Oral Bisphosphonates


 

Alendronic acid [Alendronate], Ibandronic acid [Ibandronate], Risedronate disodium, Sodium clodronate

 

[Intravenous bisphosphonates are outside the scope of this guideline and expert advice should be sought for patients who may be receiving these in the perioperative period]


  Issues for Surgery


Risk of oesophageal complications if continued during restricted fluid / nil by mouth (NBM) period (and post-operatively if patient unable to adhere to strict administration advice – see Further Information).


  Advice in the Perioperative period


Elective Surgery

Omit on day of surgery (due to large volume of liquid required to safely take dose) – including combination products (see below).

Weekly/monthly bisphosphonates may be taken one day before or one day after the due date if the patient’s usual administration day falls on the day of surgery (also see Post-operative Advice).

Combination products: -

  • Alendronic acid + colecalciferol
  • Risedronate tablet plus calcium carbonate and colecalciferol sachet (NB: if the patient is taking the calcium carbonate/colecalciferol component of the weekly cycle, this can be taken as usual on the morning of surgery)

Emergency Surgery 

If the patient has already taken their oral bisphosphonate in the morning and is admitted for same day emergency surgery, bear in mind the potential increased risk for oesophageal reactions (oesophagitis, oesophageal ulcers, oesophageal stricture and oesophageal erosions).

Perioperative Considerations

Osteonecrosis of the jaw (ONjJ has been reported very rarely in patients receiving oral bisphosphonates. Invasive dental procedures (e.g. tooth extractions) may be a factor when considering the risk of the patient developing ONJ1, 2, 3, 4. Bear this in mind for any patients undergoing elective or emergency invasive dental procedures. Concomitant use of certain medicines can also contribute to the increased risk – see Interaction(s) with other Common Medicines use in the Perioperative Period.

Post-operative Advice

Omit doses of bisphosphonates if due during post-operative period and the patient is not able to adhere to the strict directions for administration (see Further Information).

Consult product literature for advice where a dose of weekly/monthly bisphosphonate has been missed and the patient cannot take in the immediate post-operative period.

Monitor renal function and consult product literature if there is a significant reduction in renal function post-operatively.

Orthopaedic Surgery
If a patient has been admitted with an atypical fracture of the femur, discontinuation of bisphosphonate therapy should be considered pending evaluation of the patient, based on an individual benefit risk assessment (see Further Information)1, 2, 3, 4.

Gastro-intestinal Surgery
Bisphosphonates should be used with caution in patients who have undergone gastro-intestinal surgery5. Consult with the Surgical Team before re-starting post-operatively (see Further Information).


  Interaction(s) with Common Anaesthetic Agents


None1, 2, 3, 4, 5, 6, 7.


  Interaction(s) with other Common Medicines used in the Perioperative Period


Non-Steroidal Anti-inflammatory Drugs (NSAIDs)

NSAIDs are predicted to increase the risk of gastrointestinal irritation when given with bisphosphonates5. Some studies have reported an increased risk, while others have found no increased risk6. Use the combination with caution – monitor for signs of gastrointestinal irritation1, 2, 3, 4, 6, 7.

NSAIDs are predicted to increase the risk of nephrotoxicity when given with bisphosphonates and renal function should be monitored when NSAIDs are used concomitantly4, 6, 7.

Antimicrobials

Severe hypocalcaemia has been seen in patients treated with bisphosphonates and aminoglycosides (e.g. gentamicin, tobramycin)4, 5, 6. Close monitoring of calcium and magnesium levels is advised6. Bisphosphonates and aminoglycosides can induce hypocalcaemia by different mechanisms and the effects of both drugs may persist for several weeks7.

There is potential for increased nephrotoxicity when bisphosphonates are used concomitantly with aminoglycosides, trimethoprim or vancomycin5, 6.

Whilst single surgical prophylactic doses should not pose a problem, continued post-operative treatment may require close monitoring. Consult current product literature.

Interference with Bisphosphonate Absorption

Bisphosphonates are not well absorbed from the gastrointestinal tract (GIT). See also under Further Information.

