What Is Lenvatinib (Lenvima)? FDA Approval, Licensing in Turkey, and Reimbursement
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Lenvatinib (Lenvima)
- FDA-Approved: Yes (First approval: 13 February 2015)
- Brand Name: Lenvima
- Active Ingredient: Lenvatinib
- Route of Administration: Oral, capsule
- Class: Signal Transduction Inhibitor, Tyrosine Kinase Inhibitor
- Category: Targeted agent
- Manufacturer: Eisai
- Distribution in Turkey: Not yet available in Turkey
- Approved Cancers: Thyroid cancer, kidney cancer (RCC), endometrial (uterine) cancer, hepatocellular carcinoma (HCC)
What Is Lenvatinib?
Lenvatinib is the active ingredient in Lenvima, which inhibits tumor growth and angiogenesis (new blood vessel formation) as a multitarget tyrosine kinase inhibitor.
⚙️ Mechanism of Action
It targets various receptors involved in cancer cell growth and spread:
- VEGFR-1, VEGFR-2, VEGFR-3: Prevents tumors from forming blood vessels.
- FGFR (1–4): Plays a role in tumor growth and metastasis.
- PDGFR-α, KIT, RET: Blocks signals supporting tumor cell survival.
Summary: Lenvatinib targets the MAPK and PI3K–AKT–mTOR pathways, suppressing signals for cell proliferation, differentiation, and survival.
📜 FDA Approval History
- 11 August 2021: First-line RCC approval in combination with pembrolizumab
- 22 July 2021: Approval of pembro + lenva for certain advanced endometrial carcinoma types
- 17 September 2019: Combination approval for advanced EC that is not MSI-H/dMMR after systemic therapy
- 16 August 2018: First-line approval for unresectable HCC
- 13 May 2016: RCC approval in combination with everolimus (5 mg/day)
- 13 February 2015: Approval for RAI-refractory, progressive differentiated thyroid cancer
🇹🇷 Licensing in Turkey
Lenvima (lenvatinib) is currently not licensed by Turkey's Ministry of Health.
For use in a patient's treatment, an application to the Ministry of Health for off-label use must first be submitted and approved. After approval, a medical oncologist issues a prescription/report; the patient applies to the Turkish Pharmacists' Association (TEB). If accepted, the drug can be imported on the patient's behalf.
💳 Reimbursement & Price
SGK: Lenvima is not reimbursed.
Price (June 2026): 10 mg 30 capsules: 1,555.00 €; 4 mg 30 capsules: 1,455.00 €.
🧾 Cost Calculation per Cycle by Diagnosis (APPENDIX)
The calculation assumes oral daily lenvatinib use for 28 days (4 weeks) as "1 cycle." Capsule requirements are calculated for packs of 30, and the number of packs is rounded up.
| Diagnosis / Regimen | Daily lenvatinib dose | Daily capsule combination | Total capsule requirement for 28 days | Number of packs required | Approximate cycle cost (€) |
|---|---|---|---|---|---|
| Thyroid Cancer (DTC) | 24 mg/day | 2×10 mg + 1×4 mg | 10 mg: 56 capsules 4 mg: 28 capsules |
10 mg: 2 packs (60 capsules) 4 mg: 1 pack (30 capsules) |
4,565.00 € |
| RCC (With everolimus 5 mg/day) | 18 mg/day | 1×10 mg + 2×4 mg | 10 mg: 28 capsules 4 mg: 56 capsules |
10 mg: 1 pack (30 capsules) 4 mg: 2 packs (60 capsules) |
4,465.00 € |
| RCC (With pembrolizumab 200 mg IV every 3 weeks) | 20 mg/day | 2×10 mg | 10 mg: 56 capsules | 10 mg: 2 packs (60 capsules) | 3,110.00 € |
| HCC (>60 kg) | 12 mg/day | 3×4 mg | 4 mg: 84 capsules | 4 mg: 3 packs (90 capsules) | 4,365.00 € |
| HCC (<60 kg) | 8 mg/day | 2×4 mg | 4 mg: 56 capsules | 4 mg: 2 packs (60 capsules) | 2,910.00 € |
| Endometrial Cancer (With pembrolizumab 200 mg IV every 3 weeks) | 20 mg/day | 2×10 mg | 10 mg: 56 capsules | 10 mg: 2 packs (60 capsules) | 3,110.00 € |
🧬 Resistance Mechanism
- Increased expression of target receptors (RTK production ↑ → efficacy ↓)
- Changes in binding affinity (kinase domain mutations)
- HGF/c-MET pathway activation (contributes to resistance)
- Activation of alternative signaling pathways (e.g., IGF-1R)
📦 Pharmacokinetics
Absorption
Rapidly absorbed after oral administration; Cmax is reached in 1–4 hours. Food does not affect the extent of absorption; it slows the rate and delays Tmax by 2–4 hours .
