Download Chapter 6 - Diabetes and Endocrinology

CHAPTER 6
First line drugs – drugs
recommended in both
primary and secondary
care
Second line drugs –
alternatives (often in
specific conditions) in both
primary and secondary
care
ENDOCRINE SYSTEM
Specialist drugs – Drugs
where specialist input is
needed (see introduction for
definition)
Specialist only drugs –
prescribing within specialist
service only
Page:
6.1
Drugs used in diabetes
2
6.2
Thyroid and antithyroid drugs
10
6.3
Corticosteroids
10
6.4
Sex hormones
11
6.5
Hypothalamic and pituitary hormones and anti-oestrogens
15
6.6
Drugs affecting bone metabolism
18
6.7
Other endocrine drugs
22
Date
01/13
02/13
03/13
06/13
10/13
02/14
04/14
09/14
05/15
07/15
09/15
11/15
01/16
08/16
09/16
02/17
03/17
Revision
6.6.2 (MHRA safety update)
6.6.2 (MHRA safety update)
6.6.2 (NICE guidance)
6.3 (Minor amendment)
6.1.2 (NICE guidance)
6.1.1 (Drug addition), 6.1.2 (Drug addition)
6.4.1 (Drug addition)
6.1.2 (NICE guidance)
6.1.2 (Formulation addition)
6.1.2 (NICE guidance), (Drug deletion)
6.1 (NICE guidance)
6.4 ( NICE guidance)
6.1 (Formulation addition) 6.5.2 (NICE guidance)
6.6 (section review)
6.1 (NICE guidance); 6.4 (NICE guidance)
6.2 (Formulation addition)
6.1 (NICE guidance), MHRA safety update
First line drugs
Second line drugs
Contributors
A Luck
A Luck
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 1 of 22
Specialist only drugs
6.1 Drugs used in diabetes
6.1.1 Insulins
Measurement of HbA1c
The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommends the measurement
of HbA1c values in mmol per mol of unglycosylated haemoglobin. The table below shows the relationship between
IFCC values and percentages used previously.
Equivalent values
IFCC-HbA1c (mmol/mol)
DCCT-HbA1c (%)
42
6.0
48
6.5
53
7.0
59
7.5
64
8.0
75
9.0
Source – British National Formulary No.68 September 2014.
6.1 Drugs used in diabetes
6.1.1 Insulins
To avoid confusion, it is advisable to prescribe insulin by brand name.
Notes:
1)
For a full list of formulary insulin preparations please refer to the ‘Joint Formulary Summary of Insulins’
(separate page). This chart also indicates formulary inclusion and suitable pens.
2)
Initiation of insulin should only be undertaken by those teams or individuals with specialist training in
diabetes, gained through an accredited course, which includes practitioners in primary care. All insulins in the
formulary are amber to reflect this.
3) NG17 (Sept 2015) Type 1 diabetes in adults: diagnosis and management recommends multiple daily injection
basal–bolus insulin regimens as the insulin injection regimen of choice for all adults with type 1 diabetes.
a) Non-basal bolus insulin regimens (that is, twice‑ daily mixed, basal only or bolus only) are not recommended in
newly diagnosed type 1 diabetes.
b) Long-acting insulin: Offer twice daily insulin detemir as basal insulin therapy for adults with type 1 diabetes.
Consider, as an alternative basal insulin therapy for adults with type 1 diabetes:
 an existing insulin regimen being used by the person that is achieving their agreed targets
 once-daily insulin glargine or insulin detemir if twice daily basal insulin injection is not acceptable
 once daily insulin glargine if insulin detemir is not tolerated.
c) Rapid-acting insulin: Offer rapid-acting insulin analogues injected before meals, rather than rapid-acting soluble
human or animal insulins, for mealtime insulin replacement for adults with type 1 diabetes.
Do not routinely use rapid-acting insulin analogues after meals.
d) Mixed insulin: Consider a twice-daily human mixed insulin regimen if a multiple daily injection basal–bolus insulin
regimen is not possible.
Consider a trial of a twice-daily analogue mixed insulin regimen if a twice-daily human mixed insulin regimen
causes hypoglycaemia that affects quality of life.
The NPSA Rapid Response Report on Safer Administration of Insulins was issued in June 2010. Within this, the
following recommendations relating to prescribing and administration have been made:

All regular and single insulin (bolus) doses should be measured and administered using an insulin syringe or
commercial insulin pen device. Intravenous syringes must never be used for insulin administration.

