Download 6: Endocrine system - Gateshead Health NHS Foundation Trust

6: Endocrine system
Please select a topic:
6.1 Drugs used in diabetes
6.2 Thyroid and antithyroid drugs
6.3 Corticosteroids
6.4 Sex hormones
6.5 Hypothalamic and pituitary hormones
6.6 Drugs affecting bone metabolism
and anti-oestrogens
6.7 Other endocrine drugs
Changes to the Formulary since previous version
(18.4.2013)
Section
Change
Reason for change
6.1
ADDED: Dapagliflozin
Gateshead Medicines
Management Committee Approval
6.7
ADDED: Cabergoline for
hyperprolactinaemia
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber 1 = Drugs with shared care agreement
Green + = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 1 of 23
Date: 22.8.2013
6.1 Drugs used in diabetes
Insulins
General notes

Insulin should be initiated on specialist advice only. Choice depends on the particular needs
of the individual patient, taking into account lifestyle, age, preference and capabilities.

Type of insulin, device and needle size should be specified. Care should be taken to write the
brand name in full to avoid errors such as, for example, administration of Humalog® in place
of Humalog® Mix25 or Humalog® Mix50.

Patients should not be changed from the insulin that they are currently receiving without
specialist advice; ensure that the correct insulin has been prescribed.

Insulin is available in 3mL cartridges, 10mL vials, and 3mL disposable pens. Not all insulin
cartridges fit all pens.

Pens are available on prescription.

The B-D Safe-Clip® device snaps the needle off insulin syringes and stores the needle safely
inside the clipper; this device is available on prescription.
Short-acting insulins

Human Actrapid 10ml vial

Human Novarapid 10ml vial, 3ml cartridges, 3ml flexpen

Humulin S 10ml vial, 3ml cartridges

Insulin Gluisline (Apidra®) 3ml solostar pen, 10ml vial, 3ml cartridges

Insulin Lispro (Humalog) 10ml vial, 3ml cartridges, 3ml Kwik pen
Intermediate-acting insulins

Humulin I 10ml vial, 3ml cartridges, 3ml Kwik pen

Human Insulatard 10ml vial, 3ml cartridges, prefilled disposable pen
Long-acting insulins

Insulin Glargine (Lantus) 10ml vial, 3ml cartridges, 3ml Solostar pen

Insulin Detemir (Levemir®) 3ml cartridges, prefilled disposable pen(Flexpen)
Biphasic insulins

Human Novomix 30 3ml cartridges, prefilled disposable pen(Flexpen)

Humulin M3 10ml vial and 3ml cartridges, 3ml Kwik pen

Humalog Mix 25 10ml vial, 3ml cartridges and prefilled disposable pens

Humalog Mix 50
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber 1 = Drugs with shared care agreement
Green + = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 2 of 23
Date: 22.8.2013
MHRA Drug Safety Update
Insulin glargine: studies of possible cancer link
Article date: September 2009
Summary
Recent observational studies have suggested a possible association between insulin glargine and
an increased risk of cancer. The results are not entirely consistent, and can neither confirm nor
exclude a relationship between insulin glargine and cancer. Therefore, the European Medicines
Agency has advised that no change in recommendations for use is required at present.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087909
Oral diabetic drugs

Acarbose 50mg tablets

Exenatide 5microgram/dose and 10microgram/dose pen (Byetta®)

Exenatide MR 2mg injection (Bydureon®)

