netFormulary
Data extracted : 24/11/2017
 Formulary Section 6: Endocrine system
 Details...
06.01 Drugs used in diabetes

  • Good glycaemic control (HbA1c concentrations close to the normal range) has benefits in preventing microvascular complications (retinopathy, nephropathy and neuropathy) or slowing their progression. However frequency and severity of hypoglycaemia may increase. Tailor advice to the individual patient to encourage best glycaemic control without suffering frequent or severe hypoglycaemia.

  • Modification of diabetic regimen is necessary in diabetic ketoacidosis, hyperosmolar non-ketotic diabetic state, surgery, procedures involving fasting (e.g. colonoscopy and barium enema), pregnancy and myocardial infarction.

  • All women with diabetes contemplating pregnancy should be seen by the multidisciplinary team. If they are taking oral hypoglycaemics they should be switched to insulin before conception. Combined diabetic antenatal clinics are held at Leicester General Hospital and Leicester Royal Infirmary, women should attend clinic as soon as pregnancy is suspected.

  • Patients admitted with proven or suspected MI should be commenced on intravenous insulin with glucose (+/- potassium) as described in the guidelines for CCUs in the acute hospitals, with the aim of maintaining blood glucose in the normal range.

  • See also ’Drugs used in the treatment of obesity’
Link   Leicestershire Guidelines (hospital): Diabetes
Link   Leicestershire Guidelines: Diabetes
Link   NICE Guidance: Diabetes: A summary of relevant guidelines
Link   NICE NG 28: Type 2 diabetes in adults: management (Replaces NICE CG87)
Link   UHL Guidelines: Bedside monitoring of capillary blood glucose
Link   UHL Guidelines: DKA Management of Diabetic Ketoacidosis in Adults
Link   UHL Guidelines: HONK
Link   UHL Guidelines: Management of children with diabetes requiring surgery or fasting
Link   UHL Guidelines: Surgery and procedures in patients with diabetes
06.01.01 Insulins

  • Insulin is indicated for patients with Type 1 diabetes and those with Type 2 diabetes not adequately controlled by diet and oral antidiabetic agents, or during intercurrent illness.

  • Prescribe by brand name rather than generically since it is not safe to assume that similar preparations from different manufacturers will have identical effects in practice.

  • Do not abbreviate ’unit’ on prescriptions as errors may occur, e.g. 10U may be mistaken for 100.

  • Insulin vials should not be shared between patients. Use one vial per patient.

  • Bovine and porcine insulins are no longer recommended formulary choices for initiation but may be prescribed for patients already established on therapy.

  • Apidra (insulin glulisine) may be used for patients using an insulin pump or those already using the Solostar device.

  • U500 insulin is an unlicensed insulin that is 5 times more concentrated than standard insulin (U100). It should be prescribied in ’marks’ and administered with a 0.3ml or 0.5ml insulin syringe only (in which 1 mark represents 5 units of insulin).  This insulin is usually supplied from UHL pharmacies.

  • The NPSA have issued a Rapid Response Report for the safer use of insulin. See here for the report.

Devices for formulary choices


















 Company Pen for cartridges Prefilled Pen
 Lilly HumaPen Savvio KwikPen
 Novo Nordisk Novopen 4 FlexPen
 Sanofi- Aventis ClikSTAR SoloStar


Link   Leicestershire Guidelines: Long acting insulin analogues
Link   NICE CG 15: Type 1 diabetes
Link   NICE NG 17: Type 1 diabetes in adults: diagnosis and management (Replaces TA 53 Aug 2015)
Link   Safe use of insulin and you - patient information booklet
Insulins 
06.01.01.01 Short-acting insulins
First Choice:
Insuman Rapid® 
Cartridge + ClikSTAR
Second Choice:
Humulin S® 
Vial, Cartridge + HumaPen Savvio
Actrapid® 
Only available in 10ml vials.
IV Monograph available through ’Injectable Medicines Guide’ link on front page of INsite.
Humalog® 
Insulin Lispro rapid acting insulin analogue.
Vial, Cartridge + HumaPen, Kwikpen
Humalog® 200 units/ml KwikPen 
Double concentrate Insulin Lispro rapid acting insulin analogue.
Only available as a KwikPen®
Primary care initiation conditional on appropriate competency. Otherwise simple amber
Should be reserved for the treatment of patients with diabetes requiring daily doses of more than 20 units of rapid-acting insulin
NovoRapid® 
Insulin Aspart rapid acting insulin analogue.
3ml Penfill® Cartridge + Novopen 4, FlexPen
1.6ml PumpCart® Cartridge for use in Accu-Chek Insight SC insulin pump
06.01.01.02 Intermediate- and long-acting insulins
First Choice:
Insuman Basal® 
Vial, Cartridge + ClikSTAR, SoloStar
Second Choice:
Humulin I® 
Intermediate Human Isophane
Vial, Cartridge + HumaPen Savvio, KwikPen
Restricted Drug  Insulatard® 
Intermediate Human Isophane
For use only when the Innolet device is required. Restricted to patients not able to manage less expensive devices
Lantus® 
Insulin Glargine 100 unit per ml
MUST BE PRESCRIBED BY BRAND NAME
Recombinant human insulin analogue- long acting. Monophasic. Once daily dosage

