Ophthalmological Events in Patients Receiving Risedronate
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Background: In the UK, the nitrogen bisphosphonate risedronate is licensed for the prevention and treatment of osteoporosis and corticosteroid-induced osteoporosis in postmenopausal women. It is also licensed for the treatment of Paget’s disease. During a prescription-event monitoring (PEM) study on risedronate we noted a number of ophthalmological events. Recently, case reports of ophthalmological adverse drug reactions in patients taking bisphosphonates were published in the medical literature. The aim of this study was to further evaluate the association of ophthalmological events reported in relation to risedronate treatment during a PEM study on the drug.
Methods: An observational cohort study (PEM study) was conducted in England between September 2000 and June 2002. General practitioners (GPs) were asked for follow-up information on selected events. Events followed up were classified as either ‘probably’, ‘possibly’ or ‘unlikely’ to be related to risedronate, using a modified WHO classification. If insufficient information was obtained on the follow-up questionnaire, the cases were categorised as ‘unassessable’.
Results: Of the total PEM study cohort of 13 643 patients, 11 156 (82%) were females and 2398 (18%) were males. We received 359 reports of ophthalmological events in 313 patients during the entire study period. Of these we followed up 178 events in 178 patients. Nineteen events in 19 patients were assessed as possibly or probably related to risedronate. The age range for these patients was 50–92 years and the time to onset ranged from 7 days to 5 months. Dry eye (six reports), sore eye (five reports) and conjunctivitis (three reports) were the most frequently reported ophthalmological events assessed as probably or possibly related to risedronate therapy. GPs also reported several other inflammatory conditions of the eye, amongst them two events each of iritis and episcleritis as well as one of keratitis. However, the information received on follow up of these events was insufficient to make causality assessments.
Conclusion: Patients receiving risedronate can present with a variety of signs and symptoms affecting the eye with different degrees of severity. Patients may present after the first month of treatment. Doctors should have an increased awareness of possible ophthalmological adverse drug reactions in patients receiving this drug, which may affect the eyesight in a population at increased risk of fracture if they fall.
KeywordsRisedronate Causality Assessment Green Form Ocular Adverse Effect Risedronate Treatment
We would like to thank all the general practitioners who have kindly participated in this study without payment and those that completed the follow-up questionnaires. We also thank the Prescription Pricing Authority for their continuing support. Further, we would like to thank Mr Shayne Freemantle, Data Analysis Manager, the entire Drug Safety Research Unit (DSRU) team that worked on this study and Mrs Lesley Flowers for preparing this manuscript.
Funding: The DSRU is a medical charity receiving unconditional grants from pharmaceutical companies, including the manufacturers of risedronate and alendronate, and other products in osteoporosis. However, these companies have no control over our decision to conduct a study, the study protocol or the reporting of any results.
Conflicts of interest: Professor Saad Shakir has received consultancy and lecturing fees from the manufacturers of products used for the treatment of osteoporosis. Beate Aurich-Barrera, Lynda Wilton and Scott Harris have no conflicts of interest that are directly relevant to this study.
WHO statement: The WHO Collaborating Centre in Uppsala, Sweden states that, with respect to data released from the centre, “the information is not homogenous at least with respect to origin or likelihood that the pharmaceutical product caused the adverse reaction” and that “the information does not represent the opinion of the WHO”.
- 1.Actonel 5mg [summary of product characteristics]. Egham: Procter and Gamble Pharmaceuticals UK Ltd, 2002Google Scholar
- 2.Actonel 30mg [summary of product characteristics]. Egham: Procter and Gamble Pharmaceuticals UK Ltd, 2002Google Scholar
- 3.Actonel once a week 35mg [summary of product characteristics]. Egham: Procter and Gamble Pharmaceuticals UK Ltd, 2003Google Scholar
- 9.Rogers HL, Marshall D, Rogers MJ. Effects of Bisphosphonates on osteoclasts in vitro, studies by scanning electron microscopy. Bone 2002; 30: 435Google Scholar
- 11.Reszka AA, Halasy-Nagy JM, Masarachia PJ, et al. Bisphosphonates act directly on the osteoclast to induce caspase cleavage of mst1 kinase during apoptosis: a link between inhibition of the mevalonate pathway and regulation of an apoptosis-promoting kinase. J Biol Chem 1999 Dec 3; 274(49): 34967–73PubMedCrossRefGoogle Scholar
- 22.Asensio Sanchez VM, Botella Oltra G, Carrasco E. Bifosfonatos e inflamacion intraocular. Arch Soc Esp Oftalmol 2004; 2: 2–4Google Scholar
- 27.Haverbeke G, Pertile G, Claes C, et al. Posterior uveitis: an under-recognized adverse effect of pamidronate: 2 case reports. Bull Soc Belge Ophtamol 2003; (290): 71–6Google Scholar
- 30.Vinas G, Olive A, Holgado S, et al. Episcleritis secondary to risedronate. Med Clin (Barc) 2002 Apr 27; 118(15): 598–9Google Scholar
- 31.Barrera BA, Wilton L, Harris S, Shakir SA. Prescription-event monitoring study on 13,164 patients prescribed risedronate in primary care in England. Osteoporos Int 2005: Epub ahead of printGoogle Scholar
- 32.Shakir SAW. Prescription-event monitoring. In: BL Strom, editor. Pharmacoepidemiology. 4th ed. Chichester: John Wiley & Sons Ltd, 2005: 203–16Google Scholar
- 33.Shakir SA. Causality and correlation in pharmacovigilance. In: Talbot PW, editor. Stephens’ detection of new adverse drug reactions. 5th ed. Chichester: John Wiley & Sons Ltd, 2004: 329–43Google Scholar
- 34.CIOMS.WHO. International Guidelines for Biomedical Research Involving Human Subjects. Geneva: CIOMS WHO, 1993Google Scholar
- 35.Multi-Centre Research Ethics Committee Guidance Notes. Examples of enquiries and surveys in the public interest where no reference to a Research Ethics Committee is necessary. UK, MREC, 2000; Appendix C:21Google Scholar
- 36.Guidelines on practice of ethical committees in medical research involving human subjects. Royal College of Physicians of London. August 1996Google Scholar
- 40.Springuel P, McMorran M. Biphosphonates and ocular disorders; Canadian Adverse Drug Reaction Newsletter. Canada: Health Canada, 2003: 1–2Google Scholar
- 41.Topliss D, Isaacs D, Lander C, et al. Bisphosphonates and ocular inflammation. Aust Adv Drug Reactions Bull 2004; 23(2): 7–8Google Scholar