ISP orders update of oral anticoagulant brochures due to renal risk

The Public Health Institute of Chile instructed the sanitary registration holders of oral pharmaceutical products containing dabigatran, rivaroxaban, apixaban, edoxaban, acenocoumarol, or warfarin to modify their professional and patient information leaflets to warn about the risk of anticoagulant-related nephropathy. The decision is contained in exempt resolution No. E4.491, dated September 3, 2026, signed by the director of the agency, Fresia Catterina Ferreccio Readi, and published in the Official Gazette of the Republic of Chile No. 44,561, on Tuesday, September 29, 2026, Section I, General Norms (official reference: CVE 2875519).

The measure is supported by supreme decree No. 3 of 2010 of the Ministry of Health, whose article 64 empowers the Public Health Institute to require, through a reasoned resolution, the sanitary registration modifications necessary to guarantee the quality, safety, and efficacy of a pharmaceutical specialty when national or international scientific evidence provides conviction that the authorized conditions of use present a risk. The same regulatory body, in its article 71, holds the sanitary registration holder responsible for keeping the registration updated according to the state of science and technology.

What the leaflets must incorporate

The text mandates the inclusion of safety information regarding nephropathy and acute kidney injury in the adverse reactions section of both leaflets, with a frequency classified as “unknown.” The required contents are:

• Professional leaflet: warning that in patients with altered glomerular integrity or a history of kidney disease, acute kidney injury may occur, possibly associated with episodes of excessive anticoagulation and hematuria, with cases reported even in patients without pre-existing kidney disease.
• Clinical recommendation: close monitoring, including the evaluation of renal function, in patients with a supratherapeutic INR and hematuria, even microscopic.
• Patient leaflet: description of bleeding in the kidney, sometimes with the presence of blood in the urine, which can lead to the inability of the kidneys to function correctly.

Deadline and scope of the obligation

Holders must submit the modification of the leaflets for approval by the Public Health Institute within a period not exceeding 90 business days from the publication of the resolution. The requirement applies to all presentations of the six active ingredients and also to sanitary registrations granted or requested after the publication of the instrument, which must comply with the same conditions.

The instruction is issued within the framework of exempt resolution No. E140, dated January 9, 2026, which allows the Pharmacovigilance Sub-department of the National Medicines Agency Department to apply regulatory trust mechanisms and instruct the modification of leaflets, labels, and indications, as well as publish informative notes and adopt other risk mitigation measures.

International background supporting the alert

Safety Technical Report No. 25-168, dated July 14, 2026, prepared by the Medicines and Cosmetics Information and Safety Section of the Pharmacovigilance and Clinical Studies Sub-department, concluded that it was appropriate to update both leaflets to harmonize the information with technical data sheets and communications from international agencies. Among the cited precedents are:

• The 2023 bulletin from the World Health Organization, featuring the communication from the Australian agency Therapeutic Goods Administration regarding anticoagulant-related nephropathy, described as an infrequent but serious adverse event, with a risk of irreversible kidney damage and even death.
• The July 2024 bulletin from the World Health Organization, regarding the inclusion of “acute kidney injury” in the precautions for these medicines by the Japanese authorities.
• The August 2025 Health Product InfoWatch bulletin from Health Canada, which reported the update of the monographs for apixaban, dabigatran, edoxaban, rivaroxaban, and warfarin.
• Report PSUSA/00000027/202407 from the European Medicines Agency, in which the pharmacovigilance committee concluded that the information for medicines containing acenocoumarol should be modified.
• The technical data sheets from the Spanish Agency for Medicines and Health Products, which already contain information on anticoagulant-related nephropathy.

The resolution affects widely prescribed brands such as Eliquis, Xarelto, Pradaxa, Coumadin, and Marevan, and applies to the laboratories holding those sanitary registrations in Chile.

The update of the leaflets is relevant for hundreds of thousands of patients on prolonged anticoagulant treatment, as it incorporates a warning about a serious and infrequent adverse effect that until now did not appear explicitly in the material they receive with the medication. It also obliges health professionals to monitor renal function in cases of excessive anticoagulation and hematuria, and sets a limited timeframe for the pharmaceutical industry to adapt its documentation before the health regulator.

Source: Official Gazette of the Republic of Chile, No. 44,561, Tuesday, September 29, 2026, Section I, General Norms, pp. 1-4 (official reference: CVE 2875519).