The term ‘units’ is used in all contexts. Abbreviations, such as ‘U’ or ‘IU’, are never used.

An insulin syringe must always be used to measure and prepare insulin for an intravenous infusion. Insulin infusions
are administered in 50ml intravenous syringes or larger infusion bags. Consideration should be given to the supply
and use of ready to administer infusion products e.g. prefilled syringes of fast acting insulin 50 units in 50ml sodium
chloride 0.9%.
6.1.1.1 Short-acting insulins
Soluble Insulin
Insulin Aspart
Insulin Lispro
First line drugs




Actrapid®
Humulin S®
Insuman® Rapid
NovoRapid®

Humalog®
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 2 of 22
Specialist only drugs

Insulin Glulisine
Apidra®
6.1.1.2 Intermediate and long-acting insulins
 Insulatard®
Isophane insulin




Insulin Glargine
Insulin Detemir
Humulin I®
Insuman® Basal
Lantus®
Levemir®
NICE guidance for the management of Type 2 diabetes recommends that, if insulin is required in patients with
Type 2 diabetes, insulin detemir or insulin glargine may be considered for those:
 who require assistance with injecting their insulin or
 whose lifestyle is significantly restricted by recurrent symptomatic hypoglycaemic episodes or
 who would otherwise need twice-daily basal insulin injections in combination with oral antidiabetic drugs or
 who cannot use the device needed to inject isophane insulin
Neither glargine or detemir are licensed in pregnancy.
Note:
In practice, the long acting insulin analogues insulin glargine and insulin detemir are usually used in conjunction with
rapid acting insulins.
1.
Biphasic insulins
Biphasic isophane insulin
Biphasic insulin aspart
Biphasic insulin lispro





Humulin® M3
Insuman® Comb 15, 25, 50
NovoMix® 30
Humalog® MIX 25
Humalog® MIX 50
Note:
For patients with visual impairment, Innolet® prefilled disposable injection devices may be useful. Available with
Insulatard® and Levemir®.
6.1.1.3 Hypodermic equipment
Note:
A range of hypodermic equipment (injecting devices) is available on FP10. For up to date prescribing advice on
lancets and other injection devices please refer to the latest Drug Tariff. MIMS also provides a helpful table.
AutoPen® Classic
AutoPen® 24
For use with Lilly 3ml cartridges
ClikSTAR®
For use with Apidra® , Insuman® and Lantus® 3 ml cartridges
HumaPen® Luxura
For use with Humulin® and Humalog® 3-ml cartridges
Novopen® 4 +
Novopen® 3 Demi
BD Micro-fine+® needles
For use with Novonordisk® 3ml cartridges
Novofine® needles
For use with Sanofi-Aventis 3ml cartridges

8mm, 31G

5mm, 31G
8mm, 30G
6mm, 31G


Notes:
1.
6mm / 8mm needles are recommended for most patients. For children and some thin adults 5mm
needles are more suitable. If 12.7mm needles are thought necessary, please refer the patient to the
diabetic specialist team.
BD Microfine +® range is suitable for use with all pens.
First line drugs
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 3 of 22
Specialist only drugs
Joint Formulary Summary of insulins
Refs: BNF
A summary of those products included in the Joint Formulary for insulin therapy.
PRODUCT
10ml
Vial
Preparation
3ml
Pre-loaded
Cartridge
pen
NovoPen
®
Pen Compatability
HumaPen® Autopen® Autopen®
Luxura
Classic
24
ClikSTAR®
NOTES
SHORT-ACTING INSULINS
Actrapid®
Humulin S®
Insuman®
Rapid
NovoRapid®
(Aspart)


 and
1.6ml
PumpCart

Humalog®
(Lispro)



Apidra®















(Glulisine)
Human Soluble
insulins onset
of action is
about 30
minutes,
duration up to 8
hours.
Rapid acting
insulin
analogues,
ASPART
LISPRO and
GLULISINE,
onset about 20
minutes,
duration about
4 hours. May
be given at the
start of a meal.
INTERMEDIATE AND LONG-ACTING INSULINS
Insulatard®
ge
Humulin I®
Insuman®
Basal
Lantus®
(Glargine)
Levemir®
(Detemir)








