| Therapeutic Area | Formulary Choices | Cost for 28 (unless otherwise stated) | Rationale for decision / comments |
|---|---|---|---|
| NOTE ON BISPHOSPHONATES- Discuss the benefits and risks of bisphosphonate treatment with women, particularly the risk of osteonecrosis of the jaw, atypical femoral fractures and osteonecrosis of the external auditory canal. Follow the Medicines and Healthcare products Regulatory Agency/Commission on Human Medicines (MHRA/CHM) advice on bisphosphonates. |
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| 6.6 Drugs affecting bone metabolism | |||
| Osteoporosis:assessing the risk of fragility fracture NICE CG146 updated Feb 2017 | |||
| Targeting risk assessment •Consider assessment of fracture risk in: ~all women aged ≥65 years, AND ~all men aged ≥75 years. •Consider assessment of fracture risk in women <65 years and men aged <75 years in the presence of risk factors such as: ~previous fragility fracture, ~current use or frequent recent use of oral or systemic glucocorticoids, ~history of falls, ~family history of hip fracture, ~other causes of secondary osteoporosis (see Table 1), ~low BMI (<18.5 kg/m2), ~smoking, ~alcohol intake above recommended limits. •Do NOT routinely assess fracture risk in people aged <50 years unless they have major risk factors e.g. current or frequent recent use of oral or systemic glucocorticoids, untreated premature menopause or previous fragility fracture, because they are unlikely to be at high risk. •Measure BMD to assess fracture risk in people aged <40 years who have a major risk factor, such as history of multiple fragility fracture, major osteoporotic fracture, or current or recent use of high dose systemic glucocorticoids.* •Also see NICE pathway: Hip fracture | Assessment tools FRAX® Accessible at: https://www.sheffield.ac.uk/FRAX/tool.jsp QFracture® Accessible at: http://www.qfracture.org/ Note: QFracture does not include BMD in its algorithm. These algorithms give the 10-year probability of fracture for: hip fracture major osteoporotic fracture (clinical spine, forearm, hip or shoulder fracture) Table 1 Causes of secondary osteoporosis Endocrine -Hypogonadism including untreated premature menopause, treatment with aromatase inhibitors or androgen deprivation therapy hyperthyroidism, hyperparathyroidism, hyperprolactinaemia, Cushing’s disease, diabetes Gastrointestinal - Coeliac disease, inflammatory bowel disease, chronic liver disease, chronic pancreatitis, other causes of malabsorption Rheumatological -Rheumatoid arthritis, other inflammatory arthropathies Haematological - Multiple myeloma, haemoglobinopathies, systemic mastocytosis. Respiratory - Cystic fibrosis, COPD, metabolic (homocystinuria) Metabolic - Homocystinuria Other - Chronic renal disease, immobility |
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| Methods of risk assessment •Estimate absolute risk when assessing risk of fracture e.g. predicted risk of major osteoporotic or hip fracture over 10 years, expressed as a percentage. •Use either FRAX® (without a BMD value if a DXA scan has not previously been undertaken) or QFracture®, within their allowed age ranges. Above the upper age limits defined by the tools, consider people to be at high risk. •FRAX® can be used for people aged between 40 and 90 years, either with or without BMD values, as specified. QFracture® can be used for people aged between 30 and 84 years. BMD values cannot be included in the risk algorithm. •Interpret the estimated absolute risk of fracture in people aged >80 years with caution, because predicted 10-year fracture risk may underestimate their short-term fracture risk. •Take into account that risk assessment tools may underestimate fracture risk in certain circumstances, for example if a person: ~has a history of multiple fractures, ~has had previous vertebral fracture(s), ~has a high alcohol intake, ~is taking high-dose systemic glucocorticoids*, ~has other causes of secondary osteoporosis. • Take into account that fracture risk can be affected by factors that may not be included in the risk tool e.g. living in a care home, or taking drugs that may impair bone metabolism e.g. anti