Vial, Cartridge+ClikSTAR, SoloStar
Abasaglar® 
A Biosimilar of Insulin Glargine.
MUST BE PRESCRIBED BY BRAND NAME
Recommended in LLR for new patients and those undergoing review of therapy.
Levemir® 
Insulin Detemir.
Recombinant human insulin analogue – long acting. Monophasic. Twice daily dosing
Cartridge + NovoPen 4, Flexpen
Innolet also available but only for patients not able to manage less expensive device
Toujeo® 
Insulin Glargine 300 units per ml.
MUST BE PRESCRIBED BY BRAND NAME
First line concentrated insulin of choice in insulin resistant patients requiring large amounts of insulin. Please take extra care in prescribing
Restricted Drug  Tresiba® 
Insulin Degludec
For use in specific patient groups only in line with agreed algorithm.
  • Conditional Green traffic light status for GPs who have completed appropriate training.
  • Amber traffic light status for those without additional training.
  • 06.01.01.02 Biphasic insulins
    First Choice:
    Humulin® M3 
    30/70 soluble / isophane
    Vial, Cartridge + HumaPen Savvio, KwikPen
    Humalog® Mix25, Humalog®Mix50 
    Biphasic Insulin Lispro. Analogue insulin
    Vial, Cartridge + HumaPen Savvio, KwikPen
    NovoMix® 30 
    Biphasic Insulin Aspart. Analogue insulin.
    Cartridge + NovoPen 4, Flexpen
    06.01.01.03 Hypodermic equipment

    • Disposable plastic insulin syringes are marked ’single use’, but in practice many patients re-use them. Syringes should only be used once in hospital wards to prevent the possibility of cross-infection.

    • Advise patients on how to dispose of their contaminated sharps safely. B-D Safe-clip is recommended; this is a device, which clips the needle from the hub and retains the needle in a sealed unit.

    • Sharps bins are prescribable and information on disposal is available  here.

    • A variety of pen injectors are available. Human soluble and isophane insulins (and combinations of the two) are available for pen injectors, but no animal insulins are available. There is no evidence that such devices per se improve diabetic control, however many patients find them more convenient. Issue patients with spare pen or syringe and vial to use in case of breakage. Report defects in pens to Medical Devices Agency.

    • Specially adapted syringes exist, which enable visually handicapped patients to inject themselves safely. Further details are available from the Diabetes Specialist Nurses and Health Visitors.

    • The Innolet disposable pens are useful for patients who have difficulties with other pens as they are larger, easier to see and very simple to operate.  However, due to the higher cost they should only be used if patients have not been able to manage less expensive devices. 
    06.01.02 Antidiabetic drugs

    • Indicated for Type 2 diabetes when dietary measures alone are insufficient.

    • Do not use in Type 1 diabetes, ketosis, severe symptoms (including rapid weight loss), pregnancy or during intercurrent illness (e.g. surgery). Insulin should be used in these circumstances.

    • Aim to achieve the best possible control of blood glucose, both immediately and in the long-term. Targets for glycaemic control in Type 2 diabetes is HbA1c of 6.5-7.5%.

    • Co-existent hypertension, (target BP <130/80) hyperlipidaemia and obesity should be vigorously treated.

    • There is evidence that survival of Type 2 patients after acute myocardial infarction is improved if intravenous insulin with glucose +/- potassium is started on the coronary care unit and subcutaneous insulin rather than oral treatment continued afterwards.
    Link   Leicestershire Guidelines: Diabetes management algorithms
    Link   NICE NG 28: Type 2 diabetes in adults: management (Replaces TA 248 Dec 2015)
    Link   NICE NG 3: Diabetes in pregnancy (replaces CG63 February 2015)
    06.01.02.01 Sulfonylureas

    • Sulfonylureas act on the pancreatic beta cells to stimulate insulin release

    • Hypoglycaemia is the main risk associated with sulphonylureas. Inform patients about recognition and management

    • Elderly patients are particularly vulnerable to hypoglycaemia and this may be fatal. Chlorpropamide and glibenclamide should not be used in this group of patients.

    • Weight gain is associated with sulfonylurea therapy, but tends to plateau after a mean gain of 4kg.

    • With the exception of tolbutamide the sulfonylureas are similarly effective in maximum doses and there is no justification for changing drugs within this class if control deteriorates unless compliance is an issue when a decreased tablet count may be helpful.