(5ml)














Isophanes are
the most
reliable
intermediate
acting insulins,
onset of 1-2
hours, duration
of around 12-15
hours.
Long-acting
insulin
analogues may
reduce
nocturnal
hypoglycaemia.
Duration of
action up to 20
hours.
BIPHASIC INSULINS
Humulin®
M3
Insuman®
Comb 15
Insuman®
Comb 25
Insuman®
Comb 50
Novomix®
30
Humalog®
MIX 25
Humalog®
MIX 50
1





 (5ml)




















Biphasic
insulins have
activity that
reflects the
component
insulins. In
general their
onset is approx.
30 minutes with
duration of 1215 hours.
These insulins
are only
appropriate for
people with a
regular lifestyle
and diet
prefilled disposable injection device
First line drugs
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 4 of 22
Specialist only drugs
Antidiabetic Drugs
6.1.2 Oral Blood Glucose Lowering Therapy
Target HbA1c - See NG 28 (December 2015) Type 2 diabetes in adults: management for guidance on
appropriate levels.
6.1.2.1 Sulphonylureas
 Tablets 80mg
Gliclazide
 Tablets 5mg
Glipizide
 Tablets 1mg, 2mg, 3mg, 4mg
Glimepiride
Notes:
1. The UKPDS showed a significant reduction in diabetes complications in type 2 diabetic patients through tight
blood pressure control (regardless of the drug used).The lowering of blood pressure is a very high priority which
may require polypharmacy. It is appropriate to aim for HbA1c within normal range if this can be achieved without
hypoglycaemia.
2. Oral glucose lowering therapy should be considered if HbA1c does not improve after agreed trial of lifestyle
modification.
3. Sulphonylureas should be taken shortly before or with food.
4. Sulphonylureas may promote weight gain. They should be avoided in pregnancy.
5. Gliclazide is the preferred choice in those patients with renal deficiency as it is shorter acting and is principally
inactivated in the liver.
6. Glibenclamide has not been included in the formulary due to its long duration of action and increased incidence
for causing hypoglycaemia. It is recommended that this should be discontinued or alternative substituted.
6.1.2.2 Biguanides
 Tablets 500mg, 850mg
Metformin
Metformin SR

Tablets 500mg SR, 750mg SR, 1000mg SR
Where GI complications with
immediate release product.
Notes:
1. Metformin is recommended as first line therapy in all patients with Type 2 Diabetes.
2. Metformin is contraindicated in those with renal impairment (egfr < 30 ml / minute) or those at risk of sudden
deterioration of renal impairment, liver impairment and those with severe Congestive Cardiac Failure (NYHA
class 4). Exercise caution in patients with egfr < 45 ml / minute (NICE Guidance).
3. For most patients the optimum dose will be 1g twice daily – build up to this dose over 1 month.
4. NB. Metformin oral solution is much more expensive than oral powder.
6.1.2.3 Other Antidiabetic Drugs
Thiazolidinediones
 Tablets 15mg, 30mg
Pioglitazone
Pioglitazone should not be used for patients with cardiac failure or a history of cardiac failure.
MHRA drug safety update. Discontinuation of Rosiglitazone - Octoberr 2010
 A Europe-wide review of the risks and benefits of medicines containing rosiglitazone has concluded that the
benefits of treatment no longer outweigh the risks.
 The conclusion of the Europe-wide review is consistent with advice that the Medicines and Healthcare products
Regulatory Agency (MHRA) has received from the Commission on Human Medicines saying that the scientific
evidence shows that rosiglitazone is associated with an increased risk of cardiovascular disorders.
 The research has not identified any particular groups of patients for whom the benefits of rosiglitazone outweigh the risks.
As such, rosiglitazone will cease to be available in Europe.
MHRA drug safety update. Increased risk of bladder cancer with Pioglitazone - August 2011
Use of pioglitazone is associated with a small increased risk of bladder cancer.
 Patients with active bladder cancer or with a history of bladder cancer, and those with uninvestigated
haematuria, should not receive pioglitazone
 Prescribers should review the safety and efficacy of pioglitazone in individuals after 3–6 months of treatment to
ensure that only patients who are deriving benefit continue to be treated. Pioglitazone should be stopped in
patients who do not respond adequately to treatment (eg, reduction in glycosylated haemoglobin, HbA1c)
 Before starting pioglitazone, the following known risk factors for development of bladder cancer should be
assessed in individuals: age; current or past history of smoking; exposure to some occupational or
chemotherapy agents such as cyclophosphamide; or previous irradiation of the pelvic region
 Use in elderly patients should be considered carefully before and during treatment because the risk of bladder
First line drugs
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 5 of 22
Specialist only drugs
cancer increases with age. Elderly patients should start on the lowest possible dose and be regularly monitored
because of the risks of bladder cancer and heart failure associated with pioglitazone
Analysis of clinical trial data has identified an increased risk of fracture (mainly in the foot and upper limb) in women
given glitazones; recent data showed a possible risk in men with pioglitazone. The risk of fracture should be
considered in the care of patients, especially women, treated with glitazones.
Pioglitazone should be used in type 2 diabetes:
 as monotherapy ONLY in those unable to take metformin or a sulphonylurea because of intolerance/
contraindication; or
 added to either metformin or a sulphonylurea ONLY in those unable to take metformin + sulphonylurea in
combination because of intolerance/ contraindication or risk of hypoglycaemia with sulphonylurea.
Liver function tests should be monitored before therapy and periodically.
Pioglitazone is licensed for use in combination with insulin.
Pioglitazone should be prescribed generically as pioglitazone tablets (not as the proprietary brand Actos®)
for all indications (East Sussex MPC Position Statement May 2012).
Rapid Acting Insulin Secretagogues
Nateglinide