convulsants, selective serotonin reuptake inhibitors, thiazolidinediones, proton pump inhibitors and anti-retrovirals. • Following risk assessment with FRAX® (without a BMD value) or QFracture® , consider measuring BMD with DXA in people whose fracture risk is in the region of an intervention threshold** for a proposed treatment, and recalculate absolute risk using FRAX® with the BMD value. • Do NOT routinely measure BMD without prior assessment using FRAX (without a BMD value) or QFracture. • Also see NICE medtech innovation briefing; Bindex for investigating suspected osteoporosis. • Consider measuring BMD with DXA before starting treatments that may have a rapid adverse effect on bone density e.g. sex hormone deprivation treatment for breast or prostate cancer. • Consider recalculating fracture risk in the future: ~if the original calculated risk was in the region of the intervention threshold** for a proposed treatment and only after a minimum of 2 years, OR ~when there has been a change in the person's risk factors. * >7.5mg prednisolone or equivalent per day for ≥3 months **An intervention threshold is the level of risk at which an intervention is recommended |
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| Bisphosphonates for treating osteoporosis NICE TA464 2018 | |||
| Preventing fragility fractures Oral bisphosphonates (alendronic acid, ibandronic acid and risedronate sodium) are recommended as options for treating osteoporosis in adults only if the: ~person is eligible for risk assessment, AND ~10-year probability of osteoporotic fragility fracture is at least 1%. Intravenous bisphosphonates (ibandronic acid and zoledronic acid) are recommended as options for treating osteoporosis in adults only if the: ~person is eligible for risk assessment , AND ~10-year probability of osteoporotic fragility fracture is at least 10%, OR ~10-year probability of osteoporotic fragility fracture is at least 1% and the person has difficulty taking oral bisphosphonates or these drugs are contraindicated or not tolerated. Estimate the 10-year probability of fragility fracture using the FRAX® or QFracture® risk tools. Choice of treatment should be made on an individual basis after discussion between the responsible clinician and the patient and/or carers, about the advantages and disadvantages of treatments available. If several generic products are available, start treatment with the least expensive formulation, taking into account administration costs, the dose needed and the cost per dose. These recommendations are not intended to affect treatment with alendronic acid, ibandronic acid, risedronate sodium and zoledronic acid that was started in the NHS before this guidance was published. Adults having treatment outside these recommendations may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop. For additional recommendations on the use of bisphosphonates in postmenopausal women, see also: NICE TA160: Primary prevention of fragility fractures inpostmenopausal women NICE TA161: Secondary prevention of fragility fractures inpostmenopausal women MHRA (Medicines and healthcare regulatory agency) advice Bisphosphonates: atypical femoral fractures https://www.gov.uk/drug-safety-update/bisphosphonates-atypicalfemoral-fractures Bisphosphonates: osteonecrosis of the jaw https://www.gov.uk/drug-safety-update/bisphosphonates-osteonecrosisof-the-jaw Bisphosphonates: very rare reports of osteonecrosis of external auditory canal https://www.gov.uk/drug-safety-update/bisphosphonates-very-rarereports-of-osteonecrosis-of-the-external-auditory-canal Bisphosphonates: atrial fibrillation https://www.gov.uk/drug-safety-update/bisphosphonates-atrial-fibrillation |
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NICE patient decision aid-bisphophonates in osteoporosis https://www.nice.org.uk/guidance/ta464/resources/decision-support-from-nice-information-to-help-people-with-osteoporosis-and-their-health-professionalsdiscuss-the-options-pdf-4608867565 |
