Post-marketing assessment of the safety of strontium ranelate; a novel case-only approach to the early detection of adverse drug reactions

Br J Clin Pharmacol. 2008 Nov;66(5):689-94. doi: 10.1111/j.1365-2125.2008.03273.x. Epub 2008 Jul 31.

Abstract

Aims: Post licensing, the evaluation of drug safety relies heavily on the collation of sporadic, spontaneous reports on adverse effects. The aim was to assess the potential utility of a more systematic approach to the detection of adverse events that utilizes routinely collected clinical data from a large primary care population.

Methods: We used the UK General Practice Research Database to assess the risk of several recently reported adverse events linked to the use of strontium ranelate for osteoporosis in postmenopausal women. The self-controlled case-series method was used to minimize the potential for biases in the quantification of risk estimates.

Results: Age-adjusted rate ratios for venous thromboembolism, gastrointestinal disturbance, minor skin complaint and memory loss were 1.1 [95% confidence interval (CI) 0.2, 5.0], 3.0 (95% CI 2.3, 3.8), 2.0 (95% CI 1.3, 3.1) and 1.8 (95% CI 0.2, 14.1), respectively. No cases of osteonecrosis of the jaw, toxic-epidermal necrosis, Stevens-Johnson syndrome or drug rash with eosinophilia and systemic symptoms were found.

Conclusions: Although we confirmed the association between strontium ranelate and adverse events identified in the Phase III publications, there was no evidence of an association between strontium ranelate and the aforementioned potentially life-threatening adverse events. Our study demonstrates the relative ease with which this method can assess a variety of adverse events associated with a new drug in actual clinical practice. We believe this technique could be more widely adopted to assess the safety profile of new drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Density Conservation Agents / adverse effects*
  • Bone Density Conservation Agents / therapeutic use
  • Case-Control Studies
  • Databases, Factual
  • Drug Hypersensitivity
  • Family Practice / statistics & numerical data
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Humans
  • Memory Disorders / chemically induced
  • Middle Aged
  • Organometallic Compounds / adverse effects*
  • Organometallic Compounds / therapeutic use
  • Osteoporosis, Postmenopausal / drug therapy*
  • Product Surveillance, Postmarketing / methods*
  • Risk Assessment / methods
  • Thiophenes / adverse effects*
  • Thiophenes / therapeutic use
  • United Kingdom
  • Venous Thromboembolism / chemically induced

Substances

  • Bone Density Conservation Agents
  • Organometallic Compounds
  • Thiophenes
  • strontium ranelate