Tablets 60mg, 120mg, 180mg
Repaglinide

Tablets 500 microgram, 1mg, 2mg
Notes:
Nateglinide is licensed for type 2 diabetes ONLY in combination with metformin.
NICE guidance suggests a role for these agents when patients have a chaotic lifestyle.
Incretin mimetic (GLP-1 analogues)
Exenatide▼
 Byetta® Injection 250micrograms/ml

Bydureon® 2mg powder
Liraglutide▼

Injection 6mg/ml
Lixisenatide▼

Available as pre-filled pen 5 microgram/dose
or 10 microgram/dose
Available as vial + diluent for injection or prefilled pen
Available as pre-filled pen containing 18mg in
3ml. Dose range 0.6mg to 1.2mg once daily
subcutaneously.
Lymuxia® Injection 10micrograms /
dose, 20micrograms/ dose prefilled
syringe
GLP-1 analogues exenatide and liraglutide are licensed for the treatment of type 2 diabetes. They have the potential
advantage of sustained weight loss when compared with standard therapies including insulin. Weight loss seems
proportional to the weight of the patient such that the heaviest people seem to lose most.
Common side effects include nausea which improves with time and is dose related. There has been a small excess
of nonfatal pancreatitis with exenatide.
They are licensed for use with either sulphonyureas or metformin, or both. There is an increase risk of
hypoglycaemia when used with a sulphonylurea.
Patients should be advised to contact the DVLA on starting GLP-1 analogues if they hold a Group 2 licence and an
individual decision will be taken on whether they can retain licence. All those commenced on insulin must surrender
Group 2 entitlement.
Exenatide twice daily subcutaneous GLP-1 analogue is approved by NICE for use within a triple therapy regime
only. Liraglutide once daily subcutaneous GLP-1 analogue and Exenatide weekly injection are approved for use
by NICE in dual and triple therapy regimes.
Patients are eligible for treatment provided they meet the following criteria:
 Blood glucose control remains or becomes inadequate (HbA1C ≥ 7.5%)
AND
 A body mass index (BMI) ≥35kg/m 2 in those of European family origin (with appropriate adjustment for other
ethnic groups) and specific medical/ psychological problems associated with high body weight
OR
 A BMI < 35kg/m2 and insulin therapy would have significant occupational implications or weight loss would
benefit other significant obesity related co-morbidities.
In addition to this, in dual therapy regimes Liraglutide once daily and exenatide once weekly should only be use if
the patient is:
 Intolerant of / has contraindications to either metformin or a sulphonylurea
AND
 Intolerant of /has contraindications to glitazones (thiazolidinediones) and gliptins (DPP-4 inhibitors)
.
First line drugs
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 6 of 22
Specialist only drugs
NG 28 (December 2015) Type 2 diabetes in adults: management recommends that treatment with exenatide
and liraglutide are continued only if HbA1c concentration is reduced by at least 1% and a weight loss of at
least 3% is achieved within 6 months of starting treatment.
Both exenatide and liraglutide require specialist initiation but prescribing may be continued in primary care under
shared care arrangements.
Lixisenatide is currently cheaper than the other GLP-1 agonists but it has not been subject to NICE review. It

