Deutivacaftor + tezacaftor + Vanzacaftor: clinical use

Prescribing considerations

• Confirm an eligible CFTR genotype using an accurate validated method when genotype is unknown.
• Initiation and supervision should be by clinicians experienced in cystic fibrosis treatment.
• Review liver disease, previous adverse reactions to tezacaftor- or ivacaftor-containing therapy, renal impairment and interacting medicines.
• Use in moderate hepatic impairment is not recommended unless there is a clear medical need and benefit outweighs risk; exercise caution in severe renal impairment or end-stage renal disease.

Contraindications and cautions

• Hypersensitivity to deutivacaftor, tezacaftor, vanzacaftor or an excipient.
• The combination should not be used in severe hepatic impairment.

Monitoring

• Check ALT, AST and total bilirubin before treatment, every 3 months during the first year and annually thereafter; monitor more frequently with liver disease or previous transaminase elevation.
• Interrupt treatment and assess promptly if clinical or biochemical evidence of significant liver injury develops.
• Arrange baseline and follow-up ophthalmological assessment for patients under 18 because lens opacities have occurred with ivacaftor-containing regimens.
• Review INR with warfarin and monitor narrow-therapeutic-index P-glycoprotein substrates as appropriate.

Clinical pharmacology

Vanzacaftor and tezacaftor bind at different CFTR sites and improve processing and trafficking of responsive mutant protein. Deutivacaftor, a deuterated ivacaftor isotopologue, increases CFTR channel-opening probability. All three components are CYP3A substrates.

Formulation and product differences

• One film-coated tablet is purple, round and marked “V4”.
• A higher-strength purple, capsule-shaped tablet marked “V10” is also marketed; selection depends on clinical criteria.

Tablet

Route: Oral

Strengths: 50 mg + 20 mg + 4 mg, 125 mg + 50 mg + 10 mg