MHRA Drug Safety Update (February 2022): Ivacaftor, tezacaftor, elexacaftor (Kaftrio) in combination with ivacaftor (Kalydeco): risk of serious liver injury; updated advice on liver function testing.

Carbocisteine

• Capsules 375mg (£5.33 = 2.25g daily)
• Sachets 750mg/10ml sugar free oral solution (£25.20 = 2.25g daily)

Indications

• Reduction of sputum viscosity

Dose

• Adult: Initially 2.25g daily in divided doses, then 1.5g daily in divided doses as condition improves. Treatment should only be continued if there is symptomatic improvement following a 4-week trial

Notes

1. Carbocisteine sachets are licensed for adults and children over 15 years for the adjunctive therapy of respiratory tract disorders characterised by excessive, viscous mucus, including chronic obstructive airways disease (COPD).

Dornase alfa

• Nebuliser liquid ampoules 2.5mg/2.5ml

Indication

• Management of cystic fibrosis patients with a forced vital capacity (FVC) of greater than 40% of predicted to improve pulmonary function

Notes

1. A Jet Nebuliser used exclusively for dornase alfa is required for administration.

Kalydeco

(Ivacaftor)

• Tablets 75mg, 150mg
• Granules sachets 25mg, 50mg, 59.5mg, 75mg

Notes

1. See NICE TA988: Ivacaftor–tezacaftor–elexacaftor, tezacaftor–ivacaftor and lumacaftor–ivacaftor for treating cystic fibrosis (July 2024).
2. See NHS England Clinical Commissioning Policy: Ivacaftor for Cystic Fibrosis (March 2012).
3. NHS England has confirmed that ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and ivacaftor/tezacaftor/elexacaftor will be made available as treatment options for people with cystic fibrosis who have one of an expanded range of cystic fibrosis transmembrane conductance regulator (CFTR) mutations within the criteria set out in this commissioning statement.
4. NHS England and NHS Improvement and Vertex Pharmaceuticals have concluded an access agreement to enable eligible patients in England access to treatment with ivacaftor via the NHS. A new agreement has commenced, which fully incorporates and expands the terms of a previous agreement (dated 11th November 2019)
   1. The purpose of this agreement is to describe the arrangements intended to capture the data that may address the clinical uncertainties in the evidence base concerning ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and ivacaftor/tezacaftor/elexacaftor to inform a future health technology appraisal by NICE.

Orkambi

(Lumacaftor/ivacaftor)

• Tablets 100mg/125mg, 200mg/125mg
• Granules sachets 75mg/94mg, 100mg/125mg, 150mg/188mg

Notes

1. NICE TA988: Lumacaftor-ivacaftor (Orkambi) is recommended, within its marketing authorisation, for treating cystic fibrosis in people 1 year and over who have 2 copies of the CFTR gene with F508del mutation, only if the company provides it according to the commercial arrangement (July 2024).
2. NHS England has confirmed that ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and ivacaftor/tezacaftor/elexacaftor will be made available as treatment options for people with cystic fibrosis who have one of an expanded range of cystic fibrosis transmembrane conductance regulator (CFTR) mutations within the criteria set out in this commissioning statement.
3. NHS England and NHS Improvement and Vertex Pharmaceuticals have concluded an access agreement to enable eligible patients in England access to treatment with lumacaftor/ivacaftor via the NHS. A new agreement has commenced, which fully incorporates and expands the terms of a previous agreement (dated 11th November 2019)
   1. The purpose of this agreement is to describe the arrangements intended to capture the data that may address the clinical uncertainties in the evidence base concerning ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and ivacaftor/tezacaftor/elexacaftor to inform a future health technology appraisal by NICE.

Symkevi

(Tezacaftor/ivacaftor)

• Tablets 50mg/75mg, 100mg/150mg

Notes

1. NICE TA988: Tezacaftor-ivacaftor (Symkevi) plus ivacaftor (Kalydeco) alone is recommended, within its marketing authorisation, for treating cystic fibrosis in people 6 years and over who have:
   1. 2 copies of the CFTR gene with F508del mutations, or
   2. a copy of the CFTR gene with an F508del mutation and a copy of the CFTR gene with 1 of the mutations listed in section 2.2 of NICE TA988, and
   3. the company provides tezacaftor-ivacaftor according to the commercial arrangement (July 2024).
2. NHS England has confirmed that ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and ivacaftor/tezacaftor/elexacaftor will be made available as treatment options for people with cystic fibrosis who have one of an expanded range of cystic fibrosis transmembrane conductance regulator (CFTR) mutations within the criteria set out in this commissioning statement.
3. NHS England and NHS Improvement and Vertex Pharmaceuticals have concluded an access agreement to enable eligible patients in England access to treatment with tezacaftor/ivacaftor via the NHS. A new agreement has commenced, which fully incorporates and expands the terms of a previous agreement (dated 11th November 2019)
   1. The purpose of this agreement is to describe the arrangements intended to capture the data that may address the clinical uncertainties in the evidence base concerning ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and ivacaftor/tezacaftor/elexacaftor to inform a future health technology appraisal by NICE.

Kaftrio

(Ivacaftor/tezacaftor/elexacaftor)

• Tablets 37.5mg/25mg/50mg, 75mg/50mg/100mg
• Granules sachets 60mg/40mg/80mg, 75mg/50mg/100mg

Notes

1. NICE TA988: Ivacaftor-tezacaftor-elexacaftor (Kaftrio) plus ivacaftor (Kalydeco) alone is recommended, within its marketing authorisation, as an option for treating cystic fibrosis in people 2 years and over who have at least 1 F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, only if the company provides ivacaftor-tezacaftor-elexacaftor according to the commercial arrangement (July 2024).
2. NHS England has confirmed that ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and ivacaftor/tezacaftor/elexacaftor will be made available as treatment options for people with cystic fibrosis who have one of an expanded range of cystic fibrosis transmembrane conductance regulator (CFTR) mutations within the criteria set out in this commissioning statement.
3. NHS England and NHS Improvement and Vertex Pharmaceuticals have concluded an access agreement to enable eligible patients in England access to treatment with ivacaftor/tezacaftor/elexacaftor via the NHS. A new agreement has commenced, which fully incorporates and expands the terms of a previous agreement (dated 11th November 2019)
   1. The purpose of this agreement is to describe the arrangements intended to capture the data that may address the clinical uncertainties in the evidence base concerning ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and ivacaftor/tezacaftor/elexacaftor to inform a future health technology appraisal by NICE.

Mannitol

• Inhalation powder capsules with two devices 40mg

Notes

1. NICE TA266: Mannitol dry powder for inhalation (Bronchitol) is recommended as an option for treating cystic fibrosis in adults (November 2012):
   1. who cannot use rhDNase because of ineligibility, intolerance or inadequate response to rhDNase and
   2. whose lung function is rapidly declining (forced expiratory volume in 1 second [FEV1] decline greater than 2% annually) and
   3. for whom other osmotic agents are not considered appropriate.