1
6. Endocrine System 6.1 - Drugs used in Diabetes Also see SIGN 116: Management of Diabetes, 2010 http://www.sign.ac.uk/guidelines/fulltext/116
Insulin Prescribing Guidance in Type 2 Diabetes http://www.fifeadtc.scot.nhs.uk/media/6978/insulin-prescribing-in-type-2-diabetes.pdf
6.1.1 Insulins (Type 2 Diabetes) 6.1.1.1 Short Acting Insulins 1st Choice – Insuman® Rapid (Human Insulin) – Humulin S® – Actrapid® 2nd Choice – Insulin Aspart (NovoRapid®) (Insulin Analogues) – Insulin Lispro (Humalog®)
6.1.1.2 Intermediate and Long Acting Insulins 1st Choice – Isophane Insulin (Insuman Basal®) (Human Insulin) – Isophane Insulin (Humulin I®) – Isophane Insulin (Insulatard®) 2nd Choice – Insulin Detemir (Levemir®) (Insulin Analogues) – Insulin Glargine (Abasaglar®, Lantus®)
Biphasic Insulins 1st Choice – Biphasic Isophane
(Human Insulin) (Insuman Comb® ‘15’, ‘25’,’50’) – Biphasic Isophane (Humulin M3®) 2nd Choice – Biphasic Aspart (Novomix® 30) (Insulin Analogues) – Biphasic Lispro
(Humalog® Mix ‘25’ or ‘50’)
Prescribing Points
For patients with Type 1 diabetes, insulin will be initiated by a diabetes specialist with continuation of prescribing in primary care. Insulin analogues are the preferred insulins for use in Type 1 diabetes. 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. Insuman Basal®, Humulin I®, Insulatard®). Long-acting recombinant human insulin analogues (e.g. Levemir®, Lantus®) offer no significant clinical advantage for most type 2 patients and are much more expensive. In terms of human insulin. The Insuman® range is currently the most cost-effective and preferred in new patients.
KEY:- H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use Only
Fife Formulary February 2014 Last Amended August 2015 2
Patients already established on insulin should not be switched to alternative products unless recommended by a diabetes specialist. 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 always be written as ‘units’. Abbreviations such as ‘U’ or ‘IU’ should be avoided. Insulin glargine and insulin detemir (Levemir®) are restricted in patients with type 2 diabetes to those who suffer from recurrent episodes of hypoglycemia, due to individual lifestyle factors e.g. shift work or to those who require assistance with their insulin injections. In new 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 all prescriptions for insulin glargine should be prescribed by the brand name only. Insulin degludec (Tresiba®) is non SMC approved and should not be prescribed routinely in NHS Fife without the approval of an Individual Patient Treatment Request (IPTR). 6.1.1.3. Insulin Pen needles Omnican® Fine Pen Needles
6.1.2 Other antidiabetic drugs
1st Choice Metformin Glitazones 2nd Choice Pioglitazone Sulfonylureas Gliclazide (1st choice) Glipizide (2nd choice) Gliptins Sitagliptin (Januvia®) (1st choice) Saxagliptin (Onglyza®) (2nd choice) 3rd Choice GLP-1 Agonists – Lixisenatide (Lyxumia®) (1st choice) – Exenatide (Bydureon®) (2nd choice) – Liraglutide (Victoza®) (2nd choice) SGLT-2 Inhibitors (Gliflozins) R - Dapagliflozin (Forxiga®) Insulins (see section 6.1.1)
Prescribing Points
Metformin
Metformin is the recommended 1st line agent when lifestyle measures have been ineffective at controlling hyperglycaemia. Due to the risk of lactic acidosis, the dose of metformin should be reviewed in patients with an eGFR <45 ml/min/1.73m2. Metformin should be avoided in patients with an eGFR <30 ml/min/1.73m2.
KEY:- H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use Only
Fife Formulary February 2014 Last Amended August 2015 3
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. Metformin oral solution may be used in patients that are unable to swallow tablets.
Pioglitazone
Pioglitazone is the preferred 2nd line agent. 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).
Sulfonylyureas
Sulfonylureas are used as 2nd line agents. Patients prescribed sulfonylureas must be made aware of the risk of hypoglycaemia. Regular monitoring of blood glucose levels is recommended. 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.
Gliptins
Gliptins are alternative 2nd line agents. 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 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.