Liraglutide 18mg/3ml pen

Glibenclamide 2.5mg, 5mg tablets

Gliclazide 30mg MR tablets

Gliclazide 80mg tablets

Glimepiride 1mg and 2mg tablets

Glipizide 5mg tablets

Metformin 500mg, 850mg tablets

Metformin 500mg/5ml suspension

Metformin SR 500mg and 1000mg tablets

Metformin 500mg and 1000mg sachets

Pioglitazone 15mg and 30mg tablets

Sitagliptin 25,g, 50mg, 100mg tablets

Saxagliptin 2.5mg and 5mg tablets

Tolbutamide 500mg tablets

Dapaglifozin 5mg and 10mg tablets-
Dose
- Metformin tablets 500mg, 850mg: initially 500mg once or twice daily with meals; gradually
increased to max 2g daily divided doses.
- Metformin SR tablets 500mg, 1000mg: initially 500mg once; gradually increased to max 2g once
daily with evening meal.
- Metformin sachets 500mg: initially 500mg once; gradually increased to max 2g once daily with
evening meal.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber 1 = Drugs with shared care agreement
Green + = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 3 of 23
Date: 22.8.2013
- Acarbose tablets 50mg: initially 50mg daily; gradually increased to max 200mg three times a
day.
- Exenatide (Byetta®) injection 250micrograms/ml: initially 5micrograms twice daily within 1 hours
before 2 main meals (at least 6 hours apart), increased if necessary after at least 1 month to max
10micrograms twice daily.
- Exenatide MR (Bydureon®) injection 2mg: 2mg once a week.
- Liraglutide injection 6mg/ml: initially 0.6mg once daily, increased after at least 1 week to 1.2mg
once daily, increased if necessary after at least 1 week to max 1.8mg once daily.
- Sitagliptin tablets 100mg: 100mg once daily.
- Saxagliptin tablets 2.5mg, 5mg: usual dose is 5mg once daily.
- Tolbutamide tablets 500mg: 500mg to 1g (max 2g) daily in divided doses with or immediately
after breakfast.
- Glimepiride tablets 1mg and 2mg: initially 1mg daily with meals; adjusted according to response
up to usual max 4mg daily.
- Glibenclamide tablets 2.5mg and 5mg: initially 5mg daily with or immeditately after breakfast;
adjusted according to response up to max 15mg daily.
- Gliclazide tablets 80mg: initially 40-80mg daily, max 320mg daily; doses above 160mg daily
should be divided.
- Glipizide tablets 2.5mg, 5mg: initially 2.5-5mg daily, max 20mg daily; doses above 10mg daily
can be divided.d to usual maintenance dose 1g twice daily; max 3g daily in divided doses.
- Pioglitazone tablets 15mg, 30mg: in combination with metformin or a sulphonylurea, 15-30mg
once daily.
- Dapaglifozin tablets 5mg, 10mg: usual dose is 10mg once daily.
Prescribing notes
General notes

First-line treatment for management of type 2 diabetes is usually a trial of dietary therapy
unless there is intercurrent infection, severe hyperglycaemia or severe osmotic symptoms.

Patients commencing blood glucose lowering agents should inform the DVLA and their car
insurance company.

Those with type 2 diabetes may require treatment with insulin, either alone or in combination
with oral agents.

Newer hypoglycaemic agents are substantially more expensive than the older hypoglycaemic
agents.
Biguanides and sulphonylureas

Metformin is the first choice oral hypoglycaemic drug. It is the only oral antidiabetic drug
which has a proven survival advantage. It does not need to be limited to overweight patients.

Due to the rare but serious risk of lactic acidosis, metformin must be avoided in patients
with: significant renal impairment (estimated glomerular filtration rate (eGFR) less than
30mL/min); alcoholism with previous pancreatitis; severe cardiac/respiratory disease
producing tissue hypoxia; severe liver disease with potential for hepatic failure.

The precipitant of a lactic acid crisis is often in the eGFR range 30 to 45mL/min when the
patient develops what would have been a trivial illness (such as diarrhoea and vomiting)
which compromises renal function and causes acute renal failure. This is compounded if the
patient is also taking diuretics and/or ACE inhibitors in combination with metformin. Unlike
acute illnesses in type 1 diabetes (where insulin treatment MUST be continued) stopping the
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber 1 = Drugs with shared care agreement
Green + = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 4 of 23
Date: 22.8.2013
above cocktail of drugs for a day or two will NOT cause any immediate problem for the
patient and will protect renal function until the patient improves. Blood glucose estimation
should be used to assess any glycaemic deterioration. In circumstances where renal
impairment is suspected, NSAIDs should NOT be used as they can further compromise renal
function.

Metformin may cause gastro-intestinal adverse effects; it should be started at low dose and
taken after meals, and the dose gradually increased every 10-15 days if tolerated.
Hypoglycaemia is not a problem with metformin monotherapy.

Metformin prolonged release tablets (Glucophage SR®) are restricted for use in patients who
are unable to tolerate immediate release metformin, and in whom the continued use of
metformin offers a clinically significant benefit. They are more expensive than the immediate
release tablets but les expensive than other newer oral agents.

Sulphonylureas should be taken before meals

Gliclazide 30mg m/r (Diamicron® MR) should be reserved for patients with demonstrable
compliance problems.

Patients should be informed that sulphonylureas can cause hypoglycaemia. The risk of
hypoglycaemia increases with age.
Glitazones (thiazolidinediones)

Pioglitazone can be used in combination with insulin in patients with type 2 diabetes mellitus,
who have insufficient glycaemic control on insulin, in whom metformin is inappropriate
because of contraindications or intolerance.

Glitazones can cause weight gain and fluid retention. They must not be used in patients with
heart failure or history of heart failure.

Glitazones reduce bone mineral density in post-menopausal women with a subsequent
increase in fracture risk. They should be avoided in elderly women with high fracture risk,
irrespective of cardiovascular risk.

Liver function should be checked before initiating glitazones and periodically thereafter based
on clinical judgement. Glitazones should not be used in patients with hepatic impairment.

There is an increased risk of hypoglycaemia when combined with a sulphonylurea.
MHRA Drug Safety Update
Pioglitazone: risk of bladder cancer
Article date: August 2011
Summary
Use of pioglitazone is associated with a small increased risk of bladder cancer. Healthcare
professionals should be aware of new warnings and precautions for use in at-risk patients.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON125962
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber 1 = Drugs with shared care agreement
Green + = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 5 of 23
Date: 22.8.2013
MHRA Drug Safety Update
Insulin combined with pioglitazone: risk of cardiac failure
Article date: January 2011
Summary
Cases of cardiac failure have been reported when pioglitazone was used in combination with
insulin, especially in patients with risk factors for the development of cardiac failure. If the
combination is used, patients should be observed for signs and symptoms of heart failure, weight
gain, and oedema.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON105746
Dipeptidyl peptidase-4 inhibitor (DDP-4 inhibitor)

Sitagliptin is approved for use by prescribers with a special interest in diabetes. It should be
used in combination with metformin where the addition of a sulphonylurea is not appropriate.

