Drug Profile

Basic Information

Active Ingredient: Pazopanib
Brand Name: Votrient (original drug), Vopazzi (generic/equivalent)
Route of Administration: Oral tablet
Class: Signal transduction inhibitor (TKI) – tyrosine kinase inhibitor
Category: Targeted therapy agent

Manufacturer / Distribution

Original Manufacturer: GlaxoSmithKline (GSK)
Distribution in Turkey: Novartis for Votrient; Deva for Vopazzi

Approved Cancers

Approved Cancers:
- Advanced renal cell carcinoma (RCC), or kidney cancer
- Advanced soft tissue sarcoma (STS)

What Is Pazopanib?

Votrient, containing pazopanib, is a targeted therapy that blocks several tyrosine kinase inhibitors, including vascular endothelial growth factor receptors (VEGFR), platelet-derived growth factor receptors (PDGFR) and c-Kit. By suppressing tumor cells' ability to form blood vessels (angiogenesis), it inhibits tumor growth and metastasis through this biological effect.

How Does It Work?

Pazopanib targets VEGFR-1, VEGFR-2, VEGFR-3, PDGFR, FGFR and c-Kit as a multikinase inhibitor. It stops new blood vessel formation (angiogenesis) , which is important for tumor growth and spread. By cutting off the blood supply and nutrients tumor cells need, it slows or stops their growth. It also reduces their ability to spread to other parts of the body (metastasis).

FDA (US Food and Drug Administration) Approval History:

April 26, 2012: Received FDA approval for advanced soft tissue sarcoma (STS).
October 19, 2009: Received FDA approval for advanced renal cell carcinoma (RCC).

Licensing in Turkey:

Pazopanib is licensed by Turkey's Ministry of Health for the following indications:

Pazopanib is indicated as a single agent until progression in patients with unresectable locally recurrent or metastatic renal cell (kidney) cancer who have not previously received a VEGF-TKI (vascular endothelial growth factor–tyrosine kinase inhibitor).
VOTRIENT is indicated after progression following at least one and no more than two chemotherapy regimens for metastatic disease, in metastatic sarcoma of the following subtypes:
- Fibroblastic sarcomas (adult fibrosarcoma, myxofibrosarcoma, sclerosing epithelioid fibrosarcoma, malignant solitary fibrous tumor); fibrohistiocytic sarcomas (pleomorphic malignant fibrous histiocytoma, giant-cell malignant fibrous histiocytoma (also known as undifferentiated pleomorphic sarcoma, UPS), inflammatory malignant fibrous histiocytoma); leiomyosarcoma; pleomorphic or alveolar rhabdomyosarcoma; epithelioid hemangioendothelioma; angiosarcomas; epithelioid sarcomas; synovial sarcoma; alveolar soft part sarcoma; malignant glomus tumor; clear-cell sarcoma; desmoplastic small round-cell sarcoma; malignant mesothelioma; PEComa; intimal sarcoma; and malignant peripheral nerve sheath tumors.

Is It Reimbursed in Turkey?

Votrient, containing pazopanib, is covered by Turkey's Social Security Institution (SGK) in the following settings:

Treatment of locally advanced or metastatic renal cell carcinoma.
- Temsirolimus, sunitinib, sorafenib and pazopanib may not be used sequentially or in combination in metastatic renal cell carcinoma. Switching between these drugs is not considered sequential use only when an intolerable major adverse effect (grade 3-4) occurs and is specified in the Ministry of Health's off-label use approval. SGK does not cover pazopanib in patients whose disease progresses after cabozantinib.
The sarcoma subtypes listed in the product information, after progression following at least one and no more than two chemotherapy regimens.
Prescribed by medical oncologists on the basis of a 6-month medical board report that includes at least one medical oncologist and specifies the treatment protocol. To continue treatment after the report expires, a new report must state that the disease has not progressed.

Price: As of December 2025, the pharmacy retail price of Votrient 200 mg, 30 tablets, is 11342.50 TL. The retail price of Votrient 400 mg, 60 tablets, is 44926.99 TL.