    • Tablets should be taken before meals
    Link   NICE NG 28: Type 2 diabetes in adults: management (Replaces CG 87 Dec 2015)
    First Choice:
    Gliclazide 
    Mainly metabolised by the liver.
    Restricted Drug  Gliclazide MR  (Diamicron® MR)
    May be used if hypoglycaemia is a problem as associated with less hypoglycaemia than standard release gliclazide.
    06.01.02.02 Biguanides

    • Reduces glucose production by the liver without stimulating insulin release.

    • Does not cause hypoglycaemia when used as sole agent and does not promote weight gain.

    • Lowers triglyceride and LDL-cholesterol concentrations.

    • Metformin powder is now available in 500mg and 1000mg sachets.  This is significantly less costly than metformin liquid but more expensive than tablets. Reserve for patients only where clinically justified. Contents should be dissolved in water before use.
    Link   NICE NG 28: Type 2 diabetes in adults: management (Replaces CG 87 Dec 2015)
    First Choice:
    Metformin Hydrochloride 
    Drug of choice for obese/ overweight patients
    Gastro intestinal adverse events can be reduced by a gradual dose titration, e.g. 500mg od for 7 days, 500mg bd for 7 days, 1000mg am 500mg pm for 7 days etc. to maximal tolerated dose.
    Restricted Drug  Metformin Hydrochloride MR 
    For patients who are unable to tolerate GI side effects despite dose titration. A 750mg tablet and a 1000mg are now available and are less costly than using multiples of the 500mg tablet.
    06.01.02.03 Other antidiabetic drugs

    • Pioglitazone is an option as an adjunct to other hypoglycaemic drugs only where there is a contraindication or intolerance to metformin or sulphonylureas. Evidence for use in monotherapy or triple therapy is weak. It should not be used if there is any risk of heart failure and should probably be avoided in women at high risk of fracture.

    • Initiation of the DPP-4 inhibitors at UHL is restricted to specialist diabetologists. If the patient is on a sulfonylurea plus DPP-4 inhibitor, the sulfonylurea dose may require reduction to avoid hypoglycaemia.

    • GLP-1 agonists should only be initiated by specialist diabetologists or those in primary care who have received specific training. GLP-1 agonists should be prescribed as recommended by NICE and should be discontinued if the defined benefits are not seen within 6 months.

    • Prescribers should select a GLP-1 agonist  based on the individual patient’s requirements, bearing in mind that lixisenatide has the lowest acquisition cost if all else is equal.

    • Canagliflozin is available where recommended formulary choices of empagliflozin and dapagliflozin are not considered appropriate.  Use should be in line with NICE TA 315: Canagliflozin with the same traffic light status.  Patients may choose this drug in preference to formulary choices if they so wish.  Decision added August 2014. MHRA Advice: Canagliflozin (Invokana▼, Vokanamet▼): signal of increased risk of lower extremity amputations observed in trial in high cardiovascular risk patients issued June 2016

    •  Dapagliflozin, empagliflozin and canagliflozin are also supported in line with NICE TA 390  for monotherapy (July 2016) with the same formulary placings.

       

    Link   MHRA Advice: Dipeptidylpeptidase-4 inhibitors (‘gliptins’): risk of acute pancreatitis
    Link   MHRA Advice: SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin): risk of diabetic ketoacidosis
    Link   NICE NG 28: Type 2 diabetes in adults: management (Replaces CG 87 Dec 2015)
    Link   NICE TA 390:Canagliflozin, dapagliflozin and empagliflozin as monotherapies for treating type 2 diabetes
    Restricted Drug  Alogliptin  
    DPP-4 inhibitor. Use only as recommended in NICE guidance. Dosage adjustment required in renal impairment. Lower cost preparation.
    Restricted Drug  Linagliptin 
    DPP-4 inhibitor. Use only as recommended in NICE guidance. No dosage adjustment required in renal impairment
    Restricted Drug  Sitagliptin 
    DPP-4 inhibitor. For use only as recommended in NICE guidance. Dosage adjustment required in renal impairment
    Restricted Drug  Dulaglutide weekly  (Trulicity®)
    GLP-1 agonist.
    Once weekly preparation available only in line with NICE NG28
    Specialist diabetology initiation at UHL
    Primary care initiation conditional on appropriate competency. Otherwise simple amber
    Restricted Drug  Exenatide weekly  (Bydureon®)
    GLP-1 agonist.
    Once weekly preparation available only in line with NICE NG28
    Specialist diabetology initiation at UHL
    Primary care initiation conditional on appropriate competency. Otherwise simple amber
    Restricted Drug  Liraglutide 
    GLP-1 agonist.

