Product overview

Mode of action

Bisphosphonates are adsorbed onto hydroxyapatite crystals in bone, slowing their rate of growth and dissolution, and inhibiting osteoclast maturation and function, thereby reducing the rate of bone turnover (British national formulary, March 2017, Brufsky and Mathew 2015).

Regulatory status

Six bisphosphonates are available in the UK: alendronic acid (alendronate sodium), ibandronic acid (ibandronate sodium), pamidronate disodium, risedronate sodium, sodium (and disodium) clodronate and zoledronic acid (zoledronate).

The following list shows some of the licensed indications and usual dosages for bisphosphonates, focussing on those that are most relevant to the population included in this evidence summary. Other licensed indications for bisphosphonates include management of osteoporosis in men, corticosteroid-induced osteoporosis, hypercalcaemia of malignancy and Paget's disease. The medicines are administered orally, unless stated otherwise. Where a treatment frequency or duration is not stated, a single dose is used. See the summaries of product characteristics or British national formulary for more detailed information on the licensed indications and dosages for individual bisphosphonates.

  • Treating osteoporosis in postmenopausal women:

    • alendronic acid 10 mg daily or 70 mg weekly

    • ibandronic acid 150 mg monthly or 3 g intravenously (IV) every 3 months

    • risedronate sodium 5 mg daily or 35 mg weekly

    • zoledronic acid 5 mg IV yearly.

  • Preventing skeletal events in people with breast cancer and bone metastases:

    • ibandronic acid 50 mg daily or 6 mg IV every 3–4 weeks

    • zoledronic acid 4 mg IV every 3–4 weeks.

  • Managing osteolytic lesions and bone pain in people with breast cancer or multiple myeloma and bone metastases:

    • pamidronate disodium 90 mg IV every 4 weeks

    • sodium clodronate 1,600 mg daily.

Bisphosphonates may be used in some people with breast cancer, within the terms of their licenses, to prevent osteoporosis or skeletal events, or manage osteolytic lesions, bone pain or hypercalcaemia of malignancy. However, these treatments are not licensed for preventing recurrence or improving survival in people with early breast cancer, and use for this indication is off-label. In line with the guidance from the General Medical Council (GMC) on prescribing unlicensed medicines, the prescriber should take full responsibility for determining the needs of the patient and whether using bisphosphonates is suitable outside its authorised indications. Supporting information and advice is also available from the GMC.

Dosing information

Dosing information varies for the licensed indications for the bisphosphonates and, although the usual dosages are briefly listed above, more detail can be found in the summaries of product characteristics.

Dosing information for bisphosphonates for adjuvant use to prevent recurrence and improve survival in people with early breast (off-label indication) is discussed in the estimated impact for the NHS section of this evidence summary.

Cost

Table 2 lists a range of costs for the 6 bisphosphonates at the usual dosages covering most of the licensed indications. Dosages shown do not represent the full range that can be used and do not imply therapeutic equivalence. The costs shown are for 4 weeks' treatment, unless the bisphosphonate is generally administered as a single dose.

The costs shown for IV treatments do not cover the full range of available products. Also, costs are for the medicines only (excluding VAT) and do not include any local procurement discounts or other costs incurred, such as dilution and administration, standard supportive therapy (such as calcium and vitamin D), or any costs associated with attendance for day case treatment.

Table 2 Costs of bisphosphonates

Medicine

Dosage a and quantity

Cost per 28 days or single dose, as indicated, excluding VAT

Alendronic acid

10 mg daily x 28 tablets

£1.69b

70 mg weekly x 4 tablets

£0.72b

Ibandronic acid

50 mg daily x 28 tablets

£6.27b

150 mg monthly x 1 tablet

£1.13b

1 mg/ml x 2 ml vial x 1 single dose

£23.26c

1 mg/ml x 3 ml syringe x 1 single dose

£10.27c

Pamidronate disodium

9 mg/ml x 10 ml vial x 1 single dose

£4.10c

Risedronate sodium

5 mg daily x 28 tablets

£18.85b

35 mg weekly x 4 tablets

£0.85b

Sodium clodronate

1,600 mg daily, 800 mg x 56 tablets

£136.67b

Zoledronic acid

5 mg/100 ml bag x 1 single dose

£7.36c

4 mg/100 ml bag x 1 single dose

£3.94c

a Dosages are taken from the relevant SPCs. Those shown do not represent the full range that can be used and do not imply therapeutic equivalence

b Costs taken from the Drug Tariff, June 2017; excluding VAT

c Average price paid in English NHS hospital trusts over the last 4 months of 2015 taken from Drugs and pharmaceutical electronic market information; excluding VAT