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 (£5.43 = 2.25g daily)
• Sachets 750mg in 10ml sugar free oral solution (£21.56= 2.25g daily)

Indications

• Patients with a chronic cough productive of sputum

Dose

• Adults: Initially 2.25g daily in divided doses, then 1.5g daily in divided doses as condition improves

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).
2. Mucolytic therapy can be considered for patients with a chronic productive cough and continued only if there is symptomatic improvement following a 4-week trial.

Dornase alfa

• Nebuliser solution 1,000 units in 1ml

Indications

• Cystic fibrosis

Notes

1. For use undiluted with jet nebulisers only; ultrasonic nebulisers are unsuitable.

Kalydeco

(Ivacaftor)

• Tablets 150mg

Notes

1. See NHS England Clinical Commissioning Policy: Ivacaftor for Cystic Fibrosis (March 2012).
2. NHS England has confirmed that ivacaftor, lumacaftor / ivacaftor, tezacaftor / ivacaftor, and elexacaftor / tezacaftor / ivacaftor 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 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 elexacaftor / tezacaftor / ivacaftor to inform a future health technology appraisal by NICE.

Orkambi

(Lumacaftor / Ivacaftor)

• Tablets 100mg / 125mg, 200mg / 125mg

Notes

1. Whilst NICE TA398 (July 2016) states that Lumacaftor-ivacaftor is not recommended for treating cystic fibrosis in people 12 years and older who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, NHS England has confirmed that ivacaftor, lumacaftor / ivacaftor, tezacaftor / ivacaftor, and elexacaftor / tezacaftor / ivacaftor 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.
2. 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 elexacaftor / tezacaftor / ivacaftor to inform a future health technology appraisal by NICE.

Symkevi

(Tezacaftor / Ivacaftor)

• Tablets 100mg / 150mg

Notes

1. NHS England has confirmed that ivacaftor, lumacaftor / ivacaftor, tezacaftor / ivacaftor, and elexacaftor / tezacaftor / ivacaftor 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.
2. 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 elexacaftor / tezacaftor / ivacaftor to inform a future health technology appraisal by NICE.

Kaftrio

(Elexacaftor / Tezacaftor / Ivacaftor)

• Tablets 100mg / 50mg / 75mg

Notes

1. NHS England has confirmed that ivacaftor, lumacaftor / ivacaftor, tezacaftor / ivacaftor, and elexacaftor / tezacaftor / ivacaftor 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.
2. NHS England and NHS Improvement and Vertex Pharmaceuticals have concluded an access agreement to enable eligible patients in England access to treatment with elexacaftor / 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 elexacaftor / tezacaftor / ivacaftor to inform a future health technology appraisal by NICE.

Mannitol

Mannitol

• Inhalation powder capsules with device 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.