Generic Name

Tyrvaya

Mechanism

• Receptor blockade: Competitive inhibition of ATP‑binding sites on VEGFRs, FGFRs, PDGFR‑α, KIT, and RET.
• Anti‑angiogenic effect: Reduces vascular endothelial growth factor–mediated neovascularization, starving tumors of oxygen and nutrients.
• Growth‑signal suppression: Blocks fibroblast growth factor signaling and downstream pathways (RAS/MAPK, PI3K/AKT), curbing tumor cell proliferation and survival.
• Tumor micro‑environment modulation: Inhibits stromal support through PDGFR‑α blockade, disrupting the tumor micro‑environment and enhancing TKI efficacy.

Pharmacokinetics

Indications

• Metastatic Renal Cell Carcinoma (mRCC) after progression on other TKI or immune therapy.
• Radioactive‑iodine refractory differentiated thyroid cancer (RET/FKFR‑mutant tumors).
• Unresectable neuroendocrine tumors (clinical trials ongoing).

Dosing

• Standard adult dose: 20 mg orally once daily in 28‑day cycles; hold 3 days for safety on days 1–3 if any grade‑3/4 toxicity develops.
• Hepatic impairment:
• Child‑Pugh B: 15 mg daily.
• Child‑Pugh C: Not recommended.
• Renal impairment: No dose adjustment required; reduce if CrCl < 30 mL/min and liver function compromised.
• Drug interactions: Avoid strong CYP3A4 inhibitors (ketoconazole, itraconazole) or inducers (rifampin, carbamazepine).
• Timing: Take with food; avoid alcohol.

Adverse Effects

• Common (≥ 10 %):
• Hypertension (31 %)
• Fatigue (29 %)
• Diarrhea (27 %)
• Nausea (17 %)
• Decreased appetite (12 %)
• Weight loss (10 %)
• Rash (8 %)
• Serious (≥ 1 %):
• Grade ≥ 3 hypertension (3 %)
• Proteinuria (2 %)
• Severe liver injury (1 %)
• GI perforation/fistula (≤ 0.5 %)
• Cardiac events (≥ 0.1 %)

Monitoring labs: CBC, CMP, liver enzymes, KFTs before each cycle; adjust dose for any Grade ≥ 3 toxicity.

Monitoring

• Blood pressure: Baseline, weekly for first month, then monthly.
• Liver function tests (ALT, AST, bilirubin): Baseline, at weeks 4, 8, 12, then every 2–3 months.
• Renal function (eGFR): Every cycle.
• Ultrasound/MRI scans: Every 8–12 weeks to evaluate tumor response per RECIST.
• Proteinuria screen: Urinalysis at baseline and every 4 weeks.

Clinical Pearls

• Start‑up dosing: 20 mg daily; consider 15 mg in patients on concomitant CYP3A4 inhibitors to avoid toxicity.
• Hypertension strategy: Initiate antihypertensives proactively; use ACEI/ARB or calcium‑channel blocker as first line.
• Re‑dose timing: Resume at full dose only after grade 2 or lower adverse events resolve; use a “step‑down” schedule (15 mg → 10 mg → 5 mg) if intolerable.
• Drug‑drug interactions: Lenvatinib markedly increases plasma levels of drugs metabolized by CYP3A4, so monitor therapeutic drug levels (e.g., tacrolimus).
• Patient education: Emphasize adherence, regular BP monitoring, prompt reporting of any GI bleeding or sudden flank pain (signs of GI perforation or renal injury).
• Efficacy beyond mRCC: Consider lenvatinib in combination with pembrolizumab for certain urothelial cancers; ongoing trials are expanding its therapeutic spectrum.

Quick Reference
• Brand: Tyrvaya (lenvatinib)
• Class: Multitargeted TKI (VEGFR/FGFR/PDGFR/Kit/RET)
• Key Action: Inhibits angiogenesis & tumor growth signaling
• Dose: 20 mg PO qd
• Major toxicity: Hypertension, fatigue, diarrhea, proteinuria
• Monitoring: BP, LFTs, renal function, imaging

*Use this drug card as a concise reference for both academic study and bedside clinical decision making.*