6.6.2 Bisphosphonates and other drugs affecting bone metabolism

Oral bisphosphonates are absorbed very poorly; therefore counselling should be given to the patient as to how and when administration is most appropriate.

All oral bisphosphonate should be taken in combination with calcium & vitamin D (see section 9.6 Vitamins), the patient should be offered the product they like the best to achieve concordance.

Prescribers are reminded to check that an annual infusion of zoledronic acid has not been given, prior to commencing oral bisphosphonates.

Please refer to formulary guidance: Management of osteoporosis

MHRA Drug Safety Update (Nov 2009): The risk of developing osteonecrosis of the jaw with oral bisphosphonates seems to be low. The risk of is substantially greater for patients receiving I/V bisphosphonates for cancer indications than for patients receiving oral bisphosphonates for osteoporosis of Paget's disease. To minimise risk all patients should have a dental check-up before bisphosphonate treatment. All other patients who start bisphosphonates should have a dental examination only if they have poor dental status. During treatment, patients should maintain good oral hygiene, receive routine dental check-ups, and report any oral symptoms such as dental mobility, pain, or swelling.

MHRA Drug Safety Update (June 2011): Atypical femoral fractures have been reported rarely with bisphosphonate therapy, mainly in patients receiving long-term treatment for osteoporosis. They are often bilateral; therefore the contralateral femur should be examined in patients who have sustained a femoral shaft fracture. Discontinuation of therapy in patients suspected to have an atypical femur fracture should be considered while they are evaluated, and should be based on an assessment of the benefits and risks of treatment for the individual. During treatment, patients should be advised to report any thigh, hip, or groin pain. Any patient who presents with such symptoms should be evaluated for an incomplete femur fracture. The optimum duration of treatment for osteoporosis has not been established. The need for continued treatment should be re-evaluated periodically based on the benefits and potential risks of bisphosphonate therapy for individual patients, particularly after 5 or more years of use.

Alendronic acid
  • Tablets 10mg (£1.83)
  • Weekly tablets 70mg (£0.74 = 4 tablets)

Indications and dose

  • Treatment of postmenopausal osteoporosis, 10mg daily or 70mg once weekly
  • Treatment of osteoporosis in men, 10mg daily
  • Prevention and treatment of corticosteroid-induced osteoporosis in postmenopausal women not receiving hormone replacement therapy, 10mg daily

Notes

  1. Alendronic acid 70mg is a 'special container' pack of four tablets. These should not be prescribed on weekly prescriptions as the pack cannot be split by the pharmacy to provide one tablet.
  2. Severe oesophageal reactions (oesophagitis, oesophageal ulcers, oesophageal stricture and oesophageal erosions) have been reported; patients should be advised to stop taking the tablets and to seek medical attention if they develop symptoms of oesophageal irritation such as dysphagia, new or worsening heartburn, pain on swallowing or retrosternal pain
  3. Alendronate is not recommended for patients with renal impairment, GFR less than 35mL/minute
  4. NICE TA464: Bisphosphonates for treating osteoporosis. Alendronic acid is recommended as an option for treating osteoporosis in adults (August 2017)
Risedronate
  • Tablets 5mg, 30mg (£18.85 = 5mg)
  • Weekly tablets 35mg (£0.85 = 4 tablets)

Indications and dose

  • Paget's disease of bone, 30mg daily for 2 months; may be repeated if necessary after at least 2 months
  • Treatment of postmenopausal osteoporosis to reduce risk of vertebral or hip fractures, 5mg daily or 35mg once weekly
  • Prevention of osteoporosis (including corticosteroid-induced osteoporosis) in postmenopausal women, 5mg daily
  • Treatment of osteoporosis in men at high risk of fractures, 35mg once weekly

Notes

  1. Oesophageal reactions: Patients should be advised to stop taking the tablets and to seek medical attention if they develop symptoms of oesophageal irritation such as dysphagia, new or worsening heartburn, pain on swallowing or retrosternal pain
  2. The use of risedronate sodium is contraindicated in patients with severe renal impairment, avoid if GFR less than 30mL/minute
  3. NICE TA464: Bisphosphonates for treating osteoporosis. Risedronate sodium is recommended as an option for treating osteoporosis in adults (August 2017)
Ibandronic acid
  • Injection 1mg/ml (£44.68 = 2ml vial)
  • Tablets 150mg

Indications

  • Treatment of postmenopausal osteoporosis

Dose

  • Intravenous injection over 15–30 seconds, 3mg every 3 months

Notes

  1. Ibandronic acid should be used with caution in patients with renal impairment – please consult the manufacturer's information for further information.
  2. NICE TA464: Bisphosphonates for treating osteoporosis. Ibandronic acid is recommended as an option for treating osteoporosis in adults (August 2017)
Sodium clodronate
  • Capsules 400mg (£139.83 = 120)
  • Tablets 520mg (£152.59 = 60)
  • Tablets 800mg (£146.43 = 60)

Notes

  1. Consultant initiation only
  2. Clodronate is eliminated mainly via the kidneys. Please refer to the manufacturers information for guidance regarding dose alterations.
Disodium pamidronate
  • Injection 15mg vial, 30mg vial, 60mg vial, 90mg vial

Notes

  1. IV disodium pamidronate is licensed to treat hypercalcaemia, osteolytic lesions and bone pain linked to bone/ skeletal metastases and that related to Paget's disease.
  2. Disodium pamidronate may be used in the treatment of osteoporosis (unlicensed). The required dose is diluted in 0.9% sodium chloride to a concentration of not more than 60mg in 250ml and given at a rate not exceeding 1mg per minute.
Zoledronic Acid
  • Zometa® concentrate for IV infusion 800 micrograms/mL, 5ml (4mg) vial
  • Aclasta® I/V infusion 50 micrograms/ml 100ml bottle

