Votrient (pazopanib HCl)

Dosage of pazopanib hydrochloride is expressed in terms of pazopanib.

If adverse reactions occur, temporary interruption of therapy, dosage reduction, and/or discontinuance of pazopanib may be necessary. If dosage modification is required, reduce the dosage of pazopanib as described in Table 1.

Table 1. Recommended Dosage Reduction for Pazopanib Toxicity

Dosage Reduction Renal Cell Carcinoma Soft Tissue Sarcoma (Starting dosage = 800 (Starting dosage = 800 mg once daily) mg once daily) First 400 mg once daily 600 mg once daily Second 200 mg once daily 400 mg once daily Third Permanently discontinue Permanently discontinue drug drug

Pazopanib hydrochloride is administered orally once daily. Administer the drug without food (i.e., at least 1 hour before or 2 hours after a meal). Pazopanib hydrochloride tablets should be swallowed whole and should not be crushed; crushing the tablets has been shown to increase the rate of absorption and systemic exposure to the drug. Store tablets at 20-25degreesC (excursions permitted between 15-30degreesC).

Concomitant use of pazopanib with drugs affecting gastric pH may result in decreased pazopanib exposure and should be avoided. If concomitant use with a drug affecting gastric pH cannot be avoided, consider a short-acting antacid rather than a proton-pump inhibitor or histamine H2-receptor antagonist. The administration of a short-acting antacid and pazopanib should be separated by several hours.

No dosing information is available for this tab.

No dosing information is available for this tab.

Pazopanib is metabolized principally by cytochrome P-450 (CYP) isoenzyme 3A4 and, to a lesser extent, by CYP isoenzymes 1A2 and 2C8. Results of drug interaction studies in cancer patients suggest that pazopanib is a weak inhibitor of CYP isoenzymes 3A4, 2C8, and 2D6 but has no effect on CYP isoenzymes 1A2, 2C9, or 2C19. In vitro studies indicate that pazopanib may induce and/or inhibit CYP3A4, and inhibit CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 2E1.

In vitro studies indicate that pazopanib inhibits uridine diphosphate-glucuronosyltransferase (UGT) 1A1 and organic anion transport protein (OATP) 1B1; the drug appears to be a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*The manufacturer states there are no known contraindications to the use of pazopanib.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Adverse effects reported in 20% or more of patients receiving pazopanib for renal cell carcinoma include diarrhea, hypertension, hair color changes (depigmentation), nausea, anorexia, and vomiting.

Adverse effects reported in 20% or more of patients receiving pazopanib for soft tissue sarcoma include fatigue, diarrhea, nausea, decreased weight, hypertension, decreased appetite, vomiting, tumor pain, hair color changes, musculoskeletal pain, headache, dysgeusia, dyspnea, and skin hypopigmentation.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

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Safety and efficacy have not been established in pediatric patients younger than 18 years of age.

Pazopanib may cause serious adverse effects on organ development in pediatric patients, particularly in those less than 2 years of age. In animal studies conducted in juvenile rats less than 21 days old, organ toxicity (i.e., lungs, liver, heart, kidney) and death occurred following administration of pazopanib at doses significantly lower than the clinically recommended dose or doses tolerated in older animals.

Based on animal reproduction studies and its mechanism of action, pazopanib may cause fetal harm. There are no adequate and well-controlled studies in pregnant women. In animal studies, administration of pazopanib during organogenesis resulted in teratogenicity and abortion at systemic exposures lower than those observed at the maximum recommended human dose. Avoid pregnancy during therapy. If used during pregnancy or if the patient becomes pregnant while receiving pazopanib, apprise the patient of the potential fetal hazard.

It is not known whether pazopanib or its metabolites are distributed into human milk. The effects of pazopanib or its metabolites on a breast-fed infant or milk production are unknown. Because of the potential for serious adverse reactions to pazopanib in breast-fed infants, avoid breast-feeding during pazopanib treatment and for 2 weeks after the final dose of pazopanib.

The manufacturer makes no specific dosage recommendations for geriatric patients.

In an analysis of pooled clinical trial data from all pazopanib studies, 30% of patients were 65 years of age or older; ALT elevations exceeding 3 times the ULN occurred more frequently in older patients compared to younger adults. ALT elevations exceeding 3 times the ULN occurred in 23% of patients 65 years of age or older and in 18% of patients less than 65 years of age.

In an analysis of pooled data from studies involving 586 patients with renal cell carcinoma, 33% of patients were 65 years of age or older; no overall differences in safety or efficacy were observed between older and younger adults.

In an analysis of pooled data from studies involving 382 patients with soft tissue sarcoma, 24% of patients were 65 years of age or older. Patients 65 years of age or older had a higher incidence of grade 3 or 4 fatigue, hypertension, decreased appetite, ALT elevations, and AST elevations. No overall differences in efficacy were observed between patients 65 years of age or older and younger adults.