METOCLOPRAMIDE INTENSOL
Clinical safety rating: safe
CNS depressants may enhance sedative effects Can cause extrapyramidal symptoms and tardive dyskinesia.
Metoclopramide is a dopamine D2 receptor antagonist and, at higher doses, a serotonin 5-HT3 receptor antagonist. It also enhances the response to acetylcholine in the gastrointestinal tract by sensitizing muscarinic receptors, leading to increased gastric motility and accelerated gastric emptying. It has central antiemetic effects due to dopamine receptor blockade in the chemoreceptor trigger zone.
| Metabolism | Metabolized primarily in the liver via CYP2D6 to monodeethylated and hydroxylated metabolites; also undergoes glucuronidation and sulfation. |
| Excretion | Renal (approximately 85% as unchanged drug and metabolites); biliary/fecal (approximately 5-10% unchanged and metabolites); small amount metabolized via hepatic CYP2D6 and sulfation; total clearance ~0.6 L/kg/h. |
| Half-life | Terminal elimination half-life: 5–6 hours (normal renal function); prolonged to >15 hours in renal impairment (e.g., CrCl <40 mL/min); clinical context: dosing interval adjustment recommended in severe renal impairment. |
| Protein binding | 30% (primarily albumin). |
| Volume of Distribution | Vd: ~3–4 L/kg (rapid distribution to tissues including CNS; crosses blood-brain barrier). |
| Bioavailability | Oral (Intensol): 80–100% (subject to first-pass metabolism). |
| Onset of Action | Oral (Intensol): 30–60 minutes; IV: 1–3 minutes; IM: 10–15 minutes. |
| Duration of Action | Oral/IM: 1–2 hours (antiemetic effect); IV: 1–2 hours; clinical note: may persist longer with repeated dosing; prokinetic effects on GI motility last ~1 hour. |
10-15 mg orally 4 times daily, 30 minutes before meals and at bedtime.
| Dosage form | CONCENTRATE |
| Renal impairment | CrCl 40-60 mL/min: 50% dose reduction; CrCl 10-40 mL/min: 75% dose reduction; CrCl <10 mL/min: 90% dose reduction. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: 50% dose reduction; Child-Pugh Class C: avoid use. |
| Pediatric use | 0.1 mg/kg/dose orally 4 times daily, up to 0.5 mg/kg/day; maximum single dose 10 mg. |
| Geriatric use | Initial dose 5 mg orally 4 times daily; maximum 30 mg per day; monitor for tardive dyskinesia and extrapyramidal symptoms. |
| 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 breast milk; the milk-to-plasma ratio is approximately 1.0. It may stimulate prolactin release and subsequently increase milk production. Low levels in milk are considered compatible with breastfeeding, but monitor infant for extrapyramidal signs. |
| Teratogenic Risk | Metoclopramide is not associated with an increased risk of major congenital malformations. However, second and third trimester exposure may lead to extrapyramidal symptoms in the neonate. There is limited data on first trimester exposure, but no significant teratogenic signal. |
■ FDA Black Box Warning
Tardive dyskinesia: Risk increases with duration of treatment and total cumulative dose. Avoid use for longer than 12 weeks except in rare cases where therapeutic benefit outweighs risk. Discontinue if signs or symptoms of tardive dyskinesia appear.
| Common Effects | nausea/vomiting |
| Serious Effects |
["History of tardive dyskinesia","Parkinson's disease","Known hypersensitivity to metoclopramide or any component","Concurrent use of monoamine oxidase inhibitors (MAOIs)","Pheochromocytoma","History of seizure disorder","Gastrointestinal obstruction, perforation, or hemorrhage"]
| Precautions | ["Tardive dyskinesia and other extrapyramidal symptoms (EPS), including acute dystonic reactions, akathisia, and parkinsonism","Neuroleptic malignant syndrome (NMS)","Central nervous system depression and impaired mental alertness; avoid concurrent alcohol use","Risk of methemoglobinemia in neonates and infants","Hypertensive crisis in patients with pheochromocytoma","Breast cancer risk due to prolactin elevation","Rebound and withdrawal symptoms upon abrupt discontinuation"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and signs of extrapyramidal symptoms. In the neonate, observe for extrapyramidal reactions, particularly if used near term. |
| Fertility Effects | Metoclopramide can cause hyperprolactinemia, which may lead to galactorrhea, menstrual irregularities, and reversible infertility. Effects are dose-dependent and resolve upon discontinuation. |