What Is Tivozanib (Fotivda)? FDA Approval, Licensing in Türkiye and Reimbursement Status
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Targeted Therapy for Advanced Kidney Cancer: Tivozanib
An important milestone in the treatment of kidney cancer (renal cell carcinoma), Tivozanib (Fotivda®)is a powerful treatment option with an optimized side effect profile that controls disease by cutting off the tumor’s supply routes, particularly in patients who have already received multiple treatments. You can find full details of this drug below.
Drug Profile
- Brand Name: Fotivda®
- Active Ingredient: Tivozanib
- Class: TKI (Tyrosine Kinase Inhibitor)
- Category: Targeted Therapy / Antiangiogenic
- Route of Administration: Oral Capsule
- Manufacturer: AVEO Oncology / Kyowa Kirin
- License: It is not yet licensed in Türkiye. It is not available for standard sale in pharmacies.
- Access: It can be imported under “Overseas Drug” status through TEB or İbn-i Sina with TİTCK approval.
- Payment: It is not on the SGK reimbursement list (SUT). It is generally obtained at the patient’s expense.
- The price for a monthly cycle (21 capsules) is approximately $22,000 - $26,000 (US dollars). *The current price may vary.*
Approved Indications
Tivozanib targets the blood vessel-dependent growth of kidney cancer. Its FDA-approved uses are as follows:
- Relapsed or Refractory Advanced RCC: It is used to treat adult patients whose disease has progressed despite at least two previous systemic therapies (for example, drugs such as Sutent, Votrient or Opdivo).
- “Salvage” After Multiple Treatments: When immunotherapy and other targeted drugs have failed, it is an effective 3rd- or 4th-line option for bringing the disease back under control.
FDA Approval History
The drug’s approval process is noteworthy because of its success in a challenging patient population:
- March 10, 2021 (Official Approval): The FDA approved Fotivda based on the superior results of the TIVO-3 trial. This approval established it as a standard option in relapsed disease.
- TIVO-3 Phase 3 Trial: This trial compared Tivozanib with Sorafenib, an older-generation drug. Tivozanib prolonged the time without disease progression (PFS) while reducing discontinuation rates due to side effects.
What Is Tivozanib and How Does It Work?
Tivozanib is a high-tech molecule that targets the tumor’s “supply lines” (blood vessels).
Cancer cells need a constant supply of oxygen to grow and use “VEGF” signals to build new blood vessels (angiogenesis). Tivozanib stops this process as follows:
- High Selectivity (Sharpshooter): Tivozanib very powerfully blocks the 3 main receptors responsible for blood vessel formation (VEGFR 1, 2 and 3), while having very little effect on the body’s other beneficial enzymes. This helps reduce side effects.
- Disrupting Blood Vessels: It prevents the tumor from forming new vessels and disrupts the structure of existing vessels, depriving the tumor of oxygen.
- Long Duration of Action: The drug has a long half-life, allowing it to remain at effective levels in the blood for a long time.
Comparison: Tivozanib vs. Other Agents
The table below summarizes the main differences between Tivozanib and the other TKI drugs Sorafenib and Sunitinib:
| Feature | Tivozanib (Fotivda) | Sorafenib (Nexavar) | Sunitinib (Sutent) |
|---|---|---|---|
| Target Selectivity | High (Specific VEGFR) | Low (Multiple Kinases) | Moderate (Multiple Kinases) |
| Half-Life | Long (85-90 hours) | Short (20-48 hours) | Intermediate (40-60 hours) |
| Hand–Foot Syndrome | Less Common | Very Common | Common |
| Treatment Cycle | 21 Days On / 7 Days Off | Continuous (2 times daily) | 4 Weeks On / 2 Weeks Off |
Administration and Dosage
The drug has a specific cycle designed to make side effects easier to manage:
- Standard Dose: Once daily, take a 1.34 mg capsule.
- Cycle Schedule (21/7 Rule): The drug is taken for 21 consecutive days , followed by a 7-day break (rest). This 28-day cycle is repeated for as long as treatment continues.
- How Should It Be Taken? Swallow the capsules whole with a glass of water. They may be taken with or without food. Do not open the capsule.
- What If a Dose Is Missed? If a dose is missed, skip that dose and take the next dose at its scheduled time. Do not take a double dose to make up for it.
Precautions During Treatment
The following points require attention to ensure treatment proceeds safely:
- Hypertension (High Blood Pressure): High blood pressure is very common (40-50%) because of the drug’s effects on blood vessels. Patients should monitor blood pressure regularly at home and, if needed, use blood pressure medication under medical supervision.
- Proteinuria (Protein in the Urine): The drug may affect the kidneys’ filtration mechanism. Protein leakage is monitored with regular urine tests.
- Wound Healing: Because it inhibits blood vessel formation, it may delay wound healing. If major surgery is planned, the drug should be temporarily stopped (at least 24 days before the operation).
- Bleeding Risk: Problems such as nosebleeds may occur. Patients with a history of serious bleeding should be cautious.
Pharmacokinetic Properties
The drug’s journey through the body is as follows:
- Absorption: It is well absorbed after oral administration and reaches peak blood levels within 2-24 hours.
- Distribution: It is transported in the blood with 99% binding to proteins (albumin).
- Metabolism: It is processed by the CYP3A4 enzyme in the liver. Its half-life is quite long (approximately 4-5 days), so therapeutic levels of the drug remain in the body even during the “rest week.”
- Elimination: Most of it is eliminated from the body in the feces.
Drug Interactions
Tivozanib may interact with certain drugs:
These drugs may cause Tivozanib to be eliminated from the body very quickly:
- Rifampin (a tuberculosis drug)
- Carbamazepine, Phenytoin (epilepsy drugs)
- St. John’s Wort
When used with blood pressure medications, monitor for excessive falls or fluctuations in blood pressure.
Side Effects
Tivozanib is generally better tolerated than other similar drugs, but the following effects may occur:
- Very Common:
- Hypertension (45-50%): This is the most common side effect and requires management.
- Dysphonia (27%): Hoarseness or a cracking voice.
- Fatigue (26%): Usually manageable.
- Diarrhea (26%): Usually mild.
- Advantage: Side effects that impair quality of life, such as “hand–foot syndrome” (painful peeling of the hands), occur significantly less often than with Sorafenib or Sunitinib.
- Serious Effects: Risk of blocked blood vessels (thrombosis), signs of heart failure.
References
- Rini BI, Pal SK, Escudier BJ, et al. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label trial. Lancet Oncol. 2020;21(1):95-104.
- FDA (U.S. Food and Drug Administration). FDA approves tivozanib for relapsed or refractory advanced renal cell carcinoma. March 10, 2021.
- AVEO Oncology. FOTIVDA® (tivozanib) capsules, for oral use: Prescribing Information. 2021.
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