    Specialist diabetology initiation at UHL
    Primary care initiation conditional on appropriate competency.Otherwise simple amber
    Restricted Drug  Lixisenatide  
    GLP-1 agonist.
    Specialist diabetology initiation at UHL
    Primary care initiation conditional on appropriate competency. Otherwise simple amber
    Restricted Drug  Exenatide twice-daily  (Byetta®)
    Twice-daily exenatide is no longer on the formulary for new initiations however may be continued in those who are already benefitting from treatment.
    Restricted Drug  Nateglinide 
    Prandial glucose regulator. May offer advantage to patients who require flexibility with mealtimes. Alternative is Repaglinide (although this is not recommended outside the age range 18-75 years).
    Restricted Drug  Pioglitazone 
    See prescribing points.
    Restricted Drug  Xultophy® 
    Liraglutide plus Degludec insulin
    Specialist diabetology initiation at UHL
    Primary care initiation conditional on appropriate competency. Otherwise simple amber
    Dapagliflozin  
    ’Green for use in monotherapy in line with NICE TA 390

    Conditional green for use in line with NICE TA 288 as part of combination therapy. Primary care initiation conditional on appropriate competency. Otherwise simple amber

    Date of entry of decision to Formulary: July 2013
    Empagliflozin  
    For use in line with NICE TA 336
    Primary care initiation conditional on appropriate competency. Otherwise simple amber


    Date decision added to Formulary: May 15
    Restricted Drug  Canagliflozin  (Invokana®)
    Canagliflozin should be considered when dapagliflozin and empagliflozin are not suitable or not tolerated

    ’Green when used as monotherapy in line with NICE TA 390. Primary care initiation conditional on appropriate competency. Otherwise simple amber

    ’Amber Simple amber when used in combination therapy in line with NICE TA 315.

    Date decision added to Formulary: April 17
    06.01.03 Diabetic ketoacidosis
    Link   UHL Guidelines: DKA Management of Diabetic Ketoacidosis in Adults
    06.01.04 Treatment of hypoglycaemia

    • Glucagon acts on the liver to cause glycogenolysis and will be ineffective in cirrhosis, starvation or other circumstances where the hepatic glycogen stores are depleted. If there has been no recovery within 15 minutes, intravenous glucose should be given, not a further dose of glucagon.

    • Recovery after glucagon is often accompanied by nausea and vomiting, which make it difficult to ensure food intake.

    • After the emergency treatment of hypoglycaemia all patients should be given a high fibre snack to prevent a further attack.

    • All patients who have had a serious hypoglycaemic episode should be referred to the diabetes team for education about prevention.
    Link   UHL Guidelines:The Hospital Management of Hypoglycaemia in Adults with Diabetes Mellitus (DM)
    First Choice:
    Glucose oral 
    Use in conscious patients who are able to swallow. Medicinal glucose in water, tablets (e.g. Dextro Energy, Lucozade) or liquid (Lucozade) are suitable. If available fruit juice is also recommended as firstline treatment.
    First Choice:
    Glucose IV 
    For use in unconscious patients. Give up to 75ml glucose 20% intravenously into a large vein. Avoid extravasation as this is hypertonic and irritant to veins (larger volumes of less concentrated glucose solution may be a safer alternative).
    First Choice:
    Glucagon (SC/IM/IV) 
    Alternative to glucose in an unconscious patient, particularly where the intravenous route is not available. Sometimes issued to patients’ relatives for emergency use at home.
    Second Choice:
    Dextrogel ® (oral) 
    Use if unable to use other forms of oral glucose. Squeeze into the side of the mouth and massage the cheek. Glucose is absorbed from the buccal mucosa. Prescribable by GPs on FP10. Do not use in an unconscious patient as aspiration may occur, with serious consequences. Issued to relatives of patients with a history of serious hypoglycaemia and those who have ’hypoglycaemia unawareness’.
    06.01.06 Diagnostic and monitoring agents for diabetes mellitus
    Link   Blood Glucose Testing Strips: Leicestershire preferred list
    06.02 Thyroid and Antithyroid drugs
    06.02.01 Thyroid hormones

    • Levothyroxine is T4; Liothyronine is T3.

    • Monitoring of TSH required at regular but increasing intervals. Aim to maintain TSH in the lower part of the normal range, with serum-free T4 in the upper part of the normal range. A typical replacement dose is 100-150microg daily.

    • Patients with TSH deficiency require monitoring for free T4 levels (TSH levels are uninformative in this context).

    • Patients who are stable on levothyroxine replacement may be referred to The Leicestershire Thyroid Register (contact Chemical Pathology, 0116 256 3037 for further information).

    • In the elderly, patients with significant co-existing disease or where there is long-standing profound hypothyroidism, start thyroid hormones at a low dose (e.g. 25 micrograms daily) and increase gradually with caution as angina and arrhythmias can be precipitated. This is particularly important in patients with ischaemic heart disease or other cardiovascular disorder. Milder or younger patients can be started directly on levothyroxine 50-100 micrograms daily.

    • If hypo-adrenalism is also present start adrenal replacement therapy before starting thyroid replacement to avoid precipitation of adrenal crisis.