Oral Iron
Administration of oral iron preparations decreases absorption of oral bisphosphonates – consult current product literature for advice on separating administration of oral bisphosphonates and oral iron preparations to reduce this interaction5, 6.

Other Medicines
Compounds containing aluminium, calcium, iron, or magnesium, including antacids and mineral supplements and some osmotic laxatives, can also impair the absorption of bisphosphonates given orally1, 2, 3, 4, 7. Please consult product literature for guidance on separating administration of bisphosphonates from other medications.

Corticosteroids

Concomitant use of corticosteroids increases the risk of osteonecrosis of the jaw1, 2, 3, 4. This is unlikely to be an issue where corticosteroids are used as single doses to reduce post-operative nausea and vomiting or as cover for patients at risk of adrenal insufficiency. However, bear the interaction in mind should continued corticosteroid treatment be necessary.


  Further Information


Gastrointestinal Problems

Oral formulations of the bisphosphonate alendronate, ibandronate and risedronate are associated with serious oesophageal adverse reactions (e.g. oesophagitis, oesophageal ulcers, oesophageal strictures, oesophageal erosions). Clear instructions on how to take these medicines are provided in the product literature (see Directions for Administration)8.

Advice from the MHRA is as follows8: -

  • alendronate and oral ibandronate should not be given to patients with abnormalities of the oesophagus and/or other factors that delay oesophageal emptying such as stricture or achalasia and risedronate should be used with caution in such patients.
  • alendronate, oral ibandronate and risedronate should be used with caution in patients with active or recent upper gastrointestinal problems

The manufacturer of alendronic acid specifically states that caution should be used when alendronic acid is given to patients with upper gastro-intestinal problems including surgery of the upper gastrointestinal tract other than pyloroplasty1.

Atypical Fractures of the Femur

Atypical femoral fractures have been reported with bisphosphonate therapy, primarily in patients receiving long-term treatment for osteoporosis. These fractures occur after minimal or no trauma. Fractures are often bilateral. Poor wound healing of these fractures has also been reported1, 2, 3, 4.

Directions for Administration

Due to the risk of oesophageal adverse reactions oral bisphosphonates should be taken on an empty stomach at least 30 minutes (60 minutes with ibandronic acid2) before breakfast, or other oral medicines, with plenty of water (at least 200 ml) while sitting or standing; the patient should stand or sit upright for at least 30 minutes after taken5 (60 minutes with ibandronic acid and sodium clodronate2, 4).

For twice daily dosing with sodium clodronate, the first dose should be taken as detailed above. The second dose should be taken between meals, more than two hours after and one hour before eating, drinking (other than plain water), or taking any other oral drugs4.

Inability to sit or stand upright for at least 30 minutes (60 minutes with Ibrandronic acid and sodium clodronate) is a contra-indication to oral bisphosphonate administration1, 2, 3, 4.

 

  References


  1. Summary of Product Characteristics – Alendronic Acid 70 mg tablets. Aurobindo Pharma – Milpharm Ltd. Accessed via www.medicines.org.uk 26/07/2019 [date of revision of the text November 2017]
  2. Summary of Product Characteristics – Bonviva® (ibandronic) 150 mg Film-coated Tablets. Atnahs Pharma UK Ltd. Accessed via www.medicines.org.uk 26/07/2019 [date of revision of the text August 2018]
  3. Summary of Product Characteristics – Actonel® (risedronate) Once a Week 35 mg film-coated tablets. Warner Chilcott UK Limited (a subsidiary of Actavis PLC). Accessed via www.medicines.org.uk 26/07/2019 [date of revision of the text September 2018]
  4. Summary of Product Characteristics – Bonefos® (sodium clodronate) Capsules. Bayer plc. Accessed via www.medicines.org.uk 26/07/2019 [date of revision of the text October 2017]
  5. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press http://www.medicinescomplete.com [Accessed 26th July 2019]
  6. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 26th July 2019
  7. Bisphosphonates In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 26th July 2019]
  8. Medicines & Healthcare products Regulatory Agency (MHRA). Guidance: Bisphosphonates: use and safety. Published 18 December 2014. Accessed via www.gov.uk 28/07/2019