Cost Calculation per Cycle

Dose Range: The recommended daily dose is 800 mg and should not be taken with food.
Cycle Definition (for Calculation): Assumed to be 28 days (4 weeks).
Daily tablet requirement: 800 mg/day = 2 tablets of 400 mg/day (alternative: 4 tablets of 200 mg/day)
Total requirement for 28 days: 56 tablets of 400 mg (alternative: 112 tablets of 200 mg)
Using a 400 mg, 60-tablet pack (44926.99 TL):
Unit price per tablet ≈ 44926.99 / 60 = 748.78 TL
Cost for 28 days ≈ 56 × 748.78 = 41931.86 TL / cycle
Using a 200 mg, 30-tablet pack (11342.50 TL):
Unit price per tablet ≈ 11342.50 / 30 = 378.08 TL
Cost for 28 days ≈ 112 × 378.08 = 42345.33 TL / cycle
Note: This is an approximate calculation using the unit tablet cost derived from pack prices. Pharmacy supply, changes in discounts or pricing decrees, and report conditions may affect cost.

What Is Pazopanib's Status on the List of Off-Label Drugs That May Be Used Without Additional TİTCK Approval?

ENDOMETRIAL STROMAL SARCOMA:
- IN PATIENTS ABLE TO RECEIVE CHEMOTHERAPY: appropriate after disease progression following chemotherapy and hormonal treatment (aromatase inhibitor, tamoxifen, megestrol acetate).
- IN PATIENTS UNABLE TO RECEIVE CHEMOTHERAPY: appropriate after progression following hormonal treatment (aromatase inhibitor, tamoxifen, megestrol acetate).
ADVANCED CHONDROSARCOMA: Appropriate after one line of systemic chemotherapy.
ADVANCED EWING SARCOMA: Appropriate after progression following two lines of systemic chemotherapy.
ADVANCED DESMOID TUMOR (AGGRESSIVE FIBROMATOSIS): Appropriate in patients unsuitable for local treatment.
ADVANCED HEMANGIOPERICYTOMA: Appropriate after one line of systemic chemotherapy.
ADVANCED SOFT TISSUE SARCOMA: Appropriate after progression following one line of chemotherapy.
ADVANCED SOFT TISSUE SARCOMA: Appropriate as 1st-line treatment in patients unable to receive chemotherapy, excluding liposarcoma.

Mechanisms of Resistance:

Mechanisms of resistance to pazopanib include:

Overexpression of target receptors such as VEGFR-1, VEGFR-2, VEGFR-3 and PDGFR
Reduced drug-binding affinity caused by mutations in target receptors
Activation of alternative angiogenic pathways, increasing the tumor's ability to form new vessels
In the tumor microenvironment, recruitment of inflammatory cells (MDSCs)

Absorption:

Oral bioavailability ranges from 14% to 39%. Systemic levels increase when taken with food.

Distribution:

Pazopanib is >99% bound to plasma proteins.

Metabolism:

Metabolized in the liver by CYP3A4, with smaller contributions from CYP1A2 and CYP2C8. Pazopanib is eliminated through the liver, with only a small amount (approximately 4%) excreted in urine.

Dose Range:

The recommended daily dose is 800 mg and should not be taken with food. Reducing the dose to 200 mg is recommended in patients who develop hepatotoxicity.

Drug Interactions:

CYP3A4 inhibitors such as ketoconazole and clarithromycin may slow pazopanib metabolism and increase plasma levels.
CYP3A4 inducers such as phenytoin, rifampin and St. John's wort may accelerate metabolism and reduce efficacy.

Precautions:

Close Monitoring of Liver Function:
- Elevated liver enzymes (ALT, AST) are common during pazopanib treatment. Liver function tests should therefore be performed at weeks 3, 5, 7, 9 and 12 after treatment starts, then regularly.
- If ALT/AST rises to more than 3 but less than 8 times normal, treatment may continue with weekly liver function tests. If levels exceed 8 times normal, interrupt treatment and do not restart until liver enzymes normalize. Treatment may then resume at a reduced dose, for example 200 mg/day.
- Significant deterioration in liver function may require stopping pazopanib. It is also not recommended in severe hepatic impairment because clearance may decrease by 50%.
QT Prolongation and Cardiac Monitoring:
- Cardiac rhythm should be monitored closely, particularly in patients at risk of QT prolongation, such as those with congenital long QT syndrome. The QT interval should be checked by ECG at baseline and regularly.
- Electrolyte abnormalities such as hypokalemia, hypomagnesemia and hypocalcemia may trigger QT prolongation during treatment. Levels should be checked regularly and corrected if necessary.
- Risk is greater in patients taking antiarrhythmics that may prolong QT or who have other drug interactions. Concomitant drugs' potential to prolong QT, such as amiodarone and sotalol, should be considered.
Thromboembolic Events:
- Pazopanib may increase arterial thromboembolic risk, including myocardial infarction, stroke and transient ischemic attack. Risk is particularly high in people over 60 and those with cardiovascular disease. Risks and benefits should therefore be assessed carefully before treatment.
- If signs of a heart attack, stroke or other thromboembolic event appear, intervene immediately and discontinue pazopanib.
Hypertension:
- Pazopanib may cause hypertension, generally within the first 18 weeks. Blood pressure should be monitored closely. If hypertension develops, antihypertensive treatment and regular follow-up should be initiated.
- If blood pressure rises excessively, for example above 160/100 mmHg, the dose may be reduced or treatment stopped if necessary.
Hemoptysis and Cerebral Hemorrhage Risk:
- Patients with a history of hemoptysis (coughing up blood), cerebral hemorrhage or clinically significant bleeding should be assessed carefully before starting treatment. Serious bleeding risk may increase during the first 6 months, particularly in those at high risk.
- Caution is also needed in patients prone to bleeding, particularly those undergoing invasive surgery. Interrupting pazopanib at least 7 days before surgery is recommended.
Gastrointestinal Perforations and Fistulas:
- Rarely, gastrointestinal perforations or fistulas may develop during pazopanib treatment. Risk is greater when a tumor lies close to the bowel wall or pre-existing bowel damage is present, such as diverticulitis or inflammatory bowel disease.
- Patients with abdominal pain, nausea, vomiting, bleeding or signs of perforation should be assessed immediately.
Hypothyroidism and Thyroid Monitoring:
- Hypothyroidism may develop during treatment. Thyroid function tests should be performed at baseline and regularly.
- Thyroid hormone replacement may be started if dysfunction develops.
Proteinuria and Kidney Monitoring:
- Proteinuria may occur with pazopanib. Urinary protein should be checked at baseline and regularly. If severe proteinuria develops, such as nephrotic syndrome, treatment should be stopped or the dose reduced.
- Kidney function should be monitored closely, particularly in advanced renal disease.
Myelosuppression:
- Pazopanib may reduce blood cell counts, particularly causing neutropenia (low white blood cells) and thrombocytopenia (low platelets). Complete blood counts should be monitored regularly and appropriate action taken if myelosuppression develops.
- Severe myelosuppression carries a high infection risk. Patients require careful attention and appropriate supportive treatment.

Side Effects:

Listed from the most common to less frequent:

Hypertension (50%): Common in the first 18 weeks and generally controlled with antihypertensives.
Gastrointestinal symptoms: Diarrhea, nausea, vomiting and abdominal pain (up to 30%) are common.
Fatigue and weakness: Among the common side effects.
Hair color changes: Loss of pigmentation may occur.
Bleeding complications: May include epistaxis, hematuria and hemoptysis.
Thromboembolic events: Increased risk of arterial events such as myocardial infarction (MI), stroke (TIA) and angina.
Proteinuria (8%): May cause moderate urinary protein loss.
Myelosuppression: Neutropenia and thrombocytopenia are generally mild to moderate.
Hypothyroidism: Thyroid function may decline during pazopanib treatment.
Elevated liver enzymes: May occur during the first 18 weeks.
Cardiac toxicity: May cause QT prolongation and torsades de pointes.
Electrolyte abnormalities: Imbalances such as hypokalemia, hypomagnesemia, hyponatremia and hyperglycemia may occur.

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What Is Pazopanib (Votrient, Vopazzi)? FDA Approval, Licensing and Reimbursement in Turkey