GLP-1 agonists
GLP-1 agonists are injectable preparations used as 3rd line agents. 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 should only continued if the patient has had a beneficial metabolic response (a reduction of at least 0.5%
KEY:- H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use Only
Fife Formulary February 2014 Last Amended August 2015 4
(5.5mmol/mol) in HbA1c). Lixisenatide is a once daily preparation and is cheaper than alternative GLP-1 agonists. Lixisenatide has demonstrated non-inferiority to exenatide in terms of HbA1C lowering effect. 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. Liraglutide (Victoza®) is a once daily preparation. Only the 1.2mg dose is approved for use. The 1.8mg dose is non-formulary as it is not considered to be cost-effective. Liraglutide should be considered in patients when lixisenatide/exenatide is ineffective or not tolerated. Patients prescribed GLP-1 agonists should be advised to report any signs of acute pancreatitis.
Dapagliflozin
R – Dapagliflozin is approved for restricted use 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. Dapagliflozin should only be prescribed if initiated or recommended by a diabetes specialist. Dapagliflozin is not approved for use as monotherapy, as dual therapy in combination with metformin nor as triple therapy.
6.1.4 Treatment of Hypoglycaemia Glucose oral gel 40% Glucagon (GlucaGen® Hypokit)
Prescribing Points 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 3rd party intervention should be considered for admission to hospital for i.v. glucose. Oral Glucose Tolerance Test Rapilose® (unlicensed) Prescribing Points Patients requiring an oral glucose tolerance test should be prescribed Rapilose® rather than glucose powder which is significantly more expensive. 6.1.6 Monitoring agents for diabetes mellitus
Blood Glucose Strips
Type 1 Diabetes Glucomen® LX Sensor Strip Type 2 Diabetes Glucomen® GM (Reagent) strips Glucomen® Areo Sensor test strips TRUEyou® (Reagent) strips KEY:- H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use Only
Fife Formulary February 2014 Last Amended August 2015 5
Prescribing Points The use of home blood glucose monitoring is recommended in the following circumstances - o Type 1 and Type 2 patients prescribed insulin. o Type 2 patients where control is poor o Patients prone to hypoglycaemia o To monitor treatment change o Patients prescribed a sulfonylurea
Home blood glucose monitoring is not recommended for use in the following patient groups: o those treated by diet alone. o those whose control is stable and appropriate for that patient as indicated by HbA1c. o 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 or GLP-1 agonists. In these cases, a six-monthly estimate of HbA1c is adequate to monitor glycaemic control. Ketone Strips Glucomen® LX Ketone Test Strip Prescribing Points Blood testing for ketones should only be undertaken on specialist advice. 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.
6.2 - Thyroid and antithyroid drugs 6.2.1 Thyroid Hormones 1st Choice Levothyroxine 2nd Choice S – Liothyronine tablets H – Liothyronine injection
Prescribing Points
Levothyroxine should be taken as a single daily dose, preferably before breakfast.
Liothyronine has a quicker onset and shorter duration of action and is a lot more expensive than levothyroxine. Liothyronine tablets are used in severe hypothyroid states when a rapid response is required and in patients with thyroid cancer after thyroidectomy. It is also 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. 6.2.2 Antithyroid drugs 1st Choice S - Carbimazole
KEY:- H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use Only
Fife Formulary February 2014 Last Amended August 2015 6
2nd Choice S - Propylthiouracil H – Aqueous Iodine (unlicensed)
Prescribing Points
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 -
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 Prescribing Points
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.
