What is the appropriate dosing regimen for metoclopramide (Reglan) in adults and children, including adjustments for renal or hepatic impairment and maximum duration of therapy?

Metoclopramide (Reglan) Dosing Regimen

For adults, metoclopramide should be dosed at 10 mg orally or IV, administered 20–30 minutes before meals and at bedtime (four times daily), with a maximum daily dose of 40 mg and treatment duration limited to 5 days to minimize the risk of serious neurological complications. 1, 2

Standard Adult Dosing by Indication

Gastroparesis and Gastrointestinal Motility Disorders

• 10 mg orally or IV administered 20–30 minutes before each meal and at bedtime (four times daily, total 40 mg/day) 1, 3
• For severe symptoms, initiate therapy with 10 mg IM or IV given slowly over 1–2 minutes; transition to oral therapy once symptoms improve 3
• Maximum daily dose: 40 mg across all indications 1

Nausea and Vomiting (Non-Chemotherapy)

• 10 mg orally or IV three to four times daily 2
• For postoperative nausea/vomiting: 10 mg IM near the end of surgery; doses of 20 mg may be used 3

Chemotherapy-Induced Nausea and Vomiting

• For highly emetogenic regimens (cisplatin, dacarbazine): 2 mg/kg IV infused over at least 15 minutes, given 30 minutes before chemotherapy, repeated every 2 hours for two doses, then every 3 hours for three doses 3
• For less emetogenic regimens: 1 mg/kg per dose may be adequate 3
• Doses exceeding 10 mg should be diluted in 50 mL of parenteral solution 3

Migraine-Associated Nausea

• 10 mg IV or orally given 20–30 minutes before or with analgesics 4

Pediatric Dosing

Small Bowel Intubation and Radiological Examinations

• Age >14 years: 10 mg IV over 1–2 minutes 3
• Age 6–14 years: 2.5–5 mg IV over 1–2 minutes 3
• Age <6 years: 0.1 mg/kg IV over 1–2 minutes 3

Chemotherapy-Induced Nausea and Vomiting in Children

• Doses ≥2 mg/kg are associated with increased extrapyramidal reactions (15%) and akathisia (33%) 5
• Recommended starting dose: 0.25 mg/kg IV to balance efficacy and safety 6
• Concomitant diphenhydramine should be administered to reduce extrapyramidal symptoms 5

Renal Impairment Adjustments

Critical adjustment required: Metoclopramide is excreted principally through the kidneys, and failure to adjust doses in renal impairment significantly increases toxicity risk. 1, 3

• Creatinine clearance <40 mL/min: Initiate therapy at approximately 50% of the recommended dosage 3, 2
• Moderate renal impairment: Consider 10 mg twice or three times daily instead of four times daily 1
• Severe renal impairment: Reduce maintenance doses by 50–75% to avoid drug accumulation 1
• Dosage may be increased or decreased based on clinical efficacy and safety 3

Hepatic Impairment Considerations

• Metoclopramide undergoes minimal hepatic metabolism (simple conjugation only) 3
• Safe use has been described in patients with advanced liver disease when renal function is normal 3
• Use with caution in severe hepatic impairment; consider dose reduction and monitoring 2

Maximum Duration of Therapy

Treatment should be limited to short-term use (up to 5 days) to minimize the risk of tardive dyskinesia and other serious neurological complications. 2

• European regulatory agencies restrict use to ≤5 days and maximum 30 mg/day to reduce extrapyramidal disorder risk 2
• Oral preparations are recommended for 4–12 weeks maximum in specific circumstances 7
• Parenteral metoclopramide should be limited to 1–2 days 7
• Long-term therapy (beyond days-to-weeks) raises the risk of tardive dyskinesia and movement disorders 1

Contraindications and Safety Considerations

Absolute Contraindications

• Pheochromocytoma 4, 1
• Seizure disorders 4, 1
• Gastrointestinal bleeding 4, 1
• Gastrointestinal obstruction 4, 1

Common Adverse Effects

• Restlessness, drowsiness, fatigue are the most common reactions 4, 7
• Diarrhea (6%) and sedation (6%) in multiple-dose studies 6
• Extrapyramidal symptoms occur in approximately 9% of pediatric patients 6
• Dystonic reactions: Treat with 50 mg diphenhydramine IM; symptoms usually subside 3

Serious Adverse Effects (Rare)

• Tardive dyskinesia, neuroleptic malignant syndrome, dysrhythmia, and respiratory distress/arrest are rarely associated with metoclopramide use 6
• Higher total daily doses increase the likelihood of dose-dependent extrapyramidal reactions 1

Special Population Considerations

Elderly Patients

• Elderly individuals often have unrecognized renal impairment (GFR decreases by approximately 8 mL/min per decade after age 40) 1
• Failure to adjust doses accordingly can increase toxicity 1
• Dose reduction required based on renal function assessment 1

Pregnancy

• Metoclopramide is recommended as second-line therapy for hyperemesis gravidarum 2
• No increased risk of congenital defects reported 2
• Extrapyramidal effects may occur; withdraw if symptoms develop 2

Monitoring Recommendations

• Regular re-evaluation of continued need for metoclopramide, particularly when neurological adverse effects emerge 1
• Monitor for extrapyramidal symptoms, especially in children and young adults who have increased susceptibility 5
• Electrolyte monitoring when used with other medications affecting fluid balance 3

Administration Considerations

Intravenous Administration

• Doses of 10 mg should be administered slowly over 1–2 minutes 3
• For chemotherapy-induced nausea, infusions should be given over at least 15 minutes 3
• Inspect parenteral solutions for particulate matter and discoloration before administration 3

Drug Compatibility

• Compatible for 48 hours: Cimetidine, mannitol, potassium acetate, potassium phosphate 3
• Incompatible (do not mix): Cephalothin sodium, chloramphenicol sodium, sodium bicarbonate 3