METOCLOPRAMIDE HCL
Clinical safety rating: safe
CNS depressants may enhance sedative effects Can cause extrapyramidal symptoms and tardive dyskinesia.
Metoclopramide is a dopamine D2 receptor antagonist; also exhibits 5-HT4 receptor agonist activity and 5-HT3 receptor antagonist activity at high doses. It enhances gastric motility and accelerates gastric emptying by increasing acetylcholine release from postganglionic cholinergic neurons in the GI tract, and blocks dopamine-mediated emesis in the chemoreceptor trigger zone.
| Metabolism | Metoclopramide is metabolized primarily via the liver by CYP2D6 and to a lesser extent by CYP3A4 and CYP1A2. It undergoes sulfation and glucuronidation. The major metabolites are monodeethylated and hydroxy derivatives, which are excreted in urine. |
| Excretion | Approximately 85% of the dose is excreted in urine as unchanged drug and conjugates; 10% in feces. |
| Half-life | Terminal elimination half-life is 5-6 hours in normal renal function; prolonged to 12-24 hours in severe renal impairment (CrCl <10 mL/min). |
| Protein binding | Approximately 30-40%, primarily to albumin. |
| Volume of Distribution | Vd is 2-4 L/kg, indicating extensive tissue distribution and penetration into CNS. |
| Bioavailability | Oral bioavailability is 80-100%; rectal bioavailability is 50-80%. |
| Onset of Action | Oral: 30-60 minutes; Intramuscular: 10-15 minutes; Intravenous: 1-3 minutes. |
| Duration of Action | Effects persist for 1-2 hours after IV administration, up to 4-6 hours after oral administration; antiemetic effect may last longer due to central receptor binding. |
| Action Class | Dopamine (D2) receptor antagonist-Prokinetic agent |
| Brand Substitutes | Metaclopramide Injection, Perilin Injection |
10 mg orally, intramuscularly, or intravenously every 6 hours as needed. Maximum 30 mg or 0.5 mg/kg per day.
| Dosage form | Injectable |
| Renal impairment | Creatinine clearance 10-40 mL/min: reduce dose by 50%. Creatinine clearance <10 mL/min: reduce dose by 75%. |
| Liver impairment | Child-Pugh class B: reduce dose by 50%. Child-Pugh class C: use with caution; consider 25-50% of normal dose. |
| Pediatric use | 0.1-0.2 mg/kg per dose orally, intramuscularly, or intravenously every 6-8 hours as needed. Maximum 0.5 mg/kg per day. |
| Geriatric use | Initiate at 5 mg per dose; avoid prolonged use due to increased 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 | Small amounts excreted into breast milk; estimated relative infant dose <5% of maternal weight-adjusted dose. M/P ratio approximately 1.2. Considered compatible with breastfeeding; monitor infant for extrapyramidal effects if high maternal doses. |
| Teratogenic Risk | No increased risk of major congenital malformations based on large cohort studies. Data limited for first trimester; animal studies show no teratogenicity at clinically relevant doses. Metoclopramide can be used for nausea and vomiting in pregnancy but avoid in third trimester due to potential neonatal extrapyramidal symptoms. |
■ FDA Black Box Warning
WARNING: TARDIVE DYSKINESIA: Treatment with metoclopramide can cause tardive dyskinesia, a syndrome of involuntary, repetitive movements, which is often irreversible. The risk increases with duration of treatment and total cumulative dose. Metoclopramide therapy should be discontinued in patients who develop signs or symptoms of tardive dyskinesia. The risk of developing tardive dyskinesia is increased in the elderly, especially elderly women. Treatment with metoclopramide for longer than 12 weeks should be avoided in all but rare cases where therapeutic benefit is thought to outweigh the risks.
| Serious Effects |
["Hypersensitivity to metoclopramide or any component","Pheochromocytoma (risk of hypertensive crisis)","GI obstruction, perforation, or hemorrhage (stimulation of motility could worsen condition)","History of tardive dyskinesia from metoclopramide","Epilepsy (may increase seizure frequency)","Concurrent use of drugs that can cause extrapyramidal reactions (e.g., antipsychotics)","Breast cancer (due to prolactin elevation)","Parkinson's disease (may exacerbate symptoms)","Neonates and infants (use contraindicated due to risk of methemoglobinemia)"]
| Precautions | ["Tardive dyskinesia (see black box warning)","Neuroleptic malignant syndrome (rare but potentially fatal)","Extrapyramidal symptoms (dystonia, akathisia, parkinsonism), especially in children and young adults","Depression and increased risk of suicide in patients with prior history","Parkinson's disease: may exacerbate symptoms","Pheochromocytoma: may cause hypertensive crisis","Prolactin elevation leading to galactorrhea, menstrual irregularities, gynecomastia","May mask underlying toxins (e.g., in GI obstruction)","Hepatic impairment: may require dose reduction","Renal impairment: dose adjustment needed","Elderly: increased risk of tardive dyskinesia and parkinsonism"] |
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| Fetal Monitoring | Monitor maternal blood pressure due to potential for hypertensive crisis with rapid IV administration. No specific fetal monitoring required; observe neonate for extrapyramidal symptoms if used near term. |
| Fertility Effects | No known adverse effects on fertility. May increase prolactin levels which could transiently affect ovulation; clinical significance unlikely. |