TAZEMETOSTAT HYDROBROMIDE Drug Interactions: What You Need to Know

INTERACTIONS Strong or Moderate Cytochrome P450 (CYP)3A Inhibitors : Avoid coadministration of strong or moderate CYP3A inhibitors with TAZVERIK. Reduce the dose of TAZVERIK if coadministration of strong or moderate CYP3A inhibitors cannot be avoided. ( 2.3 , 7.1 ) Strong or Moderate CYP3A Inducers : Avoid coadministration with TAZVERIK. ( 7.1 )

7.1 Effect of Other Drugs on TAZVERIK Strong or Moderate CYP3A Inhibitors Coadministration of TAZVERIK with a strong or moderate CYP3A inhibitor increases tazemetostat plasma concentrations <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span>, which may increase the frequency or severity of adverse reactions. Avoid coadministration of strong or moderate CYP3A inhibitors with TAZVERIK. If coadministration of strong or moderate CYP3A inhibitors cannot be avoided, reduce TAZVERIK dose <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.4 )]</span>. Strong or Moderate CYP3A Inducers Coadministration of TAZVERIK with a strong CYP3A inducer decreases tazemetostat plasma concentrations <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> , and coadministration of TAZVERIK with a moderate CYP3A inducer may also decrease tazemetostat plasma concentrations. The decrease in tazemetostat plasma concentration may decrease the efficacy of TAZVERIK. Avoid coadministration of moderate or strong CYP3A inducers with TAZVERIK.

7.2 Effect of TAZVERIK on Other Drugs CYP3A Substrates Coadministration of TAZVERIK with CYP3A substrates, including hormonal contraceptives, can result in decreased concentrations and reduced efficacy of CYP3A substrates <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.3 ), Clinical Pharmacology ( 12.3 )]</span> .

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AND PRECAUTIONS Secondary Malignancies : TAZVERIK increases the risk of developing secondary malignancies, including T-cell lymphoblastic lymphoma, myelodysplastic syndrome, acute myeloid leukemia, and B-cell acute lymphoblastic leukemia. Monitor patients long-term for the development of secondary malignancies. ( 5.1 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise patients of potential risk to a fetus and to use effective non-hormonal contraception. ( 5.2 )

5.1 Secondary Malignancies The risk of developing secondary malignancies is increased following treatment with TAZVERIK. Across clinical trials of 758 adults who received TAZVERIK 800 mg twice daily as monotherapy, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or B-cell acute lymphoblastic leukemia (B-ALL) occurred in 1.7% of patients. One pediatric patient developed T-cell lymphoblastic lymphoma (T-LBL). Monitor patients long-term for the development of secondary malignancies.

5.2 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, TAZVERIK can cause fetal harm when administered to pregnant women. There are no available data on TAZVERIK use in pregnant women to inform the drug-associated risk. Administration of tazemetostat to pregnant rats and rabbits during organogenesis resulted in dose-dependent increases in skeletal developmental abnormalities in both species beginning at maternal exposures approximately 1.5 times the adult human exposure (area under the plasma concentration time curve [AUC 0-45h ]) at the 800 mg twice daily dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAZVERIK and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with TAZVERIK and for 3 months after the final dose <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.1 , 8.3 )]</span> .