6.1 - Drugs used in Diabetes Also see SIGN 116: Management of Diabetes,

Transcription

1 1 6. Endocrine System Drugs used in Diabetes Also see SIGN 116: Management of Diabetes, Insulin Prescribing Guidance in Type 2 Diabetes Insulins Rapid Type 1 Humalog Novorapid R - Humalog 200 Short Type 1 & 2 Humulin S Actrapid Intermediate Type 1 & 2 Humulin I Insulatard Long Type 1 Abasaglar Lantus R - Insulin Glargine (Toujeo ) R - Levemir Type 2 Abasaglar Analogue mix only for Type 1 Type 1 Humalog Mix 25 Novomix 30 Type 2 (restricted use) R - Humalog Mix 50 Human mixed only Type 2 Type 2 Humulin M3 Insuman Comb 25 All prescriptions for insulin should be brand name only. For patients with Type 1 diabetes, insulin will be initiated by a diabetes specialist with continuation of prescribing in primary care. Cartridge formulations of insulin are preferred to alternative formulations Type 2 patients who are newly prescribed insulin should usually be started on NPH isophane insulin, (e.g. Humulin I, Insulatard ). Care should be taken when prescribing/dispensing insulin products as many have similar names. Always double check to ensure the correct product is prescribed and supplied. In order to avoid dosing errors, When writing prescriptions for insulin the dose should

2 2 always be written as units. Abbreviations such as U or IU should be avoided. In new & existing patients requiring insulin glargine the preferred product is Abasaglar which is a biosimilar formulation to Lantus. In order to ensure the patient receives the correct formulation. R - Toujeo is a high strength formulation of insulin glargine. Approved for restricted use when Insulin Abasaglar are unsuitable for use in the following circumstances o o Type 1 diabetes - in patients who are at risk of or experience unacceptable frequency and/or severity of nocturnal hypoglycaemia on treatment with established insulin and for patients who require carer administration of their insulin. Type 2 diabetes - restricted to those who suffer from recurrent episodes of hypoglycaemia or require assistance with their insulin injections, or in patients who require a large volume of their established insulin Insulin Pen needles Tricare Pen Needles Other antidiabetic drugs (See prescribing notes) First step Step 2 & 3 intensification Step 4 ( If HbA1c not achieved) 1 st Choice Biguanide Metformin Sulfonylureas Gliclazide Glipizide Glitazone Pioglitazone Gliptins Alogliptin Sitagliptin SGLT-2 Inhibitors (Gliflozins) Empagliflozin Dapagliflozin Sulfonylureas Gliclazide Glipizide GLP-1 Agonists (Weekly) Exenatide (Bydureon ) Dulaglutide (Trulicity ) Insulins (see section 6.1.1)

3 3 First step Metformin Metformin is the recommended 1 st controlling hyperglycaemia. line agent when lifestyle measures have been ineffective at Due to the risk of lactic acidosis, the dose of metformin should be reviewed in patients with an egfr <45 ml/min/1.73m 2. Metformin should be avoided in patients with an egfr <30 ml/min/1.73m 2. Metformin may cause gastro intestinal adverse effects; it should be started at low dose and taken with or immediately after meals, the dose gradually increased if tolerated. Doses above 2g daily produce little added glucose lowering efficacy but do increase the risk of side effects. Metformin prolonged release tablets are expensive compared to standard metformin tablets and are restricted to use in patients unable to tolerate standard metformin at an equivalent dose or where a patient may benefit from using a once daily dose to aid compliance. Metformin prolonged release tablets should be considered in patients not able to tolerate standard metformin before switching to alternative products which are more expensive. After Metformin there is no consensus as to which therapy should be used for intensification. If intensification of antidiabetic agents should be made in addition to lifestyle measures, adherence to medication and dose optimisation. Addition of one of the intensification agents can be added to the patients monotherapy or dual therapy.the choice of agent(s) should be based on a number of individual factors including BMI, hypoglycaemia risk, lifestyle, renal function and cost. Patients failing to meet individualised HbA1c targets should be tried on a third oral agent in combination prior to considering an injectable therapy (given the cost implication) Step 2 and 3 intensification Pioglitazone Gliptins Pioglitazone is preferred in insulin resistant younger patients. i.e. younger overweight or obese patients. Pioglitazone causes weight gain and fluid retention which can lead to heart failure. It is contraindicated in patients with heart failure, active bladder cancer or a past history of bladder cancer. Use with caution in patients with other cardiovascular disease, in the elderly and those on insulin. Advise patient of risk of osteoporosis and bladder neoplasia. Patients initiated on pioglitazone should be reviewed at 6 months and treatment should only continued if the patient has had a beneficial metabolic response (a reduction of at least 0.5% (5.5mmol/mol) in HbA1c). Gliptins are preferred in patients considered at high risk of hypoglycaemia with a sulfonylurea and where weight gain is a concern. Gliptins are more expensive than sulfonylureas and pioglitazone and have limited long-term outcome and safety data. Patients initiated on gliptin therapy should be reviewed at 6 months and treatment should only be continued if the patient has had a beneficial metabolic response (a reduction of at least 0.5% (5.5mmol/mol) in HbA1c). Patients prescribed gliptins should be advised to report any signs of acute pancreatitis.

