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Pazopanib

Class
VEGF inhibitors
Subclass
Tyrosine kinase inhibitors
Generic name
PAZOPanib hydrochloride
Brand names
Votrient®
Common formulations
Film-coated tablet
Dosage and administration
Adults patients
Renal cell carcinoma
•
800 mg PO daily until disease progression or unacceptable toxicity
Soft tissue sarcoma • Advanced
•
800 mg PO daily until disease progression or unacceptable toxicity
Other off-label uses
•
Treatment of gastrointestinal stromal tumors (unresectable, metastatic)
Indications for use
Labeled indications
Adults
•
Treatment of renal cell carcinoma
•
Treatment of soft tissue sarcoma (advanced)
Off-label indications
Adults
•
Treatment of gastrointestinal stromal tumors (unresectable, metastatic)
Safety risks
Warnings and precautions
Acute hemorrhage
•
Use caution with a history of hemoptysis, intracranial bleeding, or clinically significant gastrointestinal bleeding in the previous 6 months.
ALF
•
Use caution with moderate or severe hepatic disease.
Congestive HF
•
Use caution with pre-existing cardiac dysfunction.
Exacerbation of hypercholesterolemia
•
Use caution with pre-existing Hypercholesterolemia.
Gastrointestinal perforation
•
Use caution with pre-existing gastrointestinal disorders.
Hypertensive crisis
•
Use caution with pre-existing hypertension.
Hypothyroidism
•
Use caution with a history of thyroid dysfunction.
Long QT syndrome
•
Use caution with conditions that may increase the risk of QT prolongation or receiving medications known to cause an electrolyte imbalance.
Myocardial infarction
•
Use caution with a history of angina, stroke, or TIAs.
Pneumonitis
•
Use caution with a history of pulmonary disease.
Posterior reversible encephalopathy syndrome
•
Use caution with risk factors, such as; headache, seizures, lethargy, confusion, blindness, and other visual and neurologic disturbances.
Proteinuria
•
Use caution with a history of nephrotic syndrome.
Thrombotic microangiopathy
•
Use caution who received single-agent pazopanib, or pazopanib in combination with bevacizumab or topotecan.
Tumor lysis syndrome
•
Use caution with rapidly growing tumors, a high tumor burden, renal impairment, or dehydration.
VTE
•
Use caution with thromboembolic disease.
Specific populations
Renal impairment
eGFR 30-50 mL/min/1.73 m²
•
Use acceptable. No dose adjustment required.
eGFR 10-30 mL/min/1.73 m²
•
Use with caution.
eGFR < 10 mL/min/1.73 m²
•
Use with caution.
Renal replacement therapy
Continuous renal replacement
•
Use with caution. Monitor liver function tests.
Intermittent hemodialysis
•
Use with caution. Monitor liver function tests.
Peritoneal dialysis
•
Use with caution. Monitor liver function tests.
Hepatic impairment
Child-Pugh A (mild)
•
Use acceptable. No dose adjustment required.
Child-Pugh B (moderate)
•
Reduce dose. Start at dose of 200 mg daily.
Child-Pugh C (severe)
•
Do not use.
Pregnancy and breastfeeding
Pregnancy
All trimesters • Australia Category: D
•
Avoid use. Evidence of fetal harm in humans. This drug can harm a developing fetus.
•
Adequate methods of contraception should be encouraged.
•
Verify negative pregnancy status in females of reproductive potential prior to initiating therapy.
•
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.
•
Advise females of reproductive potential to use effective contraception during therapy and for at least 2 weeks after.
•
Advise males (including those who have had vasectomies) with female partners of reproductive potential to use condoms during therapy and for at least 2 weeks after.
•
Based on findings from animal studies, this drug may impair fertility in females and males of reproductive potential.
Breastfeeding
Do not use during breastfeeding.
Unknown amount excreted in breastmilk.
Unknown drug levels in breastfed infants.
Adverse reactions
Very common > 10%
•
Alopecia, bradycardia, ↓ blood glucose, ↓ serum magnesium, ↓ serum phosphate, ↓ serum sodium, hypertension, hypoalbuminemia, hypopigmentation, ↑ blood glucose, ↑ serum ALP, ↑ serum AST, ↑ serum TBIL, ↑ serum potassium, peripheral edema, abdominal pain, asthenia, bleeding, change in taste, cough, diarrhea, dizziness, dyspnea, fatigue, hair discoloration, headache, loss of appetite, loss of appetite, musculoskeletal pain, nausea, skin rash, vomiting, weight loss, stomatitis
Common 1-10%
•
Acute pancreatitis, congestive heart failure, drug-induced liver injury, dry skin patches, facial edema, gastrointestinal perforation, hypothyroidism, ↑ serum lipase, ↑ urine protein, myocardial infarction, nail abnormality, pulmonary embolism, palmar-plantar erythrodysesthesia, pneumothorax, ↑QT interval, anal bleeding, blurred vision, chest pain, hematuria, hemoptysis, indigestion, insomnia, nosebleed, shivering, speech disturbance, transient ischemic attack, venous thromboembolism
Uncommon < 1%
•
Arterial thromboembolism, cerebrovascular accident, interstitial lung disease, torsade de pointes
Unknown frequency
•
Acute heart failure, aneurysms, aortic dissection, hypertensive crisis, ↑ RBCs, infections, nephrotic syndrome, posterior reversible encephalopathy syndrome, radiation recall reaction, arthralgia, hallucinations, muscle spasms, retinal detachment, thrombotic microangiopathy, tumor lysis syndrome
Interactions
Drug(s)
Check Interactions
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