SYMDEKO

What it is

SYMDEKO contains tezacaftor and ivacaftor in combination, and ivacaftor. It is supplied as a composite pack with morning and evening film-coated tablets. Tezacaftor is a broad-acting CFTR corrector that facilitates the cellular processing and trafficking of normal or multiple mutant forms of CFTR to increase the amount of functional CFTR protein delivered to the cell surface, resulting in increased chloride transport. Ivacaftor is a CFTR potentiator that potentiates the channel-open probability of CFTR at the cell surface to increase chloride transport.

Approved indications

— Cystic fibrosis in patients aged 6 years and older who are homozygous for the F508del mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence.

Dosing overview

Adults, adolescents and children aged 6 years and older should be dosed according to age and weight, with the morning dose taken with the evening dose approximately 12 hours apart. Tablets should be taken with fat-containing food. Food or drink containing grapefruit or Seville oranges should be avoided during treatment with SYMDEKO.

Key safety warnings

Non-congenital lens opacities without impact on vision have been reported in paediatric patients treated with SYMDEKO, as well as with ivacaftor monotherapy. Although other risk factors were present in some cases, a possible risk attributable to treatment cannot be excluded. Baseline and follow-up ophthalmological examinations are recommended in paediatric patients initiating treatment. Elevated transaminases are common in patients with CF and have been observed in some patients treated with SYMDEKO. Assessments of transaminases (ALT and AST) are recommended for all patients prior to initiating SYMDEKO, every 3 months during the first year of treatment, and annually thereafter. For patients with a history of transaminase elevations, more frequent monitoring should be considered. Hypersensitivity reactions, including cases of anaphylaxis, have been reported in the post-marketing setting. If signs or symptoms of serious hypersensitivity reactions develop during treatment, discontinue SYMDEKO and institute appropriate therapy. Dizziness has been reported in patients receiving SYMDEKO. Patients experiencing dizziness should be advised not to drive or operate machines until symptoms abate.

Contraindications

SYMDEKO is contraindicated in cases of hypersensitivity to the active substance or to any component of this medication.

PBS listing

SYMDEKO 100/150 (tezacaftor 100 mg/ivacaftor 150 mg) and SYMDEKO 50/75 (tezacaftor 50 mg/ivacaftor 75 mg) are registered on the ARTG. In November 2019, PBAC recommended SYMDEKO for cystic fibrosis in patients aged 12 years or older with at least one residual function mutation.

Regulatory history

SYMDEKO 100/150 was first listed on the ARTG on 5 March 2019, and SYMDEKO 50/75 was first listed on 29 April 2021. PBAC recommended the medicine in November 2019 for cystic fibrosis in patients aged 12 years or older with at least one residual function mutation, extending a March 2019 recommendation to include all eligible patients at no additional cost to Government.