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| Primary prevention of osteoporosis in postmenopausal women | • The March 2012 Somerset Prescribing Forum debated and then approved the off license use of Bisphosphonates (alendronate (1st) , risedronate(2nd) or ibandronate(3rd): o Patients who have sustained fragility fractures but currently excluded by NICE criteria o Patients deemed by clinicians at high risk of fragility fractures (including patients with Osteopenia if at high # risk) • The evidence of benefit from Bisphosphonate therapy comes from trials which ensured patients had intake of therapeutic doses of Calcium and Vitamin D, supplementation with Calcium and Vitamin D is therefore recommended for patients prescribed these drugs. • Where Calcium and Vitamin D is recommended, a formulation providing Calc.Carb. 1500mg and Vit D 400iu per tablet should be prescribed. A range of products is included all now of similar price; the product chosen should be made according to patient preference & encourage concordance. • Preparations such as Calcichew D3® or Calcium & Ergocalciferol BP do not provide evidence-based doses of the constituents and should normally not be prescribed. The optimal period of treatment with bisphosphonates is not known, evidence of benefit has been measured for up to 5 years. NICE recommends research into the long-term effects and prescribers should be aware of the possible adverse effects on bone quality when bisphosphonates are taken for extended periods. Bisphosphonate ‘drug holidays’: No formal guidance exists on this topic which is advocated by some secondary care centres. Local policy is to follow MHRA alert & assess people individually. The absolute numbers of atypical stress fractures in patients on long-term bisphosphonates is very low; it is not at all clear whether these are because of BPP therapy or simply random events. |
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| First-line: | Alendronic Acid Effervescent as Binosto 70mg® | 70mg tablets: £0.78 (4) 70mg/100ml solution: £27.36 (4x100ml) 70mg effervescent tablets £22.80 (4) | Tablets dissolve in 120mls water. Does contain 600mg of sodium. Alternative for patients with swallowing difficulties |
| Risedronate 35mg | 35mg tablets: £0.89 (4) | ||
| Second-line: | Ibandronate 150mg | 150mg tablet: £1.10 (1) | |
| Third-line: | Denosumab* | 60mg/ml prefilled syringe: £183.00 (1) 120mg Injection (Xgeva®) is NOT for treatment of osteoporosis |
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| *Also for men at increased risk of fracture Denosumab is associated with a risk of osteonecrosis of the jaw (ONJ) and with a risk of hypocalcaemia. MHRA September 2014 Before starting denosumab, a dental examination and appropriate preventative dentistry recommended. |
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| All with calcium and vitamin D supplement | Although the formulary only highlights first line cost effective calcium and colecalciferol preparations, all other licensed makes remain on formulary as options where the patient has specific taste or other formulation preferences which would increase patient concordance compared to the first line options. Recommended daily intake of elemental calcium is >1000 mg and 20 micrograms of colecalciferol (equivalent to 800 IU vitamin D3) tablets per day (minimum). 2.5G of calcium carbonate is equivalent of 1G of elemental calcium. |
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| TheiCal D3® chewable tablets 1000mg/880IU | £2.95 (30 tablets) | Once daily dose with or without food | |
| Accrete D3® tablets 600mg/800IU | £2.95 (60) | Twice daily tablet | |
| Adcal D3® caplets 300mg/200IU | £2.95 (112) | Two caplets twice daily | |
| Evacal D3® chewable tablets 1500mg/400IU | £2.75 (56) | Twice daily dosage | |
| Calci-D®chewable tablets 1000mg/1000IU | £2.25 (28) | Once daily dosage | |
