Pazopanib

FDA label

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Renal No adjustment needed (not studied in severe renal impairment or dialysis)

Hepatic Mild: no adjustment. Moderate (bilirubin >1.5–3× ULN): consider alternatives; if used, 200 mg QD. Severe (bilirubin >3× ULN): not recommended

Toxicity dose reductions differ by indication: RCC 800→400→200 mg QD; STS 800→600→400 mg QD; discontinue if second reduction not tolerated

Instructions

• Take without food (≥1 h before or 2 h after a meal)
• Swallow tablets whole; do not crush (increases absorption/exposure)
• Missed dose: skip if <12 h until next dose
• Strong CYP3A4 inhibitors: avoid; if unavoidable, reduce to 400 mg QD
• Strong CYP3A4 inducers: avoid; not recommended if chronic use unavoidable
• Avoid gastric acid-reducing agents; if needed, use short-acting antacid separated by several hours (not PPIs/H2RAs)
• Withhold ≥1 week before elective surgery; do not give for ≥2 weeks after major surgery and until adequate wound healing

Cautions

• Hepatotoxicity (boxed): monitor LFTs at baseline, weeks 3/5/7/9, months 3 and 4, then periodically; weekly if ALT elevated; age >65 at greater risk; concomitant simvastatin increases ALT-elevation risk
• QT prolongation/torsades de pointes: monitor ECG and electrolytes; correct K/Mg/Ca before and during treatment; avoid other QT-prolonging drugs
• Cardiac dysfunction (decreased LVEF, CHF): baseline/periodic LVEF in at-risk patients (e.g., prior anthracycline)
• Fatal hemorrhagic events; not studied with recent hemoptysis, cerebral or significant GI hemorrhage (past 6 months)
• Arterial thromboembolic events (can be fatal): permanently discontinue if they occur
• Venous thromboembolism incl. fatal PE
• Thrombotic microangiopathy (TTP/HUS): permanently discontinue
• GI perforation and fistula (can be fatal)
• Interstitial lung disease/pneumonitis (can be fatal): permanently discontinue
• Posterior reversible encephalopathy syndrome: permanently discontinue
• Hypertension incl. hypertensive crisis: do not initiate with uncontrolled BP; monitor and treat
• Impaired wound healing
• Hypothyroidism: monitor thyroid tests
• Proteinuria: baseline and periodic urinalysis; discontinue for nephrotic syndrome
• Tumor lysis syndrome (some fatal)
• Serious/fatal infections
• Embryo-fetal toxicity: effective contraception required

Adverse reactions

• RCC (≥20%): diarrhea, hypertension, hair color changes, nausea, anorexia, vomiting
• STS (≥20%): fatigue, diarrhea, nausea, weight loss, hypertension, decreased appetite, vomiting, tumor pain, hair color changes, musculoskeletal pain, headache, dysgeusia, dyspnea, skin hypopigmentation
• Labs: ALT/AST elevation (~50%), hyperglycemia, hyperbilirubinemia, leukopenia, neutropenia, thrombocytopenia, lymphocytopenia
• Postmarketing: pancreatitis, retinal detachment/tear, polycythemia, arterial (incl. aortic) aneurysms/dissections/rupture, TLS

Pregnancy Can cause fetal harm (teratogenicity/abortion in animals below human exposure); verify pregnancy status first; females use effective contraception during and ≥2 wk after; males use condoms during and ≥2 wk after

Lactation Do not breastfeed during treatment and for 2 weeks after final dose