METOCLOPRAMIDE

Clinical safety rating: safe

Human studies have proved safety

How it works

Metoclopramide is a dopamine D2 receptor antagonist and a 5-HT4 receptor agonist. It increases lower esophageal sphincter pressure and promotes gastric motility by enhancing acetylcholine release from myenteric neurons.

What the body does with it

Metabolism	Metoclopramide undergoes hepatic metabolism via CYP2D6, CYP1A2, and CYP3A4. Major metabolite is metoclopramide N-oxide. Approximately 20% of the drug is excreted unchanged in urine.
Excretion	Renal: ~85% (free and conjugated metabolites); fecal/biliary: ~10%; unchanged drug: ~20-30%.
Half-life	Terminal elimination half-life: 4-6 hours (normal renal function); prolonged to 12-24 hours in severe renal impairment (CrCl <10 mL/min).
Protein binding	~30% bound to plasma proteins (primarily albumin).
Volume of Distribution	2-4 L/kg; suggests extensive tissue distribution, including crossing the blood-brain barrier and placenta.
Bioavailability	Oral: 80-100% (first-pass metabolism minimal); IM: 74-96%; rectal: 50-100% (variable due to absorption).
Onset of Action	IV: 1-3 minutes; IM: 10-15 minutes; Oral: 30-60 minutes.
Duration of Action	IV/IM: 1-2 hours (gastrointestinal effects); oral: 1-2 hours. Anti-emetic effects may persist up to 6 hours.

Classification & Brands

Dosing & administration

5–10 mg orally, intramuscularly, or intravenously every 6–8 hours as needed; maximum 30 mg/day or 0.5 mg/kg/day.

Dosage form	INJECTABLE
Renal impairment	CrCl 40–59 mL/min: 50% of normal dose; CrCl 10–39 mL/min: 50% of normal dose; CrCl <10 mL/min: 25–50% of normal dose.
Liver impairment	Child-Pugh Class A: no adjustment; Class B: reduce dose by 50%; Class C: use with caution, reduce dose by at least 50% and consider avoiding use.
Pediatric use	0.1–0.2 mg/kg/dose orally, intramuscularly, or intravenously every 6–8 hours; maximum 0.5 mg/kg/day.
Geriatric use	Initiate at 5 mg orally, intramuscularly, or intravenously every 8 hours; maximum 20 mg/day due to increased risk of tardive dyskinesia and dystonic reactions.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

CNS depressants may enhance sedative effects Can cause extrapyramidal symptoms and tardive dyskinesia.

Breastfeeding	Metoclopramide is excreted into breast milk with an M/P ratio of approximately 1.0. Relative infant dose is estimated to be 0.7-4.7% of maternal weight-adjusted dose. It is compatible with breastfeeding, but monitor infant for extrapyramidal effects and drowsiness. Avoid in mothers with galactosemia or if infant is jaundiced.
Teratogenic Risk	Metoclopramide is considered low risk in pregnancy. Large cohort studies show no significant increase in major malformations, miscarriage, or stillbirth. However, due to limited data in first trimester, use only if clearly needed. Avoid in third trimester due to potential for extrapyramidal symptoms in neonate.

Warnings & precautions

■ FDA Black Box Warning

Tardive dyskinesia (TD) may develop with long-term or high-dose use, especially in elderly patients, particularly women. The risk increases with duration of treatment and total cumulative dose. Therapy should not exceed 12 weeks.

Side Effect Profile

Common Effects	nausea/vomiting
Serious Effects

Absolute Contraindications

History of tardive dyskinesia; Parkinson's disease; pheochromocytoma; gastrointestinal hemorrhage, obstruction, or perforation; known hypersensitivity; concurrent use of drugs causing EPS; epilepsy (may increase seizure frequency).

Clinical Precautions

Precautions

Risk of tardive dyskinesia, especially with prolonged use; extrapyramidal symptoms (EPS), particularly in children and young adults; neuroleptic malignant syndrome (rare); QT prolongation; hypotension; increased risk of depression and suicide; use with caution in renal impairment (dose adjustment required) and hepatic impairment.

Clinical Tips & Counseling

Drug interactions

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