4 4 SGLT-2 Inhibitors SGLT-2 inhibitors should be reviewed after 6 months. If there is no adequate clinical response then treatment should be stopped. SGLT-2 inhibitors are to be used with caution in cardiovascular conditions due to increased risk of volume depletion. Caution must be exercised when using diuretics concomitantly. Empaglifozin dose is restricted to 10mg daily. There is little evidence of further benefit with higher doses. These should not be used in Type 1 and ketosis prone Type 2 patients. Empagliflozin is approved for restricted use by the SMC in the following circumstances: In combination with insulin, when insulin, diet and exercise do not provide adequate glycaemic control. Empagliflozin is a cheaper alternative to the use of GLP-1 agonists for this indication. As dual therapy in combination with metformin when metformin alone with diet and exercise does not provide adequate glycaemic control and a sulphonylurea is inappropriate. As triple therapy in combination with metformin and a sulphonylurea, as an alternative to a dipeptidyl peptidase-4 (DPP-4) inhibitor. Empagliflozin should only be prescribed if initiated or recommended by a diabetes specialist. Dapagliflozin is approved for restricted use by the SMC in the following circumstances: In combination with insulin, when insulin, diet and exercise do not provide adequate glycaemic control. Dapagliflozin is a cheaper alternative to the use of GLP-1 agonists for this indication. As dual therapy in combination with metformin when metformin alone with diet and exercise does not provide adequate glycaemic control and a sulphonylurea is inappropriate. As triple therapy in combination with metformin and a sulphonylurea, as an alternative to a dipeptidyl peptidase-4 (DPP-4) inhibitor. Dapagliflozin should only be prescribed if initiated or recommended by a diabetes specialist. Sulfonylureas Individuals with marked osmotic symptoms may benefit from sulphonylurea therapy initially (First step) before more appropriate treatments have time to take effect. Patients prescribed sulfonylureas must be made aware of the risk of hypoglycaemia. Regular monitoring of blood glucose levels is required in line with DVLA guidance. M/R gliclazide 30mg tablets (Diamicron MR ) are more expensive than standard gliclazide tablets and should only be prescribed in patients who are unable to comply with the dosage regimen for the standard tablets. Step 4 (If patients HbA1c is not achieved)

5 5 GLP-1 agonists GLP 1 agonist use is only initiated after step 1,2 intensification. Patients being started on GLP-1 agonists must have their gliptins stopped on commencement of the GLP-1. GLP-1 agonists are more expensive than oral preparations and have limited long-term outcome and safety data. They should normally be used in patients before considering insulin. Patients initiated on GLP-1 agonists should be reviewed at 6 months and treatment with GLP-1 agonist should only continue if the HbA1c falls by at least 11 mmol/l (1%) and weight loss by 3% of the initial bodyweight in 6 months. Bydureon, a once-weekly exenatide preparation, is approved for use in patients where a weekly preparation will aid compliance, to improve tolerance to exenatide or in patients where a once weekly preparation would aid administration by healthcare professionals. Patients prescribed GLP-1 agonists should be advised to report any signs of acute pancreatitis Treatment of Hypoglycaemia Glucose oral gel 40% Glucagon (GlucaGen Hypokit) Following administration of glucagon and oral glucose, it is important to give supplementary carbohydrate to restore liver glycogen and prevent secondary hypoglycaemia. Glucagon may be repeated once after 10 minutes if necessary. If there is no response, then hospital admission should be considered. Patients with hypoglycaemia requiring 3 rd party intervention should be considered for admission to hospital for i.v. glucose. Oral Glucose Tolerance Test Rapilose (unlicensed) Patients requiring an oral glucose tolerance test should be prescribed Rapilose rather than glucose powder which is significantly more expensive Monitoring agents for diabetes mellitus Blood Glucose Strips Type 1 Diabetes Type 2 Diabetes Glucomen Areo sensor Strip (Areo 2k meter) Aviva strips (Expert meter only) Glucomen Areo Sensor TRUEyou Glucomen GM Sensor

