Metoclopramide Disease Interactions

Metoclopramide has been reported to cause mental depression in patients with and without a prior history of depression. Symptoms have ranged from mild to severe and have included suicidal ideation and suicide. Therapy with metoclopramide in patients with a history of mental depression, especially suicidal tendencies, should be administered cautiously, and only if benefits are anticipated to outweigh the potential risks. Some patients who experience depression with metoclopramide have improved following temporary discontinuation of the drug and reinstitution at a lower dosage with gradual titration.

The use of metoclopramide is contraindicated in patients with conditions where stimulation of gastrointestinal motility might be harmful, such as mechanical bowel obstruction, bowel perforation, or gastrointestinal hemorrhage.

Although not a neuroleptic agent, metoclopramide has antidopaminergic effects and may rarely precipitate or aggravate a potentially fatal symptom complex known as Neuroleptic Malignant Syndrome (NMS). Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, involuntary movements, altered mental status and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac arrhythmias). Metoclopramide therapy should not be initiated in patients with active NMS and should be immediately discontinued if currently being administered in such patients. In patients with a history of NMS, introduction or reintroduction of metoclopramide or other antidopaminergic therapy should be carefully considered, since NMS may recur.

The use of metoclopramide is contraindicated in patients with pheochromocytoma. In a study involving patients with essential hypertension, intravenously administered metoclopramide was shown to induce the release of catecholamines. Hypertensive crises may occur in patients with pheochromocytoma due to induction of catecholamine release from the tumor.

The use of metoclopramide is contraindicated in patients with seizure disorders. Metoclopramide may increase the frequency and severity of seizures.

Metoclopramide may precipitate symptoms of tardive dyskinesia (TD) following chronic administration. Elderly patients, particularly women, are most susceptible. Both the risk of developing TD and the likelihood that it will become irreversible increase with the duration and total cumulative dose of metoclopramide or other antidopaminergic therapy administered. Metoclopramide therapy should be discontinued in patients who develop signs or symptoms of tardive dyskinesia. There is no known treatment for tardive dyskinesia. In some patients, symptoms may lessen or resolve after metoclopramide treatment is stopped. Treatment with metoclopramide for longer than 12 weeks should be avoided in all but rare cases where therapeutic benefit is thought to outweigh the risk of developing tardive dyskinesia. In patients with preexisting drug-induced TD, initiating or increasing the dosage of metoclopramide therapy may temporarily mask the symptoms of TD but may eventually worsen the condition.

Metoclopramide produces a transient increase in plasma aldosterone and may cause fluid retention and volume overload in susceptible patients. Therapy with metoclopramide should be administered cautiously in patients with or at risk for fluid overload (e.g., cirrhosis, congestive heart failure). If these side effects occur at any time during metoclopramide therapy, the drug should be discontinued.

In a study involving patients with essential hypertension, intravenously administered metoclopramide was shown to induce the release of catecholamines. Therapy with metoclopramide should be administered cautiously in patients with hypertension because of potential increases in blood pressure.

Metoclopramide has antidopaminergic effects and may cause parkinsonian-like symptoms such as akinesia, bradykinesia, tremors, pill-rolling motion, cogwheel rigidity, and postural abnormalities including stooped posture and shuffling gait. The onset is usually within the first six months following initiation of therapy but occasionally after longer periods. Symptoms generally subside within 2 to 3 months after drug discontinuation. Therapy with metoclopramide should be administered cautiously, if at all, in patients with Parkinson's disease or parkinsonian symptoms.

Renal function affects the clearance of metoclopramide. In patients with varying degrees of renal impairment, a reduction in creatinine clearance was correlated with a reduction in plasma clearance, renal clearance, and non-renal clearance, and increase in elimination half-life of metoclopramide. Therapy with metoclopramide should be administered cautiously in patients with impaired renal function. A dosage reduction may be appropriate to avoid drug accumulation.