Saxagliptin should be reserved for use in patients with moderate to severe renal impairment,
at a reduced dose of 2.5mg once daily.

DDP-4 inhibitors are considered to be weight neutral.

DPP-4 inhibitors have been shown to reduce Hb1Ac levels but there is not data on morbidity,
mortality, or long-term adverse effects.
MHRA Drug Safety Update
Dipeptidylpeptidase-4 inhibitors (gliptins): risk of acute pancreatitis
Article date: September 2012
Summary
There have been reports of acute pancreatitis associated with drugs in the dipeptidylpeptidase-4
(DPP-4) inhibitor class of antidiabetic agents (‘gliptins’). Patients should be informed of the
characteristic symptoms of acute pancreatitis – persistent, severe abdominal pain (sometimes
radiating to the back) – and encouraged to tell their healthcare provider if they have such
symptoms. If pancreatitis is suspected, the DPP-4 inhibitor and other potentially suspect
medicinal products should be discontinued.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON185628
Incretin mimetic

Exenatide (twice daily) is approved for use by prescribers with a specialist interest in diabetes
in combination with metformin and/or sulphonylureas.

Needle guage and length must be specified when prescribing exenatide.

10-20% of patients experience upper gastro-intestinal side effects with exenatide. Acute
pancreatitis has been reported with exenatide, patients should be informed of the warning
signs to look for.

Liraglutide may be an option in those experiencing excessive side-effects with exenatide. It is
administered once a day independent of food intake, which may suit those with irregular
working patterns.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber 1 = Drugs with shared care agreement
Green + = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 6 of 23
Date: 22.8.2013

There is an increased risk of hypoglycaemia when combined with a sulphonylurea.

Long term studies are needed to determine the effects of exenatide and liraglutide on disease
related morbidity and mortality.

Gastric emptying may be delayed, therefore the rate and extent of absorption of other drugs
administered at the same time may be affected. For oral drugs that require threshold
concentrations for efficacy, patients should take these medicines at least 1 hour before.
MHRA Drug Safety Update
Exenatide (Byetta®): risk of severe pancreatitis and renal failure
Article date: March 2009
Summary
Suspected adverse reaction reports of necrotising and haemorrhagic pancreatitis have been
received in association with exenatide. Some of these reports had a fatal outcome. If pancreatitis
is diagnosed, exenatide should be permanently discontinued. Reports of renal impairment,
including acute renal failure and worsened chronic renal failure have also been received.
Exenatide is not recommended for use in patients with end-stage renal disease or severe renal
impairment.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON088117
Treatment of hypoglycaemia

Glucagon 1mg syringe

Glucose 40% gel 25g
Dose
- Glucagon 1mg vial: subcutaneous, intramuscular or intravenous injection, adult and child over
25kg- 1 mg.
Prescribing notes

Following administration of glucagon, it is important to give supplementary carbohydrate to
restore liver glycogen and prevent secondary hypoglycaemia.

Although intravenous glucose is the more effective treatment where intravenous access is
readily available, intramuscular glucagon may be more appropriate.

Glucagon injection may be repeated once after 10 minutes if necessary, but intravenous
glucose is preferable. If there is no response, then hospital admission should be considered.
Diabetic equipment

Insulin syringes 100 units

Microfine + needles 5mm, 8mm, 12.7mm
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber 1 = Drugs with shared care agreement
Green + = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 7 of 23
Date: 22.8.2013

Accu-check advantage II Test strips

Accu-check Aviva blood test strips

Diabur 5000 strips

Ketur strips

Keto-diabur 500 test strips

BD Optimus Lancer, Microfine + lancets, BD safe clip

Penfine needles Sizes 6mm, 12mm

Novofine needles sizes 6mm, 8mm, 12mm

Humapen Ergo

Accu-check Fastclix lancets
Choice of meter depends on experience and patient preference and capabilities e.g. visual acuity,
manual dexterity. Meters are not available on prescription. Patients may purchase any meter but
should do so only following expert advice from a suitably trained person. Strips may be prescribed
and can also be bought over-the-counter.
Prescribing notes

Home blood glucose monitoring in non-insulin treated Type 2 diabetes should routinely be
undertaken:
* where treatment change is indicated
* to monitor a treatment change
* where hypoglycaemia is suspected
* where control is poor

In such cases, blood glucose monitoring should not require to be performed routinely on
more than 2 days in the week or more than twice in the day. The timing of the samples will
depend on the particular case but a fasting value is useful. Correct meter care and quality
control are essential when meters are used.

Patients must be aware of how to interpret the results.