6 6 The use of home blood glucose monitoring is recommended in the following circumstances - o o o Type 1 and Type 2 patients prescribed insulin. Type 2 patients prescribed sulfonylurea Patients prone to hypoglycaemia Home blood glucose monitoring is not recommended for use in the following patient groups: o o those treated by diet alone. those patients where control is appropriate and they are treated by drugs where hypoglycaemia is unlikely (and not co-prescribed a sulfonylurea) e.g. metformin, pioglitazone, gliptins, SGLT-2 or GLP-1 agonists. In these cases, a six-monthly estimate of HbA1c is adequate to monitor glycaemic control. Ketone Strips Blood testing for ketones should only be undertaken on specialist advice. Glucomen Areo 2 Ketone Strips It is important to test for ketones where there is significant risk of ketoacidosis, such as may occur with significant intercurrent illness. Urine monitoring of ketones is not recommended Thyroid and antithyroid drugs Thyroid Hormones Levothyroxine H - Liothyronine injection Levothyroxine should be taken as a single daily dose, preferably before breakfast. Liothyronine is given by slow intravenous injection to treat hypothyroid coma. Prescribing of Armour Thyroid is not recommended by NHS Fife endocrinologists as it is an unlicensed drug and there is considerable variability in formulations Antithyroid drugs S - Carbimazole S - Propylthiouracil H - Aqueous Iodine (unlicensed) Carbimazole is the recommended antithyroid agent for use in the treatment of hyperthyroidism. In rare cases carbimazole may suppress the bone marrow. The CSM has issued a warning about the risks of neutropenia and agranulocytosis -

7 7 Patients should be instructed to report any symptoms and signs suggestive of infection, especially sore throat, mouth ulcers, bruising, fever or malaise. A white blood cell count should be performed if there is any clinical evidence of infection. Carbimazole should be stopped promptly if there is clinical or laboratory evidence of neutropenia. Propylthiouracil is more expensive than carbimazole and is used if patients cannot tolerate carbimazole. Beta-Blockers S - Propranolol (standard tablets) Propranolol is used for the rapid relief of thyrotoxic symptoms and may be used with antithyroid drugs or as an adjunct to radioactive iodine. Beta-blockers can be withdrawn when a euthyroid state has been achieved Corticosteroids Replacement therapy Glucocorticoid therapy S - Fludrocortisone (Florinef ) S - Hydrocortisone Prednisolone (standard tablets including soluble tablets) S - Hydrocortisone S - Dexamethasone Prednisolone enteric coated (e/c) is non-formulary. There is no evidence it is reduces the risk of peptic ulceration. Prednisolone e/c is more expensive than standard tablets and may cause erratic absorption from the GI tract. Patients should be given a steroid card to carry, giving details of therapy including drug, dose and possible complications. All patients receiving oral or parenteral corticosteroids for purposes other than replacement should be considered at high risk of severe chickenpox (unless they have had chickenpox). These individuals should avoid close personal contact with chickenpox or herpes zoster and seek urgent medical attention if they are exposed. When long-term (>4 weeks) corticosteroid treatment is discontinued, the dose should be gradually reduced over a period of several weeks or months, depending on the dosage and duration of therapy. Patients receiving the equivalent of at least 7.5mg prednisolone daily for 3 months or longer are at particular risk of osteoporosis (see section and Appendix 6A for further advice). No osteoporosis prophylaxis is indicated when corticosteroids are used as replacement therapy. Orthostatic hypertension S - Fludrocortisone (Florinef ) (off-label) Midodrine (Bramox)

