Drug interactions of Enasidenib

1. Certain CYP1A2 Substrates  

Avoid concomitant use with IDHIFA unless otherwise recommended in the Prescribing  Information for CYP1A2 substrates where minimal concentration changes may lead to serious  adverse reactions. Consider reducing the frequency of caffeine intake from various food and  beverages in a 24 hour period while taking IDHIFA because IDHIFA may increase the effect of  caffeine in patients who are sensitive to it.

Enasidenib is a CYP1A2 inhibitor. Concomitant use of IDHIFA increases the exposure of  CYP1A2 substrates , which may increase the risk of adverse  reactions related to the substrates.

2. Certain CYP2C19 substrates  

Avoid concomitant use with IDHIFA unless otherwise recommended in the Prescribing  Information for CYP2C19 substrates where minimal concentration changes may lead to serious  adverse reactions.  

Enasidenib is a CYP2C19 inhibitor. Concomitant use of IDHIFA increases the exposure of  CYP2C19 substrates , which may increase the risk of adverse  reactions related to these substrates.

3. Certain CYP3A substrates  

Avoid concomitant use with IDHIFA unless otherwise recommended in the Prescribing  Information for CYP3A substrates where minimal concentration changes may lead to reduced  efficacy.  Do not administer IDHIFA with anti-fungal agents that are substrates of CYP3A due to expected  loss of antifungal efficacy.  Co-administration of IDHIFA may decrease the concentrations of hormonal contraceptives.  Consider alternative methods of contraception in patients receiving IDHIFA.

Enasidenib is a CYP3A inducer. Concomitant use of IDHIFA decreases the exposure of CYP3A  substrates , which may reduce the efficacy of the substrates.

4. Certain OATP1B1, OATP1B3, and BCRP Substrates  

Avoid coadministration of IDHIFA with OATP1B1, OATP1B3, and BCRP substrates, for which  minimal concentration changes may lead to serious toxicities. If coadministration cannot be  avoided, decrease the OATP1B1, OATP1B3, and BCRP substrates dosage(s) in accordance with  the respective Prescribing Information.

Enasidenib is an OATP1B1, OATP1B3, and BCRP transporter inhibitor. Concomitant use of  IDHIFA increases the exposure of OATP1B1, OATP1B3, and BCRP substrates , which may increase the risk of adverse reactions related to these substrates.

5. Certain P-glycoprotein (P-gp) Substrates  

When coadministered with IDHIFA, follow recommended P-gp substrates Prescribing  Information and monitor more frequently for adverse reactions related to these substrates.

Enasidenib is a P-gp transporter inhibitor. Concomitant use of IDHIFA increases the exposure of  P-gp substrates, which may increase the risk of adverse  reactions related to the substrates.

FDA,2023.12