Drug Interactions between E-Mycin and ivacaftor / lumacaftor

ADJUST DOSE: Coadministration with moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of ivacaftor, which is primarily metabolized by the isoenzyme. In study subjects, ivacaftor peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 2.5- and 3.0-fold when it was administered concomitantly with fluconazole, a moderate CYP450 3A4 inhibitor. When lumacaftor/ivacaftor was coadministered with ciprofloxacin, another moderate CYP450 3A4 inhibitor, lumacaftor Cmax and AUC decreased by 12% and 14%, respectively, while ivacaftor Cmax and AUC increased by 29% each. These changes are not considered clinically significant. Physiologically based pharmacokinetic (PBPK) simulations suggest that coadministration with moderate CYP450 3A4 inhibitors may increase elexacaftor AUC by 1.9- to 2.3-fold and tezacaftor AUC by approximately 2.1-fold.

MANAGEMENT: Please consult manufacturer's product labeling for complete dosing information.
For ivacaftor - For patients aged 6 months and older the frequency of dosing should be reduced to 1 tablet or packet once a day when coadministered with moderate CYP450 3A4 inhibitors. Patients should continue to receive the same tablet or oral granule packet strength, but instead of dosing twice a day, the frequency should be reduced to once a day. For example, ivacaftor 150 mg twice a day should be 150 mg once a day, ivacaftor 50 mg twice a day should be 50 mg once a day, etc. Use of ivacaftor with moderate or strong CYP450 3A4 inhibitors is not recommended in patients less than 6 months of age.
For lumacaftor/ivacaftor - No dosage adjustment is necessary when coadministered with moderate CYP450 3A4 inhibitors.
For tezacaftor/ivacaftor - The frequency of dosing should be reduced to a single morning dose of one tezacaftor/ivacaftor tablet alternating with one ivacaftor tablet every other morning during treatment with moderate CYP450 3A4 inhibitors. The evening dose of ivacaftor should not be taken.
For elexacaftor/tezacaftor/ivacaftor - The frequency of dosing should be reduced to a single morning dose of two elexacaftor /tezacaftor /ivacaftor tablets alternating with one ivacaftor tablet every other day during treatment with moderate CYP450 3A4 inhibitors. The evening dose of ivacaftor should not be taken.

Switch to consumer interaction data

GENERALLY AVOID: Coadministration with lumacaftor may decrease the plasma concentrations and therapeutic efficacy of drugs that are substrates of CYP450 3A4. Lumacaftor is a potent CYP450 3A4 inducer in vivo. Coadministration of lumacaftor with ivacaftor, a sensitive CYP450 3A4 substrate, decreased ivacaftor systemic exposure (AUC) by approximately 80%.

MANAGEMENT: Concomitant use of lumacaftor is not recommended with sensitive CYP450 3A4 substrates (e.g., oral midazolam, triazolam, lovastatin, simvastatin) or CYP450 3A4 substrates with a narrow therapeutic index (e.g., immunosuppressants such as cyclosporine, everolimus, sirolimus, and tacrolimus). Lumacaftor should also be avoided in patients receiving certain antibiotics (e.g., clarithromycin, erythromycin, telithromycin) and azole antifungal agents (e.g., itraconazole, ketoconazole, posaconazole, voriconazole). Alternatives to these agents should be considered. Some authorities recommend avoiding coadministration of lumacaftor-ivacaftor and itraconazole from 2 weeks before, during and for 2 weeks after treatment with itraconazole.

Switch to consumer interaction data