Medication Guide App

Pazopanib Dosage

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Usual Adult Dose for:

Additional dosage information:

Usual Adult Dose for Renal Cell Carcinoma

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

The dose of pazopanib should not exceed 800 mg.

Usual Adult Dose for Soft Tissue Sarcoma

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

The dose of pazopanib should not exceed 800 mg.

Renal Dose Adjustments

Because renal impairment is not expected to influence pazopanib exposure, dose adjustment is not necessary.

Liver Dose Adjustments

Alternatives to pazopanib should be considered in patients with moderate hepatic impairment; however, if pazopanib is used in patients with moderate hepatic impairment, the dose should be reduced to 200 mg per day.

There are no data in patients with severe hepatic impairment. Therefore, the use of pazopanib is not recommended in patients with severe hepatic impairment.

Patients who develop isolated ALT elevations between 3 times ULN and 8 times ULN may be continued on pazopanib with weekly monitoring of liver function until ALT returns to grade 1 or baseline. Patients who develop isolated ALT elevations of greater than 8 times ULN should have pazopanib interrupted until they return to grade 1 or baseline. If the potential benefit for reinitiating treatment with pazopanib is considered to outweigh the risk for hepatotoxicity, then pazopanib may be reintroduced at a reduced dose of no more than 400 mg once daily and serum liver tests should be monitored weekly for 8 weeks. Following reintroduction of pazopanib, if ALT elevations greater than 3 times ULN recur, then pazopanib should be permanently discontinued. If ALT elevations greater than 3 times ULN occur concurrently with bilirubin elevations greater than 2 times ULN, pazopanib should be permanently discontinued.

Dose Adjustments

In renal cell carcinoma (RCC), the initial dose reduction should be 400 mg. Additional dose decreases or increases should be in 200 mg steps based on individual tolerability. In soft tissue sarcoma (STS), a decrease or increase should be in 200 mg steps based on individual tolerability. The dose of pazopanib should not exceed 800 mg.


Concomitant Strong CYP450 3A4 Inhibitors:
The concomitant use of strong CYP450 3A4 inhibitors (e.g., ketoconazole, ritonavir, clarithromycin) may increase pazopanib concentrations and should be avoided. An alternate concomitant medication with no or minimal potential to inhibit CYP450 3A4 should be considered. If coadministration of a strong CYP450 3A4 inhibitor is warranted, reduce the dose of pazopanib to 400 mg. Further dose reductions may be needed if adverse effects occur during therapy. This dose is predicted to adjust the pazopanib AUC to the range observed without inhibitors. However, there are no clinical data with this dose adjustment in patients receiving strong CYP450 3A4 inhibitors.

Concomitant Strong CYP450 3A4 Inducer:
The concomitant use of strong CYP450 3A4 inducers (e.g., rifampin) may decrease pazopanib concentrations and should be avoided. Pazopanib should not be used in patients who cannot avoid chronic use of strong CYP450 3A4 inducers.

Precautions

Severe and fatal hepatotoxicity has occurred. Serum liver tests should be monitored before initiation of treatment with pazopanib and at least once every four weeks for at least the first four months of treatment or as clinically indicated. Periodic monitoring should then continue after this time period. Patients with isolated ALT elevations between 3 times ULN and 8 times ULN may be continued on pazopanib with weekly monitoring of liver function until ALT returns to grade 1 or baseline. Patients with isolated ALT elevations of greater than 8 times ULN should have pazopanib interrupted until they return to grade 1 or baseline. If the potential benefit for reinitiating treatment with pazopanib is considered to outweigh the risk for hepatotoxicity, then pazopanib may be reintroduced at a reduced dose of no more than 400 mg once daily and serum liver tests should be monitored weekly for 8 weeks. Following reintroduction of pazopanib, if ALT elevations greater than 3 times ULN recur, then pazopanib should be permanently discontinued. If ALT elevations greater than 3 times ULN occur concurrently with bilirubin elevations greater than 2 times ULN, pazopanib should be permanently discontinued. Patients should be monitored until resolution. Pazopanib is a UGT1A1 inhibitor. Mild, indirect (unconjugated) hyperbilirubinemia may occur in patients with Gilbert's syndrome. Patients with only a mild indirect hyperbilirubinemia, known Gilbert's syndrome, and elevation in ALT greater than 3 times ULN should be managed as per the recommendations outlined for isolated ALT elevations.

Pazopanib should be used with caution in patients with a history of QT interval prolongation, in patients taking antiarrhythmics or other medications that may prolong QT interval, and those with relevant preexisting cardiac disease. When using pazopanib, baseline and periodic monitoring of electrocardiograms and maintenance of electrolytes (e.g., calcium, magnesium, potassium) within the normal range should be performed.

Cardiac dysfunction, including decreased left ventricular ejection fraction (LVEF) and congestive heart failure, has occurred in clinical trials. Monitor blood pressure and manage hypertension promptly. Baseline and periodic evaluation of LVEF is recommended in patients at risk of cardiac dysfunction.

Venous thromboembolic (VTE) events including venous thrombosis (VT) and fatal pulmonary embolus (PE) have occurred. Monitor for signs and symptoms of VTE and PE.

Gastrointestinal perforation or fistula has been reported including fatal perforation events. Symptoms of gastrointestinal perforation or fistula should be monitored.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS) has been reported and may be fatal. RPLS is a neurological disorder which can present with headache, seizure, lethargy, confusion, blindness and other visual and neurologic disturbances. Mild to severe hypertension may be present. The diagnosis of RPLS is optimally confirmed by magnetic resonance imaging. Discontinue pazopanib in patients developing RPLS.

Hypertension and hypertensive crisis have been reported. Hypertension typically occurs early in the course of treatment (90% of cases occurred in the first 18 weeks). Blood pressure should be well controlled prior to initiating pazopanib. Patients should be monitored for hypertension and treated as needed with antihypertensive therapy and pazopanib dose reduction or interruption. Pazopanib should be discontinued if there is evidence of hypertensive crisis or if hypertension is severe and persistent despite antihypertensive therapy and pazopanib dose reduction.

No formal studies on the effect of pazopanib on wound healing have been conducted. Since vascular endothelial growth factor receptor (VEGFR) inhibitors such as pazopanib may impair wound healing, treatment with pazopanib should be stopped at least seven days prior to scheduled surgery. The decision to resume pazopanib after surgery should be based on clinical judgment of adequate wound healing. Pazopanib should be discontinued in patients with wound dehiscence.

In RCC and STS trials, hypothyroidism has been reported as an adverse reaction. Proactive monitoring of thyroid function tests is recommended.

Proteinuria has been reported in patients treated with pazopanib. Baseline and periodic urinalysis during treatment is recommended with follow-up measurement of 24-hour urine protein as clinically indicated. Interrupt pazopanib and dose reduce for 24-hour urine protein greater than or equal to 3 grams; discontinue pazopanib for repeat episodes despite dose reductions.

Serious infections (with or without neutropenia), including some with fatal outcome, have been reported. Monitor patients for signs and symptoms of infection. Institute appropriate anti-infective therapy promptly and consider interruption or discontinuation of pazopanib for serious infections.

Safety and effectiveness have not been established in pediatric patients (less than 18 years of age).

Dialysis

Data not available

Other Comments

Pazopanib should be taken at least 1 hour before or 2 hours after a meal. Tablets should be taken whole with water and must not be crushed 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 less than 12 hours until the next dose.

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