Lenvima
Lenvima
Generic Name
Lenvima
Mechanism
- Multitarget inhibition: blocks VEGFR‑1/2/3, FGFR1‑4, PDGFR‑α, KIT, and RET signaling pathways.
- Anti‑angiogenic: inhibits endothelial cell proliferation and new vessel formation, reducing tumor blood supply.
- Direct tumor cell effects: inhibits growth factor receptors on tumor cells, inducing apoptosis and growth arrest.
- Impressive downstream blockade: suppression of the MAPK/ERK and PI3K/AKT pathways, essential for tumor survival.
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Pharmacokinetics
| Parameter | Detail |
| Absorption | Oral, ~80 % bioavailability; peak plasma concentration at ≈4 h post‑dose. |
| Distribution | High plasma protein binding (>95 %), volume of distribution ~225 L. |
| Metabolism | Primarily CYP3A4; minor CYP1B1 involvement. |
| Elimination | Renal (~17 %) and fecal route; terminal half‑life ~28 h. |
| Drug interactions | Strong CYP3A4 inhibitors increase exposure; inducers decrease it. Avoid concomitant strong CYP3A4 inhibitors or inducers. |
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Indications
- Unresectable, locally advanced, or metastatic radio‑iodine‑refractory differentiated thyroid cancer *(first‑line systemic therapy)*.
- Unresectable, symptomatic, or metastatic hepatocellular carcinoma (first‑line systemic therapy).
- Investigational use: renal cell carcinoma (phase III), anaplastic thyroid cancer (phase I/II).
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Contraindications
| Category | Items |
| Contraindications | *Pregnancy, lactation, hypersensitivity to lenvatinib or excipients.* |
| Worry‑Warnings |
• Severe hypertension or uncontrolled hypertension < 140/90 mm Hg. • Proteinuria > 20 mg/m²/d or > 0.5 g/day. • Bleeding diathesis or need for major surgery. • QT prolongation (rare but documented). • Hepatic impairment: use cautiously in Child‑Pugh B; not recommended for C. |
| Precautions |
• Cardiovascular disease (heart failure, ischemic heart disease). • Concurrent use of platelet‑activating agents. • Liver disease: monitor LFTs. |
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Dosing
- Standard dose: 12 mg orally once daily (with or without food).
- Initial treatment: 12 mg for thyroid cancer; 12 mg for HCC.
- Dose adjustment: Down‑titrate by 4 mg increments (to 8 mg or 4 mg) for intolerance or adverse events; up‑titrate only in select scenarios.
- Storage: 15 – 30 °C (room temperature), protected from light.
- Missed dose: If < 8 h since the last dose, take the missed dose; otherwise skip and resume next scheduled dose.
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Adverse Effects
Common (≥10 %)
• Hypertension
• Fatigue
• Diarrhea
• Decreased appetite / weight loss
• Nausea / vomiting
• Anorexia
• Proteinuria
• Headache
• Arthralgia / myalgia
Serious (≥1 %)
• Hypertensive Crisis
• Severe proteinuria → possible nephrotic syndrome
• Bleeding (gastrointestinal, epistaxis, hemoptysis)
• Cardiac events (heart failure, arrhythmias)
• Impaired wound healing (post‑operative)
• Severe liver dysfunction (transaminitis)
Monitoring
- Blood pressure: ≥ twice weekly, especially after dose changes.
- Urine output and proteinuria: urinalysis at baseline, monthly, and when clinically indicated.
- Liver function tests: baseline, week 4, then every 4 weeks.
- Platelet count & coagulation profile: baseline, every 4‑6 weeks.
- Electrocardiogram (ECG): baseline, as clinically indicated (QTc).
- Pregnancy test: baseline and every 3 months.
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Clinical Pearls
- “Off‑by‑Clock” dose‑timing matters: A 12‑hr delay can be clinically significant; counsel patients on strict daily timing.
- CYP3A4 interplay: Ketoconazole, ritonavir dramatically ↑ lenvatinib levels; rifampin may restore too low. Adjust dose or monitor closely.
- Hydration & proteinuria: Encourage adequate fluid intake (≥2 L/day) to dilute urinary protein excretion.
- Hypertension management: Add or titrate an ACE inhibitor or ARB; avoid non‑steroidal anti‑inflammatory drugs that may worsen proteinuria.
- Bleeding risk with surgery: Discontinue lenvatinib ≥4 weeks pre‑op; resume 2‑4 weeks post‑op or per surgical protocol.
- Comparative advantage vs. sorafenib: Lenvatinib offers higher objective response rates in HCC but a higher incidence of proteinuria; suitable patient selection is key.
- Use in thyroid cancer: The benefit is largely progression‑free survival (PFS); monitor Tg levels to gauge response early.
- Patient education: Emphasize reporting early signs of bleeding, proteinuria (dark urine), and uncontrolled BP.
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• References
• GLOBOCAN 2023, ESMO Clinical Practice Guidelines, FDA label (Lenvima, 2023).
• J. Clin. Oncol. 2020;38:723‑734 (lenvatinib for HCC).
• Thyroid 2021;31:1143‑1155 (lenvatinib in RAI‑DTC).
*Use this drug card as a quick reference; consult the product label and the latest clinical trials for comprehensive guidance.*