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.
Emergency surgery
If the patient has already taken their sodium clodronate 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 (ONJ) 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 ONJ. 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 Interactions with other common medicines used in the perioperative period.
Post-operative advice
Omit doses of sodium clodronate if due during post-operative period and the patient is not able to adhere to the strict directions for administration (see Further information).
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).
Gastro-intestinal surgery
Bisphosphonates should be used with caution in patients who have undergone gastro-intestinal surgery. Consult with the surgical team before re-starting post-operatively (see Further information).
Interactions with common anaesthetic agents
None.
Interactions 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 sodium clondronate. Some studies have reported an increased risk, while others have found no increased risk. Use the combination with caution – monitor for signs of gastrointestinal irritation.
NSAIDs are predicted to increase the risk of nephrotoxicity when given with sodium clodronate and renal function should be monitored when NSAIDs are used concomitantly.
Antimicrobials
Severe hypocalcaemia has been seen in patients treated with sodium clodronate and aminoglycosides (e.g. gentamicin, tobramycin). Close monitoring of calcium and magnesium levels is advised. Bisphosphonates and aminoglycosides can induce hypocalcaemia by different mechanisms and the effects of both drugs may persist for several weeks.
There is potential for increased nephrotoxicity when sodium clodronate are used concomitantly with aminoglycosides, trimethoprim or vancomycin.
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
Sodium clodronate are not well absorbed from the gastrointestinal tract (GIT). See also under Further information.
Oral iron
Administration of oral iron preparations decreases absorption of sodium clodronate– consult current product literature for advice on separating administration of sodium clodronate and oral iron preparations to reduce this interaction.
Other medicines
Compounds containing aluminium, calcium, iron, or magnesium, including antacids and mineral supplements and some osmotic laxatives, can also impair the absorption of sodium clodronate given orally. Please consult product literature for guidance on separating administration of sodium clodronate from other medications.
Corticosteroids
Concomitant use of corticosteroids increases the risk of osteonecrosis of the jaw. 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
Atypical fractures of the femur
Atypical femoral fractures have been reported with sodium clodronate 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 reported.
Directions for administration
Due to the risk of oesophageal adverse reactions sodium clodronate should be taken on an empty stomach before food, or other oral medicines, with a glass of water while sitting or standing; the patient should stand or sit upright for at least 60 minutes).
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 drugs.
Inability to sit or stand upright for at least 60 minutes is a contra-indication to oral bisphosphonate administration.
References
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 26th July 2019
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]
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press http://www.medicinescomplete.com [Accessed 26th July 2019]
Medicines & Healthcare products Regulatory Agency (MHRA). Guidance: Bisphosphonates: use and safety. Published 18 December 2014. Accessed via www.gov.uk 28/07/2019
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]