8 8 Midodrine is licensed for the treatment of severe orthostatic hypotension due to autonomic dysfunction Sex hormones Female sex hormones Also see Appendix 6B: Guidance on Management of Menopausal Symptoms General Tablets are considered the first choice formulation as they are more cost-effective and avoid problems with detachment from skin and local side-effects. Patches may be appropriate in patients in whom there is a clinical need to avoid first pass metabolism of oestrogens (e.g. patients with liver disease, or diabetes), in those who are at risk of venous thromboembolism and those who cannot tolerate tablets or express a strong preference for patches. Patient preference is important for compliance, therefore a range of suitable products are suggested. HRT should be prescribed by brand name to avoid confusion and ensure continuity of supply. Patients should be started on low dose preparations and the dose increased if there is inadequate symptom control. Symptom relief can take up to 3 months. Patients should be continued on the same preparation for at least 3 months then reviewed before switching to alternatives due to lack of efficacy. The on-going need for HRT should be reassessed at least annually. Blood pressure should be checked 6-12 monthly. Stopping HRT abruptly can cause the return of vasomotor symptoms in some women. Consideration should be given to the gradual withdrawal of treatment over a 3-6 month period. In women with an intact uterus a combined HRT formulation is required. Sequential combined therapy (cyclical) (for use in women with an intact uterus) Tablets Elleste Duet (estradiol 1mg or 2mg, norethisterone 1mg) Femoston (estradiol 1mg or 2mg, dydrogesterone 10mg) R-Tridestra (estradiol 2mg, medroxyprogesterone acetate 20mg) Patches Evorel Sequi (estradiol 50mcg/24hrs, norethisterone 170mcg/24hrs) FemSeven Sequi (estradiol 50mcg/24hrs, levonorgestrol 10mcg/24hrs)

9 9 Women under 54 years of age or within 12 months of last menstrual period should receive cyclical HRT. Prolonged use of cyclical HRT can increase the risk of endometrial cancer. Women should not normally be kept on cyclical therapy for longer than 5 years. After 5 years they should be changed to a continuous combined regimen instead (see below). R -Tridestra is approved for restricted use for women with infrequent periods who are not yet suitable for continuous combined HRT. Switching between different types of progesterone may improve tolerability in some patients. Continuous combined therapy (for use in women with an intact uterus) Tablets Kliovance (estradiol 1mg + norethisterone 500mcg) Kliofem (estradiol 2mg + norethisterone 1mg) Premique Low Dose (oestrogen (equine) + medroxyprogesterone acetate) Tibolone (Livial ) Patches Evorel Conti (estradiol 50mcg/24hrs + norethisterone 170mcg/24hrs) FemSeven Conti (estradiol 50mcg/24hrs + levonorgestrol 7mcg/24hrs) Continuous combined therapy should only be used by women who are 54 years of age or older or who are at least a year past the menopause. Both oestrogen and progestogen are taken daily to give a period free regimen. Continuous combined therapy is also used as add-back HRT for women on long-term gonadorelin analogues. The first few months of use may result in erratic bleeding patterns. Switching between different types of progesterone may improve tolerability in some patients. The progestogen-only intrauterine device (Mirena IUS) may also be used to provide the progestogen part in women on HRT. If used under these circumstances, it is only licensed for 4 years of use. The Mirena IUS is also used for contraception and menstrual disorders. See Chapter 7 for further

10 10 details. Tibolone is a synthetic steroid compound with mixed oestrogenic, progestogenic and androgenic properties, and can be used for women with an intact uterus. It relieves menopausal vasomotor and urogenital symptoms. It has beneficial effects on libido, mood and bone loss. Tibolone is the preferred choice in women with a history of endometriosis and in women with reduced libido not resolved by conventional HRT or psychological intervention. Tibolone has a higher risk of venous thromboembolism than other types of HRT. Tibolone is not suitable for use in the pre-menopausal stage or within 12 months of the last menstrual period Oestrogen only (only for use in women who have had a hysterectomy or have a Mirena IUS in situ) Tablets Elleste-Solo (estradiol 1mg or 2mg) Patches Transdermal gel Evorel (estradiol 25mcg-100mcg/24 hrs) Estradot (estradiol 25mcg-100mcg/24 hrs) R - Oestrogel (Estradiol 0.06%) R - Transdermal gel should only be used in patients who are unable to tolerate tablet and patch formulations Progestogens Norethisterone Medroxyprogesterone acetate Progestogens can be used for vasomotor symptom control in women with contra-indications to oestrogen. See Chapter 7 for the use of progestogens in the management of menstrual disorders. Progesterone receptor modulators S - Ulipristal 5mg (Esmya ) Ulipristal 5mg (Esmya ) is approved as an oral alternative to gonadorelin analogues for the pre-operative treatment of moderate severe uterine fibroids Male sex hormones and antagonists Testosterone and esters S - Testogel S - Nebido injection

