pazopanib

Contraindicated in:

Severe hepatic impairment
History of hemoptysis, 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 (may cause fetal harm)
Lactation: Lactation.

Use Cautiously in:

Congenital prolonged QTc interval or concurrent medications/diseases that prolong QTc (may ↑ risk of torsades de pointes)
Electrolyte abnormalities (correct prior to use; may ↑ risk of potentially serious arrhythmia)
Patients at risk for gastrointestinal 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: HF, MI, DEEP VEIN THROMBOSIS, bradycardia, hypertension, chest pain, QT interval prolongation.

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

GU: HEMOLYTIC UREMIC SYNDROME, ↓ fertility, proteinuria.

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

Endo: hypothyroidism.

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

Metab: ↑lipase, weight loss.

MS: arthralgia, muscle spasms.

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

Resp: INTERSTITIAL LUNG DISEASE, PULMONARY EMBOLISM.

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.

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.

Implementation ⬆ ⬇

Do not confuse pazopanib with ponatinib.
May impair wound healing. Hold pazopanib at least 1 wk prior to elective surgery. Do not administer for at least 2 wks following major surgery and until adequate wound healing.
Recommended Dose Reductions: For Renal Carcinoma, 1st reduction: 400 mg once daily; 2nd reduction: 200 mg once daily. For Soft Tissue Sarcoma, 1st reduction: 600 mg once daily; 2nd reduction: 400 mg once daily.
PO: Administer at least 1 hr before or 2 hr after a meal. DNC: Swallow tablets whole; do not crush tablets.

US Brand Names ⬆ ⬇

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Availability ⬆ ⬇

Tablets: 200 mg;

Time/Action Profile ⬆ ⬇

(blood levels)

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

Assessment ⬆ ⬇

Monitor BP during frequent therapy; may cause hypertension. BP should be well-controlled prior to initiating therapy. If Grade 2 or 3 hypertension occurs, reduce dose and start or adjust antihypertensive therapy. Permanently discontinue pazopanib if hypertension remains Grade 3 despite dose reduction(s) and adjustment of antihypertensive therapy. If Grade 4 hypertension or hypertensive crisis occur, permanently discontinue pazopanib. Baseline and periodic evaluation of LVEF is recommended in patients at risk of cardiac dysfunction. If LVEF is symptomatic or Grade 3, hold pazopanib until improved to Grade <3. Resume therapy based on medical judgement. If LVEF is Grade 4, permanently discontinue pazopanib.
Obtain baseline ECG and monitor periodically during therapy. Maintain serum calcium, magnesium, and potassium within normal range during therapy. Monitor patients who are at risk of developing QTc prolongation (patients with a history of QT interval prolongation, patients taking antiarrhythmics or other medications that may prolong QT interval, those with relevant preexisting cardiac disease). Monitor ECG and electrolytes (calcium, magnesium, potassium) at baseline and as indicated. Correct hypokalemia, hypomagnesemia and hypocalcemia prior to starting and during therapy.
Monitor for signs and symptoms of GI perforation and fistula (abdominal pain; swelling in stomach area; vomiting blood; black sticky stools; GI bleeding) during therapy. If Grade 2 or 3 GI fistula occurs, hold pazopanib and resume based on medical judgement. If Grade 4 fistula occurs, permanently discontinue pazopanib.
Monitor for signs and symptoms of bleeding. If Grade 2 symptoms occur, hold pazopanib until improvement to Grade 1. Resume at reduced dose. If Grade 2 symptoms recur after dose interruption and reduction or Grade 3 or 4 symptoms occur, permanently discontinue pazopanib.
Monitor for signs and symptoms of arterial thromboembolic events (MI, stroke, TIA). If symptoms occur, permanently discontinue pazopanib.
Monitor for signs and symptoms on venous thromboembolic events (venous thrombosis, pulmonary embolism). If Grade 3 symptoms occur, hold pazopanib and resume at same dose if managed with appropriate therapy for at least 1 wk. If Grade 4 symptoms occur, permanently discontinue pazopanib.
Monitor for pulmonary symptoms indicative of interstitial lung disease/pneumonitis. Permanently discontinue pazopanib in patients who develop ILD or pneumonitis.
Monitor for signs and symptoms of PRES (headache, seizure, lethargy, confusion, blindness, mild hypertension). Diagnosis is confirmed by MRI. Discontinue pazopanib permanently if PRES occurs.