    • Thyroid replacement in patients with normal thyroid function tests and ‘hypothyroid’ symptoms is not recommended. Randomised trials show no benefit of levothyroxine replacement in these circumstances. Seek an alternative explanation for symptoms.
    Link   British Thyroid Association Statement: Armour are NOT supported
    Link   Royal College of Physicians statement: The Diagnosis and Management of Primary Hypothyroidism
    First Choice:
    Levothyroxine Sodium  (Levothyroxine)
    Long half life (about 7 days) so full effects may not be seen for several weeks. Do not monitor or adjust dose more frequently than every 2-3 months
    Restricted Drug  Liothyronine Sodium 
    For prescription on specialist advice only. Please see LLR guidance.
    For severe hypothyroidism where a rapid response is required. More potent than thyroxine with a more rapid onset and shorter duration (24-48 hours) of action.
    Liothyronine 20 micrograms is approximately equivalent to 100 micrograms thyroxine
    Randomised trials and meta-analyses show no systematic benefit of combined T4/T3 replacement. It may be used occasionally for initiation only by endocrinologists according to strict criteria and discontinuation if no improvement after 12 months.

    Also used by specialists in psychiatry for treatment of depression where other therapies have failed unlicensed use)
    06.02.02 Antithyroid drugs

    • Carbimazole and propylthiouracil may cause agranulocytosis. Perform full blood count and differential before starting therapy (but beware that thyrotoxicosis per-se may be associated with mild neutropenia). Patients should be asked to report unexplained fever, malaise or sore throat – and stop treatment immediately should these occur pending an urgent (same day) full blood count CSM warning.

    • Most patients become euthyroid within 4-12 weeks. Once daily dosing of carbimazole is usually adequate for initiation and maintenance therapy, but a more rapid response may be obtained initially if given in divided doses.

    • Propranolol (40-80mg 3 times daily) may be used to control symptoms whilst thyroid function returns to normal but has no effect on underlying disease.

    • The three alternative therapeutic options of antithyroid drugs, radioactive iodine and thyroidectomy should be discussed with every patient.

    • The UHL Thyrotoxicosis Shared-care Scheme (endocrinology@uhl-tr.nhs.uk; 0116 258 5702 or via ‘Choose and Book’) is happy to advise on choice and dose adjustment of antithyroid drug therapy – both before and after any outpatient attendance.

    • If a course of antithyroid drugs is chosen then the usual treatment length is 18 months.

    • Caution in pregnancy. Specialist advice and monitoring is desirable.
    First Choice:
    Carbimazole 
    Typical starting doses: Free T4 >30 - Carbimazole 40mg once daily (2x20mg tablets) for 1 month then reduced to 20mg once daily with repeat thyroid function tests at 6 weeks. Free T4 <30 - Carbimazole 20mg once daily.
    Second Choice:
    Propylthiouracil 
    Restricted Drug  Iodine and Iodide  (Aqueous Iodine Oral Solution)
    Preparation for thyroidectomy. Start about 2 weeks preoperatively
    Restricted Drug  Propranolol IV 
    Can be given I.V in doses of 1mg up to 5mg in thyrotoxic crisis. Hydrocortisone and aqueous iodine should also be given (seek specialist advice)
    See also section 2.4
    06.03 Corticosteroids

    • The CSM has issued a notice that every patient prescribed a systemic corticosteroid should receive the patient information leaflet supplied by the manufacturer. Steroid treatment cards should also be issued where appropriate.

    • To minimise long-term adverse effects use the lowest effective dose for the shortest possible time.

    • Avoid abrupt withdrawal following long term therapy for 3 weeks or more. See BNF advice  

    • Steroid doses may need to be increased to cover the stress of acute illness or surgery.  This is often overlooked and can result in serious illness and even death.  BNF advice for patients undergoing surgery and recommendations from the Addison’s Disease Self-Help group (ADSH) are available via the links below.  The latter are also relevant to patients with hypopituitarism and those on supraphysiological doses of steroids (e.g. >5mg/day).

    • Serious infections may be masked by corticosteroid therapy (e.g. septicaemia, tuberculosis); clinical presentation may be atypical.

    • Suppressive therapy should not be given in infection without appropriate anti-infective agents
    Corticosteroids 
    06.03.01 Replacement therapy
    Fludrocortisone Acetate 
    Mineralocorticoid for replacement therapy. Required in primary adrenal insufficiency
    Hydrocortisone 
    Glucocorticoid for replacement therapy. Also has some mineralocorticoid activity
    Usual replacement dose is 10mg in morning, 5mg at lunchtime and 5mg in evening. Further dose adjustments are usually based on response.
    Hydrocortisone Injection  (Emergency HC Injection Kit)
    Kit for patients with Addison’s disease or high risk due to long term steroid use. Dose to be recommended by specialist, normally 50 or 100mg.
    06.03.02 Glucocorticoid therapy
    First Choice:
    Hydrocortisone sodium succinate injection 
    For disease suppression
    First Choice:
    Prednisolone 
    For disease suppression.
    Enteric coated tablets are not routinely stocked at UHL.
    The potential advantage of soluble or enteric coated preparations to reduce the risk of gastric ulcers is speculative. They are considerably more costly.
    Prednisolone soluble can be up to 200 times more costly than plain tablets depending on the setting. Plain tablets can be crushed and dispersed (unlicensed).

