What are the usage guidelines and potential side effects of Reglan (metoclopramide)?

Metoclopramide (Reglan) Usage Guidelines and Side Effects

Metoclopramide is the first-line treatment and only FDA-approved medication for gastroparesis, with recommended dosing of 10 mg three times daily before meals, but should be limited to 12 weeks of use due to the risk of tardive dyskinesia. 1

Indications and Mechanism of Action

• Primary FDA-approved indication: Treatment of diabetic gastroparesis 1
• Off-label uses: Various gastrointestinal motility disorders, severe gastroesophageal reflux, and as an antiemetic 1, 2
• Mechanism: Functions as a dopamine (D2) receptor antagonist with:
  • Prokinetic properties (increases gastric emptying)
  • Antiemetic effects (acts on chemoreceptor trigger zone)
  • Increases lower esophageal sphincter pressure 1, 2

Dosing Guidelines

• Standard dosing: 10 mg three times daily before meals 1
• Duration: Should not exceed 12 weeks due to risk of tardive dyskinesia 1, 3
• Administration routes:
  • Oral (tablets, solution)
  • Intravenous (IV)
  • Intramuscular (IM) 3
• Parenteral use should be limited to 1-2 days 2

Major Side Effects and Risks

Neurological Side Effects (Most Concerning)

• Movement disorders (account for nearly one-third of all drug-induced movement disorders) 4:

  • Tardive dyskinesia (involuntary movements of face, tongue, limbs)
  • Akathisia (restlessness)
  • Dystonia (muscle spasms of face, neck, body)
  • Parkinsonism (shaking, stiffness, balance problems)
  • Neuroleptic Malignant Syndrome (rare but serious: high fever, muscle stiffness, altered thinking, rapid heartbeat) 3, 4, 5

• Risk factors for movement disorders:

  • Female sex (3:1 female-to-male ratio)
  • Advanced age
  • Diabetes
  • Duration of treatment 4, 5, 6

Other Common Side Effects

• Sedation: Drowsiness, fatigue, sleepiness
• Cognitive: Confusion, anxiety, depression
• Gastrointestinal: Fluid retention
• Cardiovascular: QT prolongation (with long-term use) 1, 3

Contraindications and Precautions

• Absolute contraindications:

  • Pheochromocytoma (may worsen symptoms) 1
  • History of tardive dyskinesia
  • Seizure disorders

• Use with caution in:

  • Patients with Parkinson's disease (may worsen symptoms) 3
  • Pregnancy (safety not established) 3
  • Breastfeeding (passes into breast milk) 3
  • Diabetes (may require insulin dose adjustments) 1, 3
  • Breast cancer 3

Drug Interactions

• Increased risk of extrapyramidal symptoms when combined with:

  • Antipsychotics
  • MAO inhibitors
  • Other dopamine antagonists 1, 3

• Increased sedation when combined with:

  • Sedatives
  • Sleep medications
  • Narcotics 1, 3

• Avoid alcohol (increases sedative effects) 3

Monitoring Recommendations

• Assess for neurological side effects at each visit 1
• Monitor for signs of tardive dyskinesia
• Consider QTc monitoring with long-term use 1
• Patients should be instructed to report any abnormal movements immediately

Important Caveats and Pitfalls

• Black box warning: Risk of tardive dyskinesia, which can be irreversible
• The risk of tardive dyskinesia appears to be lower than previously estimated (approximately 0.1% per 1000 patient-years rather than 1-10%) 6
• Movement disorders may persist for months after discontinuation in some cases 7
• Symptoms of movement disorders are often not recognized as medication-related, leading to continued exposure and increased risk 5
• Metoclopramide should be discontinued immediately if neurological side effects occur

Special Considerations

• For diabetic gastroparesis, optimize glycemic control in addition to metoclopramide therapy 1
• Consider withdrawing medications that can worsen gastroparesis (opioids, anticholinergics, GLP-1 receptor agonists) 1
• Combination therapy with antiemetics may provide better symptom control for patients with predominant nausea/vomiting 1