Lab Test Considerations:

Verify negative pregnancy status prior to starting therapy.
Monitor serum liver tests before initiation and wks 3, 5, 7, and 9, then at mo 3 and mo 4 if symptoms occur. Monitor periodically after mo 4. If isolated ALT ↑ between 3 and 8 times the upper limit of normal, therapy may continue with weekly monitoring of liver function until ALT returns to Grade 1 or baseline. If isolated ALT ↑ >8 times the upper limit of normal, stop therapy until ALT returns to Grade 1 or baseline. If benefit outweighs risk, may reintroduce at reduced dose of 400 mg/day with weekly serum liver tests for 8 wk. Following reintroduction, if ALT ↑ >3 times the upper limit of normal recurs, permanently discontinue pazopanib. If ALT ↑ occurs concurrently with ↑ serum bilirubin >2 times the upper limit of normal, discontinue pazopanib permanently. Monitor liver function tests until return to baseline. Patients with only mild indirect hyperbilirubinemia (Gilbert's syndrome) and ↑ ALT >3 times the upper limit of normal should be managed as per recommendations for ↑ ALT.
- Monitor thyroid function periodically during therapy. May cause hypothyroidism.
- Obtain baseline urinalysis and monitor periodically with follow up with 24-hour urine protein as indicated. If 24–hr urine protein 3 g, hold pazopanib until improvement to Grade 1. Resume at a reduced dose. Permanently discontinue if 24-hour urine protein 3 grams does not improve or recurs despite dose reductions or if nephrotic syndrome is confirmed. May cause proteinuria. Discontinue therapy if Grade 4 proteinuria develops.
- May cause leukopenia, neutropenia, thrombocytopenia, and lymphocytopenia.
- May cause ↑ AST and ↓ serum phosphorous, sodium, and magnesium. May cause ↑ or ↓ serum glucose.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take pazopanib on an empty stomach as directed. Take missed doses as soon as remembered; if less than 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 increase amounts of pazopanib absorbed.
Advise patient to notify health care professional immediately if signs and symptoms of liver problems (yellowing of skin or whites of eyes, unusual darkening of urine, unusual tiredness, pain in the right upper stomach area), heart failure (shortness of breath), 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 (new chest pain, trouble breathing or shortness of breath that starts suddenly; leg pain; swelling of arms and hands, or legs and feet; cool or pale arm or leg), bleeding problems (unusual 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, and problems thinking), severe increase in BP (severe chest pain, severe head ache, blurred vision, confusion, nausea and vomiting, severe anxiety, shortness of breath, seizures, unconsciousness), interstitial lung disease (persistent cough, shortness of breath), tumor lysis syndrome (irregular heartbeat, seizures, confusion, muscle cramps or spasms, decrease in urine output) or severe infections (fever; cold symptoms such as runny nose or sore throat that do not go away; flu symptoms such as cough, tiredness, and body aches; pain when urinating; cuts, scrapes or wounds that are red, warm, swollen or painful) 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 (depigmentation) of skin or hair may occur during therapy. Explore methods of coping.
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 at least 7 days prior to surgery due to the effects on healing and held for at least 2 wks 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 at least 2 wk after discontinuing therapy, and to notify health care professional immediately if pregnancy is suspected. Advise patient to avoid breast feeding during therapy and for 2 wks after final dose. Inform patients that pazopanib may impair fertility for both men and women during therapy.

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Pronunciation ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Contraind./Precautions ⬆ ⬇