| Secondary prevention of osteoporosis in postmenopausal women | See Summary of NICE TA161 below Somerset Prescribing Forum approved Zoledronic acid annual infusion (Sep-10) & Denosumab (Jan-12) as third-line treatments for secondary prevention of osteoporosis Raloxifene is not recommended as a treatment option for primary prevention of osteoporotic fractures. Bisphosphonates (1st alendronate or risedronate, 2nd ibandronate) are recommended first line for the secondary prevention of osteoporotic fracture in women with confirmed osteoporosis who have also sustained a clinically apparent osteoporotic fracture. In addition, in March 2012, Somerset Prescribing Forum approved the off license use of Bisphosphonates in patients with previous fragility fractures or deemed by clinicians at high risk of fragility fractures for patients with Osteopenia. Where an oral bisphosphonate is not appropriate, denosumab and annual infusion of zoledronic acid are approved by Somerset Prescribing Forum as 3rd line treatments or raloxifene (subject to BMD, age & other risk factors). Teriparetide is a treatment option following assessment in secondary care where other therapies are not appropriate. Teriparetide is a RED drug under the traffic light classification. This information is summarised in the flow chart below. The FRAX algorithm is a tool to calculate 10 year probablilty of hip and other major osteoporotic fractures using the same risk factors as NICE plus glucocorticoid use and smoking status • http://www.shef.ac.uk/FRAX/?lang=en NB Local agreement for women aged over 75 years: DEXA not required. |
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| First-line: | Alendronic Acid effervescent as Binosto 70mg® | 70mg tablets: £0.78 (4) 70mg/100ml solution: £27.36 (4x100ml) 70mg effervescent tablets £22.80 (4) | Tablets dissolve in 120 mls water. Does contain 600mg of sodium. Alternative for patients with swallowing difficulties |
| Risedronate 35mg | 35mg tablets: £0.89 (4) | ||
| Second-line: | Ibandronate 150mg | 150mg tablet: £1.10 (1) | |
| Third-line: | Denosumab* | 60mg/ml prefilled syringe: £183.00 (1) 120mg Injection (Xgeva®) is NOT for treatment of osteoporosis | *Also for men at increased risk of fracture Denosumab is associated with a risk of osteonecrosis of the jaw (ONJ) and with a risk of hypocalcaemia. MHRA September 2014 Before starting denosumab, a dental examination and appropriate preventative dentistry recommended. |
| Raloxifene 60mg | 60mg tablets: £3.73 (28) | ||
| or All with calcium and vitamin D supplement | Although the formulary only highlights first line cost effective calcium and colecalciferol preparations, all other licensed makes remain on formulary as options where the patient has specific taste or other formulation preferences which would increase patient concordance compared to the first line options. Recommended daily intake of elemental calcium is >1000 mg and 20 micrograms of colecalciferol (equivalent to 800 IU vitamin D3) tablets per day (minimum). 2.5G of calcium carbonate is equivalent of 1G of elemental calcium. |
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| ThieCal D3® chewable tablets 1000mg/880IU | £2.95 (30 tablets) | Benefit of once daily dose with or without food | |
| Accrete D3® tablets 600mg/800IU | £2.95 (60) | Twice daily tablet | |
| Adcal D3® caplets 300mg/200IU | £2.95 (112) | Two caplets twice daily | |
| Evacal D3® chewable tablets 1500mg/400IU | £2.75 (56) | Twice daily dosage | |
| CaLci-D® chewable tablets 1000mg/1000IU | £2.25 (28) | Once daily dosage | |
| Steroid induced osteoporosis (6 months at >7.5mg Prednisolone equivalent) | Alendronic Acid Effervescent as Binosto 70mg® | 70mg tablets: £0.78 (4) 70mg/100ml solution: £27.36 (4x100ml) 70mg effervescent tablets £22.80 (4) | To reduce the risk of osteoporosis doses of oral corticosteroids should be as low as possible and courses of treatment as short as possible. The risk of osteoporosis may be related to cumulative dose of corticosteroids; even intermittent courses can therefore increase the risk. The greatest rate of bone loss occurs during the first 6–12 months of corticosteroid use and so early steps to prevent the development of osteoporosis are important. Long-term use of high-dose inhaled corticosteroids may also contribute to corticosteroid-induced osteoporosis. Patients taking (or who are likely to take) an oral corticosteroid for 3 months or longer should be assessed and where necessary given prophylactic treatment; those aged over 65 years are at greater risk. Patients taking oral corticosteroids who have sustained a low-trauma fracture should receive treatment for osteoporosis. The therapeutic options for prophylaxis and treatment of corticosteroid-induced osteoporosis are the same: • a bisphosphonate • calcitriol [unlicensed indication] • hormone replacement: HRT in women, testosterone in men [unlicensed indication] |
