Pazopanibdosage

Recommended Dosage: 800 mg orally once daily without food (at least 1 hour before or 2 hours after a meal).

Moderate Hepatic Impairment: 200 mg orally once daily.

2.1 Recommended

Dosage The recommended dosage of pazopanib tablets is 800 mg (four 200 mg tablets) orally once daily without food (at least 1 hour before or 2 hours after a meal) until disease progression or unacceptable toxicity. The dosage should be modified for hepatic impairment and in patients taking certain concomitant drugs. Swallow tablets whole. Do not crush tablets due to the potential for increased rate of absorption, which may affect systemic exposure. If a dose is missed, it should not be taken if it is <12 hours until the next dose.

2.2 Dosage Modifications for

Adverse Reactions Table 1 summarizes the recommended dose reductions. Table 1. Recommended Dose Reductions of Pazopanib tablets for Adverse Reactions Dose Reduction For Renal Cell Carcinoma For Soft Tissue Sarcoma First 400 mg orally once daily 600 mg orally once daily Second 200 mg orally once daily 400 mg orally once daily Permanently discontinue pazopanib tablets in patients unable to tolerate the second dose reduction. Table 2 summarizes the recommended dosage modifications for adverse reactions. Table 2. Recommended Dosage Modifications of Pazopanib Tablets for Adverse Reactions Adverse Reaction Severity a Dosage Modification Hepatic Toxicity Isolated ALT elevations between 3 x ULN and 8 x ULN Continue and monitor liver function weekly until ALT returns to Grade 1 or baseline. Isolated ALT elevations of > 8 x ULN Withhold until improvement to Grade 1 or baseline. If the potential benefit for resuming treatment with pazopanib tablets is considered to outweigh the risk for hepatotoxicity, then resume at a reduced dose of no more than 400 mg once daily and measure serum liver tests weekly for 8 weeks. Permanently discontinue if ALT elevations > 3 x ULN recur despite dose reduction(s). ALT elevations > 3 x ULN occur concurrently with bilirubin elevations > 2 x ULN Permanently discontinue and continue to monitor until resolution. Patients with only a mild, indirect (unconjugated) hyperbilirubinemia, known as Gilbert's syndrome, and ALT elevations > 3 x ULN should be managed per the recommendations outlined for isolated ALT elevations. Left Ventricular Systolic Dysfunction Symptomatic or Grade 3 Withhold until improvement to Grade < 3. Resume treatment based on medical judgement. Grade 4 Permanently discontinue. Hemorrhagic Events Grade 2 Withhold until improvement to Grade ≤ 1. Resume at reduced dose (see Table 1). Permanently discontinue if Grade 2 recurs after dose interruption and reduction. Grade 3 or 4 Permanently discontinue. Arterial Thromboembolic Events Any grade Permanently discontinue. Venous Thromboembolic Events Grade 3 Withhold pazopanib tablets and resume at same dose if managed with appropriate therapy for at least one week. Grade 4 Permanently discontinue. Thrombotic Microangiopathy Any grade Permanently discontinue. Gastrointestinal Perforation Any grade Permanently discontinue. Gastrointestinal Fistula Grade 2 or 3 Withhold and resume based on medical judgement. Grade 4 Permanently discontinue. Interstitial Lung Disease / Pneumonitis Any grade Permanently discontinue. Posterior Reversible Encephalopathy Syndrome Any grade Permanently discontinue. Hypertension Grade 2 or 3 Reduce dose (see Table 1) and initiate or adjust anti-hypertensive therapy. Permanently discontinue if hypertension remains Grade 3 despite dose reduction(s) and adjustment of anti-hypertensive therapy. Grade 4 or hypertensive crisis Permanently discontinue. Proteinuria 24-hour urine protein ≥ 3 grams Confirmed nephrotic syndrome Withhold until improvement to Grade ≤ 1. Resume at a reduced dose (see Table 1). Permanently discontinue if 24-hour urine protein ≥ 3 grams does not improve or recurs despite dose reductions. Permanently discontinue.

Abbreviations: ALT, alanine aminotransferase; ULN, upper limit of normal. a National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.

2.3 Dosage Modifications for

Hepatic Impairment Moderate and Severe Hepatic Impairment In patients with moderate hepatic impairment [total bilirubin > 1.5 to 3 x upper limit of normal (ULN) and any alanine aminotransferase (ALT) value], consider alternatives to pazopanib tablets. If pazopanib tablets are used in patients with moderate hepatic impairment, reduce the pazopanib tablets dose to 200 mg orally once daily. Pazopanib tablets are not recommended in patients with severe hepatic impairment (total bilirubin > 3 x ULN and any ALT value). Strong CYP3A4 Inducers Avoid concomitant use of strong CYP3A4 inducers by use of an alternate concomitant medication with no or minimal enzyme induction potential. Pazopanib tablets are not recommended in patients who cannot avoid chronic use of strong CYP3A4 inducers. Gastric Acid-Reducing Agents Avoid concomitant use of gastric acid-reducing agents. If concomitant use of a gastric acid-reducing agent cannot be avoided, consider short-acting antacid in place of proton pump inhibitors (PPIs) and H 2 -receptor antagonists. Separate short-acting antacid and pazopanib tablets dosing by several hours.