11 11 The choice of formulation is determined by patient preference. The gel formulation is preferred by most patients. Testosterone undecanoate oily injection (Nebido ) is more expensive than alternative intramuscular formulations but offers the advantage of reduced frequency of dosing with less inter-dose fluctuation of testosterone levels. Also see Anti-androgens Appendix 7D Lower Urinary Tract Symptoms Pathway Fife Formulary section 7.4 Prescribing points Cyproterone 5α-reductase inhibitors Finasteride S - Dutasteride (Avodart ) 5α-reductase inhibitors (finasteride, dutasteride) are used in the treatment of BPH. They reduce prostate size, reducing obstructive symptoms and increasing urinary flow rate. 5α-reductase inhibitors are normally used in men with an enlarged prostate or severe symptoms. They may also be recommended when alpha blockers are ineffective, contra-indicated or not tolerated. Treatment should be continued for at least 4-6 months to obtain benefits. It may take up to one year for treatment to have maximum effect and patients may require long-term treatment. A combination of an alpha blocker and 5α-reductase inhibitor may be used for severe symptoms when benign prostatic enlargement is the most likely cause of symptoms. Combodart (dutasteride + tamsulosin) should only be prescribed in patients when a combination of finasteride + tamsulosin is unsuitable/ineffective. Cyproterone acetate is indicated for treatment of male hypersexuality. It is also used as an adjunct in prostatic cancer (see section ) Hypothalamic and pituitary hormones and anti-oestrogens Hypothalamic and anterior pituitary hormones and anti-oestrogens Anti-Oestrogens Clomifene Tamoxifen Clomifene is used in the treatment of female infertility. Clomifene should not normally be used for longer than 6 cycles. Patients who experience side-effects with clomifene may be switched to tamoxifen following discussion with the infertility team.

12 12 Anterior pituitary hormones Tetracosactide is used to test adrenocorticol function. H - Tetracosactide 250mcg/ml (Synacthen ) Gonadotrophins Various preparations of gonadotrophins are used in the treatment of female infertility. Growth Hormone S - Somatropin (Genotropin ) Somatropin is used in children with growth failure. It may also be used in specific circumstances in adults with growth hormone deficiency. Somatropin products should be prescribed by brand name only. The preferred brand in NHS Fife is Genotropin. However, alternative brands may be recommended depending on individual patient circumstances. Hypothalamic hormones H - Gonadorelin Hypothalamic hormones are used in the treatment of endometriosis and infertility Posterior pituitary hormones and antagonists Posterior pituitary hormones Desmopressin tablets Desmomelt H - Terlipressin H - Tolvaptan (Jinarc ) The prescribing of desmopressin for diabetes insipidus should only be on the recommendation of a specialist. Due to an increased risk of hyponatraemia, desmopressin nasal spray is no longer indicated for

13 13 nocturnal enuresis unless treatment is associated with multiple sclerosis. Desmopressin standard tablets are the preferred formulation but Melt tablets can be used in patients who have trouble swallowing. Terlipressin is used in treatment of bleeding oesophageal varices. Due to different formulations of tolvaptan being licensed for different indications prescribe by brand name only. Tolvaptan as the brand Jinarc is approved for use to slow the progression of cyst development and renal insufficiency of autosomal dominant polycystic kidney disease (ADPKD) in adults with CKD stages 1-3 at initiation of treatment with evidence of rapidly progressing disease. Prescribing should be in line with local protocol. Tolvaptan is also available as the brand Samsca for the treatment of adult patients with hyponatraemia secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH). SMC have not approved use for this indication due to a company non-submission. Requires submission and approval of an Individual Patient Treatment Request (IPTR) before prescribing. Antidiuretic hormone antagonists H - Demeclocycline Demeclocycline is used to treat hyponatraemia associated with inappropriate secretion of antidiuretic hormone Drugs affecting bone metabolism Also see Appendix 6A: Diagnosis and management of osteoporosis. WHO Fracture Risk Assessment tool NICE CG Osteoporosis: assessing the risk of fragility fracture, August Recommendations for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis Appendix 9C Advice on Prescribing of Vitamin D 3 Products Vitamin D and Bone Health: A Practical Clinical Guideline for Patient Management Daily Calcium Intake Calculator Bisphosphonates and other drugs affecting bone metabolism Alendronic acid Risedronate

