[Adverse drug reactions of strontium ranelate(Protelos(®) in France].

OBJECTIVE

Study of side effects (SE) associated with strontium ranelate required by the French Drug agency (Afssaps).

METHODS

SE associated with strontium ranelate and spontaneously reported until March 2009 to the manufacturer or to the French Regional Pharmacovigilance Centers and the periodic safety reports have been analyzed. Utilisation and sales data have been obtained from the manufacturer.

RESULTS

During the 3 years of the study, 844 SE have been reported in France in patients treated with strontium ranelate. The 199 severe SE are cardiovascular (52%), cutaneous (26%), hepatodigestive (6%), neurological (5%), haematological (3%), osteomuscular (3%) and various (3%). Venous thromboembolic events (VTEE) are the most frequent cardiovascular SE (93/104) with an incidence of 1/31,052 months of treatment. At least one VTEE risk factor is present in 26 (28%) patients. DRESS syndrome which median delay of advent is 35 days is the most frequent cutaneous SE (19/51 SE) with an incidence of 1/13,725 months of treatment. The 14 severe hepatodigestive SE are hepatitis (n=5), pancreatitis (n=2) and various others SE (n=7). The 10 severe neurological SE are confusion/amnesia (n=5), convulsions (n=4) and parenthesis (n=1). The seven severe haematological SE are pancytopenia (n=5), erythroblastopenia (n=1) and thrombocytopenic purpura (n=1). Among the seven deaths, only three (two pulmonary embolisms, one DRESS syndrome) are attributable to strontium ranelate. Apart from the severe SE, 685 SE have also been reported because strontium ranelate was the only drug with an imputability "suspect".

CONCLUSIONS

Anti-fractural effect of strontium ranelate is at least as equal as those of bisphosphonates. Its usual SE are benign but two severe risks of strontium ranelate i.e. VTEE and DRESS syndrome are confirmed. The profile of tolerability, different from the one of bisphosphonates makes strontium ranelate as an alternative when bisphosphonates are not recommended or contraindicated (renal insufficiency for example).

CONCLUSIONS

If DRESS syndrome is unpredictable, the one of VTEE could be reduced by a strontium ranelate contraindication for patients with a history of VTEE and by stopping the drug if a new VTEE risk situation happens.