Zopanib

Pazopanib blocks several tyrosine kinases at once. These include vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2 and VEGFR-3, platelet-derived growth factor receptor (PDGFR)-α and -β, and fibroblast growth factor receptor (FGFR)-1 and -3. It also acts on the cytokine receptor (Kit), interleukin-2 receptor-inducible T-cell kinase (Itk), lymphocyte-specific protein tyrosine kinase (Lck), and the transmembrane glycoprotein receptor tyrosine kinase (c-Fms). In vitro, it stopped ligand-induced autophosphorylation of the VEGFR-2, Kit and PDGFR-β receptors.

Absorption: Pazopanib is taken by mouth, and the median time to peak concentration is 2 to 4 hours after the dose. With daily dosing at 800 mg, the geometric mean AUC is 1,037 mcg/mL and the Cmax is 58.1 mcg/mL (equivalent to 132 µM). Going above 800 mg did not give a consistent rise in AUC or Cmax.

Distribution: In vivo, more than 99% of Pazopanib binds to human plasma protein, and this did not depend on concentration across the range of 10 to 100 mcg/mL. In vitro studies suggest Pazopanib is a substrate for P-gp and BCRP.

Metabolism: In vitro studies showed that CYP3A4 metabolizes Pazopanib, with a minor contribution from CYP1A2 and CYP2C8.

Elimination: After the recommended dose of 800 mg, the mean half-life of Pazopanib is 30.9 hours. Most of it leaves through the feces, and the kidneys account for less than 4% of the administered dose.

Pazopanib can cause harm to the baby when it is given to a pregnant woman. There are no data in pregnant women that could show how big the risk from the medicine is. Pregnant women, and women who could become pregnant, should be told about the possible risk to a baby.

No information is available on whether pazopanib or its metabolites pass into human milk, or what effect they have on a breastfed infant or on milk production. Because pazopanib could cause serious adverse reactions in breastfed infants, a woman who is breastfeeding should be advised not to breastfeed during treatment and for 2 weeks after the final dose.

Females: Zopanib can harm an unborn baby when it is given to a pregnant woman. Women who could become pregnant should be advised to use effective contraception during treatment and for at least 2 weeks after the last dose of Zopanib.

Males: A male patient whose female partner could become pregnant should be advised to use condoms during treatment with Zopanib and for at least 2 weeks after the last dose. This applies even to men who have had a vasectomy, and it is meant to avoid exposing a pregnant partner, or a partner who could become pregnant, to the medicine.

Pediatric Use: The safety and effectiveness of Zopanib in children have not been established.

Doses of Zopanib up to 2000 mg have been tested in clinical trials. At 2000 mg daily, 1 of 3 patients had dose-limiting toxicity (Grade 3 fatigue), and at 1000 mg daily, 1 of 3 patients had Grade 3 hypertension. If someone takes an overdose of Zopanib, treatment should be general supportive measures, as there is no specific antidote. Hemodialysis is not expected to help remove Zopanib from the body, because Zopanib is not significantly excreted by the kidneys and is highly bound to plasma proteins.

Keep Pazopanib Hydrochloride below 30° C, in a cool and dry place away from sunlight. Keep it out of reach of children.