Deutivacaftor with tezacaftor and vanzacaftor

How it works

Tezacaftor and vanzacaftor act as correctors that improve the processing and trafficking of CFTR protein to the cell surface, while deutivacaftor acts as a potentiator that increases the channel-open probability of the CFTR protein at the membrane, enhancing chloride transport.

Prescribing in practice

• Confirm the patient carries a CFTR mutation responsive to this combination before initiating, and monitor liver function as serious hepatobiliary events including hepatic failure have been reported with CFTR modulator therapy.
• Potency is affected by co-administration of CYP3A inducers and inhibitors, so review concomitant therapy and adjust as directed by current prescribing references.
• Baseline and periodic ophthalmological assessment is advised in children given the risk of lens opacities reported with the modulator class.

Monitoring

Monitor liver transaminases and bilirubin before treatment and periodically thereafter, with ophthalmological review in paediatric patients.

Counselling the patient

• Take the doses with fat-containing food to aid absorption.
• Report any jaundice, dark urine, abdominal pain or unusual tiredness promptly.
• Avoid grapefruit and Seville orange products, which can interact with the medicine.

Evidence & guidelines

CFTR modulator therapy is recommended within NHS access arrangements for eligible cystic fibrosis patients, supported by registration trials showing improvements in lung function and sweat chloride.