What is the use of Metoclopramide (MCP)?

From the Guidelines

Metoclopramide should be used at a dose of 5-20 mg tid-qid for the treatment of gastroparesis, with treatment duration limited to 12 weeks or less to minimize side effect risks, as recommended by the most recent guidelines 1. The typical adult dose of metoclopramide is 10 mg taken orally three to four times daily before meals and at bedtime.

• Metoclopramide works by blocking dopamine receptors in the chemoreceptor trigger zone of the brain and increasing motility in the upper gastrointestinal tract.
• Common side effects include drowsiness, restlessness, and fatigue, while serious concerns include tardive dyskinesia (involuntary movements) with long-term use.
• This medication should be used cautiously in elderly patients, those with kidney or liver impairment, and is contraindicated in patients with seizure disorders, pheochromocytoma, or gastrointestinal obstruction.
• Patients should avoid alcohol while taking metoclopramide as it can increase drowsiness and impair coordination.
• The level of evidence regarding the benefits of metoclopramide for the management of gastroparesis is weak, and given the risk for serious adverse effects, its use in the treatment of gastroparesis beyond 12 weeks is no longer recommended by the FDA or the European Medicines Agency 1.
• Other treatment options include domperidone (available outside the U.S.) and erythromycin, which is only effective for short-term use due to tachyphylaxis 1.
• Gastric electrical stimulation using a surgically implantable device has received approval from the FDA, although its efficacy is variable and use is limited to individuals with severe symptoms that are refractory to other treatments 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Metoclopramide Overview

• Metoclopramide is a dopamine receptor antagonist with 5HT3 receptor antagonist and 5HT4 receptor agonist activity, used as an antiemetic and gastroprokinetic for almost 50 years 2.
• It is the only drug approved by the Food and Drug Administration for diabetic gastroparesis 3.

Mechanism of Action and Side Effects

• Metoclopramide acts on several different receptors, primarily as a dopamine receptor antagonist, improving gastric emptying peripherally and resulting in an anti-emetic effect centrally 3.
• Side effects include drowsiness, restlessness, hyperprolactinemia, and tardive dyskinesia (TD), a movement disorder that may be irreversible 3, 4.

Risk of Tardive Dyskinesia

• The risk of tardive dyskinesia from metoclopramide is low, in the range of 0.1% per 1000 patient years 2.
• High-risk groups include elderly females, diabetics, patients with liver or kidney failure, and patients with concomitant antipsychotic drug therapy 2.
• Available data show that the risk of tardive dyskinesia from metoclopramide use is likely to be <1%, much less than the estimated 1-10% risk previously suggested in national guidelines 4.

Clinical Context and Use

• Metoclopramide carries a black box warning for use >12 weeks due to the risk of TD, but gastroparesis patients often require prolonged treatments 3.
• Physicians and patients look forward to FDA approval of new agents for gastroparesis with better efficacy and safety profiles 3.
• The risk of tardive dyskinesia and the influence of known risk factors should be considered when starting a course of metoclopramide for treatment of gastroparesis 2.