LENVIMA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LENVIMA (LENVIMA).
Lenvatinib is a multikinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR1, VEGFR2, VEGFR3), fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3, FGFR4), platelet-derived growth factor receptor alpha (PDGFRα), KIT, and RET. It inhibits angiogenesis, tumor growth, and progression by blocking these receptor tyrosine kinases.
| Metabolism | Lenvatinib is primarily metabolized by CYP3A4 and aldehyde oxidase (AO). The major metabolite is desmethyl-lenvatinib (M2), which is formed by CYP3A4. Minor metabolites include lenvatinib N-oxide (M1) and other oxidative products. |
| Excretion | Approximately 71% of the dose is excreted in feces (34% as unchanged drug) and 25% in urine (0.4% as unchanged). |
| Half-life | Terminal elimination half-life is approximately 28 hours, supporting once-daily dosing. |
| Protein binding | 99.3% bound to human plasma proteins (primarily albumin, with minor binding to alpha-1-acid glycoprotein). |
| Volume of Distribution | Apparent volume of distribution is approximately 1.1 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 72% relative to an intravenous reference dose. |
| Onset of Action | Time to peak plasma concentration (Tmax) is 1–4 hours post oral dose; clinical effect onset may be observed within 2 weeks. |
| Duration of Action | Sustained inhibition of tyrosine kinase receptors for 24 hours with daily dosing; duration of clinical effect varies with tumor type. |
| Action Class | Tyrosine kinase inhibitors |
| Brand Substitutes | Lenvat 4 Capsule, Lenvamed 4mg Capsule, Lentykine 4 Capsule, Lenced 4mg Capsule, Lenvatol 4mg Capsule, Lenvamed 10mg Capsule, Bdfoie 10mg Capsule, Lenced 10mg Capsule, Lentykine 10 Capsule, Lenvatol 10mg Capsule |
24 mg orally once daily for differentiated thyroid carcinoma; 18 mg orally once daily plus everolimus 5 mg orally once daily for renal cell carcinoma; 12 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks for endometrial carcinoma; 8 mg orally once daily (or 10 mg for patients with body weight ≥60 kg) plus pembrolizumab 200 mg intravenously every 3 weeks for hepatocellular carcinoma.
| Dosage form | CAPSULE |
| Renal impairment | CrCl ≥30 mL/min: no adjustment. CrCl <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 5 mg if starting dose is 24 mg, by 2 mg if starting dose is 18 mg, by 2 mg if starting dose is 14 mg, by 1 mg if starting dose is 10 mg. Child-Pugh C: not recommended. |
| Pediatric use | Not approved for pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment based on age alone; monitor renal function and consider age-related decline in CrCl. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LENVIMA (LENVIMA).
| Breastfeeding | No data on human breast milk; animal studies show excretion into milk. M/P ratio unknown. Discontinue breastfeeding during therapy and for at least 1 month after last dose due to potential for serious adverse reactions in breastfed infants. |
| Teratogenic Risk | Lenvatinib is teratogenic and embryotoxic in animal studies. It is contraindicated in pregnancy. Risk in first trimester: high risk of congenital malformations including skeletal and cardiovascular anomalies. Second and third trimester: risk of fetal growth retardation, oligohydramnios, and fetal demise due to antiangiogenic effects. |
■ FDA Black Box Warning
None
| Serious Effects |
["None known"]
| Precautions | ["Hypertension (monitor blood pressure and manage with antihypertensives)","Cardiac dysfunction (risk of decreased left ventricular ejection fraction)","Arterial thromboembolic events","Hepatotoxicity (elevated liver enzymes, risk of hepatic encephalopathy in HCC)","Renal toxicity (proteinuria, renal impairment)","Diarrhea (may cause severe dehydration)","Hypothyroidism (monitor thyroid function)","Wound healing complications (consider interruption before surgery)","Posterior reversible encephalopathy syndrome (PRES)"] |
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| Fetal Monitoring | Pregnancy test before initiation. Monitor for hypertension, proteinuria, thyroid function, hemorrhage, GI perforation, and fistula formation. Fetal monitoring via ultrasound for growth and amniotic fluid volume if unintentional exposure occurs. |
| Fertility Effects | Lenvatinib may impair fertility in females based on animal studies showing ovarian follicular atresia. In males, testicular degeneration and hypospermia observed. Human reproductive effects unknown but potential for reduced fertility. |