What are the contraindications and side effects of Metoclopramide (Reglan)?

Metoclopramide Contraindications and Side Effects

Absolute Contraindications

Metoclopramide is absolutely contraindicated in patients with pheochromocytoma, gastrointestinal hemorrhage, mechanical obstruction or perforation, seizure disorders, and known hypersensitivity to the drug. 1

The FDA label specifies these critical contraindications:

• Pheochromocytoma: The drug can trigger a potentially fatal hypertensive crisis by causing catecholamine release from the tumor, which may result in multi-organ injury including myocardial infarction, acute respiratory distress syndrome, and cardiogenic shock 1, 2
• GI hemorrhage, mechanical obstruction, or perforation: Stimulation of gastrointestinal motility in these conditions is dangerous and can worsen the underlying pathology 1, 3
• Seizure disorders: Metoclopramide can increase seizure frequency and severity 1, 4
• Concurrent use with drugs causing extrapyramidal reactions: This combination increases the frequency and severity of movement disorders 1

Serious Side Effects and Black Box Warnings

Tardive Dyskinesia (Most Critical)

The FDA requires a black box warning for tardive dyskinesia, a potentially irreversible movement disorder that can develop with metoclopramide use, particularly with treatment exceeding 12 weeks. 1

• The actual risk is approximately 0.1% per 1,000 patient-years, which is substantially lower than previously estimated 5
• In long-term follow-up studies, 71% of patients (15 of 21) still had persistent symptoms 6 months or more after discontinuing metoclopramide 6
• Treatment duration should never exceed 12 weeks to minimize this risk 1
• High-risk groups include elderly females, diabetics, patients with liver or kidney failure, and those on concurrent antipsychotic therapy 5, 7

Acute Dystonic Reactions

• Uncontrolled spasms of face, neck, body, arms, and legs typically occur within the first 2 days of treatment 1
• These reactions are more common in children and adults under age 30 1
• Symptoms include abnormal movements and body positions that require immediate medical attention 3

Neuropsychiatric Effects

• Depression, suicidal ideation, and completed suicide have been reported with metoclopramide use 1
• Patients should be monitored for depressive symptoms and thoughts of self-harm 1

Neuroleptic Malignant Syndrome (NMS)

• A rare but life-threatening condition requiring immediate hospitalization 1
• Cardinal symptoms: high fever, muscle rigidity, altered mental status, tachycardia, and diaphoresis 1

Parkinsonism

• Symptoms include tremor, bradykinesia, rigidity, and balance difficulties 1
• Patients with pre-existing Parkinson's disease will experience worsening of symptoms and should generally avoid metoclopramide 7, 1
• If absolutely necessary in PD patients, limit duration to under 12 weeks with close neurological monitoring 7

Common Side Effects

The most frequently reported adverse effects include 3, 1:

• Restlessness and drowsiness (most common) 3, 8
• Fatigue and exhaustion 1, 8
• Dizziness 3, 1
• Headache 1
• Confusion 1
• Insomnia 1
• Diarrhea and GI upset 3
• Muscle weakness 3

Special Precautions and Monitoring

High-Risk Populations Requiring Dose Adjustment or Avoidance

• Renal impairment: Requires dose reduction due to altered drug clearance 1
• Hepatic impairment or heart failure: May cause fluid retention 1
• Diabetes mellitus: Insulin dosing may require adjustment due to changes in gastric emptying 1
• Pregnancy: Unknown fetal risk; use only if clearly needed 1
• Breastfeeding: Metoclopramide passes into breast milk and may harm the infant 1

Drug Interactions

Avoid or use with extreme caution when combined with 1:

• MAO inhibitors (contraindicated) 3, 1
• Tricyclic antidepressants 9
• Other dopamine antagonists or antipsychotics (increases extrapyramidal symptom risk) 5
• CNS depressants, sedatives, narcotics (additive sedation) 1
• Alcohol (enhances sedative effects) 1

Monitoring Requirements

Regular neurological monitoring for extrapyramidal symptoms is essential, especially with prolonged use 4:

• Assess for involuntary movements at each visit
• Monitor for signs of depression or mood changes 1
• Evaluate for parkinsonism symptoms 1

Safer Alternatives

When metoclopramide is contraindicated or high-risk, consider 4, 7:

• Domperidone: Does not cross the blood-brain barrier, minimal extrapyramidal effects (preferred for PD patients) 7
• Erythromycin or azithromycin: Motilin agonists for gastroparesis 4, 7
• Prucalopride: 5-HT4 receptor agonist without cardiac or QT interval risks 4, 7

Critical Clinical Pitfalls

• Never use for more than 12 weeks regardless of indication 1
• Avoid rapid IV administration to prevent acute anxiety, restlessness, and subsequent sedation 1
• Screen for pheochromocytoma in patients with unexplained hypertension before administration 1, 2
• Do not operate machinery or drive until individual response is known due to sedation risk 1