of the trunk and/or extremities; movements may be choreoathetotic in appearance (see WARNINGS ).

Motor restlessness (akathisia) may consist of feelings of anxiety, agitation, jitteriness, and insomnia, as well as inability to sit still, pacing, and foot tapping.

These symptoms may disappear spontaneously or respond to a reduction in dosage.

Neuroleptic Malignant Syndrome Rare occurrences of neuroleptic malignant syndrome (NMS) have been reported.

This potentially fatal syndrome is comprised of the symptom complex of hyperthermia, muscular rigidity, altered consciousness, and autonomic instability (see WARNINGS ).

Endocrine Disturbances Galactorrhea, amenorrhea, gynecomastia, impotence secondary to hyperprolactinemia (see PRECAUTIONS).

Fluid retention secondary to transient elevation of aldosterone (see CLINICAL PHARMACOLOGY ).

Cardiovascular Hypotension, hypertension, supraventricular tachycardia, bradycardia, fluid retention, acute congestive heart failure, and possible atrioventricular (AV) block (see CONTRAINDICATIONS and PRECAUTIONS ).

Gastrointestinal Nausea and bowel disturbances, primarily diarrhea.

Hepatic Rarely, cases of hepatotoxicity, characterized by such findings as jaundice and altered liver function tests, when metoclopramide was administered with other drugs with known hepatotoxic potential.

Renal Urinary frequency and incontinence.

Hematologic A few cases of neutropenia, leukopenia, or agranulocytosis, generally without a clear-cut relationship to metoclopramide.

Methemoglobinemia, in adults and especially with overdosage in neonates (see OVERDOSAGE ).

Sulfhemoglobinemia in adults.

Allergic Reactions A few cases of rash, urticaria, or bronchospasm, especially in patients with a history of asthma.

Rarely, angioneurotic edema, including glossal or laryngeal edema.

Miscellaneous Visual disturbances, Porphyria.

Transient flushing of the face and upper body, without alterations in vital signs, following high doses intravenously.