Usage
Metoclopramide is prescribed for the relief of symptoms associated with acute and recurrent diabetic gastroparesis (delayed gastric emptying), gastroesophageal reflux disease (GERD), nausea, and vomiting (including post-operative nausea and vomiting and chemotherapy-induced nausea and vomiting). It is also used to facilitate small bowel intubation and to aid in radiological examinations of the stomach and small intestine.
It is pharmacologically classified as a prokinetic agent and antiemetic.
Metoclopramide primarily acts as a dopamine D2 receptor antagonist in the chemoreceptor trigger zone (CTZ) in the brain, which reduces nausea and vomiting. It also enhances acetylcholine activity in the gut, increasing gastrointestinal motility and promoting gastric emptying.
Alternate Names
International and regional variations of the name include Metoclopramidum and Métoclopramide.
Brand names: Reglan, Maxolon, Maxeran.
How It Works
Pharmacodynamics: Metoclopramide exerts its prokinetic and antiemetic effects through dopamine D2 receptor antagonism and cholinergic agonism. It increases the resting tone of the lower esophageal sphincter (LES), improves antral and duodenal contractions, accelerates gastric emptying, and reduces small intestinal transit time. Its antiemetic action is primarily mediated by blocking dopamine D2 receptors in the CTZ.
Pharmacokinetics:
- Absorption: Metoclopramide is rapidly absorbed after oral administration, with peak plasma concentrations reached within 1-2 hours.
- Metabolism: It undergoes hepatic metabolism via conjugation and oxidation, primarily by CYP2D6.
- Elimination: Metoclopramide is primarily eliminated renally, with a half-life of approximately 4-6 hours.
Mode of Action: At the cellular level, metoclopramide blocks dopamine D2 receptors in the CTZ, which reduces the sensitivity of this area to emetogenic stimuli. In the gastrointestinal tract, it enhances acetylcholine activity by increasing its release and sensitivity, leading to increased motility.
Receptor Binding/Enzyme Inhibition: Metoclopramide is a dopamine D2 receptor antagonist. While it does not directly inhibit specific enzymes related to its therapeutic effects, its metabolism is influenced by CYP2D6.
Elimination Pathways: Metoclopramide is primarily excreted by the kidneys (approximately 85%), with the remaining amount excreted in bile.
Dosage
Standard Dosage
Adults:
- Diabetic Gastroparesis: 10 mg orally four times daily, 30 minutes before meals and at bedtime, for 2-8 weeks. Maximum dose: 40 mg/day.
- GERD: 10-15 mg orally four times daily, 30 minutes before meals and at bedtime, for 4-12 weeks. Maximum dose: 60 mg/day.
- Nausea and Vomiting: 10 mg orally/IM/IV up to three times daily. Maximum dose: 30 mg/day or 0.5 mg/kg/day. Maximum treatment duration: 5 days.
Children: Dosing is weight-based and should be determined by a doctor. Pediatric safety is a crucial consideration due to the increased risk of extrapyramidal side effects (EPS) in children.
Special Cases:
- Elderly Patients: Start with a lower dose (5 mg four times daily) and titrate based on response and tolerability. The maximum daily dose should be reduced, considering age-related decline in renal and hepatic function.
- Patients with Renal Impairment: Dosage adjustments are necessary based on creatinine clearance.
- Patients with Hepatic Dysfunction: Reduce the dose in moderate or severe hepatic impairment.
- Patients with Comorbid Conditions: Caution should be exercised in patients with diabetes, cardiovascular disease, and other conditions.
Clinical Use Cases:
- Intubation: 10 mg IV.
- Surgical Procedures: Dosage varies depending on the specific procedure.
- Mechanical Ventilation: Dosage is determined by the patient’s needs and clinical status.
- Intensive Care Unit (ICU) Use: Dosage is individualized based on patient response.
- Emergency Situations: Dosage depends on the specific emergency.
Side Effects
Rare but Serious Side Effects: Tardive dyskinesia, neuroleptic malignant syndrome (NMS), seizures, methemoglobinemia, supraventricular tachycardia, hypotension, QT prolongation.
Long-Term Effects: Tardive dyskinesia can be irreversible.
