ivacaftor: clinical use

Prescribing considerations

• Confirm genotype using an accurate validated method; assess the poly-T variant when R117H is present.
• Initiation and supervision should be by clinicians experienced in cystic fibrosis.
• Review hepatic and renal function, transplantation history, interacting medicines and herbal products.
• Monotherapy is not recommended for people homozygous for F508del because clinical benefit was not established.

Contraindications and cautions

• Hypersensitivity to ivacaftor or any formulation excipient.
• Selected formulations contain lactose and should not be used in rare hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
• Use requires particular caution in advanced liver disease and severe renal impairment; organ-transplant recipients were not studied.

Monitoring

• Check ALT, AST and total bilirubin before treatment, frequently during the first year and regularly thereafter; monitor more closely with liver disease or previous abnormalities.
• Interrupt treatment and investigate significant liver-test abnormalities or clinical features of liver injury.
• Arrange baseline and follow-up eye examinations for paediatric patients because non-congenital lens opacities have been reported.
• Monitor INR with warfarin and relevant narrow-therapeutic-index P-glycoprotein substrates.

Clinical pharmacology

Ivacaftor increases the open probability of responsive CFTR channels. It is primarily metabolised through CYP3A and can weakly inhibit CYP3A and P-glycoprotein, with potential CYP2C9 inhibition.

Formulation and product differences

• Film-coated tablets must be swallowed whole.
• Granules are supplied in single-use sachets and mixed with suitable soft food or liquid.
• Formulation selection depends on age, weight and whether ivacaftor is used alone or within an approved combination.

Sachet

Route: Oral

Strengths: 13.4 mg, 25 mg, 50 mg, 59.5 mg, 75 mg