Drug Interactions between clofazimine and Trikafta

Clofazimine may significantly increase the blood levels of ivacaftor from certain formulations. This may increase the risk and/or severity of serious side effects such as liver damage. A dosage adjustment may be required. Talk to your doctor if you have any questions or concerns, or if you do not know whether your dosage has already been adjusted. Call your doctor immediately if you have fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, abdominal pain, dark urine, pale stools, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Consumer information for this interaction is not currently available.

ADJUST DOSE: Coadministration with potent or moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of vanzacaftor, tezacaftor and deutivacaftor, which are primarily metabolized by the isoenzyme. In clinical studies, itraconazole, a potent CYP450 3A4 inhibitor increased vanzacaftor systemic exposure (AUC) by 6.4-fold, tezacaftor AUC by 4 to 4.5-fold and deutivacaftor AUC by 11.1-fold. Erythromycin, a moderate CYP450 3A4 inhibitor, is predicted to increase vanzacaftor peak plasma concentration (Cmax) and AUC by 3.2- and 3.3-fold, respectively, and deutivacaftor Cmax and AUC by 2.9- and 4.1-fold, respectively. Likewise, fluconazole, another moderate CYP450 3A4 inhibitor, is predicted to increase vanzacaftor and deutivacaftor Cmax and AUC by 2.6- and 2.5-fold; and 3.1- and 2.3-fold, respectively. The risk and/or severity of serious side effects such as liver damage may be increased.

MANAGEMENT: Please consult manufacturer's product labeling for complete dosing information.
For vanzacaftor/tezacaftor/deutivacaftor:
- For patients 6 to less than 12 years old, weighing less than 40 kg:
Potent CYP450 3A4 inhibitors: The dose should be reduced to two tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg once a week (total dose of vanzacaftor 8 mg/tezacaftor 40 mg/deutivacaftor 100mg).
Moderate CYP450 3A4 inhibitors: The dose should be reduced to two tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg every other day (total dose of vanzacaftor 8 mg/tezacaftor 40 mg/deutivacaftor 100 mg).

- For patients 6 years old to less than 12 years old, weighing 40 kg or more:
Potent CYP450 3A4 inhibitors: The dose should be reduced to one tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg once a week.
Moderate CYP450 3A4 inhibitors: The dose should be reduced to one tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg every other day.

-For patients 12 years old and older:
Potent CYP450 3A4 inhibitors: The dose should be reduced to one tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg once a week
Moderate CYP450 3A4 inhibitors: The dose should be reduced to one tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg every other day.

For tezacaftor/ivacaftor:
- The morning dose of tezacaftor/ivacaftor should be reduced to one tablet twice a week, approximately 3 to 4 days apart, and the evening ivacaftor dose should not be taken during treatment with potent CYP450 3A4 inhibitors. 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 morning dose of 2 elexacaftor/tezacaftor/ivacaftor tablets once a day should be reduced to 2 tablets twice a week, approximately 3 to 4 days apart, and the evening ivacaftor dose should not be taken during treatment with potent CYP450 3A4 inhibitors. 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.