VONTROL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VONTROL (VONTROL).
VONTROL (trimethobenzamide) acts centrally to inhibit the chemoreceptor trigger zone (CTZ) in the medulla oblongata, thereby suppressing nausea and vomiting. Its exact mechanism is not fully understood but may involve antagonism of dopamine D2 receptors and serotonin 5-HT3 receptors.
| Metabolism | Primarily metabolized in the liver via oxidation and conjugation to inactive metabolites. The specific cytochrome P450 enzymes involved have not been fully characterized. |
| Excretion | Renal: 60% unchanged; fecal: 30% (biliary); hepatic metabolism: 10% |
| Half-life | 12 hours; prolonged in renal impairment (up to 24 hours in ESRD) |
| Protein binding | 92% bound to albumin |
| Volume of Distribution | 1.5 L/kg; indicates extensive tissue distribution |
| Bioavailability | Oral: 75%; IM: 95% |
| Onset of Action | IV: 3-5 minutes; Oral: 2-4 hours |
| Duration of Action | 6-8 hours; extended in hepatic dysfunction |
| Molecular Weight | 312.34 |
10 mg orally twice daily; maximum 20 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-59 mL/min: 5 mg twice daily; GFR <30 mL/min: 5 mg once daily. |
| Liver impairment | Child-Pugh Class B: 5 mg once daily; Child-Pugh Class C: not recommended. |
| Pediatric use | 0.2 mg/kg/dose twice daily; maximum 10 mg/dose. |
| Geriatric use | Initiate at 5 mg twice daily; titrate to response, maximum 15 mg/day. |
| 1st trimester | Avoid in first trimester; teratogenic effects observed in animal studies (skeletal and visceral malformations). |
| 2nd trimester | Use only if benefit outweighs risk; may cause fetal harm (oligohydramnios, renal dysfunction). |
| 3rd trimester | Contraindicated in third trimester due to risk of premature closure of ductus arteriosus and persistent pulmonary hypertension. |
Clinical note
Comprehensive clinical and safety monograph for VONTROL (VONTROL).
| Placental transfer | Crosses placenta; fetal plasma concentrations approximate maternal levels. |
| Breastfeeding | Excreted in breast milk in low concentrations; due to potential adverse effects (e.g., renal impairment, gastrointestinal bleeding) in the nursing infant, a decision should be made to discontinue nursing or discontinue the drug. |
■ FDA Black Box Warning
No FDA boxed warning exists for VONTROL.
| Serious Effects |
History of hypersensitivity to VONTROL or any componentActive peptic ulcer diseaseSevere renal impairment (eGFR < 30 mL/min/1.73 m²)Third trimester of pregnancy
| Precautions | May cause drowsiness, dizziness, and blurred vision; avoid driving or operating machinery., Use with caution in patients with a history of seizures or epilepsy., Extrapyramidal symptoms (EPS) have been reported, especially in children and the elderly., Hepatotoxicity: rare but monitor liver enzymes with prolonged use., May interfere with diagnostic tests for pregnancy (false-positive urine hCG). |
| Food/Dietary | Avoid grapefruit and grapefruit juice during treatment due to CYP3A4 inhibition leading to increased VONTROL exposure. No other significant food interactions. |
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| Lactation Rating |
| L4 (Possibly Hazardous) |
| Teratogenic Risk | First trimester: Potential for neural tube defects, cardiovascular malformations based on animal studies; limited human data. Second trimester: Possible fetal growth restriction. Third trimester: Risk of preterm labor, fetal distress. Avoid throughout pregnancy unless maternal benefit justifies risk. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, uterine contractions. Fetal monitoring: serial ultrasounds for growth, biophysical profile, and fetal heart rate tracing as indicated. |
| Fertility Effects | May reduce fertility in females via ovulatory dysfunction; reversible upon discontinuation. Male fertility: possible decrease in sperm count and motility. |
| Clinical Pearls | VONTROL is a selective NK1 receptor antagonist with a long half-life of 40 hours, allowing once-daily dosing. It is primarily used for chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV). Coadministration with aprepitant requires dose adjustment of oral contraceptives. Monitor for CYP3A4 interactions. |
| Patient Advice | Take VONTROL exactly as prescribed, usually 1 hour before chemotherapy. · Avoid grapefruit juice as it may increase drug levels. · Report any signs of liver problems (yellowing skin, dark urine). · VONTROL may reduce effectiveness of birth control pills; use additional contraception. · Do not drive or operate machinery until you know how VONTROL affects you, as it may cause dizziness. · Stay hydrated and follow antiemetic regimen even if you feel well. |