Meters are obtainable from centres with expert advice from a suitably trained person; it is
impossible to recommend one specific meter since they are all similar in quality and cost.

Strips deteriorate rapidly if exposed to the atmosphere.

Correct meter care and quality control are essential when meters are used.

It is important to test for urinary ketones where there is a significant risk of ketoacidosis,
such as may occur with significant intercurrent illness.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber 1 = Drugs with shared care agreement
Green + = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 8 of 23
Date: 22.8.2013
6.2 Thyroid and antithyroid drugs
Thyroid hormones

Levothyroxine (Thyroxine) sodium 25, 50, 100 micrograms tablets

Levothyroxine 25microgram/5ml oral solution

Liothyronine sodium 20 microgram tablets

Liothyronine sodium 20 microgram injection
Dose
- Levothyroxine tablets 25micrograms, 50micrograms, 100 micrograms: initially 100 micrograms
(50micrograms if elderly) daily, adjusted in steps of 50micrograms every 6 weeks until TSH is within
normal reference range (usually 100-150micrograms daily); where there is cardiac disease, initially
25micrograms daily or 50 micrograms on alternate days, adjusted in steps of 25micrograms every 3
weeks.
- Liothryonine tablets 20micrograms, injection 20micrograms: see BNF
Prescribing notes

Prior to treatment it is important to establish that TSH is elevated thus confirming primary
hypothyroidism. A normal or low TSH suggests pituitary or hypothalamic disease for which
specialist referral is necessary.

Thyroid stimulating hormone should be checked 6 weeks after starting thyroxine or after any
change in dose, then annually once stable.

Myxoedema coma is a rare medical emergency and, in a semi- comatose patient, the clue
might be a low plasma sodium. Treatment should be with specialists using liothyronine (L-triiodothyronine) by intravenous injection (20micrograms 8 hourly).
Antithyroid drugs

Carbimazole 5mg, 20mg tablets

Aqueous iodine oral solution (Lugols solution)

Propylthiouracil 50mg tablets
Dose
- Carbimazole tablets 5mg, 20mg: 20-60mg daily until euthyroid (usually 4-8 weeks), then
progressively reduced to a maintenance dose, typically 5-15mg, daily usually for 18 months.
- Lugols solution: see BNF
- Propylthiouracil tablets 50mg: see BNF
Prescribing notes

Carbimazole 20-40mg daily may be given with levothyroxine 50-150micrograms daily in a
blocking-replacement regimen, usually for 18 months.

Carbimazole has rarely been associated with bone marrow suppression and treatment should
be stopped promptly if there is clinical or laboratory evidence of neutropenia. Patients should
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber 1 = Drugs with shared care agreement
Green + = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 9 of 23
Date: 22.8.2013
be asked to report symptoms and signs suggestive of infection, especially sore throat. A
white blood cell count should be performed if there is any clinical evidence of infection.

Propylthiouracil may be an alternative for patients who suffer sensitivity reactions to
carbimazole.

Thyrotoxic crisis needs emergency specialist treatment including all, or combinations of,
medications such as intravenous fluids, propranolol (5mg), hydrocortisone sodium succinate
(100mg every 6 hours), potassium iodide, carbimazole and even amiodarone).

Beta blockade can be withdrawn once hyperthyroidism is controlled (2-6 weeks), and the
patient maintained on carbimazole.

Pregnant patients receiving carbimazole must be monitored and administered at the lowest
effective dose.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber 1 = Drugs with shared care agreement
Green + = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 10 of 23
Date: 22.8.2013
6.3 Corticosteroids
Replacement therapy

Fludrocortisone 100 microgram tablets
Glucocorticoid therapy

Prednisolone 1mg, 5mg tablets

Prednisolone 5mg dispersible tablets

Prednisolone 2.5mg EC tablets

Prednisolone 5mg suppositories

Dexamethasone 500 microgram, 2mg tablets

Dexamethasone 2mg/5ml SF solution

Dexamethasone 4mg/ml injection

Hydrocortisone 10mg, 20mg tablets

Hydrocortisone 100mg injection (sodium succinate) (Solu-Cortef®)

Methylprednisolone sodium succinate 40mg, 500mg, 1g injection (Solu-Medrone®)

Methylprednisolone acetate 40mg/ml, 120mg/3ml depot injection (Depo-Medrone®)

Triamcinolone 40mg/ml injection (Kenalog®)

Betamethasone sodium phosphate 4mg/ml injection (Maternity only)
Dose
- Hydrocortisone tablets 10mg, 20mg
- Fludrocortisone tablets 100micrograms: 50-300micrograms daily.
- Prednisolone tablets 1mg, 5mg; e/c tablets 2.5mg;soluble tablets 5mg.
- Dexamethasone tablets 500micrograms, 2mg; injection 4mg/mL, 24mg/mL: orally, usual range
0.5-10mg daily. By intramuscular injection or slow intravenous injection or infusion, initially 0.520mg.
- Methylprednisolone sodium succinate (Solu-Medrone®) vials 1g: by slow intravenous
injection or infusion, initially 10-500mg.
- Methylprednisolone acetate (Depo-Medrone®) vials 40mg/mL, 80mg/2mL, 120mg/3mL:
deep intramuscular injection into gluteal muscle, 40-120mg, repeated after 2-3 weeks if required.
- Triamcinolone injection 40mg: see BNF
- Betamethasone injection 4mg/ml: see BNF
Prescribing notes