    Second Choice:
    Dexamethasone 
    For disease suppression. Preferred choice in cerebral oedema as it has less mineralocorticoid activity. Also used in vomiting associated with cancer chemotherapy.
    Second Choice:
    Methylprednisolone sodium succinate injection 
    For disease suppression when larger doses of corticosteroid are required.
    06.04 Sex hormones
    06.04.01 Female sex hormones and their modulators
    06.04.01.01 Oestrogens and HRT



    • HRT is sometimes appropriate for alleviating menopausal symptoms such as vaginal atrophy or vasomotor instability.

    • HRT increases the risk of venous thromboembolism, stroke and after some years of use, breast cancer. Unopposed oestrogen and tibolone increase the risk of endometrial cancer. Women must be made aware of the risks and treatment should be reviewed at least annually.

    • Each decision to start HRT should be made on an individual basis. 

    • For osteoporosis alternative treatments should be considered first.

    • For the treatment of menopausal symptoms the benefits of short term HRT outweigh the risks in the majority of women, especially in those aged under 60 years.  Further information on risks associated with HRT and choice of preparation is available in the BNF.

    • In non-hysterectomised women combined HRT, whilst protecting against endometrial cancer, has an increased risk of breast cancer compared to unopposed oestrogen.

    • In non-hysterectomised women the risk of endometrial cancer and breast cancer for each woman should be carefully assessed taking individual risk factors into account.

    • There is little comparative data to favour one product over the other.  Formulary choices are based on rationalisation of commonly used preparations and cost. A comparative list of formulary choices is available here

    • Progesterone pessaries (Cyclogest) and gel (Crinone) have been supported by TAS for use by the Assisted Conception Unit
    Climagest® 
    Sequential combined HRT for women with an intact uterus
    Now discontinued - Elleste Duet is the alternative choice
    Elleste-Duet® 
    Sequential combined HRT for women with an intact uterus
    Evorel®Sequi 
    Sequential combined HRT for women with an intact uterus
    Ellest-Duet Conti® 
    Continuous combined HRT for women with an intact uterus
    FemSeven® Conti Patch 
    Continuous combined HRT for women with an intact uterus.
    Kliofem® 
    Continuous combined HRT for women with an intact uterus
    Premique® 
    Continuous combined HRT for women with an intact uterus
    Climaval® 
    Unopposed oestrogen only. For hysterectomised women and non-hysterectomised women following individual risk / benefit assessment.

    Now discontinued - Elleste Solo is an alternative choice
    Elleste-Solo® 
    Unopposed oestrogen only. For hysterectomised women and non-hysterectomised women following individual risk / benefit assessment.
    Estradot® 
    Unopposed oestrogen only. For hysterectomised women and non-hysterectomised women following individual risk / benefit assessment.
    Evorel® 
    Unopposed oestrogen only. For hysterectomised women and non-hysterectomised women following individual risk / benefit assessment.
    Hormonin® 
    Unopposed oestrogen only. For hysterectomised women and non-hysterectomised women following individual risk / benefit assessment.
    Premarin® 
    Unopposed oestrogen only. For hysterectomised women and non-hysterectomised women following individual risk / benefit assessment.
    Gynest® 
    Cream (0.01%)
    Ortho-Gynest® 
    Pessary 500 microgram. Oestrogen only
    Ovestin® 
    Oestrogen only
    Vagifem® 
    06.04.01.02 Progestogens and progesterone receptor modulators

    • Progestogens have been used to treat severe dysmenorrhoea but an oral contraceptive is probably more appropriate. Evidence of efficacy in premenstrual syndrome and habitual abortion is lacking.

    • In menorrhagia luteal phase progestogens have been shown to be relatively ineffective (use tranexamic acid, or non-steroidal anti-inflammatory drugs). Prescription for 21days with a 7 day break can be effective over the short term.  

    • Progestogens are used in combination with oestrogen for hormone replacement therapy ,  in combined oral contraceptives, progestogen-only contraceptives and for emergency contraception

    • Medroxyprogesterone acetate is also used in malignant disease but this is not covered by the formulary at present.

    • A Mirena coil may be used with unopposed oestrogen to reduce the risk of endometrial cancer.
    Link   NICE CG44: Heavy menstrual bleeding
    Norethisterone 
    Derivative of testosterone. May have androgenic side effects
    Medroxyprogesterone Acetate Injection  (Depo-Provera®)
    Long acting injection. Derivative of the natural hormone progesterone.
    NB: Reduction of menstrual bleeding is an unlicensed indication. Long term (>2years) use has been linked to an increased risk of osteoporosis.
    Also used for contraception.
    06.04.02 Male sex hormones and antagonists
    • Androgens are used for replacement therapy in hypogonadal males but will not restore fertility or relieve impotence in men with normal testosterone levels. In the normal male they suppress both pituitary gonadotrophins and spermatogenesis.
    • Treatment should be under expert supervision.

