Dosage And Administration of Pazopanib

Indication: Pazopanib is an anti-cancer drug. It is a potent and selective multi-targeted receptor tyrosine kinase inhibitor that inhibits tumor growth and angiogenesis. Pazopanib is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) and adult patients with selective subtypes of advanced Soft Tissue Sarcoma (STS) who have received chemotherapy previously for the metastatic disease or who have progressed within twelve months following (neo) adjuvant therapy.

Recommended Dosing: Pazopanib tablets are available in 200-mg tablets. The recommended dose of Pazopanib is 800 mg orally once daily without food (at least 60 minutes before or 120 minutes after a meal). The Pazopanib dose should not be exceeded 800 mg. It is not recommended to crush the tablets due to the risk for increased absorption rate which may be responsible for affecting the systemic exposure.

Dose Modification Guidelines: The initial dose reduction should be 400 mg, and the additional dose decrease or increase should be in 200 mg steps based on individual tolerability. The dose of Pazopanib should not be exceeded 800 mg.

Hepatic Impairment: The pazopanib dosage in recipients with a moderate hepatic impairment needs to be reduced to 200 mg daily. There are no specific findings in recipients with severe hepatic impairment; therefore, the use of Pazopanib tablets is not recommended in these recipients.

Concomitant Strong CYP3A4 Inhibitors: The concomitant use of strong CYP3A4 inhibitors (eg, ritonavir, ketoconazole, clarithromycin) may increase the concentrations of pazopanib and should be avoided. If coadministration of ritonavir, ketoconazole, and clarithromycin are warranted, reduce the Pazopanib dose to 400 mg. Further dose reductions may be required in case adverse effects occur during pazopanib therapy. This dosage is predicted to adjust the pazopanib AUC to the range observed without inhibitors. However, there are no clinical findings with this dose adjustment in patients with strong CYP3A4 inhibitors.

Concomitant Strong CYP3A4 Inducer: The concomitant use of strong CYP3A4 inducers (eg, rifampin) may reduce the concentrations of pazopanib and should be avoided. The pills of Pazopanib should not be used in patients who can not avoid chronic use of strong CYP3A4 inducers.

Missed Dose: If a dose of Pazopanib is missed, it should not be taken if it is less than 12 hours until the next scheduled dose.

Overdose: Pazopanib doses of up to 2000 mg have been assessed in the clinical trials. The grade-3 fatigue & grade-3 hypertension were each noticed in 1 of 3 patients dosed at 2000 mg and 1000 mg daily, respectively. Treatment of overdoses with pazopanib tablets should consist of general supportive measures. There is no specific antidote for overdose of pazopanib. The hemodialysis is not expected to enhance the elimination of pazopanib because it is not significantly renally excreted and is highly bound to plasma proteins. In order to manage a suspected drug overdose, immediately call your health specialist.

Dosage Forms, Strengths, Composition & Packaging: The Pazopanib 200 mg tablets are modified capsule-shaped, gray, film-coated with GS JT debossed on one side, and come in the bottles of 120 tablets. The tablet core contains the following excipients; sodium starch glycolate, magnesium stearate, microcrystalline cellulose, and povidone (K30). The tablet coating contains the following excipients; hypromellose, iron oxide black (E172), polysorbate 80, macrogol, and titanium dioxide (E171).