Alendronate

1. Alendronate

2. Options for local implementationNPC. Key therapeutic topics – Medicines management options for local implementation. Second update July 2011. Promote the use of generic alendronate as the first line bisphosphonate for osteoporosis. Ensure that women who receive bisphosphonates have an adequate calcium intake and are vitamin D replete; supplementation may be required. Ensure that ibandronate and zoledronic acid▼ are used only in limited situations for osteoporosis.

3. Key questions Why is generic alendronate the first choice bisphosphonate for prevention of osteoporotic fragility fractures in NICE guidance? What about risedronate now generic preparations are available? Do the newer bisphosphonates, ibandronate and zoledronic acid▼, offer any advantages over the older ones? Which patients should take calcium and vitamin D supplements?

4. Why is generic alendronate the first choice bisphosphonate for prevention of osteoporotic fragility fractures in NICE guidance?

5. Primary preventionNICE. TA160. January 2011 • Alendronate is recommended for women in the following groups: • Age > 70 years, with 1 RF or ILB, and confirmed osteoporosis • In women >75 years with ≥2 RF or ILB; a DEXA scan may not be required if the responsible clinician considers it to be clinically inappropriate or unfeasible • Age 65–69 years, with 1 RF, and confirmed osteoporosis • Age <65 years, with 1 RF, and ≥1 ILB, and confirmed osteoporosis Confirmed osteoporosis: A T score < –2.5SD at the hip or spine on DEXA scan RF: Independent clinical risk factors: Parental history of hip fracture; alcohol intake of >4 units per day; rheumatoid arthritis ILB: Indicators of low BMD: Low body mass index (<22 kg/m2); medical conditions e.g. ankylosing spondylitis, Crohn’s disease, rheumatoid arthritis; prolonged immobility, untreated premature menopause

6. Secondary preventionNICE. TA161. January 2011 • Alendronate is recommended for women: • Who have sustained a clinically apparent osteoporotic fragility fracture and have confirmed osteoporosis • In women aged 75 years or older a DEXA scan may not be required if the responsible clinician considers it to be clinically inappropriate or unfeasible Clinically apparent osteoporotic fragility fracture: A fracture sustained as the result of a force equivalent to the force of a fall from a height equal to, or less than, that of an ordinary chair

7. Why generic?NICE. TA160 & 161. January 2011 • When the decision has been made to initiate treatment with alendronate, the preparation prescribed should be chosen on the basis of the lowest acquisition cost available

8. What about risedronate now generic preparations are available?

9. Primary preventionNICE. TA160. January 2011 • Risedronate and etidronate are recommended for women who: • Are unable to comply with the special administration instructions for alendronate, or have a contraindication to it, or who are unable to tolerate it, and • Fit within one of the groups in the table below:

10. Secondary preventionNICE. TA161. January 2011 • Risedronate and etidronate are recommended for women: • Who are unable to comply with the special administration instructions for alendronate, or have a contraindication to it, or who are unable to tolerate it, and • Fit within one of the groups in the table below:

11. Evidence for oral bisphosphonatesNICE. TA160 & 161. January 2011 * This includes both symptomatic and asymptomatic (radiographically determined) fractures The baseline risk will determine the absolute benefit, e.g. NNT

12. Cost of formulations of alendronate & risedronateBNF 61. March 2011; Drug Tariff. August 2011

13. Do the newer bisphosphonates, ibandronate and zoledronic acid▼, offer any advantages over the older ones?

14. What about newer bisphosphonates?BNF 61. March 2011 Vestergaard P, et al. Fracture prevention in postmenopausal women. Clinical Evidence. Search date June 2009 • Ibandronate – likely to be beneficial • 150mg once-monthly oral preparation • Reduce vertebral fracture but has not been shown to reduce non-vertebral fracture • Zoledronic acid▼ – beneficial • IV infusion once per year • Long term safety? • Reduces vertebral and non-vertebral fracture vs. placebo ‘Evidence suggests that once-yearly zoledronic acid intravenous infusion is not inferior to oral bisphosphonates in the treatment of osteoporosis; however zoledronic acid may be associated with higher incidence of serious adverse events, renal dysfunction and impairment in particular.’ CADTH HTA review. 4th July 2010

15. Costs of therapiesBNF 61. March 2011; Drug Tariff. August 2011

16. Prescribing comparatorAlendronate generic prescribing rate www.nhsbsa.nhs.uk/PrescriptionServices/3334.aspx 100% 95%

17. Prescribing comparatorAlendronate as % of all bisphosphonateswww.nhsbsa.nhs.uk/PrescriptionServices/3334.aspx 91% 54%

18. Which patients should take calcium and vitamin D supplements?

19. Calcium and vitamin D Calcium and vitamin D supplementation is generally recommended for: • High risk women (i.e. those living in care homes and/or the frail elderly) who do not have an adequate calcium intake and who may not be vitamin D replete (i.e. those with inadequate dietary intake and insufficient exposure to sunlight) • Co-administration with bisphosphonates unless clinicians are confident that women have an adequate calcium intake and are vitamin D replete NICE. TA160 & 161. January 2011 • Recommended dietary intake of calcium = 700mg per day. Food rich in calcium includes dairy products and green vegetables • Daily exposure to natural sunlight April to October will provide required vitamin D. Food rich in vitamin D includes oily fish, liver, eggs and fortified breakfast cereals Food Standard Agency. Eat well, be well

20. Key messages • Alendronate is the first choice bisphosphonate for the primary and secondary prevention of osteoporotic fragility fractures in postmenopausal women. • Choose the preparation on the basis of the lowest acquisition cost available. • Risedronate or etidronate, subject to the patient meeting additional risk criteria , as an alternative if alendronate cannot be used, e.g. can’t cope with administration instructions, contraindicated, not tolerated. • Ibandronate and zoledronic acid▼ should generally not be used first or second line. • Calcium and/or vitamin D supplementation should be considered, unless confident that the patient is vitamin D replete and there is an adequate calcium intake.