Stop to the indiscriminate consumption of gastroprotectors with the new crackdown decided by the Italian Medicines Agency (Aifa) through Note N01. This small revolution in medical prescriptions aims to guarantee free treatments only to those who have a real and documented need. The necessity to protect citizens from side effects and the urgency to cut economic waste pushed the authorities to rewrite the rules in agreement with experts. Thus, the way of managing therapies that involve millions of people every day throughout Italy changes radically.
WHAT NOTE N01 PROVIDES
With determination number 238 of March 4, 2026, published in the Official Gazette on March 7 of the same year, the Italian Medicines Agency officially established Note N01. This new regulation unifies and fully replaces the previous Notes 1 and 48, simplifying the discipline for prescriptions charged to the National Health Service (Ssn).
The provision concerns five specific active ingredients, namely esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole. Other drugs such as famotidine and misoprostol remain excluded, now falling under class A without the limitations provided by the old notes. The reform stems from a long coordination process started in June 2024 within a technical table that involved representatives of general medicine and specialists in the sector.
HOW PROTON PUMP INHIBITORS WORK AND WHAT THEY ARE FOR
Proton pump inhibitors, explains the Mario Negri Institute, are widely used drugs that act by inhibiting the H+/K+ ATPase enzyme, located in the parietal cells of the stomach. This enzyme is responsible for the production of hydrochloric acid, and its blockade allows a drastic reduction of gastric secretion for a duration between 18 and 24 hours.
These medicines are technically pro-drugs that require an acidic environment to activate once they reach the target cells. Although they remain in the blood for a limited time, their therapeutic efficacy persists until the body produces new molecules of the inhibited enzyme. The main clinical applications include the treatment of peptic ulcer, gastritis, and gastroesophageal reflux disease.
REIMBURSEMENT CRITERIA AND CLINICAL APPROPRIATENESS
With the new regulation, the reimbursement of proton pump inhibitors is now linked to precise clinical conditions and usage timings. For the initial treatment of gastroesophageal reflux disease, free therapy is provided for a period of 4-8 weeks, after which a medical reassessment must take place.
Long-term maintenance therapy is justified only in the presence of frequent relapses or complicated diseases such as severe erosive esophagitis, always using the minimum effective dosage.
Regarding the prophylaxis of gastric complications due to other drugs, Note N01 limits reimbursement to high-risk patients. This group includes subjects over 65 years old or with serious comorbidities who chronically take non-steroidal anti-inflammatory drugs, anticoagulants, or corticosteroids. Secondary prevention is instead guaranteed to those with a documented clinical history of digestive hemorrhages or previous ulcers.
WHY MODIFY THE REGULATION
The regulatory revision became necessary due to an excessive and often inappropriate use of this class of drugs. In Italy, in fact, states the Mario Negri Institute, about 10.5 million people use these medicines, with a usage prevalence of 17.8% of the total population.
In 2024, reminds Quotidiano Sanità, public pharmaceutical expenditure for these products reached 619.80 million euros. Aifa aims to reduce this figure below the threshold of 585.71 million euros within the first year of application of the new Note. If the savings targets are not met, the Agency has provided the possibility to initiate ex officio procedures for price renegotiation with pharmaceutical companies. The control of prescriptive appropriateness is entrusted to the Regions and Local Health Authorities, which will have to monitor the work of doctors in the territory.
RISKS ASSOCIATED WITH PROLONGED AND IMPROPER USE
Chronic unjustified use of proton pump inhibitors entails significant risks to patients’ health. In particular, prolonged use is associated with the development of nutritional deficiencies, especially vitamin B12 and magnesium. At the skeletal level, a possible increase in the risk of osteoporosis and bone fractures is observed. Furthermore, alterations in gastric pH can favor the onset of dangerous intestinal infections such as those caused by Clostridium Difficile and alter the balance of the intestinal microbiota, generating dysbiosis. In elderly patients, a link has been found with a higher incidence of nephropathies and pneumonias. Another problem is represented by the rebound effect that causes an acute return of symptoms if the treatment is abruptly stopped after a long period of use.
THE OPINION OF EXPERTS AND SCIENTIFIC SOCIETIES
The main medical organizations, including the Italian Society of Gastroenterology and Endoscopy (Sige) and the Italian Federation of General Practitioners (Fimmg), have expressed satisfaction with Aifa’s work. Experts emphasize the importance of bureaucratic simplification, such as overcoming the obligation of gastroscopy as a binding step for prescribability in certain scenarios.
However, the Italian Federation of Societies of Digestive Diseases (Fismad) has pointed out some technical criticalities in the text of the Note. One of the objections concerns the apparent exclusion of reimbursement for prophylaxis in patients taking low-dose aspirin without having already suffered gastric lesions. Also noted is the lack of explicit inclusion of eosinophilic esophagitis among reimbursable indications despite the pathology being mentioned in the scientific bibliography referenced by the provision.