has a once daily dosage

may not be as effective at reducing HbA1c levels as exenatide

appears to be weight neutral unlike exenatide which promotes weight loss

Has a lower incidence of side effects than exenatide.
It may be used as an alternative to exenatide and liraglutide only in accordance with NG 28 (December 2015) Type
2 diabetes in adults: management
Dipeptidylpeptidase-4 (DPP-4) inhibitors
Linagliptin▼
Sitagliptin▼


Tablets 5mg
Tablets 100mg
Note:
All DPP-4 inhibitors should be used in accordance with NG 28 (Dec 2015) Type 2 diabetes in adults:
management
When glycaemic control is inadequate with existing treatment sitagliptin (DPP-4 inhibitor) can be added to
metformin or a sulphonylurea or both if insulin is unacceptable.
Treatment should only be continued if HbA1c is reduced by at least 0.5% within 6 months of starting treatment.
Evidence suggests all DPP-4 inhibitors demonstrate similar efficacy and tolerability and the choice of DPP-4
inhibitors on the formulary gives the broadest coverage for all indications.
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. See MHRA Safety Update September 2012
Canagliflozin▼
Dapagliflozin▼
Empagliflozin▼

Tablets 100mg, 300mg

Tablets 5mg,10mg

Tablets 10mg, 25mg
NICE TA288 (November 2016) recommends that dapagliflozin is used in combination with metformin to treat type 2
diabetes in accordance with NICE CG87 (May 2009)
NICE TA 315 (June 2014) recommends canagliflozin to treat type 2 diabetes in combination with metformin only if a
sulphonylurea is contraindicated or not tolerated or the person is at significant risk of hypoglycaemia or its
consequences.
Canagliflozin can also be used in a triple therapy regimen in combination with metformin and a sulfonylurea or
metformin and a thiazolidinedione or in combination with insulin in the management of type 2 diabetes.
NICE TA 336 (March 2015) recommends empagliflozin to treat type 2 diabetes in combination with metformin only
if a sulphonylurea is contraindicated or not tolerated or the person is at significant risk of hypoglycaemia or its
consequences.
Empagliflozin can also be used in a triple therapy regimen in combination with metformin and a sulfonylurea or
metformin and a thiazolidinedione or in combination with insulin in the management of type 2 diabetes.
NICE TA 390 (May 2016) recommends Canagliflozin, dapagliflozin and empagliflozin as monotherapies for treating
type 2 diabetes in adults for whom metformin is contraindicated or not tolerated and when diet and exercise alone
do not provide adequate glycaemic control, only if:
 a dipeptidyl peptidase‑ 4 (DPP‑ 4) inhibitor would otherwise be prescribed
and
 a sulfonylurea or pioglitazone is not appropriate
NICE TA 418 (November 2016) recommends dapagliflozin in a triple therapy regimen as an option for treating type
2 diabetes in adults, only in combination with metformin and a sulfonylurea.
An MHRA safety update (March 2017) warns of an increased risk of lower-limb amputation (mainly toes) in
patients with type 2 diabetes taking cangliflozin. Evidence does not show an increased risk for dapagliflozin and
empagliflozin, but the risk may be a class effect
First line drugs
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 7 of 22
Specialist only drugs
Related Guidelines
NG 28 (December 2015) Type 2 diabetes in adults: management
NG18 (Aug 2015): Diabetes (type 1 and type 2) in children and young people: diagnosis and management
NG19 (Aug 2015): Diabetic foot problems: prevention and management
6.1.3 Diabetic ketoacidosis
Insulin infusion combined with fluid/electrolyte replacement – hospital policy on
intranet
6.1.4 Treatment of hypoglycaemia
 Injection 1mg vial with pre-filled syringe containing water for injection
GlucoGen® Hypokit
 Glucose oral ampoule 9.2g / 23g
GlucoGel®
 Intravenous infusion 20%
Glucose
Self Treatment of Hypoglycaemia (Low blood sugar/glucose)
