European Medicines Agency starts review of Protelos / Osseor
Evidence relating to cardiovascular and cutaneous toxicity to be considered again
The European Medicines Agency has started a review of the strontium-ranelate-containing osteoporosis medicines Protelos and Osseor, to determine whether the cases of venous thromboembolism and drug rash with eosinophilia and systemic symptoms have an impact on their benefit-risk profile and conditions of use.
Protelos and Osseor, from Les Laboratoires Servier, were authorised via the centralised procedure on 21 September 2004 and are indicated for treatment of postmenopausal osteoporosis to reduce the risk of vertebral and hip fractures.
Venous thromboembolism (VTE) and drug rash with eosinophilia and systemic symptoms (DRESS) are known risks of these medicines. The risk of VTE was identified in clinical trials and the risk of DRESS through spontaneous reporting soon after the granting of the initial marketing authorisation, and warnings are included in the product information. The risks are addressed in the risk-management plan and have been kept under close review by the Agency's Committee for Medicinal Products for Human Use (CHMP).
A study analysing the side effects associated with strontium ranelate spontaneously reported in France from January 2006 to March 2009 to Les Laboratoires Servier or the French competent authority (Afssaps) noted 199 severe adverse reactions, of which 52% were cardiovascular (most frequently VTE events) and 26% were cutaneous. The authors concluded that DRESS syndrome is unpredictable, but that the VTE risk could be reduced by adding a contraindication for patients with a history of VTE and by stopping treatment if a new VTE risk situation occurs. Based on a recent pharmacovigilance update and pending an EU-wide review, Afssaps recommended restricting the use of strontium ranelate to those patients who are under 80 years of age, at high risk of fractures and who cannot take bisphosphonates.
The CHMP is now reviewing all relevant data on the cardiovascular and cutaneous safety concerns, taking into account existing risk-minimisation measures and their impact on the benefit-risk balance for Protelos and Osseor. The Committee will issue an opinion on measures necessary to ensure the safe and effective use of these medicines and whether or not the marketing authorisations for these medicines should be changed, suspended or revoked.
While this assessment is ongoing no changes to the conditions for use of Protelos and Osseor are being recommended Europe-wide.
- The European review of Protelos and Osseor is being conducted in the context of a formal review, initiated at the request of the European Commission under Article 20 of Regulation (EC) No 726/2004 on 14 October 2011.
- The reference to the French study is as follows: Ranélate de strontium (Protelos): effets indésirables rapporté en France; Presse Med. 2011; 40(10):e453-e462.
- All other opinions and documents adopted by the CHMP at its October 2011 plenary meeting will be published on Friday, 21 October 2011 at 12.00 noon UK time on a dedicated web page.