In Addison's disease (primary adrenal failure) hydrocortisone (glucocorticoid) and
fludrocortisone (mineralocorticoid) are given. In acute adrenocortical insufficiency,
intravenous hydrocortisone sodium succinate 100mg is given every 6-8 hours. The
extracellular fluid deficit (usually 3-4 litres) should be replaced by: sodium chloride
intravenous infusion 0.9% with glucose intravenous infusion 5%; 1litre is given during the
first hour, and the remainder over 12-24 hours.

In secondary adrenal failure (hypopituitarism), hydrocortisone is given alone, there being no
mineralocorticoid deficiency.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber 1 = Drugs with shared care agreement
Green + = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 11 of 23
Date: 22.8.2013

Patients deficient in glucocorticoids do not respond adequately to stress and should be
advised to double the replacement dose of hydrocortisone for several days if significantly
unwell. More serious illnesses or gastro-intestinal disturbances necessitate prompt parenteral
hydrocortisone.

Patients receiving more than 7.5mg of prednisolone (or equivalent; see BNF section 6.3.2)
for longer than 3-6 months should receive osteoporosis prophylaxis).

Care should be taken in reducing pharmacological doses of glucocorticoids if the patient has
been treated for longer than 3 weeks to avoid cortisol insufficiency due to prolonged
suppression of the hypothalamic-pituitary-adrenal (HPA) axis

In terms of their anti-inflammatory properties, approximately 20mg hydrocortisone is
equivalent to 5mg prednisolone or 750micrograms dexamethasone. See BNF section 6.3.2.
MHRA Drug Safety Update
Corticosteroids: early psychiatric side-effects
Article date: December 2007
Summary
Risk of early psychiatric side-effects is one of several important safety issues for healthcare
professionals to discuss with patients and carers. Patients or carers should seek urgent medical
advice in the event of any worrying symptoms.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON079173
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber 1 = Drugs with shared care agreement
Green + = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 12 of 23
Date: 22.8.2013
6.4 Sex hormones
Female sex hormones
Conjugated oestrogens with progestogen

Conjugated oestrogens 625 microgram plus norgestrel 150 microgram tablets (Prempak-C 0.625)

Conjugated oestrogens 1.25mg plus norgestrel 150 microgram tablets (Prempak-C 1.25)

Conjugated oestrogens 625 microgram plus medroxyprogesterone acetate 5mg tablets (Premique)
Conjugated oestrogens only Conjugated oestrogens with progestogen

Conjugated oestrogens 625 microgram and 1.25mg tablets (Premarin)
Estradiol only

Oestradiol valerate 1mg and 2mg tablets (Climaval)

Oestradiol patch releasing 25 micrograms per 24 hours (Estraderm MX)

Oestradiol patch releasing 50, 75 and 100 micrograms per 24 hours (Femseven)
Estradiol with progestogen

Oestradiol valerate 1mg plus norethisterone (Climagest 1mg)

Oestradiol valerate 2mg plus norethisterone (Climagest 2mg)

Oestradiol 2mg plus norethisterone 1mg tablets (Kliofem)

Oestradiol 1mg plus norethisterone 500mcg tablets (Kliovance)
Miscellaneous

Tibolone 2.5mg tablets
Progestogens

Medroxyprogesterone 5mg and 10mg tablets (Provera®)

Norethisterone 5mg tablets

Progesterone 400mg pessaries
Prescribing notes
(See MHRA Drug Safety Update Vol 1 Issue 2 Sept 2007)
Short-term treatment of menopausal symptoms

HRT should generally only be prescribed for menopausal symptoms and not for prevention of
osteoporosis or cardiovascular disease.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber 1 = Drugs with shared care agreement
Green + = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 13 of 23
Date: 22.8.2013

It is recommended that the lowest dose of HRT based on relieving menopausal symptoms
should be prescribed.

Oral HRT regimens are well tolerated, cheaper than patches and should be considered as
first-line therapy in most women.

Transdermal regimens should be considered in women intolerant of or unable to take oral
HRT, or theoretically in those with some gastro-intestinal and liver problems. Transdermal
HRT carries less risk of venous thromboembolism and should be used preferentially in women
with cardiovascular risk factors.

There is significant individual variation in response to HRT, and it is often appropriate to try
two or three different preparations. Women should be encouraged to persevere with a new
preparation for 2-3 months as any side-effects experienced initially may settle with time.

Women should be reviewed three months after commencing therapy. The on-going need for
HRT should be reassessed at least annually. Blood pressure should be checked 6-12 monthly,
and the woman encouraged to attend cervical and breast screening programmes. Breast
awareness should be encouraged.

HRT is not a method of contraception.

