pazopanib

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);
Rep: 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.

Adv. Reactions/Side Effects ⬆ ⬇

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

Interactions ⬆ ⬇

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.

Availability ⬆ ⬇

(Generic available)

Tablets: 200 mg

Route/Dosage ⬆ ⬇

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.

Hepatic Impairment

PO (Adults ): Moderate hepatic impairment: 200 mg once daily until disease progression or unacceptable toxicity.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

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.

Therapeutic effects:

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

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

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.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	PO	2–4 hr	24 hr

Patient/Family Teaching ⬆ ⬇

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.
Rep: 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.

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Indications ⬇

Contraind./Precautions ⬆ ⬇