1. Clinical Overview
Lenvatinib is an oral, small-molecule, multi-targeted tyrosine kinase inhibitor (TKI) that selectively inhibits the kinase activities of vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), platelet-derived growth factor receptor alpha (PDGFRα), RET, and KIT. It is a cornerstone therapy for advanced thyroid cancer and hepatocellular carcinoma (HCC) in the Indian context, often used after failure of sorafenib in HCC.
| Onset | Duration | Bioavailability |
|---|---|---|
| Pharmacodynamic effects (e.g., blood pressure elevation) may be observed within days. Antitumor effects are typically assessed after 8-12 weeks of therapy. | The pharmacodynamic effects are sustained with continuous daily dosing. The terminal half-life supports once-daily administration. | Approximately 85% (range: 82-90%) following oral administration. |
2. Mechanism of Action
Lenvatinib is a multi-kinase inhibitor that potently blocks the intracellular kinase domains of multiple pro-angiogenic and oncogenic pathway receptors. Its primary antitumor activity is attributed to inhibition of VEGFR1-3 and FGFR1-4, leading to reduced tumor angiogenesis. Additional inhibition of PDGFRα, RET, and KIT contributes to direct antitumor effects and stromal modulation.
3. Indications & Uses
- Locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC)
- First-line treatment of unresectable hepatocellular carcinoma (HCC)
- Advanced renal cell carcinoma (RCC) in combination with pembrolizumab (first-line) or everolimus (after prior anti-angiogenic therapy)
4. Dosage & Administration
Adult Dosage: DTC & HCC: 12 mg (for body weight ≥60 kg) or 8 mg (for body weight <60 kg) orally once daily. RCC (with pembrolizumab): 20 mg orally once daily. RCC (with everolimus): 18 mg orally once daily. The 4mg strength is used for dose titration and adjustment.
Administration: Take at the same time each day, with or without food. Swallow capsule whole with a glass of water. Do not open or crush the capsule. If a dose is missed, it can be taken if less than 12 hours have passed; if more than 12 hours, skip the dose and take the next dose at the usual time. Do not take two doses to make up for a missed dose.
5. Side Effects
Common side effects may include:
- Hypertension (up to 73%)
- Fatigue (58%)
- Diarrhea (54%)
- Decreased appetite (50%)
- Weight loss (46%)
- Nausea (41%)
- Proteinuria (34%)
- Palmar-plantar erythrodysesthesia syndrome (Hand-foot skin reaction) (32%)
- Dysphonia (31%)
- Arthralgia/Myalgia (31%)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Strong CYP3A4 Inducers (e.g., Rifampicin, Phenytoin, Carbamazepine, St. John's Wort) | Decrease lenvatinib plasma concentrations, potentially reducing efficacy. | Major |
| Strong CYP3A4 Inhibitors (e.g., Ketoconazole, Itraconazole, Clarithromycin, Ritonavir) | Increase lenvatinib plasma concentrations, potentially increasing toxicity. | Major |
| Midazolam (CYP3A4 substrate) | Lenvatinib may increase midazolam exposure. | Moderate |
| Warfarin | Increased risk of bleeding due to potential pharmacodynamic interaction. Monitor INR closely. | Moderate |
| Antihypertensive Agents | Lenvatinib-induced hypertension may necessitate dose escalation of antihypertensives. | Moderate |
| Other QT-prolonging drugs (e.g., certain antiarrhythmics, antipsychotics, antibiotics) | Additive risk of QTc prolongation. | Moderate |
7. Patient Counselling
- DO take your blood pressure regularly as advised by your doctor.
- DO maintain a daily symptom diary to track side effects.
- DO report any severe headache, vision changes, chest pain, or shortness of breath immediately.
- DO use effective contraception during and after treatment.
- DO maintain good oral hygiene and inform your dentist you are on lenvatinib before any dental procedure.
- DONT take the capsule with a high-fat meal. Take consistently with or without food.
- DONT crush, chew, or open the capsule.
- DONT start any new medicine (including OTC, herbal like St. John's Wort) without consulting your doctor.
- DONT ignore signs of infection, bleeding, or severe diarrhea.
8. Toxicology & Storage
Overdose: Expected symptoms would be exacerbations of known adverse reactions: severe hypertension, renal failure, hepatic dysfunction, severe fatigue, and hemorrhage.
Storage: Store below 30°C. Keep in the original blister pack or bottle to protect from moisture. Keep out of reach of children.