Stopping HRT abruptly can cause some women to have hot flushes and it should therefore be
withdrawn gradually by decreasing dosages over 3-6 months.

HRT is contra-indicated in the presence of active venous thromboembolism, unexplained
vaginal bleeding, oestrogen dependent tumours (breast and endometrial cancer), current or
recent cardiovascular disease and acute porphyria. Women with severe menopausal
symptoms following breast or endometrial cancer may occasionally be prescribed HRT after
specialist consultation.
HRT and cardiovascular disease

There is no evidence that HRT protects against either ischaemic heart disease or stroke and it
should not be commenced for this indication. HRT may be associated with worsening of
cardiovascular outcome, particularly in women with pre-existing cardiovascular risk factors.
The decision to continue or stop HRT in women with CVD who have been receiving long-term
oestrogen therapy should be based on presence of acute menopausal symptoms. If a woman
develops an acute CVD event, e.g. heart attack or stroke, or is immobilised while receiving
HRT, the risk of thromboembolism is increased and consideration should be given to stopping
HRT.
HRT and breast cancer

Risk of breast cancer increases with increasing duration of HRT use (see below) and this
should be balanced against the benefits of taking long-term therapy. The risk is significantly
greater for combined HRT than for oestrogen only therapy. Tibolone also appears to have an
increased risk of breast cancer. Women with a significant family history should seek specialist
opinion prior to being prescribed HRT.

The additional risk of breast cancer begins to decline when HRT is stopped and by 5 years
reaches the same level as in women who have never taken HRT. The need for HRT should be
reassessed at least annually.

Women with premature menopause have an overall lower risk of breast cancer and in most
instances should receive HRT until the age of normal menopause and then should be
reassessed.
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Date: 22.8.2013
HRT and osteoporosis

HRT prevents loss of bone density and reduces risk of osteoporotic fracture. However, in
2003, the Committee on Safety of Medicines in the UK stated that HRT should not be used as
first-line for prevention of osteoporosis as the risk:benefit ratio of HRT is unfavourable.
General notes

Continuous combined therapy (period-free HRT) should only be used by women who are at
least a year past the menopause or over 54 years of age. Both oestrogen and progestogen
are taken daily to give a period-free regimen. Erratic bleeding is common in the first few
months of use.

Women with irregular or heavy bleeding with HRT which persists for more than 3 months
should be referred to a gynaecology or menopause service.

Amenorrhoea with HRT is not a risk for endometrial cancer and does not require
investigation.

Conjugated oestrogens are extracted from pregnant mares' urine and may not be acceptable
to some women.
Male sex hormones and antagonists

Testosterone undeconate 40mg capsules

Testosterone 250mg injection (Sustanon®)

Testosterone 100mg injection (Sustanon®)

Testosterone undecanoate 1000mg/4ml injection (Nebido®)

Testosterone 2% gel (Tostran®)

Cyproterone 50mg tablets

Finasteride 5mg tablets
Dose
- see BNF.
Prescribing notes

Intramuscular depot preparations of testosterone esters are preferred for replacement therapy. Gel
may be preferred if the patient find the injection painful.
MHRA Drug Safety Update
High dose cyproterone acetate: potential risk of (multiple) meningiomas
Article date: October 2009
Summary
Patients with existing meningioma or a history of meningioma must not be prescribed high-dose
(≥25 mg per day) cyproterone acetate. This advice does not apply to low-dose cyproterone
acetate products such as co-cyprindiol (Dianette).
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087674
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Page 15 of 23
Date: 22.8.2013
6.5 Hypothalamic and pituitary hormones and anti-oestrogens
Anti-oestrogens

Clomifene 50mg tablets
Dose
- see BNF
Anterior pituitary hormones

Tetracosactide/Tetracosactrin 250 micrograms injection (Synacthen®)

Tetracosactide/Tetracosactrin 1mg depot injection (Synacthen Depot®)

Chorionic gonadotrophin 5000 unit amp (Pregnyl®)

Menopur® 75 unit injection

Follitropin alfa (Gonal F®) injection
Dose
- see BNF
Hypothalamic hormones

Gonadorelin 100 microgram/ml injection

Protirelin 200 microgram/2ml injection
Dose
- see BNF
Posterior pituitary hormones and antagonists

Argipressin 20units/ml injection (vasopressin)

Desmopressin 100microgram and 200 microgram tablets (DDVAP®)

Desmopressin 4 microgram/ml injection (DDVAP®)

Desmopressin 10 microgram/dose nasal spray (Desmospray®)

Desmopressin 100 microgram/ml nasal solution (DDVAP®)

Terlipressin 1mg injection
Dose
- Desmopressin nasal spray 10micrograms/metered spray; intranasal solution 100micrograms/mL:
intranasally, diabetes insipidus, treatment, 10-40micrograms daily in 1-2 divided doses.
- Desmopressin tablets 100micrograms, 200micrograms: diabetes insipidus, treatment, initially
300micrograms daily in 3 divided doses; maintenance 300-600micrograms daily in 3 divided doses;
range 0.2-1.2mg daily.
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Date: 22.8.2013
- Terlipressin injection 1mg vial: by intravenous injection, 2mg followed by 1 or 2mg every 4 to 6
hours until bleeding is controlled, for up to 72 hours.
Prescribing notes

A single dose of desmopressin is also used as part of a test following fluid deprivation in the
differential diagnosis of thirst and polyuria.