Distribution
Plasma protein binding: 98–99% ; extensive distribution.
Metabolism
- CYP3A and aldehyde oxidase -mediated metabolism
- Nonenzymatic pathways also contribute
Excretion
- Approximately 64% in feces
- Approximately 25% in urine
Terminal half-life ≈ 28 hours.
💉 Dosing
- Thyroid Cancer (DTC): Once daily: 24 mg (with or without food).
- RCC:
- Everolimus 5 mg/day with: 18 mg/day lenvatinib.
- Pembrolizumab 200 mg IV every 3 weeks with: 20 mg/day lenvatinib.
- HCC: >60 kg: 12 mg/day; <60 kg: 8 mg/day.
- Endometrial Cancer: Pembrolizumab 200 mg IV every 3 weeks with: 20 mg/day.
🔄 Drug Interactions
CYP3A4 Inducers
- Phenytoin, carbamazepine, rifampin, phenobarbital, St. John's Wort → metabolism ↑, levels ↓, efficacy may decrease.
CYP3A4 Inhibitors
- Ketoconazole, itraconazole, erythromycin, clarithromycin → metabolism ↓, levels ↑, toxicity risk ↑.
During concomitant use, efficacy and adverse effects should be monitored closely.
⚠️ Precautions
- Blood pressure control: Regular monitoring; discontinue in a hypertensive crisis.
- Cardiac function: Monitor LVEF; interrupt/reduce for G3 dysfunction, discontinue for G4.
- Arterial thromboembolism: Discontinue if MI/stroke or similar events occur.
- Liver function: Monitor LFTs; G3+ toxicity → interrupt, then resume at a lower dose after recovery; discontinue for failure.
- Kidney function: Monitor creatinine and other tests regularly.
- Proteinuria: ≥2 g/24 h → interrupt treatment; when <2 g/24 h, resume at a lower dose .
- QT prolongation: Monitor ECG and electrolytes; avoid high-risk drug combinations.
- RPLS/PRES: Headache, seizures, visual impairment; if suspected, stop treatment and obtain brain MRI.
- Electrolyte monitoring: Check K, Mg, and Ca regularly.
- Thyroid hormones: Monitor TSH regularly; replacement as needed.
- Wound healing: If surgery is planned, interrupt treatment ≥1 week beforehand.
- Hepatotoxicity: Interruption/discontinuation in G3+ cases.
- Pregnancy/breastfeeding: Fetotoxic; should not be used during pregnancy. Effective contraception during treatment and for ≥1 month afterward; breastfeeding is not recommended
Adverse Effects
Ranges reflect typical all-grade and G3–4 incidence rates for lenvatinib (alone or in combination) across different indications and studies.
| Adverse effect | All grades (%) | G3–4 (%) | Brief management note |
|---|---|---|---|
| Hypertension | 45–75 | 20–45 | Start antihypertensive treatment; G3: interrupt/reduce, G4: discontinue. |
| Diarrhea | 30–60 | 5–15 | Fluids + loperamide; reduce dose/interrupt if persistent. |
| Loss of Appetite / Weight Loss | 30–50 | 5–10 | Dietary support; symptomatic treatment, dose reduction if needed. |
| Fatigue / Asthenia | 30–60 | 5–15 | Assess causes; consider treatment interruption/dose reduction. |
| Proteinuria | 20–35 | 5–15 | ≥2 g/24 h: interrupt treatment/reduce dose; discontinue for nephrotic syndrome. |
| Hypothyroidism | 10–30 | <5 | Monitor TSH; levothyroxine if needed. |
| Mucositis / Stomatitis | 15–40 | 2–8 | Oral care; analgesic/antimicrobial mouthwashes; interrupt if needed. |
| Hand–Foot Skin Reaction (HFSR) | 15–30 | 2–6 | Appropriate care/creams; reduce dose/interrupt for Grade ≥2. |
| Nausea / Vomiting | 15–45 | 1–5 | Antiemetics; hydration, interrupt if needed. |
| Hepatotoxicity (AST/ALT↑, bilirubin) | 10–25 | 2–8 | Monitor LFTs closely; interrupt/reduce at thresholds, discontinue if severe. |
| Bleeding (mostly mild) | 10–20 | 1–4 | Caution with anticoagulants/antiplatelets; discontinue for serious events. |
| Renal Dysfunction / AKI | 5–15 | 2–5 | Hydration; avoid nephrotoxins; interrupt/reduce. |
| Arterial Thromboembolism (MI, Stroke) | 2–5 | 1–3 | Discontinue immediately; emergency management. |
| GI Perforation / Fistula | 1–4 | 1–3 | Discontinue; surgical/gastroenterology consultation. |
| QT Prolongation | <5 | <1 | Monitor ECG + electrolytes; avoid QT-prolonging drugs. |
| RPLS / PRES | <1 | <1 | Urgent assessment; confirm with MRI, discontinue the drug. |
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