Pazopanib

What is Pazopanib?

• Pazopanib (Votrient) is a kinase inhibitor used in the therapy of advanced renal cell carcinoma and soft tissue sarcomas.

Pazopanib structure

What are the uses of this medicine?

Votrient is a prescription medicine used to treat adults with:

• advanced renal cell cancer (RCC)
• advanced soft tissue sarcoma (STS) who have received chemotherapy in the past

How does this medicine work?

• Pazopanib (paz oh’ pa nib) is an orally available, multi-kinase inhibitor, most potently inhibiting the tyrosine kinase receptors of vascular endothelial growth factor (VEGF) 1, 2 and 3 which are associated with tumor growth and angiogenesis.
• Pazopanib also has activity against c-KIT (an abnormal tyrosine kinase found in gastrointestinal stromal tumors) and the platelet derived growth factor (PDGF) receptor.
• Clinical trials of pazopanib in malignant diseases in humans have shown activity against renal cell carcinoma and soft tissue sarcoma and promising effects in ovarian and thyroid cancer.

Who Should Not Use this medicine ?

Limitations of Use:

• It is not known if Votrient is effective in treating certain soft tissue sarcomas or certain gastrointestinal tumors.
• It is not known if Votrient is safe and effective in children under 18 years of age.

What drug interactions can this medicine cause?

• Avoid coadministration of Votrient with strong CYP3A4 inhibitors. Coadministration of pazopanib with strong inhibitors of CYP3A4 increases pazopanib concentrations.
• Votrient is not recommended if chronic use of strong CYP3A4 inducers cannot be avoided.Coadministration of strong CYP3A4 inducers may decrease plasma pazopanib concentrations.
• Avoid concomitant use of Votrient with strong inhibitors of P-gp or BCRP.
• The concomitant use of Votrient with agents with narrow therapeutic windows that are metabolized by CYP3A4, CYP2D6, or CYP2C8 is not recommended.
• Concomitant use of Votrient with simvastatin is not recommended.
• Avoid concomitant use of Votrient with gastric acid-reducing agents.
• Avoid coadministration of Votrient with drugs known to prolong the QT/QTc interval.

Is this medicine FDA approved?

• Pazopanib received approval for use in the United States in 2012 and current indications include advanced renal cell cancer and soft tissue sarcomas.

How should this medicine be used?

Recommended dosage:

• The recommended dosage of Votrient is 800 mg (four 200 mg tablets) orally once daily without food (at least 1 hour before or 2 hours after a meal) until disease progression or unacceptable toxicity.

Moderate Hepatic Impairment: 200 mg orally once daily.

Administration:

• Take Votrient exactly as your healthcare provider tells you. Your healthcare provider will tell you how much Votrient to take.
• Your healthcare provider may change your dose.
• Take Votrient on an empty stomach, at least 1 hour before or 2 hours after food.
• Swallow Votrient tablets whole. Do not crush Votrient tablets. It may increase the amount of Votrient in your body.
• Do not eat grapefruit or drink grapefruit juice during treatment with Votrient. Grapefruit products may increase the amount of Votrient in your body.
• If you miss a dose, take it as soon as you remember. Do not take it if it is close (within 12 hours) to your next dose. Just take the next dose at your regular time. Do not take more than 1 dose of Votrient at a time.
• Your healthcare provider will test your urine, blood, and heart before you start and while you take Votrient.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 200 mg

This medicine is available in fallowing brand namesː

• Votrient

What side effects can this medication cause?

The most common side effects of this medicine include:

• diarrhea
• change in hair color
• nausea or vomiting
• loss of appetite

Other common side effects in people with advanced soft tissue sarcoma who take Votrient include:

• feeling tired
• decreased weight
• tumor pain
• muscle or bone pain
• stomach pain
• headache
• taste changes
• trouble breathing
• change in skin color

What special precautions should I follow?

