ISP orders update of lithium medication leaflets in Chile

The Institute of Public Health of Chile (ISP) has ordered the holders of sanitary registrations to update the professional and patient information leaflets for pharmaceutical products containing lithium, incorporating new safety information. The instruction was formalized through exempt resolution No. 4,010, dated August 10, 2026, published in the Official Gazette of the Republic of Chile No. 44,532, on Monday, August 24, 2026, with the code CVE 2855186.

The decision is based on alerts from the Spanish Agency of Medicines and Medical Devices (AEMPS), the scientific conclusions of the Coordination Group for Mutual Recognition and Decentralised Procedures (CMDh) of the European Medicines Agency (EMA), and Technical Safety Report No. 24-115, prepared by the ISP’s own Pharmacovigilance Sub-department.

Background and regulatory framework

Lithium has been registered in Chile since 1972 and is part of the explicit health guarantees (GES), indicated for bipolar disorder in people aged 15 and over. In June 2024, the EMA published the CMDh conclusions establishing a possible causal relationship between lithium and certain adverse reactions, while the AEMPS disseminated new safety information derived from the evaluation of pharmacovigilance data in its April 2024 bulletin.

The measure is supported by articles 63, 64, and 71 of Supreme Decree No. 3 of 2010 from the Ministry of Health, which empower the ISP to require, through a reasoned resolution, the registration modifications necessary to guarantee the quality, safety, and efficacy of pharmaceutical specialties.

New adverse reactions incorporated

The leaflets must incorporate information on new adverse reactions and clinically relevant situations:

• Brugada Syndrome, which lithium can unmask or aggravate and which can lead to cardiac arrest or sudden death.
• Parathyroid disorders: hypercalcemia, hyperparathyroidism, parathyroid adenoma, and hyperplasia.
• Drug interaction with topiramate, with reported cases of lithium toxicity.
• Lithium toxicity after bariatric surgery, which may require a lower maintenance dose.
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

Technical Safety Report No. 24-115 collects 14 notifications of suspected adverse reactions associated with lithium registered between 2013 and December 2025 in the National Pharmacovigilance System, including metal poisoning (6), overdose effect (5), enhancing drug interaction (1), and increased drug effect (2).

Deadlines and scope

Holders of sanitary registrations must submit the modification of leaflets for ISP approval within a period not exceeding 90 business days from the publication of the resolution. Any sanitary registration for lithium products granted or requested thereafter must comply with the new requirements. The measure applies only to systemic-use pharmaceutical products that are not homeopathic in nature.

The resolution was signed by the director of the ISP, Fresia Catterina Ferreccio Readi, and its full text was published on the institutional website and in the Official Gazette.

Relevance for patients

The update of the leaflets seeks to ensure that both healthcare professionals and patients have up-to-date information on the risks of lithium, a drug widely used in the treatment of bipolar disorder. The incorporation of warnings regarding Brugada syndrome, interactions with topiramate, and toxicity following bariatric surgery will allow for safer prescription and use, reducing the risk of serious adverse reactions.

Source: Official Gazette of the Republic of Chile, No. 44,532, August 24, 2026, General Norms, p. 1-4 (official reference: CVE 2855186).