FOI release

Freedom of Information request on the clinical details of the suspected adverse reactions of lens opacities with cystic fibrosis transmembrane conductance regulator modulators (FOI /614)

Published 27 March 2023

FOI 22/614

16th May 2022

Dear

Thank you for your correspondence on the 13th April, where you asked for clinical details of the suspected adverse drug reaction reports the MHRA has received of lens opacities with cystic fibrosis transmembrane conductance regulator (CFTR) modulators (ivacaftor, lumacaftor, tezacaftor and elexacaftor).

Following a search of our database up to and including 2nd May 2022, we can confirm that the MHRA has received two spontaneous UK suspected Adverse Drug Reaction (ADR) reports of lens opacities with a minimum of one CFTR modulator. In our ADR database, lens opacities is grouped under the higher level term cataract conditions. We also carried out a broader search for cases of cataract conditions to provide you with additional reports that may be of interest.

Including the two reports of lens opacities, the MHRA has received 9 UK spontaneous suspected ADR reports of cataract conditions with a minimum of one CFTR modulator up to and including 2nd May 2022. Please see attached a line listing (Table 1a) of the reports. Please note that patient sex and age are provided as aggregated data in Table 1b and Table 1c. Table 1a lists the following information:

• Drug ingredient

• Drug name as classified

• Dose

• Time to onset

• Route of administration

• Reaction

• Reaction outcome

• Patient medical history

Please note, dose, time to onset, route of administration, reaction outcome, and patient medical history in table 1a are not mandatory fields in a Yellow Card report; reporters can submit a Yellow Card without providing this information. Therefore, please be aware, the columns with unknown indicate the reporter did not provide this information.

When assessing the data provided, it is important to note that a report of a suspected reaction to the Yellow Card scheme does not necessarily mean that the medicine or vaccine caused it, only that the reporter has a suspicion it may have. Therefore, not all events have been medically confirmed or diagnosed, as we encourage patients and healthcare professionals to report on the basis of suspicion alone. Reports submitted to MHRA may be due to concurrent diagnosed or undiagnosed illness, other medicines or purely coincidental events that would have occurred anyway in the absence of therapy.

Furthermore, the number of reports received should not be used to determine the incidence of a reaction as neither the total number of reactions occurring nor the number of patients receiving the drug is included in this data. Please refer to the following link where you can search for the Summary of medicinal Product Characteristics (SmPC) for CFTR modulators, which documents the recognised warnings and side effects of CFTR modulators with their associated frequencies: https://products.mhra.gov.uk/.

As you may be aware, there is a warning on cataracts in section 4.4 of the SmPCs for CFTR modulators, which could be used as evidence to further support your work on forming a consensus among clinicians for eye screening and monitoring for people with cystic fibrosis. You may also be interested to know that the MHRA has a platform called Interactive Drug Analysis Profiles (iDAPs) that shows all the spontaneously reported adverse drug reactions associated with a drug substance.

I hope the information provided is helpful, but if you are dissatisfied with the handling of your request, you have the right to ask for an internal review. Internal review requests should be submitted within two months of this response’s date and can be addressed to this email address.

Yours sincerely,

FOI Team,

Vigilance and Risk Management of Medicines Division