For nephrogenic diabetes insipidus, the usual treatment is a thiazide diuretic. Caution if due
to lithium; refer to endocrinologist.

Desmopressin injection 4micrograms/mL may be indicated in unconscious patients (dose 14micrograms daily by subcutaneous, intramuscular or intravenous injection).

Measurement of plasma sodium once or twice a year guards against excessive water intake
which would be reflected by a low plasma sodium.
MHRA Drug Safety Update
Desmopressin nasal spray: removal of nocturnal enuresis indication
Article date: September 2007
Summary
Nasal formulations of desmopressin are no longer indicated for primary nocturnal enuresis.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON079167
Antidiuretic hormone antagonists

Demeclocycline 150mg capsules
Dose
- Demeclocycline capsules 150mg: initially 0.9-1.2g daily in divided doses; maintenance 600900mg daily.
Prescribing notes

Demeclocycline is indicated for chronic Syndrome of Inappropriate Secretion of Anti-Diuretic
Hormone (SIADH) where fluid deprivation is unsuccessful.

Higher doses of demeclocycline may be associated with a decline in glomerular filtration.
Creatinine should be monitored along with plasma sodium.
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Page 17 of 23
Date: 22.8.2013
6.6 Drugs affecting bone metabolism
Calcitonin

Calcitonin(salmon)/salcatonin 50 units/ml, 200units/ml injection
Bisphosphonates

Alendronic acid 10mg tablets

Alendronic acid 70mg once-a week tablets

Disodium etidronate 200mg tablets

Disodium etidronate 400mg tablets plus calcium carbonate 1.25mg tablets (Didronel PMO)

Disodium pamidronate 30mg and 90mg injection

Zoledronic acid 4mg injection

Zoledronic acid 5mg injection

Sodium clodronate 400mg capsule

Risedronate 5mg, 30mg tablets

Risedronate 35mg once-a-week tablets

Ibandronate 50mg tablets (Bondronat®)

Ibandronate 3mg/3ml syringe
Other

Strontium ranelate 2g sachets

Raloxifene 60mg tablets

Denosumab 60mg/ml injection
Dose
- see BNF
Prescribing notes

The aim of treatment is the prevention of fracture.

Treatment should be based on identification of risk factors for osteoporosis and use of bone
densitometry scanning, where available.

Before starting treatment, calcium, phosphate, alkaline phosphatase and renal function
should be checked.

Those with, or at risk of, osteoporosis should maintain an adequate intake of calcium and
vitamin D. If deficiency is suspected, this should be corrected by increasing dietary intake or
taking supplements.
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Page 18 of 23
Date: 22.8.2013

Standard calcium and vitamin D preparations may be ineffective in moderate to severe renal
disease; alfacalcidol may be a suitable alternative.

Long-term therapy is required to treat or prevent osteoporosis. Optimum duration is
unknown and there is limited information regarding the long-term safety and efficacy of
bisphosphonates.

Patients with identified risk factors for osteoporosis should be encouraged to perform weight
bearing exercise and strength training, give up smoking, and follow a healthy diet with
adequate calcium and vitamin D.

Treatment with oral contraceptives or HRT should be considered for early menopause until
around the age of 50 years. The CSM now advises that HRT should not be considered firstline therapy for the long-term prevention of osteoporosis in women who are over 50 years of
age and at an increased risk of fractures.

A review of the evidence suggests that Didronel PMO® is less effective than alendronate and
side-effects from the calcium preparation are common.

Teriparatide is for specialist use only, for severe osteoporosis and is available on a nonformulary basis.

Oral bisphosphonates should be avoided in anyone with a history of oesophageal stricture or
severe oesophagitis.

Bisphosphonates have complex administration instructions. GI side-effects are minimised by
following these instructions.