Notes

  1. NICE TA464: Bisphosphonates for treating osteoporosis. Zoledronic acid is recommended as an option for treating osteoporosis in adults (August 2017)

Monoclonal antibodies

Denosumab
  • Subcutaneous injection, pre-filled syringe 60mg per mL (£183.00 = 1ml syringe) (for South Devon patients this is provided by specialist service at Torbay Hospital)
  • Injection 70mg per ml 1.7ml (120mg) vial

Indications and dose

  • Prevention of osteoporotic fragility fractures in postmenopausal women, in line with NICE TA204, subcutaneous injection, 60mg every 6 months
  • Prevention of skeletal-related events in adults with bone metastases from breast cancer and from solid tumours other than prostate, in line with NICE TA265, by subcutaneous injection, 120mg every 4 weeks

Notes

  1. See here for the NEW Devon CCG Specialised Medicines Service Guideline for Denosumab (Prolia®) for osteoporosis (Western Locality)
  2. To avoid unnecessary out of pocket expenses, practices or pharmacies should order Prolia® direct from Movianto: www.prolia.co.uk/HCP/how_to_order_prolia.html
  3. MHRA Drug Safety Update (Oct 2012) The following precautions should be followed to minimise the risk of hypocalcaemia with denosumab:
    1. Denosumab 120mg (for cancer indications) should not be used in patients with severe, untreated hypocalcaemia
    2. Denosumab 60mg (for osteoporosis indications) should not be used in patients with hypocalcaemia, regardless of severity (the contraindications vary between the two doses, because their indications are different)
  4. NICE TA204: Denosumab for the prevention of osteoporotic fractures in postmenopausal women (October 2010)
  5. NICE TA265: Denosumab for the prevention of skeletal-related events in adults with bone metastases from solid tumours (October 2012)
  6. MHRA Drug Safety Update (Feb 2013): Atypical femoral fractures have been reported rarely in patients with postmenopausal osteoporosis receiving long-term (2.5 years or longer) treatment with denosumab 60mg in a clinical trial. During denosumab treatment, patients presenting with new or unusual thigh, hip or groin pain should be evaluated for an incomplete femoral fracture. Discontinuation of denosumab therapy should be considered if an atypical femur fracture is suspected, while the patient is evaluated
  7. MHRA Drug Safety Update July 2015 and MHRA Drug Safety Update June 2017:
    • Before prescribing denosumab or intravenous bisphosphonates:
      1. give patients the patient reminder card for their medicine
      2. explain the risk of osteonecrosis of the jaw, and osteonecrosis of the external auditory canal, and advise patients on precautions to take
      3. do not prescribe denosumab 120mg (cancer indication) to patients with unhealed lesions from dental or oral surgery
      4. advise patients to report any problems with their mouth or teeth, any ear pain, discharge from the ear, or an ear infection during denosumab treatment
      5. please continue to report suspected side effects to denosumab, bisphosphonates or any other medicines on a Yellow Card.

Strontium ranelate

Strontium ranelate
  • Granules 2g sachet (£27.08 = 28 sachets)

Indications

  • See MHRA warning in notes below

Notes

  1. Strontium ranelate was discontinued at the end of August 2017, patients taking this medication require a review and a fracture risk assessment.
  2. Use of strontium ranelate is now restricted to treatment of severe osteoporosis: i) in postmenopausal women at high risk of fracture; ii) in men at increased risk of fracture (see MHRA warning below).
  3. MHRA Drug Safety Update (April 2013) Strontium ranelate (Protelos): risk of serious cardiac disorders—restricted indications, new contraindications, and warnings
    • Treatment should only be initiated by a physician with experience in the treatment of osteoporosis, and the decision to prescribe strontium ranelate should be based on an assessment of the individual patient's overall risks
    • Strontium ranelate should not be used in patients with: ischaemic heart disease, peripheral arterial disease; cerebrovascular disease; a history of these conditions; or in patients with uncontrolled hypertension
    • Prescribers are advised to assess the patient's risk of developing cardiovascular disease before starting treatment and thereafter at regular intervals
    • Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with strontium ranelate after careful consideration
    • Treatment should be stopped if the patient develops ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, or if hypertension is uncontrolled
    • Healthcare professionals should review patients at a routine appointment and consider whether or not to continue treatment
  4. Strontium should be taken in-between meals, preferably at bedtime at least two hours after food, milk products or calcium supplements. Ensure patients can comply with this regimen.
  5. Strontium should not be used in patients with severe renal impairment (creatinine clearance less than 30mL/min).
  6. Laboratory measurements of serum calcium are unreliable for patients taking strontium.
  7. Reductions in vertebral and non-vertebral fractures have been demonstrated but reductions in hip fracture only apparent in those aged over 74 years with T score of -2.4SD.
  8. Strontium reduces the absorption of tetracyclines and quinolones: therapy should be suspended for the duration of the antibiotic course.
  9. Strontium should not be used during pregnancy or lactation.
  10. Severe hypersensitivity syndromes including drug rash with eosinophilia and systemic symptoms (DRESS) has been reported with strontium.
  11. NICE TA160: Strontium ranelate is recommended as an alternative treatment option for the primary prevention of osteoporotic fragility fractures in postmenopausal women (August 2017)
  12. NICE TA161: Strontium ranelate is recommended as an alternative treatment option for the secondary prevention of osteoporotic fragility fractures in postmenopausal women (August 2017)

 

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