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. |
| Molecular Weight | 426.85 |
| 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 | Based on its mechanism as a tyrosine kinase inhibitor (TKI) and animal studies showing teratogenicity (skeletal abnormalities, visceral defects) at subtherapeutic doses, lenvatinib is contraindicated in first trimester due to high risk of embryofetal toxicity. |
| 2nd trimester | Continued exposure may cause fetal harm, including growth retardation and developmental anomalies; animal data also indicate risk of late pregnancy complications such as oligohydramnios and fetal renal impairment. |
| 3rd trimester | Significant risk of fetal toxicity, including potential for fetal renal dysfunction and oligohydramnios due to VEGFR inhibition; elective delivery or alternative therapy is strongly recommended if possible. |
Clinical note
Comprehensive clinical and safety monograph for LENVIMA (LENVIMA).
| Placental transfer | Lenvatinib is a small molecule with molecular weight below 500 Da, and extensive animal data confirm placental transfer (fetal plasma concentrations up to 30% of maternal). In humans, based on its physicochemical properties and the known ability of TKIs to cross the placenta, transfer is expected. The FDA labeling notes in animal studies lenvatinib crosses the placenta and is detected in fetal tissues. |
■ FDA Black Box Warning
None
| Serious Effects |
Pregnancy (based on animal data showing teratogenicity and embryofetal toxicity, and the mechanism of action)Breastfeeding (due to potential for serious adverse reactions in nursing infants)
| 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) |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase LENVIMA concentrations. No other specific food interactions known. |
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| Breastfeeding | It is unknown if lenvatinib is excreted in human milk. Due to its long half-life (approx. 28 hours), high protein binding (>99%), and potential for serious adverse reactions in breastfed infants (e.g., hypertension, diarrhea, hepatotoxicity), the manufacturer recommends discontinuing breast-feeding during treatment and for at least 1 month after the last dose. |
| Lactation Rating | L5 (Contraindicated) |
| 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. |
| 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. |
| Clinical Pearls | Monitor blood pressure monthly; if uncontrolled, withhold LENVIMA. For proteinuria, check urine dipstick at baseline and periodically; if ≥2+, hold dose until resolves. Manage diarrhea aggressively with loperamide and hydration; dose interruption may be needed. Avoid concomitant strong CYP3A4 inducers or inhibitors; adjust dose per PI. In patients with thyroid cancer, monitor TSH monthly and adjust thyroid hormone as LENVIMA can cause hypothyroidism. |
| Patient Advice | Take LENVIMA at the same time each day with or without food. · Do not open or crush capsules; swallow whole with water. · Notify your doctor immediately if you experience severe diarrhea, nausea, vomiting, or decreased appetite. · Measure your blood pressure regularly and report high readings. · Report any signs of infection, including fever, chills, or sore throat. · Women of childbearing age should use effective contraception during treatment and for at least 30 days after the last dose. · Avoid breastfeeding during treatment and for at least 1 week after the last dose. |