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, as it is the only FDA-approved medication for this condition, despite its potential for serious adverse effects 1.

Key Considerations

• The medication works by blocking dopamine receptors in the brain's chemoreceptor trigger zone and by enhancing gastrointestinal motility.
• Common side effects include drowsiness, restlessness, and fatigue, while more serious concerns include extrapyramidal symptoms and tardive dyskinesia with long-term use.
• Treatment duration is typically limited to 12 weeks or less due to the risk of serious adverse effects.
• Metoclopramide should be used cautiously in elderly patients, those with kidney or liver impairment, and is contraindicated in conditions like gastrointestinal obstruction, pheochromocytoma, and in patients taking medications that might interact with it.

Clinical Context

• Gastroparesis is a challenging condition to treat, and metoclopramide is often reserved for severe cases that are unresponsive to other therapies 1.
• Other treatment options include domperidone, erythromycin, and gastric electrical stimulation, but their use is limited by factors such as availability, efficacy, and potential for adverse effects.
• The level of evidence regarding the benefits of metoclopramide for the management of gastroparesis is weak, and its use should be carefully weighed against the potential risks 1.

Patient Management

• Patients should be closely monitored for signs of adverse effects, particularly extrapyramidal symptoms and tardive dyskinesia.
• The medication should be used at the lowest effective dose and for the shortest duration necessary to minimize the risk of adverse effects.
• Alternative treatment options should be considered for patients who experience adverse effects or who do not respond to metoclopramide therapy 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 used to treat diabetic gastroparesis, a chronic disorder of the stomach characterized by delayed gastric emptying without mechanical obstruction 2.
• It acts on several different receptors, primarily as a dopamine receptor antagonist, improving gastric emptying peripherally and resulting in an anti-emetic effect centrally 2.

Efficacy and Safety

• Metoclopramide is effective in treating and preventing various types of vomiting, as well as oesophageal reflux disease, gastroparesis, dyspepsia, and functional gastrointestinal disorders 3.
• However, it carries a black box warning for use >12 weeks due to the risk of tardive dyskinesia (TD), a movement disorder that may be irreversible 2.
• The risk of TD from metoclopramide is low, in the range of 0.1% per 1000 patient years, with high-risk groups including elderly females, diabetics, patients with liver or kidney failure, and patients with concomitant antipsychotic drug therapy 4.

Pharmacokinetics and Administration

• Metoclopramide can be administered subcutaneously, with peak concentrations reached at 30 minutes and trough levels returning to normal by 4 hours 5.
• Serum prolactin levels may provide a bioassay of efficacy and a marker for monitoring compliance 5.
• Metoclopramide is also available for intravenous administration, with good results achieved in preventing severe vomiting associated with cisplatin 3.

Drug-Drug Interactions

• Metoclopramide may interact with other drugs, including antidiabetic agents, antiemetic agents, and prokinetic agents, due to shared metabolic pathways 6.
• Potential drug-drug interactions (DDIs) should be considered when co-administering metoclopramide with other agents, as they may lead to undesired clinical outcomes 6.