Tezacaftor/Ivacaftor

Mechanism :

Tezacaftor: Facilitates the cellular processing and trafficking of normal and select mutant forms of CFTR (including F508del-CFTR) to increase the amount of mature CFTR protein delivered to the cell surface.
Ivacaftor: CFTR potentiator that facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the CFTR protein at the cell surface.

Indication :

• Treatment of cystic fibrosis (CF) in patients who are homozygous for the F508del mutation or have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to tezacaftor/ivacaftor.

Contraindications :

No contraindications.

Dosing :

Adverse Effect :

Dizziness, headache, Nausea, sinus congestion, cataract, gastrointestinal obstruction.

Interaction :

Dosing schedule change with CYP3A inhibitors:
Coadministration with moderate CYP3A inhibitors (e.g., erythromycin, fluconazole): On day 1, administer tezacaftor 100 mg/ivacaftor 150 mg once daily in the morning, and on day 2, administer ivacaftor 150 mg once daily in the morning; continue this dosing schedule with tezacaftor 100 mg/ivacaftor 150 mg or ivacaftor 150 mg on alternate days in the morning; the evening dose of ivacaftor 150 mg should not be administered.
Coadministration with strong CYP3A inhibitors (e.g., clarithromycin, itraconazole, ketoconazole, posaconazole, telithromycin, voriconazole): On day 1, administer tezacaftor 100 mg/ivacaftor 150 mg once daily in the morning; do not administer any tablets on days 2 and 3; on day 4, administer tezacaftor 100 mg/ivacaftor 150 mg once daily in the morning. Continue dosing with tezacaftor 100 mg/ivacaftor 150 tablets twice a week, administered ~3 to 4 days apart; the evening dose of ivacaftor 150 mg should not be administered.

Hepatic Dose :