14 14 3rd Choice Malignancies S - Denosumab 60mg/ml (Prolia ) H - Zoledronic acid IV infusion H - Teriparatide (Forsteo ) H - Denosumab 70mg/ml (Xgeva ) H - Disodium pamidronate IV infusion S - Ibandronic acid 50mg tablets H - Sodium clodronate H - Zoledronic acid IV infusion Treatment of Postmenopausal Women at High Risk of Fragility Fractures First choice: alendronic acid + calcium with vitamin D 3 /vitamin D 3 risedronate + calcium with vitamin D 3 /vitamin D 3 Second choice: denosumab + calcium with vitamin D 3 /vitamin D 3 Treatment with HRT or oral contraception for bone protection should be considered for early menopause up to the age of 50 years but should not be considered first-line therapy for the long-term prevention of osteoporosis in women who are over 50 years of age. All patients should have a DEXA scan to guide treatment unless very frail or immobile, but treatment may commence whist waiting for the scan. Men at High Risk of Fragility Fractures First choice: alendronic + calcium with vitamin D 3 /vitamin D 3 Osteoporosis in men <60 years of age is often secondary to other medical conditions; specialist referral is recommended to exclude underlying causes e.g. hypogonadism, hyperparathyroidism, osteomalacia. Although the licensed dose of alendronic acid for osteoporosis in men is 10mg daily, local specialists recommend 70mg once weekly to aid compliance. Adequate dietary or supplementary calcium and vitamin D is necessary to ensure effective fracture risk reduction. Corticosteroid-Induced Osteoporosis (Treatment and Prevention) First choice: alendronic acid + calcium with vitamin D 3 /vitamin D 3 Second choice: risedronate + calcium with vitamin D 3 /vitamin D 3 Patients receiving the equivalent of at least 7.5mg prednisolone daily for 3 months or longer are at particular risk of osteoporosis. Treatment in patients under 65 years should ideally be guided by DEXA scanning. Patients at high risk, e.g. those over 65 and those with a prior fragility fracture, should be advised to commence bone protection therapy at the time of starting glucocorticoids.

15 15 Although the licensed dose of alendronate for corticosteroid induced osteoporosis is 5mg or 10mg daily, local specialists recommend 70mg once weekly to aid compliance. All at risk patients should take calcium + vitamin D/vitamin D supplementation while receiving oral steroids. When oral steroids are stopped, patients receiving bone protection medication should have a DEXA scan to confirm if bone protection medication is still required. Oral Bisphosphonates ( Alendronic acid, risedronate) Oral bisphosphonates should be avoided in anyone with a history of oesophageal stricture or severe oesophagitis. Weekly alendronic acid and weekly risedronate are recommended 1 st line choices for the prevention and treatment of osteoporosis. Risedronate is used if alendronic acid is not tolerated and in patients with underlying oesophageal disease such as GORD or hiatus hernia. Bisphosphonates have complex administration instructions. GI side effects are minimised by following these instructions (see BNF for further details). Oral bisphosphonates are associated with a low risk of osteonecrosis of the jaw and atypical femoral fractures (See BNF). Unless there is a sufficient dietary intake, patients should also be prescribed daily calcium + vitamin D /vitamin D supplementation. Patients considered at high fracture risk (the very elderly, immobile patients and those with multiple pathologies) should continue oral bisphosphonates treatment on a long term basis. Other patients who have received continuous oral bisphosphonates for 5 years should be referred for a DEXA scan to ascertain the need for continuing use. Denosumab 60mg/ml (Prolia ) Zoledronic Acid Denosumab 60mg/ml (Prolia ) is a 2 nd line option in postmenopausal women for whom oral bisphosphonates are unsuitable. Treatment may be initiated in the community on the recommendation of a specialist. For the treatment of osteoporosis, denosumab should be administered every 6 months. Practices should ensure that 6 month patient recall is set up. There is a 1 month window around the administration of each 6 monthly dose of denosumab. Before commencing denosumab, check bloods - bone profile (calcium corrected for albumin, alkaline phosphate, albumin), urea and electrolytes, vitamin D. These bloods should be checked before each denosumab injection (except for vitamin D levels which need to be only checked annually). Hypocalcaemia is a contraindication to denosumab administration. Levels should be corrected before initiating denosumab. Unless there is a sufficient dietary intake, patients should also be prescribed daily calcium + vitamin D/vitamin D supplementation. Denosumab has been associated with rare cases of atypical femoral fractures (see BNF). Patients should be advised to report any pain in the hip, thigh or groin region. It is important to ensure that denosumab is not co-prescribed with oral bisphosphonates. Unless there is a sufficient dietary intake, patients should also be prescribed daily calcium + vitamin

