ivacaftor + tezacaftor: clinical use

Prescribing considerations

• Confirm an eligible CFTR genotype using an accurate validated assay.
• Prescribing should be led by a clinician experienced in cystic fibrosis.
• Review hepatic and renal function, transplantation history, pregnancy status and interacting medicines.
• Use caution in advanced liver disease and severe renal impairment or end-stage renal disease.
• Use after organ transplantation is not recommended because it has not been studied and important immunosuppressant interactions are possible.

Contraindications and cautions

• Hypersensitivity to tezacaftor, ivacaftor or any excipient.
• Do not prescribe for F508del heterozygosity with a second mutation outside the licensed list.

Monitoring

• Check liver function before and regularly during treatment; consider more frequent testing with previous transaminase elevation or liver disease.
• Interrupt treatment and investigate clinically significant transaminase elevations; reassess benefits and risks before restarting.
• Arrange baseline and follow-up ophthalmological examinations for paediatric patients.
• Monitor INR with warfarin and monitor narrow-therapeutic-index P-glycoprotein substrates as clinically appropriate.

Clinical pharmacology

Tezacaftor corrects CFTR processing and trafficking, while ivacaftor potentiates channel opening. Both are extensively metabolised mainly through CYP3A4 and CYP3A5; ivacaftor also weakly inhibits CYP2C9 and P-glycoprotein.

Formulation and product differences

• The selected product is a yellow, capsule-shaped film-coated tablet marked V100.
• A lower-strength white tablet marked V50 is available for some paediatric patients.
• Tablets should be swallowed whole because alternative administration methods have not been clinically established.

Tablet

Route: Oral

Strengths: 50 mg + 75 mg, 100 mg + 150 mg