METOCLOPRAMIDE

METOCLOPRAMIDE HCL

10mg Tablet

10mg/2ml Solution for Injection

DRUG CATEGORY: Anti-Emetic

BRAND NAME: Plasil

FORMULATION

Each tablet contains:

Metoclopramide (as hydrochloride)...........10mg

Each mL in ampule contains:

Metoclopramide (as hydrochloride)...........5mg

INDICATIONS

Disturbances of gastrointestinal motility, including gastroesophageal reflux and diabetic gastroparesis (diabetic gastric statis).

Nausea and vomiting of central and peripheral origin associated with surgery, metabolic diseases, infectious disease, migraine headache, or drugs including cancer chemotherapy.

To facilitate small bowel intubation and radiological procedures of gastrointestinal tract.

DOSAGE AND ADMINISTRATION

Adult

Tablets: 1 tablet orally three times a day 10 minutes before meals

Injectiable: 1 ampule every eight hours (I.M. or I.V.)

Radiological Examination of Gastrointestinal Tract

1 to 2 ampules, I.M. or I.V., 10 minutes before starting the procedures.

CONTRAINDICATIONS

Contraindicated in patients with a history of hypersensitivity to metoclopramide or any of the components.

Metoclopramide should not be used whenever stimulation of gastrointestinal motility might dangerous, e.g. in the presence of gastrointestinal hemorrhage, mechanical obstruction, or perforation. Metoclopramide is contraindicated in patients with pheochromocytoma because the drug may cause a hypertensive crisis, probably due to release of catecholamines from the tumor. Such hypertensive crises may be controlled by phentolamine.

Metoclopramide should not be used in epileptics or patients receiving other drugs which are likely to cause extrapyramidal reactions, since the frequency and severity of seizures or extrapyramidal reactions may be increased.

WARNINGS/PRECAUTIONS

Pediatrics/Geriatics

Extrapyramidal symptoms may occur in patients treated with metoclopramide. These occur more frequently in children and young adults and may occur after a single dose. These most often consist of feelings of restlessness; occasionally they may include involuntary movements of limbs and facial grimacing; rarely, torticollis, oculogyric crisis, rhythmic protrusion of tongue, bulbar type of speech or trismus. The development or tardive dyskinesia has been reported in elderly patients when treated for extended periods.

Metoclopramide ampules contain sodium metabisulfite which may cause allergic type reactions including anaphylactic symptoms and life-threatening or less severe asthma episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

Intravenous injections of metoclopramide should be made slowly over a 1- to 2- minutes period since a transient but intense feeling of anxiety and restlessness, followed by drowsiness, may occur with rapid administration.

Patients should be cautioned about engaging in activities requiring mental alertness for a few hours after the drug has been administered.

Pregnancy and Lactation

Reproduction studies performed in rats, mice, and rabbits by I.V., I.M., S.C. and oral routes at maximum levels ranging from 12 to 250 times the human dose have demonstrated no impairment of fertility or significant harm to the fetus due to metoclopramide. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Metoclopramide is secreted in breast milk and infants should not be breast fed by a patient receiving metoclopramide unless in the physician's judgment the potential benefit to the patient outweighs the potential risk to the infant.

DRUG INTERACTIONS

The effects of metoclopramide on gastrointestinal motility are antagonized by anticholinergic drugs and narcotic analgesics. Additive sedative effects can occur when metoclopramide is given with alcohol, sedatives, hypnotics, narcotics or tranquilizers. The finding that metoclopramide releases catecholamines in patients with essential hypertension suggests that it should be used cautiously, if at all, in patients receiving monamine oxidase inhibitors. Absorption of drugs from the stomach may be diminished (e.g. digoxin) by metoclopramide, whereas absorption of drugs from the small bowel may be accelerated (e.g. acetaminophen, tetracycline, levodopa, ethanol).

Diabetic patients

Gastroparesis (gastric stasis) may be responsible for poor diabetic control in some patients. Exogenously administered insulin may begin to act before food has left the stomach and lead to hypoglycemia. Because the action of metoclopramide may quicken the delivery of food to the intestines and thus rate of absorption, insulin dose or timing of administration may require adjustment.

Patients with Renal Impairment

Since metoclopramide is excreted principally through the kidneys, in those patients whose creatinine clearance is below 40mL/min, therapy should be initiated at approximately one-half the recommended dosage. Depending upon clinical efficacy and safety considerations, the dosage may be increased or decreased as appropriate.

Patients with Breast Cancer

Metoclopramide can increase prolactin levels and should be considered in patients with previously detected breast cancer.

ADVERSE REACTIONS (SEE WARNINGS)

The most frequent adverse reactions to metoclopramide are restlessness, drowsiness, fatigue and lassitude, which occur in approximately ten percent of patients. Less frequently, extrapyramidal symptoms, insomnia, headache, dizziness, nausea, galactorrhea, gyecomastia, rash including urticaria or bowel disturbance may occur.

OVERDOSAGE

Symptoms of overdosage may include drowsiness,, disorientation and extrapyramidal reactions. Anticholinergic or antiparkinson drugs and antihistamines with anticholinergic properties may be helpful in controlling extrapyramidal reactions. Symptoms are self-limiting and usually disappear within 24 hours. Dialysis is not likely to be an effective method of drug removal in overdose situations.

CLINICAL PHARMACOLOGY

Metoclopramide, a dopamine antagonist, stimulation motility of the upper gastrointestinal tract without stimulation gastric, biliary, or pancreatic secretions. Its mode of actions is unclear. It seems to sensitize tissue to the action of acetylcholine. The effect of metoclopramide or 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) contraindications, relaxes the pyloric sphincter and the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower esophageal sphincter. Peak plasma levels are reached 30 to 60 minutes following an oral dose. Excretion is primarily in the urine. The plasma half-life is about 3 hours. Metoclopramide undergoes minimal hepatic metabolism, except for simple conjugation. Its safe use has been described in patients with advanced liver disease whose renal function was normal.

STORAGE

Store at temperatures not exceeding 30^oC