Unwanted effects and precautions

Unwanted effects include:

• oral bisphosphonates commonly cause gastrointestinal disturbances
  • for example - diarrhoea, constipation, indigestion and abdominal pain
  • alendronate - severe oesophageal effects have been reported e.g. oesophagitis, oesophageal ulcers, oesophageal strictures
  • etridronate - there has also been exacerbation of peptic ulcers with a few patients (1)
  • risedronate - reported to result in fewer gastric ulcers than alendronate but this may reflect fewer post-marketing data for risedronate than alendronate
• atypical fractures of the femur have been reported rarely after long term use (2)
• iritis - rarely associated with bisphosphonate treatment

Precautions include:

• calcium and mineral metabolism disturbances (e.g. parathyroid hormone dysfunction, vitamin D deficiency) should be corrected before starting a bisphosphonate
• if dietary intake is inadequate then calcium and vitamin D supplements should be given with alendronate and risedronate
• bisphosphonates should not be administered in renal impairment (creatinine clearance < 30ml/L)
• alendronate - contraindicated if delay in oesophageal emptying e.g. achalasia, stricture. If active gastrointestinal problems (e.g. dysphagia, oesophageal disease, gastritis, duodenitis, ulcers) then manufacturer advises should be used with "caution" and patients should be advised to stop alendronate and consult doctor if symptoms such as dysphagia, worsening or new heartburn, retrosternal pain or pain on swallowing develop
  • alendronate should be taken first thing in the morning and at least 30 minutes before food, drink (other than water) or medicines(e.g. antacids and mineral supplements containing calcium)
• etidronate - advised to be taken at a point 2 hours before and 2 hours after meals or medicines containing calcium, magnesium, aluminium or iron
• risedronate - according to manufacturer, the drug should be used with "special caution" ifa history of oesophageal disorders that delay oesophageal emptying or transit
  • can be taken at least 30 minutes before going to bed, or first thing in the morning (like alendronate) or between meals (like etidronate)
• upper gastrointestinal effects can be reduced by taking a bisphonate tablet with a full glass of water, while standing or sitting upright, and by remaining upright for at least 30 minutes after taking the bisphosphonate tablet

Note:

• failure to take bisphosphonates correctly may result in an apparent lack in efficacy - this is because of their low bioavailability
• patients who are on bisphosphonate therapy should be advised to report any thigh, hip, or groin pain and if these symptoms are present, the patient should be evaluated for an incomplete femur fracture (2).

Reference:

• (1) Drug and Therapeutics Bulletin (2001), 39(9), 68-72.
• (2) Medicines and Healthcare products Regulatory Agency (MHRA). Bisphosphonates: atypical femoral fractures. Drug Safety Update 2011;4(11)