    Link   SCA: Testosterone for Male Hypogonadism
    Sustanon 250® 
    3-weekly injection
    Testosterone Enantate Injection 
    Testosterone Gel 
    Testogel and Tostran are stocked by UHL.
    Testosterone Undecanoate  (Nebido®)
    06.04.02 Dutasteride and finasteride
    Link   Leicestershire Guidance: Male Lower Urinary Tract Symptoms - Prescribing Pathway
    First Choice:
    Finasteride  
    Restricted Drug  Combodart ®(Dutasteride + Tamsulosin) 
    In line with pathway
    06.05 Hypothalamic and pituitary hormones and anti-oestrogens
    The following drugs have been supported by TAS for use by the Assisted Conception Unit: Choriogonadotropin Alfa, Follitropin Alfa, Follitropin Alfa with Lutropin Alfa,  Follitropin Beta, Human Chorionic Gonadotrophin. Human Menopausal Gonadotrophin 
    06.05.01 Hypothalamic and anterior pituitary hormones and anti-oestrogens
    Restricted Drug  Somatropin  
    Supported in line with NICE guidance only
    06.05.02 Posterior pituitary hormones and antagonists

    • The main licensed roles of posterior pituitary hormones are in the treatment of cranial diabetes insipidus and in bleeding oesophageal varices.

    • Desmopressin (analogue of vasopressin) may be used in the treatment of cranial diabetes insipidus.

    • Desmopressin may be administered as a nasal spray. Please be aware that if desmopressin nasal spray is prescribed for diabetes insipidus, it is crucial that it is administered and that omission may be life-threatening.

    • Patients with oesophageal varices should be stabilised using appropriate cardiovascular support (including blood transfusion if necessary) prior to treatment.

    • A Sengstaken tube should only be inserted by someone experienced in the technique; otherwise contact a Gastroenterologist. Also consider using propranolol (e.g. 40mg three times a day) to keep heart rate below 60 beats/minute and reduce the risk of further bleeding.

    • Caution in severe vascular disease. If necessary use a glyceryl trinitrate patch to prevent anginal attacks and myocardial ischaemia.

    • Water retention may occur
    06.05.02 Posterior pituitary hormones
    Link   NICE CG 141: Acute upper GI bleeding
    First Choice:
    Restricted Drug  Terlipressin  (Glypressin®)
    First choice for bleeding oesophageal varices. Administered by intermittent injection.
    Also used for hepatorenal syndrome in patients with cirrhosis
    Second Choice:
    Restricted Drug  Argipressin 
    Alternative choice for bleeding oesophageal varices. Administer infusion via a large vein (avoid extravasation as high risk of tissue necrosis)

    Also supported for use in myomectomy - specialist use only
    Restricted Drug  Desmopressin acetate 
    Amber traffic light for Diabetes Insipidus
    06.05.02 Antidiuretic hormone antagonists
    Restricted Drug  Tolvaptan 
    Specialist renal use
    Commissioned by CCGs in line with NICE TA 358 only


    Date of entry of decision to formulary: January 2016
    06.06 Drugs affecting bone metabolism
    06.06 Osteoporosis
    06.06.02 Bisphosphonates and other drugs affecting bone metabolism

    • Prescribe for osteoporosis only in line with NICE criteria for primary or secondary prevention

    • All patients at risk of osteoporosis should be offered lifestyle advice i.e. smoking cessation, avoiding excess alcohol, weight-bearing and resisted exercise and adequate intake of calcium and vitamin D.

    • Biphosphonates decrease the risk of vertebral fracture. In addition alendronate and risedronate reduce non vertebral fractures.

    • HRT is no longer considered the first line option for osteoporosis in women over 50 years.

    • Bisphosphonates reduce the rate of bone turnover in Paget’s disease and can produce remission for varying lengths of time. They may also help relieve associated bone pain.

    • Calcium and vitamin D (Adcal D3/ Calceos) is recommended for all elderly institutionalised women unless contra-indicated as has been shown to be effective in reducing hip fractures in this group of patients. (Section 9.6.4)

    • All patients who have been receiving corticosteroids at a dose equivalent to 7.5mg/day prednisolone (or more) for 3 months or longer should be assessed. Review dose and duration of treatment. Evidence-based guidelines recommend that men and women over 65 years or with a previous history of fragility fracture should be offered bone protection (bisphosphonates) when starting steroid therapy. In other patients, if steroid therapy is to continue for at least 3 months, then bone densitometry should be considered. A T-score of –1.5 or lower may indicate the need for intervention with a bone sparing agent. Treatment should usually be on specialist advice only.

    • Ibandronic acid is available as a 150mg monthly preparation in treatment of osteoporosis for those where compliance is a significant problem. It may also be used for bone metastases in breast cancer if initiated by an appropriate specialist. For the latter it is given by IV infusion or as an oral preparation at a dose of 50mg daily.