16 16 D /vitamin D supplementation. In individuals with osteoporosis there should be a break in treatment with zoledronic acid after 3 years. The recommended duration for the break in treatment is 3 years before retreatment should be considered. In the intervening period no osteoporosis medication other than calcium + vitamin D /vitamin D supplementation should be prescribed. Teriparatide (Forsteo ) Malignancies Teriparatide is restricted to the treatment of established severe osteoporosis in post-menopausal women. Maximum duration of treatment is 24 months and treatment should not be repeated. Bisphosphonates, disodium pamidronate and sodium clodronate are all used in the treatment of malignancies. Denosumab 70mg/ml (Xgeva ) is approved for specialist use for 1 st line treatment of all breast cancer patients with metastatic bone disease who would be eligible for treatment with i.v. zoledronic acid. Patients should also be prescribed daily calcium + vitamin D supplementation. Xgeva is not approved by the SMC for bone loss associated with hormone ablation in men with prostate cancer who are at increased risk of fractures. Calcium and Vitamin D 3 Supplementation Also see section Also see Appendix 9C Advice on Prescribing of Vitamin D 3 Products Unless there is sufficient dietary intake, all patients prescribed bisphosphonates, denosumab or strontium require calcium and vitamin D/vitamin D supplementation. (Excludes patients who are at risk of hypercalcaemia e.g sarcoidosis; have had renal stones in the last 12 months or have significant renal impairment). Adcal D 3 is the formulary choice calcium and vitamin supplement. Adcal D 3 is available as several formulations e.g. caplets, chewable tablets, effervescent tablets. Caplets can be swallowed whole and are preferred but the formulation prescribed should be done in agreement with the patient to aid compliance. Colecalciferol preparations (Fultium D 3 and Desunin ), in association with an adequate dietary calcium intake, may be used in patients when Adcal D 3 is unsuitable/not tolerated. For the appropriate prescribing of colecalciferol products refer to Appendix 9C. All patients in care homes or who are housebound should be considered at high risk of vitamin D deficiency and should receive appropriate supplements. To avoid any potential interaction with a bisphosphonate, consider prescribing calcium and vitamin D supplements as one dose at lunchtime and one dose at bedtime Other endocrine drugs Bromocriptine and other dopaminergic drugs S - Cabergoline

17 17 S - Quinagolide Cabergoline is the drug of choice for long term treatment of hyperprolactinaemia and the suppression of lactation following loss of pregnancy. Excessive daytime sleepiness and sudden onset of sleep can occur and patients should be warned of these possible effects and exercise caution when driving, operating machinery or working at heights Drugs affecting gonadotrophins S - Danazol Danazol is used in the treatment of endometriosis and benign fibrocystic breast disease. Buserelin can also be used in endometriosis. Gonadorelin analogues S - Triptorelin (Decapeptyl ) S - Leuprorelin (Prostap ) S - Goserelin (Zoladex ) S - Nafarelin (Synarel ) Gonadorelin analogues are used in the treatment of endometriosis, infertilitry and uterine fibroids in women and also for the treatment of prostate cancer in men (see section )