• Advanced renal cell carcinoma.
• Advanced soft tissue sarcoma in patients who have previously received chemotherapy.

Contraindicated in:

• Severe hepatic impairment
• History of hemoptysis or cerebral or GI bleeding in preceding 6 mo
• Risk/history of arterial thrombotic events, including MI, angina, or ischemic stroke within preceding 6 mo
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Congenital prolonged QTc interval or concurrent medications/diseases that prolong the QTc interval (may ↑ risk of torsades de pointes)
• Electrolyte abnormalities (correct prior to use; may ↑ risk of potentially serious arrhythmia)
• Patients at risk for GI perforation/fistula
• Surgery (interruption of therapy recommended)
• Hypertension (control before therapy is initiated)
• Hypothyroidism (may worsen condition)
• Moderate hepatic impairment (dose ↓ recommended)
• Patients of East Asian descent (↑ risk of neutropenia, thrombocytopenia, and palmar-plantar erythrodysesthesia)
• Rapidly growing tumors, high tumor burden, renal impairment, or dehydration (↑ risk of tumor lysis syndrome)
• Patients with genetically reduced UGT1A1 activity (presence of UGT1A1*28/*28 allele) (↑ risk of hyperbilirubinemia)
• Patients positive for HLA-B*5701 allele (↑ risk of hepatotoxicity)
• Women of reproductive potential and men with female partners of reproductive potential
• Pedi: Safety and effectiveness not established in children
• Geri: ↑risk of hepatotoxicity in older adults.

CV: bradycardia, hypertension, chest pain, DEEP VEIN THROMBOSIS (DVT), HF, MI, QT interval prolongation.

Derm: hair color changes (depigmentation), alopecia, facial edema, impaired wound healing, palmar-plantar erythrodysesthesia (hand-foot syndrome), rash, skin depigmentation.

Endo: hypothyroidism.

GI: abdominal pain, anorexia, diarrhea, nausea, vomiting, ↓ weight, dyspepsia, GI PERFORATION/FISTULA, HEPATOTOXICITY, PANCREATITIS.

GU: ↓fertility, HEMOLYTIC UREMIC SYNDROME, proteinuria.

Hemat: BLEEDING, neutropenia, thrombocytopenia, THROMBOTIC THROMBOCYTOPENIC PURPURA.

MS: arthralgia, muscle spasms.

Neuro: fatigue, weakness, dysgeusia, POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES), STROKE.

Resp: INTERSTITIAL LUNG DISEASE (ILD), PULMONARY EMBOLISM (PE).
Misc: TUMOR LYSIS SYNDROME.

Drug-Drug:

• Strong CYP3A4 inhibitors, including ketoconazole, ritonavir, and clarithromycin, may ↑ levels and risk of toxicity; avoid concurrent use; if concurrent use unavoidable, ↓ pazopanib dose.
• Strong CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.
• May ↑ levels and risk of toxicity of CYP3A4 substrates, CYP2D6 substrates, or CYP2C8 substrates that have narrow therapeutic windows; concurrent use is not recommended.
• ↑risk of hepatotoxicity with simvastatin.
• Proton pump inhibitors and H₂ receptor antagonists may ↓ levels; avoid concurrent use; use short-acting antacid instead.
• Antacids may ↓ levels; separate doses by several hrs.
• QT interval prolonging drugs may ↑ risk of QT interval prolongation; avoid concurrent use.

Drug-Food:

• Grapefruit juice may ↑ levels; avoid concurrent use.

(Generic available)

• Tablets: 200 mg;

• PO (Adults): 800 mg once daily until disease progression or unacceptable toxicity; Concurrent use of strong CYP3A4 inhibitors: 400 mg once daily until disease progression or unacceptable toxicity.

Votrient

• Acts as a tyrosine kinase inhibitor of several vascular endothelial growth factor receptors, platelet-derived growth factor receptor, fibroblast growth factor receptor, cytokine receptor, interleukin-2 receptor inducible T-cell kinase, leukocyte-specific protein tyrosine kinase, and transmembrane glycoprotein receptor tyrosine kinase. Overall effect is decreased angiogenesis in tumors.

• Decreased growth and spread of renal cell carcinoma.
• Improvement in progression-free survival

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Absorption: Well absorbed following oral administration; crushing tablet and ingesting food ↑ absorption.

Distribution: Unknown.

Protein Binding: >99%.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme and to a lesser extent by the CYP1A2 and CYP2C8 isoenzymes; primarily eliminated in the feces, with <4% excreted by the kidneys.

Half-life: 30.9 hr.

(plasma concentrations)

• Instruct patient to take on an empty stomach as directed. Take missed doses as soon as remembered; if <12 hr before next dose, omit dose. Advise patient to read the Medication Guide prior to taking pazopanib and with each Rx refill; new information may be available.
• Advise patient to avoid drinking grapefruit juice or eating grapefruit during therapy; may ↑ pazopanib absorption.
• Advise patient to notify health care professional immediately if signs and symptoms of liver problems (yellowing of skin or whites of eyes, dark urine, tiredness, right upper abdominal pain); HF, heart attack or stroke (chest pain or pressure; pain in arms, back, neck, or jaw; shortness of breath; numbness or weakness on one side of body; trouble talking; headache; dizziness); blood clots (sudden shortness of breath; leg pain; or coolness, pallor, swelling of extremities); bleeding problems (easy bleeding, bruising, wounds that do not heal); GI perforation or fistula; PRES (headaches, seizures, lack of energy, confusion, high BP, loss of speech, blindness or changes in vision, problems thinking); ILD (persistent cough, shortness of breath); tumor lysis syndrome (irregular heartbeat, seizures, confusion, muscle cramps or spasms, ↓ urine output); or severe infections occur.
• Inform patient that diarrhea frequently occurs. Instruct patient on ways to manage diarrhea and to notify health care professional if moderate to severe diarrhea occurs.
• Inform patient that loss of color of skin or hair may occur during therapy.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Advise patient to notify health care professional of any impending surgery. Pazopanib must be stopped for 7 days prior to surgery due to the effects on healing and held for 2 wk after major surgery or until adequate healing.
• Advise females of reproductive potential and male patients with partners of reproductive potential to use effective contraception during therapy and for 2 wk after discontinuing therapy and to notify health care professional immediately if pregnancy is suspected. Advise patient to avoid breastfeeding during therapy and for 2 wk after final dose. Inform patient that pazopanib may impair fertility for both men and women during therapy.

pah-ZOE-puh-nib