6.3 - Corticosteroids 6.3.1 Replacement therapy S - Fludrocortisone (Florinef®) S - Hydrocortisone 6.3.2 Glucocorticoid therapy 1st Choice S - Hydrocortisone Prednisolone (standard tablets including Prednesol®) 2nd Choice S - Dexamethasone Prescribing Points 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 KEY:- H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use Only
Fife Formulary February 2014 Last Amended August 2015 7
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 6.6.2. and Appendix 6A for further advice). No osteoporosis prophylaxis is indicated when corticosteroids are used as replacement therapy. 6.4 - Sex hormones 6.4.1 Female sex hormones
Also see Appendix 6B: Guidance on Management of Menopausal Symptoms http://www.fifeadtc.scot.nhs.uk/formulary/sections/FF%20Appendix%206B.pdf General Prescribing Points 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 1st Choice ® Elleste Duet (estradiol 1mg or 2mg, norethisterone 1mg) 2nd Choice Femoston® (estradiol 1mg or 2mg, dydrogesterone 10mg) R-Tridestra® (estradiol 2mg, medroxyprogesterone acetate 20mg) Patches Evorel Sequi® 1st Choice (estradiol 50mcg/24hrs, norethisterone 170mcg/24hrs) 2nd Choice FemSeven Sequi® KEY:- H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use Only
Fife Formulary February 2014 Last Amended August 2015 8
(estradiol 50mcg/24hrs, levonorgestrol 10mcg/24hrs)
Prescribing Points
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 1st Choice ® Elleste Duet Conti (estradiol 2mg + norethisterone 1mg) 2nd Choice ® Femoston Conti (estradiol + dydrogesterone) ® Kliofem (estradiol 2mg + norethisterone 1mg) ® Kliovance (estradiol 1mg + norethisterone 500mcg) Premique®, Premique® Low Dose (oestrogen (equine) + medroxyprogesterone acetate) 3rd Choice Tibolone (Livial®) Patches Evorel Conti® 1st Choice (estradiol 50mcg/24hrs + norethisterone 170mcg/24hrs) FemSeven Conti® 2nd Choice (estradiol 50mcg/24hrs + levonorgestrol 7mcg/24hrs) Prescribing Points Continuous combined therapy should only be used by women who are 54 years of age or older or who
KEY:- H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use Only
Fife Formulary February 2014 Last Amended August 2015 9
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 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 1st Choice Elleste- Solo® (estradiol 1mg or 2mg) 2nd Choice Climaval® (estradiol 1mg or 2mg) Patches 1st Choice Evorel® (estradiol 25mcg-100mcg/24 hrs) ® 2nd Choice Estradot (estradiol 25mcg-100mcg/24 hrs) Transdermal Gel R- Oestrogel® (estradiol 0.06%)
Prescribing Points
R- Transdermal gel should only be used in patients who are unable to tolerate tablet and patch formulations. 6.4.1.2 Progestogens 1st Choice Norethisterone 2nd Choice Medroxyprogesterone acetate
Prescribing Points
Progestogens can be used for vasomotor symptom control in women with contra-indications to oestrogen.
KEY:- H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use Only
Fife Formulary February 2014 Last Amended August 2015 10
See Chapter 7 for the use of progestogens in the management of menstrual disorders.
Progesterone receptor modulators H – Ulipristal 5mg (Esmya®)
Prescribing Points
Ulipristal 5mg (Esmya®) is approved as an oral alternative to gonadorelin analogues for the pre- operative treatment of moderate–severe uterine fibroids. 6.4.2 Male sex hormones and antagonists Testosterone and esters 1st Choice S – Tostran® gel, Testogel® 2nd Choice S – Nebido® injection
Prescribing Points
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.
Anti-androgens Also see Appendix 7D – Lower Urinary Tract Symptoms Pathway http://www.fifeadtc.scot.nhs.uk/media/2315/ff-appendix-7d.pdf Fife Formulary section 7.4 Cyproterone 5α-reductase inhibitors 1st Choice Finasteride 2nd Choice S – Dutasteride (Avodart®)
Prescribing points
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
KEY:- H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use Only
Fife Formulary February 2014 Last Amended August 2015 11
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 8.3.4.2). 6.5 - Hypothalamic and pituitary hormones and anti-oestrogens 6.5.1 Hypothalamic and anterior pituitary hormones and anti-oestrogens Anti-Oestrogens 1st Choice Clomifene 2nd Choice Tamoxifen
Prescribing Points
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.
Anterior pituitary hormones
H – Tetracosactide 250mcg/ml
(Synacthen®) Prescribing Points Tetracosactide is used to test adrenocorticol function.
Gonadotrophins
Prescribing Points
Various preparations of gonadotrophins are used in the treatment of female infertility.
Growth Hormone S – Somatropin (Genotropin®) Prescribing Points 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.
KEY:- H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use Only
Fife Formulary February 2014 Last Amended August 2015 12
Hypothalamic hormones H - Gonadorelin
Prescribing Points
Hypothalamic hormones are used in the treatment of endometriosis and infertility. 6.5.2 Posterior pituitary hormones and antagonists Posterior pituitary hormones Desmopressin tablets Desmomelt® H - Terlipressin
Prescribing Points
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 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.
