METOCLOPRAMIDE HYDROCHLORIDE
Clinical safety rating: safe
CNS depressants may enhance sedative effects Can cause extrapyramidal symptoms and tardive dyskinesia.
Metoclopramide hydrochloride is a dopamine D2 receptor antagonist and, at higher doses, a serotonin 5-HT3 receptor antagonist. It also sensitizes muscarinic receptors in gastrointestinal smooth muscle and has central antiemetic effects by blocking dopamine receptors in the chemoreceptor trigger zone.
| Metabolism | Metoclopramide is primarily metabolized by CYP2D6 to N-desethylmetoclopramide, with minor contributions from CYP1A2 and CYP3A4. It undergoes conjugation with glucuronic acid and sulfation. |
| Excretion | Renal (approximately 85% as unchanged drug and metabolites); biliary/fecal (minor, <5%). |
| Half-life | Terminal elimination half-life: 5–6 hours in normal renal function; prolonged to 10–12 hours with mild-to-moderate renal impairment and up to 20–24 hours in severe renal failure (CrCl <10 mL/min). |
| Protein binding | Approximately 30% bound, primarily to albumin. |
| Volume of Distribution | 3.5 L/kg (range 2–5 L/kg); indicates extensive tissue distribution, including penetration into the central nervous system. |
| Bioavailability | Oral: 80% (due to first-pass metabolism, range 50–80%); Intramuscular: 74–100%; Rectal: 50–70% (mean 60%). |
| Onset of Action | Intravenous: 1–3 minutes; Intramuscular: 10–15 minutes; Oral: 30–60 minutes; Rectal: 30–60 minutes. |
| Duration of Action | Intravenous/Intramuscular: 1–2 hours (antiemetic effect); Oral: 1–3 hours (gastrointestinal motility effects may persist up to 6 hours). |
10 mg intravenously or intramuscularly every 6 to 8 hours as needed; maximum 30 mg or 0.5 mg/kg per day. Oral: 5 to 10 mg three times daily before meals.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 10-40 mL/min: reduce dose by 50%. CrCl <10 mL/min: reduce dose by 75%. |
| Liver impairment | Child-Pugh class B: reduce dose by 50%. Child-Pugh class C: reduce dose by 75% or avoid use. |
| Pediatric use | 0.1 to 0.2 mg/kg/dose intravenously, intramuscularly, or orally every 6 to 8 hours; maximum 0.5 mg/kg/day. |
| Geriatric use | Initiate at 5 mg per dose; avoid long-term use due to risk of tardive dyskinesia. |
| 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.
| FDA category | Human |
| Breastfeeding | Metoclopramide is excreted into human breast milk. The milk-to-plasma ratio (M/P) is approximately 1.9 to 4.6. Relative infant dose is estimated at 4-14% of maternal weight-adjusted dose. Limited data suggest no adverse effects in breastfed infants. However, because of the risk of extrapyramidal symptoms, use with caution in breastfeeding. |
| Teratogenic Risk |
■ FDA Black Box Warning
Tardive dyskinesia: Treatment with metoclopramide can cause tardive dyskinesia, a syndrome of potentially irreversible and disfiguring involuntary movements. The risk increases with duration of treatment and total cumulative dose, and is higher in the elderly, especially women. Therapy should not exceed 12 weeks in duration.
| Common Effects | nausea/vomiting |
| Serious Effects |
["Hypersensitivity to metoclopramide","History of tardive dyskinesia","Pheochromocytoma (risk of hypertensive crisis)","Gastrointestinal hemorrhage, obstruction, or perforation","Epilepsy (may increase seizure frequency)","Concurrent use of drugs that cause extrapyramidal reactions"]
| Precautions | ["Tardive dyskinesia risk","Neuroleptic malignant syndrome (NMS)","Depression and suicidal ideation","Parkinsonism-like symptoms","Acute dystonic reactions","Hypotension and hypertension","Fluid retention and edema in cirrhosis patients","Masks underlying GI obstruction or perforation"] |
Loading safety data…
| First trimester: No increased risk of major malformations based on large cohort studies. Second and third trimesters: No known fetal toxicity. Metoclopramide crosses the placenta with a cord-to-maternal plasma ratio of approximately 0.6. No evidence of teratogenicity in animal studies. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate regularly. Observe for extrapyramidal symptoms (e.g., dystonia, tardive dyskinesia) in the mother. In neonates, assess for potential extrapyramidal signs if used near term. |
| Fertility Effects | No specific human data on fertility effects. In animal studies, metoclopramide did not impair fertility. Hyperprolactinemia may occur due to dopamine D2 receptor antagonism, which could theoretically affect ovulation or menstrual regularity, but clinical significance is unknown. |