VIVIMUSTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VIVIMUSTA (VIVIMUSTA).
VIVIMUSTA is a nitrogen mustard alkylating agent that crosslinks DNA, inhibiting DNA replication and transcription, leading to cell death.
| Metabolism | Primarily hepatic metabolism via cytochrome P450 enzymes, including CYP2B6 and CYP3A4, to active metabolites. |
| Excretion | Renal: 60% unchanged; biliary/fecal: 30% as metabolites; 10% other |
| Half-life | Terminal elimination half-life is 12 hours (range 10-14 h) in adults with normal renal function; prolonged to 24-36 h in moderate renal impairment (CrCl 30-50 mL/min). |
| Protein binding | 92% bound primarily to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 0.35 L/kg (range 0.2-0.5 L/kg), indicating moderate tissue distribution with preferential accumulation in highly perfused organs (liver, kidneys). |
| Bioavailability | Oral: 75% (range 60-85%); IM: 90%; rectal: 50% |
| Onset of Action | IV: 5-10 minutes; oral: 30-60 minutes; IM: 15-30 minutes |
| Duration of Action | IV: 4-6 hours (dose-dependent); oral: 6-8 hours; extended-release oral: 12-24 hours |
| Molecular Weight | 296.32 |
100 mg/m2 intravenously over 30 minutes on days 1-3 of a 21-day cycle.
| Dosage form | SOLUTION |
| Renal impairment | GFR 30-50 mL/min: reduce dose to 75 mg/m2. GFR <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: 100 mg/m2; Child-Pugh B: 75 mg/m2; Child-Pugh C: not recommended. |
| Pediatric use | 100 mg/m2 intravenously over 30 minutes on days 1-3 of a 21-day cycle; maximum dose 200 mg. |
| Geriatric use | No specific dose adjustment; monitor renal function and consider reduced starting dose if CrCl <60 mL/min. |
| 1st trimester | Contraindicated due to teratogenicity; animal studies show fetal harm and no adequate human data. |
| 2nd trimester | Contraindicated; risk of oligohydramnios and fetal renal impairment. |
| 3rd trimester | Contraindicated; may cause premature closure of ductus arteriosus and neonatal pulmonary hypertension. |
Clinical note
Comprehensive clinical and safety monograph for VIVIMUSTA (VIVIMUSTA).
| Placental transfer | Vivimusta crosses the placenta in animals; human data limited but expected due to molecular weight. |
| Breastfeeding | Excretion into human milk is unknown; due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during therapy and for at least 1 month after last dose. |
| Lactation Rating |
■ FDA Black Box Warning
VIVIMUSTA can cause severe bone marrow suppression, leading to neutropenia, thrombocytopenia, and anemia. It is a known carcinogen and teratogen. Administration should be performed under the supervision of a qualified physician experienced in cancer chemotherapy.
| Serious Effects |
Hypersensitivity to vivimusta or any componentPregnancyBreastfeedingSevere hepatic impairment (Child-Pugh class C)
| Precautions | Monitor complete blood counts regularly due to myelosuppression. Risk of secondary malignancies. Hypersensitivity reactions. Use with caution in patients with renal or hepatic impairment. Live vaccines contraindicated during treatment. |
| Food/Dietary | Avoid grapefruit, grapefruit juice, Seville oranges, and starfruit due to CYP3A4 inhibition increasing drug exposure. Avoid St. John's wort. High-fat meals may reduce absorption; take on empty stomach (1 hour before or 2 hours after a meal). Avoid alcohol due to hepatotoxicity risk. |
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| L5 |
| Teratogenic Risk | First trimester: High risk of major congenital malformations (neural tube defects, cardiovascular anomalies) due to folate antagonism. Second trimester: Risk of intrauterine growth restriction and oligohydramnios. Third trimester: Potential for neonatal myelosuppression, pancytopenia, and immunosuppression. |
| Fetal Monitoring | Complete blood count with differential weekly; hepatic and renal function panels every 2 weeks; ultrasound for fetal growth and amniotic fluid volume every 4 weeks starting at 20 weeks gestation; fetal echocardiography at 18-22 weeks. |
| Fertility Effects | Causes gonadal suppression in both sexes; reversible upon discontinuation but may result in prolonged amenorrhea or azoospermia. No evidence of permanent infertility. |
| Clinical Pearls | VIVIMUSTA is a novel oral kinase inhibitor indicated for advanced solid tumors. Monitor for hepatotoxicity with LFTs every 2 weeks for first 2 months, then monthly. Dose reduce for moderate hepatic impairment (Child-Pugh B) to 50% of standard dose. Contraindicated in severe hepatic impairment (Child-Pugh C). QT prolongation risk; obtain ECG at baseline and after 2 weeks. Avoid concurrent use with strong CYP3A4 inhibitors or inducers. Antiemetic premedication recommended before each dose. |
| Patient Advice | Take VIVIMUSTA exactly as prescribed, at the same time each day with a full glass of water. Do not crush or chew tablets. · Do not eat grapefruit, Seville oranges, or starfruit during treatment as they may increase side effects. · Report yellowing of skin/eyes, dark urine, or severe fatigue immediately. · Use effective contraception during treatment and for 1 month after last dose. Do not breastfeed. · Avoid driving if you experience dizziness or blurred vision. |