• Severe and fatal hepatotoxicity has occurred. Monitor liver tests at baseline, regularly during treatment and as clinically indicated. Withhold Votrient and resume at reduced dose with continued weekly monitoring for 8 weeks, or permanently discontinue with weekly monitoring until resolution based on severity of hepatotoxicity.
• Monitor patients who are at significant risk of developing QT interval prolongation. Monitor electrocardiograms (ECGs) and electrolytes at baseline and as clinically indicated. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating Votrient and during treatment.
• Cardiac dysfunction, including decreased left ventricular ejection fraction (LVEF) and congestive heart failure, have occurred. Monitor blood pressure and manage as appropriate. Monitor for clinical signs or symptoms of congestive heart failure. Conduct baseline and periodic evaluation of LVEF in patients at risk of cardiac dysfunction. Withhold or permanently discontinue Votrient based on severity of cardiac dysfunction.
• Fatal hemorrhagic events have occurred. Votrient has not been studied in patients who have a history of hemoptysis, cerebral hemorrhage, or clinically significant gastrointestinal hemorrhage in the past 6 months. Withhold Votrient and resume at reduced dose or permanently discontinue based on severity of hemorrhagic events.
• Arterial thromboembolic events have been observed and can be fatal. Votrient has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months. Permanently discontinue Votrient in case of an arterial thromboembolic event.
• Venous thromboembolic events (VTEs) have been observed, including fatal pulmonary emboli (PE). Monitor for signs and symptoms of VTE and PE. Withhold Votrient and then resume at same dose or permanently discontinue based on severity of VTE.
• Thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), has been observed. Permanently discontinue Votrient if TMA occurs.
• Fatal perforation events have occurred. Monitor for signs and symptoms of gastrointestinal perforation or fistula. Withhold Votrient in case of Grade 2 or 3 gastrointestinal fistula and resume based on medical judgement. Permanently discontinue Votrient in case of gastrointestinal perforation or Grade 4 gastrointestinal fistula.
• Interstitial Lung Disease/Pneumonitis may occur which Can be fatal. Monitor patients for pulmonary symptoms. Permanently discontinue Votrient in patients who develop interstitial lung disease (ILD) or pneumonitis.
• Posterior Reversible Encephalopathy Syndrome may occur which Can be fatal. Permanently discontinue Votrient in patients who develop posterior reversible encephalopathy syndrome (PRES).
• Hypertension, including hypertensive crisis, has been observed. Do not initiate Votrient in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Votrient. Monitor blood pressure as clinically indicated and initiate and adjust antihypertensive therapy as appropriate. Withhold and then dose reduce Votrient or permanently discontinue based on severity of hypertension.
• Votrient increases the risk of impaired wound healing. Withhold Votrient for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Votrient after resolution of wound healing complications has not been established.
• Monitor thyroid tests at baseline, during treatment and as clinically indicated and manage hypothyroidism as appropriate.
• Proteinuria may occur. Perform baseline and periodic urinalysis during treatment with follow up measurement of 24-hour urine protein as clinically indicated. Withhold Votrient then resume at a reduced dose or permanently discontinue based on severity of proteinuria. Permanently discontinue in patients with nephrotic syndrome.
• Tumor Lysis Syndrome may occur. Cases of tumor lysis syndrome (TLS) (some fatal) have been reported in patients with RCC and STS. Closely monitor patients at risk and treat as clinically indicated.
• Serious infections (with or without neutropenia), some with fatal outcome, have been reported. Monitor for signs and symptoms of infection. Institute appropriate anti-infective therapy promptly. Consider interruption or discontinuation of Votrient.
• Votrient Can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and patients to use effective contraception.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• hypertension
• fatigue

Management of overdosage:

• Provide general supportive measures to manage an overdose.
• Hemodialysis is not expected to enhance the elimination of Votrient because pazopanib is not significantly renally excreted and is highly bound to plasma proteins.

Can this medicine be used in pregnancy?

• Votrient can cause fetal harm when administered to a pregnant woman.
• There are no available data on Votrient use in pregnant women to evaluate for a drug-associated risk.

Can this medicine be used in children?

• The safety and effectiveness of Votrient in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

Active ingredient: pazopanib. Inactive ingredients:

• Tablet core: Magnesium stearate, microcrystalline cellulose, povidone, and sodium starch glycolate. Coating: Gray or pink film-coated tablets: Hypromellose, iron oxide black, macrogol/polyethylene glycol 400 (PEG 400), polysorbate 80, and titanium dioxide.

Who manufactures and distributes this medicine?

• Distributed by: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey

What should I know about storage and disposal of this medication?

• Store Votrient at room temperature between 68°F and 77°F (20°C to 25°C).
• Keep Votrient and all medicines out of the reach of children.

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• Dailymed label info on Pazopanib
• FDA Pazopanib

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