| Plus calcium and vitamin D supplement: | Calcium carbonate 1500 mg) and 10 micrograms of colecalciferol (equivalent to 400 IU vitamin D3) tablets: | ||
| TheiCal D3® chewable tablets 1000mg/880IU | £2.95 (30) | Once daily tablet | |
| Accrete D3® 600mg/400IU | £2.95 (60) | Twice daily dosage | |
| Adcal D3® caplets 300mg/200IU | £2.95 (112) | Two caplets twice daily | |
| Evacal D3® chewable tablets 1500mg/400IU | £2.75 (56) | Twice daily dose | |
| Calci-D® chewable tablets 1000mg/1000IU | £2.25 (28) | Once daily dosage | |
| Breast cancer treatment - induced bone loss: | Bisphosphonates should be offered to women identified by the algorithms in Guidance for the management of breast cancer treatment-induced bone loss: a consensus position statement from aUK expert group (see appendix 2 of NICE's full guideline). NICE advice July 2017 Early breast cancer (preventing recurrence andimproving survival): adjuvant bisphosphonates Algorithm 1: Women who experience premature menopause – The development of treatment-induced menopause or planned ovarian suppression before the age of 45 years are indications for evaluation of BMD by DEXA. and any type of concomitant endocrine treatment. Any patient with a documented vertebral fragility fracture or previous low trauma hip fracture should receive prophylactic bisphosphonate treatment irrespective of baseline BMD (p.19 in consensus guidance) Algorithm 2: Postmenopausal women – The use of an aromatase inhibitor is an indication for evaluation of BMD by DEXA. Monitoring and treatment thereafter depends on baseline BMD, age & presence of any major risk factors for osteoporotic fracture. For women over the age of 75 years with one or more major risk factors, bone protection therapy with a bisphosphonate treatment is recommended irrespective of baseline BMD (p.21 in consensus guidance) |
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| Breast cancer - adjuvant bisphosphonate treatment: | Sodium clodronate Zoledronic acid | 400mg cap, £139.83 (120) 5mg/100ml soln for inf in vial, 1=£253.38. | Offer bisphosphonates (zoledronic acid or sodium clodronate)as adjuvant therapy to postmenopausal women with node-positive invasive breast cancer. Consider bisphosphonates (zoledronic acid or sodium clodronate) as adjuvant therapy for postmenopausal women with node-negative invasive breast cancer and a high risk of recurrence. |
| Osteoporosis in Men | NB All young men with osteoporosis should be referred for specialist advice. | ||
| First-line: | Alendronic Acid Effervescent as Binosto 70mg® | 70mg tablets: £0.78 (4) 70mg/100ml solution: £27.36 (4x100ml) 70mg effervescent tablets £22.80 (4) | |
| Risedronate 35mg | 35mg tablets: £0.89 (4) | ||
| Second-line: | Denosumab | 60mg/ml prefilled syringe: £183.00 (1) | Somerset Prescribing Forum (Nov 11) approved use of denosumab in men when NICE criteria are fulfilled. Prescribers should ensure that patients are aware that the product is being used outside of its licence. |
| Denosumab is associated with a risk of osteonecrosis of the jaw (ONJ) and with a risk of hypocalcaemia. MHRA September 2014 Before starting denosumab, a dental examination and appropriate preventative dentistry recommended. |
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| Plus calcium and vitamin D supplement: | Calcium and vitamin D supplement | Calcium carbonate 1000 mg and 20 micrograms of colecalciferol (equivalent to 800 IU vitamin D3) per day |
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| TheiCal D3 chewable tablets® 1000mg/880IU | £2.95 (30) | Benefit of once daily dosage | |
| Accrete D3® 600mg/400IU | £2.95 (60) | Twice daily tablet | |
| Adcal D3® caplets 300mg/200IU | £2.95 (112) | Two caplets twice daily | |
| Evacal D3 chewable® 1500mg/400IU | £2.75 (56) | Twice daily dosage | |
| Calci-D® chewable 1000mg/1000IU | £2.25 (28) | Once daily dosage | |