by Ruggiero Corcella
Aifa’s response to requests for intervention from patient associations. The shortage of the beta blocker, due to “production problems”, has already been known since July 2023. Precarious situation until 8 March 2024. Possible alternatives. The associations: we need to identify structural solutions to the problem
Patients with hereditary heart diseases must, in fact, be patient: the “hunt” for nadolol will continue until at least March. This, in essence, is the response that the Product Quality and Pharmaceutical Crime Office of the Italian Medicines Agency (Aifa) gave to the request for urgent intervention following the nadolol shortage which has been occurring since October 2023 requested last December 4th by Professor Franco Cecchi, president of Aicarm Aps (Italian Cardiomyopathies Association) an association of patients and doctors, and by Professor Alessandro Mugelli, of the same association.
What is nadolol
Nadolol is a beta blocker, initially registered for conditions such as angina and arterial hypertension, which is essential in patients with hypertrophic obstructive cardiomyopathy, and a lifesaver for genetic diseases associated with risk of sudden death, including long QT syndrome and ventricular tachycardia catecholaminergic characterized by a high risk of heart rhythm irregularities which can cause syncope (loss of consciousness) and sudden death due to cardiac arrest, especially during conditions of physical and emotional stress. In the letter signed by the director, Domenico Di Giorgio, the “chronology” of the facts is explained and indications are given on how to look for nadolol despite the shortage in pharmacies.
Aifa’s response: the history and suggestions for finding the drug
Here’s what the letter says
1) The shortage of Nadolol 80 mg was made public as soon as the AIFA office received the information from the MA holder, i.e. in July 2023.
2) Following the assessment of the deficiency, deemed critical, the office had constant contact with the owner to acquire more information and implement mitigation actions.
3) The shortage is due to production problems (lack of availability of the active ingredient).
4) As regards the mitigation actions, some were not possible to apply: the owner was not able to import the similar medicinal product authorized in France as it was also lacking, while the extraordinary productions, such as those for which the Military Chemical Pharmaceutical Plant of Florence is usually involved in, would have required an implementation time not compatible with the short-term resolution necessary for the case study.
5) “Mitigation” actions:
– on 10/31/2023 one was published on the institutional portal Important Information Note on the shortage of the medicine, aimed at optimizing the use of the medicine still available; the same was sent to medical specialists and associations, to spread the news of the shortage as widely as possible, in order to find alternative solutions;
– the office issues authorizations for the import of analogues authorized abroad to the requesting healthcare facilities, according to one known and consolidated practice;
– imported medicines cannot be sold in pharmacies but can be delivered by the structures (ASL/hospital pharmacies) to citizens to continue home therapy;
– the imported medicines for which the undersigned office has issued the authorization are the following: •CORGARD (nadolol) 80mg 28 tablets, marketed in France •NADOLOL (nadolol) 80mg 100 tablets – marketed in CANADA •NADOLOL (nadolol) 80mg tablets – marketed in the UK;
– it is possible to use galenic preparations, prepared in the pharmacy based on a medical prescription intended for a specific patient.
The alternatives: galenic drug or hospital request
In essence, there are two “alternatives” indicated by AIFA: the importation of medicines based on the same active ingredient, but only by hospital pharmacies or local health authorities; the galenic in the pharmacy. In Italy, however, it is increasingly difficult to obtain galenic nadolol precisely because the active ingredient is in short supply even in pharmacies, as patients explain. Some pharmacies had told the patients themselves that perhaps in January 2024 the active ingredient would be available again but at the moment there is no confirmation. The option of purchasing directly from Swiss pharmacies remains but the costs are exorbitant: in Italy a pack of 30 tablets costs around 11-12 euros. In Switzerland, 100 euros for 100 pills. And the same amount is spent on the galenic preparation, considering the shipping costs.
However, as regards the request from hospital pharmacies, the path is bumpy: «It is a somewhat complex mechanism – explains Professor Cecchi -. We asked the hospital pharmacists. We await the answers. In practice, the hospital pharmacist who needs a drug, obviously requested by a hospital doctor, can contact Aifa and request authorization to purchase it directly abroad. It is a mechanism, let’s say, to safeguard the needs of hospital doctors for a specific drug.”
Finding the right mechanism
Drug shortages are now a chronic and multi-faceted problem. «We need to activate a mechanism that prevents this situation from occurring in the future, either for patients who have hypertrophic heart disease or for other patients – reflects Professor Cecchi -. Where drugs are missing, the mechanism must be such that already at the time of notification by the manufacturing company, patients are informed which drugs can be considered equivalent, or alternatively how and where the drug can be found abroad and possibly supplied by hospital pharmacies. within a reasonable time.”
The missed “promises” of the Ministry of Health
«It is disheartening to see that Aifa is unable to provide an answer to the hundreds of families waiting for the drug nadolol to become available again – adds Professor Silvia Priori, director of the Molecular Cardiology Operational Unit in the Experimental Medicine area, at the Scientific Institutes of Irccs Maugeri of Pavia — We had received news from qualified sources that the Ministry of Health wanted to establish a supply agreement on a national scale to meet the needs of families. Unfortunately we have no longer been notified of any updates. We receive dozens of emails daily from patients: there are families who ask us for which family member it is most important to reserve the few tablets available in the family.”
Aifa’s suggestion: use propranolol
To make up for the lack of nadolol, Aifa had previously recommended using propranolol. « Aifa’s suggestion to replace the deficient nadolol with propranolol (a drug in the same class as nadolol) is not incorrect advice but cannot be sufficient for those who have children and family members affected by pathologies for which, according to Aifa itself, nadolol “is a drug that can be supplied by the national health service as published in the Official Journal 01-04-2014.n76″ – underlines Professor Priori -. Unfortunately, patients, also through their associations, are well aware that “being a drug of the same class” does not guarantee the same antiarrhythmic protection that is conferred by nadolol. Therefore, those who have family members affected by genetic diseases cannot be satisfied with a drug that works “well enough”, having to give up maximum protection from the onset of a fatal arrhythmia.”
Potential negative effects
This is confirmed by a study published in JAMA Cardiology, by Professor Priori in collaboration with colleagues from various countries around the world: «Nadolol therapy in patients suffering from catecholaminergic ventricular tachycardia (CPVT) is associated with a residual probability of having a cardiac arrest of 0.8 % per year. Propranolol is less effective and is associated with a residual risk of 2.1% per year. Finally, the use of selective beta-blocking drugs (all other beta-blockers) is associated with a residual risk of serious arrhythmic events of 4.2% per year. Together with the patients of Association “A family for the Heart” and to those of all the other associations on the national territory, we hope to see a rapid solution to the nadolol shortage in the coming months.”
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January 6, 2024 (modified January 6, 2024 | 08:01)
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