What are the precautions for Voranigo (Vorasidenib)?

In clinical studies of Voranigo (Vorasidenib) in the treatment of patients with grade 2 astrocytoma or oligodendroglioma and with predisposing IDH1 or IDH2 mutations, the most important warnings and precautions included hepatotoxicity and embryo-fetotoxicity. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Hepatotoxicity:Voranigo may cause an increase in liver transaminases, leading to liver failure, hepatic necrosis and autoimmune hepatitis. In clinical studies, 58% of patients experienced an increase in alanine aminotransferase (ALT), and 44% of patients experienced an increase in aspartate aminotransferase (AST)elevated, a total of34% of patients had gamma-glutamyl transferase (GGT), 4.8% of patients had elevated bilirubin, and 9% of patients had elevated alkaline phosphatase. Two patients met the laboratory criteria for Hy's law with concurrent elevations of ALT or AST >3 times the upper limit of normal and total bilirubin elevations >2 times the upper limit of normal; these events were associated with cases of autoimmune hepatitis and liver failure.

Patients Before initiating Voranigo, monitor liver laboratory tests (AST, ALT, GGT, total bilirubin, and alkaline phosphatase) every 2 weeks for the first 2 months of treatment, then monthly for the first 2 years of treatment, and more frequently as clinically indicated in patients with elevated transaminases. Reduce dose, suspend, or permanently discontinue Voranigo based on severity.

2. Embryo-Fetal toxicity: According to the results of animal studies, Voranigo can cause harm to the fetus when administered to pregnant women. In animal embryo-fetal development studies, oral administration of vorasidenib to pregnant rats during organogenesis resulted in embryo-fetal toxicity at doses ≥45 times the human exposure, based on the area under the concentration-time curve (AUC) at the highest recommended dose. Based on AUC at the highest recommended dose, oral administration of vorasidenib to pregnant rabbits during organogenesis resulted in embryo-fetal toxicity at doses ≥8 times the human exposure.

Inform pregnant women and women of reproductive potential of the potential risks to the fetus. Advise females of reproductive potential to use effective non-hormonal contraceptives during treatment with Voranigo and for 3 months after the last dose, as Voranigo may cause some hormonal contraceptives to be ineffective. Advise male patients with a female partner of reproductive potential to use an effective method of contraception during treatment and for 3 months after the last dose.

In addition, patients need to tell their doctor about all medications they are taking, including prescription and over-the-counter medications, vitamins, and herbal supplements. Voranigo may affect the way other medicines work, and other medicines may affect how Voranigo works.