Idelalisib

Strong CYP3A Inhibitors : Additional monitoring required if alternative therapy is not available. ( 7.1 ) Strong CYP3A Inducers : Avoid coadministration of strong CYP3A inducers. ( 7.1 ) CYP3A Substrates : Avoid coadministration of sensitive CYP3A substrates. ( 7.2 )

7.1 Effects of Other Drugs on Zydelig Table 6 lists the potential effects of the coadministration of strong CYP3A modulators on Zydelig. Table 6 Drug Interactions with Zydelig that affect Idelalisib Concentrations Strong CYP3A Inhibitors Clinical Impact Coadministration with strong CYP3A inhibitors may increase idelalisib concentrations [see Clinical Pharmacology (12.3) ] . Increased idelalisib concentrations may increase the risk of exposure related adverse reactions. Prevention or Management Use other drugs that are not strong CYP3A inhibitors. If unable to use alternative drugs, monitor patients more frequently for Zydelig adverse reactions [see Adverse Reactions (6.1) ] .

Strong CYP3A Inducers Clinical Impact Coadministration with strong CYP3A inducers may decrease idelalisib concentrations [see Clinical Pharmacology (12.3) ] . Decreased idelalisib concentrations may reduce efficacy. Prevention or Management Avoid coadministration of Zydelig with strong CYP3A4 inducers.

7.2 Effects of Zydelig on Other Drugs The coadministration of Zydelig with a CYP3A substrate may increase the concentrations of this CYP3A substrate. Avoid coadministration of Zydelig with sensitive CYP3A substrates [see Clinical Pharmacology (12.3) ].

8.1 Pregnancy Risk Summary Based on findings in animal studies and the mechanism of action [see Clinical Pharmacology (12.1) ] , Zydelig may cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of idelalisib to pregnant rats during organogenesis resulted in decreased fetal weight and congenital malformations in rats at maternal exposures (AUC) 12 times those reported in patients at the recommended dosage of 150 mg twice daily (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage of clinically recognized pregnancies 2–4% and 15–20%, respectively. Data Animal Data In an embryo-fetal development study in rats, pregnant animals receiving oral doses of idelalisib during the period of organogenesis (implantation to closure of the hard palate), embryo-fetal toxicities were observed at the mid- and high-doses that also resulted in maternal toxicity, based on reductions in maternal body weight gain.

Adverse findings at idelalisib doses ≥ 75 mg/kg/day included decreased fetal weights, external malformations (short tail), and skeletal variations (delayed ossification and/or unossification of the skull, vertebrae, and sternebrae). Additional findings were observed at 150 mg/kg/day dose of idelalisib and included urogenital blood loss, complete resorption, increased post-implantation loss, and malformations (vertebral agenesis with anury, hydrocephaly, and microphthalmia/anophthalmia). The dose of 75 and 150 mg/kg/day of idelalisib in rats resulted in exposures (AUC) of approximately 12 and 30 times, respectively, the human exposure at the recommended dose of 150 mg twice daily.