Antidiuretic hormone antagonists H – Demeclocycline
Prescribing Points
Demeclocycline is used to treat hyponatraemia associated with inappropriate secretion of anti-diuretic hormone. 6.6 - Drugs affecting bone metabolism
Also see Appendix 6A: Diagnosis and management of osteoporosis. www.fifeadtc.scot.nhs.uk/formulary/sections/FF%20appendix%206A.pdf
WHO Fracture Risk Assessment tool www.shef.ac.uk/FRAX/tool.jsp
NICE CG 146 - Osteoporosis: assessing the risk of fragility fracture, August 2012 http://www.nice.org.uk/guidance/CG146
Recommendations for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis www.rheumatology.org/practice/clinical/guidelines/GIOP_Guidelines_Nov_2010.pdf
Appendix 9C – Advice on Prescribing of Vitamin D3 Products
KEY:- H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use Only
Fife Formulary February 2014 Last Amended August 2015 13
http://www.fifeadtc.scot.nhs.uk/formulary/sections/FF%20Appendix%209C.pdf
Vitamin D and Bone Health: A Practical Clinical Guideline for Patient Management www.nos.org.uk/document.doc?id=1352
Daily Calcium Intake Calculator www.cgem.ed.ac.uk/research/rheumatological/calcium-calculator
Bisphosphonates and other drugs affecting bone metabolism 1st Choice Alendronic acid Or Risedronate 2nd Choice S - Denosumab 60mg/ml (Prolia®) 3rd Choice H - Zoledronic acid IV infusion H - Teriparatide (Forsteo®) Malignancies 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 D3 /vitamin D3 risedronate + calcium with vitamin D3 /vitamin D3 Second choice: denosumab + calcium with vitamin D3 /vitamin D3 Prescribing Points 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 D3 /vitamin D3
Prescribing Points
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.
KEY:- H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use Only
Fife Formulary February 2014 Last Amended August 2015 14
Corticosteroid-Induced Osteoporosis (Treatment and Prevention)
First choice: alendronic acid + calcium with vitamin D3 /vitamin D3 Second choice: risedronate + calcium with vitamin D3 /vitamin D3 Prescribing Points 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. 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.
Prescribing Points
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 1st 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®) Denosumab 60mg/ml (Prolia®) is a 2nd 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 KEY:- H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use Only
Fife Formulary February 2014 Last Amended August 2015 15
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. Zoledronic Acid Unless there is a sufficient dietary intake, patients should also be prescribed daily calcium + vitamin 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®)
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. Malignancies Bisphosphonates, disodium pamidronate and sodium clodronate are all used in the treatment of malignancies. Denosumab 70mg/ml (Xgeva®) is approved for specialist use for 1st 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 D3 Supplementation
Also see section 9.6.4.
Also see Appendix 9C – Advice on Prescribing of Vitamin D3 Products http://www.fifeadtc.scot.nhs.uk/formulary/sections/FF%20Appendix%209C.pdf
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 D3 is the formulary choice calcium and vitamin supplement. Adcal D3 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 D3 and Desunin ), in association with an adequate dietary KEY:- H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use Only
Fife Formulary February 2014 Last Amended August 2015 16
® calcium intake, may be used in patients when Adcal D3 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.
6.7 - Other endocrine drugs 6.7.1 Bromocriptine and other dopaminergic drugs 1st Choice S – Cabergoline 2nd Choice S – Quinagolide
Prescribing Points
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.
6.7.2 Drugs affecting gonadotrophins S - Danazol
Prescribing Points
Danazol is used in the treatment of endometriosis and benign fibrocystic breast disease. Buserelin can also be used in endometriosis. Gonadorelin analogues 1st Choice S - Triptorelin (Decapeptyl®) 2nd Choice S - Leuprorelin (Prostap®) S - Goserelin (Zoladex®) S - Nafarelin (Synarel®)
Prescribing Points
Gonadorelin analogues are used in the treatment of endometriosis, infertility and uterine fibroids in women and also for the treatment of prostate cancer in men (see section 8.3.4.2.)
KEY:- H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use Only
Fife Formulary February 2014 Last Amended August 2015