    • Biphosphonates may also be given by IV infusion in treatment of osteoporosis and in Paget’s disease in specific circumstances only. Patient selection criteria.  

    • There have been reports of oespophageal cancer in association with bisphosphonate use. The CSM has concluded that evidence is not strong enough to show that oral bisphosphonates increase risk of oesophageal cancer.  For full information see MHRA link below. 

    • There have also been reports of osteonecrosis of the jaw (ONJ) associated with bisphosphonate use. The risk appears to be higher for those who have had IV bisphosphonate rather than oral ones. (Please see EMEA link below for more information).

    • Raloxifene is also an option for use in line with NICE TA 161.
    Link   EMEA: CHMP Assessment report on bisphosphonates and osteonecrosis of the jaw
    Link   Leicestershire Guidelines: Osteoporosis Post Fragility Fracture
    Link   MHRA Advice: Bisphosphonates and atypical femoral fractures
    Link   MHRA advice: Bisphosphonates and oesophageal cancer risk
    Link   MHRA Advice: Bisphosphonates: very rare reports of osteonecrosis of the external auditory canal
    Link   MHRA Advice: Denosumab 60mg (Prolia▼): rare cases of atypical femoral fracture with long-term use
    Link   MHRA Advice: Denosumab: fatal cases of severe symptomatic hypocalcaemia, and risk of hypocalcaemia at any time during treatment – monitoring recommended.
    Link   MHRA Advice: Denosumab: updated recommendations - Minimising the risk of osteonecrosis of the jaw; monitoring for hypocalcaemia.
    Link   MHRA Advice: important safety information for bisphosphonates
    Link   MHRA Advice: Strontium ranelate: cardiovascular risk—restricted indication and new monitoring requirements
    Link   NICE TA 160: Osteoporosis - primary prevention
    Link   NICE TA 161: Osteoporosis - secondary prevention including strontium ranelate
    First Choice:
    Alendronic Acid 
    70mg weekly for Osteoporosis.
    Second Choice:
    Risedronate Sodium 
    Daily (5mg) or weekly (35mg) for Osteoporosis.
    If intolerant or unable to comply with alendronic acid (as per NICE recommendations)
    Due to lower incidence of gastric side effects should be used in preference to alendronic acid for those with a history of peptic ulceration.
    Also available for treatment of Paget’s disease.
    Restricted Drug  Strontium Ranelate 
    If intolerant to both alendronate and risedronate.
    Severe allergic reactions have been reported. Advise patients to stop taking if skin rash develops and consult their doctor.
    The MHRA has advised that strontium ranelate should not be used in patients with current or previous venous thromboembolism (VTE) or temporary or permanent immobilisation because of risk of VTE. Rare serious skin reactions may occur within the first weeks of treatment. See link below for further details
    Restricted Drug  Alendronic Acid effervescent tablet  (Binosto®)
    Osteoporosis treatment only for patients who cannot swallow alendronic acid tablets. Not for use in patients with a feeding tube
    Restricted Drug  Denosumab  (Prolia®)
    Prescribe in line with NICE TA 204 only
    Restricted Drug  Denosumab  (Xgeva®)
    Prescribe in line with NICE TA 265 only

    Date of entry of decision to Formulary: January 2013
    Restricted Drug  Ibandronic Acid - Oral  (ibandronate)
    Prevention of skeletal events (pathological fractures, bone complications requiring radiotherapy or surgery) in patients with breast cancer as per NICE CG80
    Restricted Drug  Teriparatide  
    For use in line with NICE guidance only for 18 months treatment
    Restricted Drug  Zoledronic Acid  (Aclasta®)
    06.07 Other endocrine drugs

    06.07.01 Bromocriptine and other dopaminergic drugs

    Second Choice:
    Restricted Drug  Cabergoline  (Dostinex®)
    For Hyperprolactinaemic disorders only

    Second Choice:
    Restricted Drug  Cabergoline  (Dostinex®)
    For suppression of lactation post delivery

    06.07.02 Drugs affecting gonadotrophins
    Ulipristal acetate (Esmya) is also available for preoperative treatment of fibroids.  

    Cetrorelix and Buserelin have been supported by TAS for use by the Assisted Conception Unit
    Link   Leicestershire Evaluation: Ulipristal in Fibroids
    Link   Simple Amber: Gonadorelin analogues for treatment of endometriosis and preoperative treatment of uterine fibroids
    Link   Simple Amber: Ulipristal for preoperative treatment of fibroids
    Restricted Drug  Triptorelin 
    Preferred gonadotrophin choice for endometriosis and preoperative treatment of fibroids

    Also supported for use for precocious puberty
    Restricted Drug  Goserelin 
    For treatment of endometriosis and preoperative treatment of fibroids.
    Restricted Drug  Leuprorelin acetate 
    For treatment of endometriosis and preoperative treatment of fibroids.
    06.07.04 Somatomedins
     ....