Contraindications
Absolute contraindications include: pheochromocytoma, gastrointestinal obstruction, perforation, hemorrhage, seizure disorder, history of tardive dyskinesia or dystonic reactions to metoclopramide, concomitant use with drugs that increase EPS risk, and infants <1 year of age. Relative contraindications include Parkinson’s disease, depression, and breastfeeding.
Drug Interactions
Metoclopramide interacts with numerous medications, including anticholinergics, dopamine agonists, MAO inhibitors, antipsychotics, CNS depressants (alcohol, benzodiazepines, opioids), digoxin, cyclosporine, levodopa, tetracycline. Interactions can also occur with OTC drugs, supplements, and food (alcohol, grapefruit juice).
Pregnancy and Breastfeeding
Pregnancy Safety Category: While generally considered safe during pregnancy, metoclopramide should be used cautiously and only when the benefits outweigh the risks.
Drug excretion in breast milk can occur, with potential for neonatal side effects such as drowsiness or gastrointestinal upset. The decision to continue or discontinue breastfeeding during metoclopramide therapy should be individualized.
Drug Profile Summary
- Mechanism of Action: Dopamine D2 receptor antagonist and cholinergic agonist.
- Side Effects: Drowsiness, fatigue, EPS, tardive dyskinesia, NMS.
- Contraindications: Pheochromocytoma, GI obstruction, perforation, seizure disorder.
- Drug Interactions: Anticholinergics, dopamine agonists, MAOIs, CNS depressants.
- Pregnancy & Breastfeeding: Generally safe in pregnancy; caution advised during breastfeeding.
- Dosage: Varies depending on indication and patient factors.
- Monitoring Parameters: Monitor for EPS, NMS, cardiac effects, and efficacy.
Popular Combinations: Metoclopramide is sometimes combined with analgesics for migraine treatment and with other antiemetics in chemotherapy regimens.
Precautions
Pre-screening is essential for allergies, metabolic disorders, organ dysfunction. Specific precautions exist for pregnant/breastfeeding women, children, elderly patients, and individuals with specific medical conditions. Lifestyle factors like alcohol and smoking may exacerbate side effects. Driving or operating machinery should be avoided if drowsiness occurs.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Metoclopramide?
A: Dosage varies depending on the indication, patient age, and other factors. Consult the dosage section above for specific recommendations.
Q2: What are the most serious side effects of Metoclopramide?
A: Tardive dyskinesia, neuroleptic malignant syndrome (NMS), and seizures are the most serious potential side effects.
Q3: Can Metoclopramide be used in pregnant women?
A: While generally considered safe during pregnancy, metoclopramide should be used cautiously and only when the benefits outweigh the risks.
Q4: Is it safe to breastfeed while taking Metoclopramide?
A: Metoclopramide can pass into breast milk. Most reports have not listed any side effects in nursing infants. The decision to breastfeed during treatment should be made in consultation with a physician, weighing the benefits of breastfeeding against potential risks to the infant.
Q5: What are the common drug interactions with Metoclopramide?
A: Metoclopramide interacts with many medications, including anticholinergics, dopamine agonists, MAO inhibitors, and CNS depressants. Consult the drug interactions section above for more information.
Q6: How does Metoclopramide work in the body?
A: Metoclopramide acts as a dopamine D2 receptor antagonist and a cholinergic agonist, influencing both the central nervous system and the gastrointestinal tract.
Q7: What should patients avoid while taking Metoclopramide?
A: Patients should avoid alcohol and other CNS depressants while taking metoclopramide, as these substances can exacerbate side effects like drowsiness. They should also avoid driving or operating machinery if drowsiness occurs.
Q8: What are the signs of Neuroleptic Malignant Syndrome (NMS)?
A: Signs of NMS include high fever, muscle rigidity, altered mental status, and autonomic instability (irregular heart rate, blood pressure fluctuations, sweating). NMS is a medical emergency requiring immediate treatment.
A: EPS, such as dystonia, akathisia, and parkinsonism, can occur with metoclopramide. If EPS develop, consider discontinuing metoclopramide and administering an anticholinergic medication like diphenhydramine or benztropine.
Q10: How long can a patient safely take Metoclopramide for GERD?
A: Treatment for GERD should not exceed 12 weeks. Prolonged use increases the risk of serious side effects, particularly tardive dyskinesia.