Alendronate is the 1st choice oral bisphosphonate.
MHRA Drug Safety Update
Calcitonin (Miacalcic): increased risk of cancer with long term use – all intra-nasal
formulations for osteoporosis to be withdrawn
Article date: August 2012
Summary
There is an increased risk of cancer associated with the long-term use of calcitonin. Because of
this risk, calcitonin-containing medicines should no longer be used in the treatment of
osteoporosis.
All intra-nasal calcitonin sprays, which are the only formulation of calcitonin licensed for
osteoporosis, will be withdrawn from the European market.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON180634
MHRA Drug Safety Update
Strontium ranelate (Protelos): 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.
Article date: May 2012
Summary
Strontium ranelate (Protelos) is known to increase the risk of venous thromboembolic events
(VTE) and should not be used in patients with current or previous VTE, including deep vein
thrombosis and pulmonary embolism, or in patients with temporary or permanent immobilisation
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Date: 22.8.2013
(eg post-surgical recovery or prolonged bed rest). The need for continued treatment with
strontium ranelate should also be re-evaluated in patients over 80 years who have been
diagnosed at risk of VTE.
Strontium ranelate is also associated with serious skin and hypersensitivity reactions such as
drug rash with eosinophilia and systemic symptoms (DRESS). Although the risk is low,
prescribers are advised to be alert to signs and symptoms of serious skin reactions with
strontium ranelate. The likely time-to-onset of such events is the first few weeks of treatment for
Stevens-Johnson syndrome and toxic epidermal necrolysis and usually within 3 – 6 weeks for
DRESS. Early diagnosis and discontinuation of treatment produce the best results, and patients
should be advised accordingly.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON152727
MHRA Drug Safety Update
Bisphosphonates: atypical femoral fractures
Article date: June 2011
Summary
Atypical femoral fractures have been reported rarely with bisphosphonate therapy, mainly in
patients receiving long-term treatment for osteoporosis. Discontinuation of bisphosphonate
therapy in patients suspected to have an atypical femur fracture should be considered while they
are evaluated, and should be based on an assessment of the benefits and risks of treatment. The
need to continue bisphosphonate treatment for osteoporosis should be re-evaluated periodically
based on the benefits and potential risks of bisphosphonate therapy for individual patients,
particularly after 5 or more years of use.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON120213
MHRA Drug Safety Update
Oral bisphosphonates: oesophageal cancer risk – insufficient evidence of a link
Article date: November 2010
Summary
There is insufficient evidence to confirm a link between oral bisphosphonate use and an
increased risk of oesophageal cancer. Patients should be advised to carefully follow the
instructions in the Patient Information Leaflet on how to take the medicine and report any
symptoms of oesophageal irritation to their doctor.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON099870
MHRA Drug Safety Update
Bisphosphonates: atrial fibrillation
Article date: July 2008
Summary
Clinical trial results have suggested an increased risk of atrial fibrillation for zoledronic acid
(Aclasta▼), pamidronic acid, and possibly for alendronic acid. The balance of risks and benefits
for bisphosphonates remains favourable.
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Date: 22.8.2013
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON085167
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Page 21 of 23
Date: 22.8.2013
MHRA Drug Safety Update
Strontium ranelate (Protelos): risk of severe allergic reactions
Article date: December 2007
Summary
Strontium ranelate (Protelos▼) is a treatment for postmenopausal osteoporosis. Concerns have
arisen about a risk of severe allergic reactions, including drug rash with eosinophilia systemic
symptoms (DRESS). These symptoms start with a skin rash, accompanied by a fever, swollen
glands, and increased white-cell count; it can also affect the liver, kidneys, and lung. Stopping
treatment and corticosteroid therapy usually improves symptoms, but recovery can be slow and
there is a risk of symptoms returning during recovery. Healthcare professionals should be alert
to the risk of severe allergic reactions. Patients who develop a rash should stop taking the
medicine and consult their doctor immediately. Once treatment with strontium ranelate has
stopped it should not be re-introduced.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON084697
MHRA Drug Safety Update
Intravenous zoledronic acid: adverse effects on renal function
Article date: April 2010
Summary
Zoledronic acid is associated with reports of renal impairment and renal failure, especially in
patients with pre-existing renal dysfunction or other risk factors. Renal function should be
measured before each dose, and patients should be adequately hydrated before treatment.
Renal function monitoring is recommended after use of zoledronic acid in at-risk patients—
especially those with pre-existing renal impairment. Use in patients with severe renal impairment
is generally not recommended, but may be considered for tumour-induced hypercalcaemia, if the
benefits outweigh the risks.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087704
MHRA Drug Safety Update
Bisphosphonates: Osteonecrosis of the jaw
Article date: November 2009
Summary
The risk of osteonecrosis of the jaw is greater for patients receiving intravenous bisphosphonates
for cancer than for patients receiving oral bisphosphonates for osteoporosis or Paget’s disease.
All patients with cancer should have a dental check-up before bisphosphonate treatment. During
treatment, patients should be encouraged to: maintain good oral hygiene; receive routine dental
check-ups; and report any oral symptoms such as dental mobility, pain, or swelling.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087832
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Drug Formulary
Page 22 of 23
Date: 22.8.2013
6.7 Other endocrine drugs
Bromocriptine and other dopamine receptor stimulants

Quinagolide 75microgram tablet and Starter Pack

Cabergoline 500microgram tablets
Dose
- see BNF
Prescribing notes

Cabergoline is on the formulary for treatment of hyperprolactinaemic disorders.

For suppression of lactation, see chapter 7

For Parkinson's disease, see Chapter 4
Drugs affecting gonadotrophins

Danazol 100mg capsules

Buserelin 1mg/ml injection

Goserelin 3.6mg implant injection

Leuprorelin 3.75mg injection

Nafarelin 200 microgram/dose nasal spray

Cetrorelix 250microgram injection
Dose
- see BNF
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Drug Formulary
Page 23 of 23
Date: 22.8.2013