For the self treatment of hypoglycaemia, use the 10 rule. If the blood glucose is under 4mmol/l, patients should be
advised to:
 Take 10g quick acting carbohydrate (see below).
 Wait for 10 minutes and then test again, after washing hands
 If the blood glucose is still under 4mmol/l, take a further 10g carbohydrate
 Wait for 10 minutes and test again
Please note that the following foods are listed according to how quickly they raise the blood glucose level.
Dextrose tablets are the quickest acting and Coca Cola the slowest.
1. Quick acting carbohydrate - amount that contains 10g carbohydrate (approximate figures):
 Dextrose / glucose tablets 3 to 4 tablets
 Lucozade (original) 60mls (1/6th of 380ml bottle)
 Lucozade (sport) 155ml (1/3rd of 500ml bottle)
 Maynards Wine Gums 3 sweets
 Bassetts Jelly Babies 2 sweets
 Bassetts Liquorice Allsorts 2 to 3 sweets
 Jelly beans 8 to 10 sweets
 Fanta 75 ml (1/4 of 330ml can)
 Ribena 72ml (1/4 of 288ml carton)
 Coca Cola (not diet) 90 ml (1/4 of 330ml can)
2. Slow release carbohydrate
There is a danger that blood glucose levels could drop again so it is important to advise patients to eat some slow
release carbohydrate containing food. If it is time for a meal then patients should have a meal, otherwise they
should have a sandwich, biscuits, a bowl of cereal or a piece of fruit.
Remember - something SWEET then something STARCHY
For further information about treating low blood glucose levels, contact the diabetes care nurse, dietitian or doctor.
6.1.6 Diagnostic and monitoring agents for diabetes mellitus
Patients should only self monitor blood glucose if results are to be acted upon. CBGSM should be offered to newly
diagnosed patients as part of an education programme.
NG17 (Sept 2015) Type 1 diabetes in adults: diagnosis and management says:
1. Glycosylated haemoglobin (HbA1c) levels should be measured every 3–6 months in adults with type 1 diabetes.
2. Consider measuring HbA1c levels more often in adults with type 1 diabetes if the person's blood glucose control
is suspected to be changing rapidly; for example, if the HbA1c level has risen unexpectedly above a previously
sustained target.
3. Aim for a target HbA1c level of 48 mmol/mol (6.5%) or lower, to minimise the risk of long‑ term vascular
complications.
4. Agree individualised HbA1c targets in type 1 diabetes, taking into account factors such as daily activities,
aspirations, likelihood of complications, comorbidities, occupation and history of hypoglycaemia.
5. Diabetes services should document the proportion of adults with type 1diabetes in a service who achieve an
HbA1c level of 53 mmol/mol (7%) or lower.
Guidelines on capillary blood glucose self-monitoring (CBGSM)
CBGSM is an integral part of self-management of diabetes in most patients. It is, however, a painful procedure for
the patient and costly to the NHS. It is therefore very important to ensure this method of glucose monitoring is only
First line drugs
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 8 of 22
Specialist only drugs
recommended to patients if it will help them, or their carers, to manage their diabetes better, psychosocially or
biochemically.
Unilet® ComforTouch lancets are suitable for use with all finger pricking devices except the Softclix® range.
When might CBGSM be considered?
Insulin treated patients: Advise routine self-monitoring of blood glucose levels for all adults with type 1 diabetes, and
recommend testing at least 4 times a day, including before each meal and before bed.
Test at least 4 times a day, and up to 10 times a day if any of the following apply:
 the desired target for blood glucose control, measured by HbA1c level (see recommendation 1.6.6), is not
achieved
 the frequency of hypoglycaemic episodes increases
 there is a legal requirement to do so (such as before driving, in line with the Driver and Vehicle Licensing
Agency [DVLA] (At a glance guide to the current medical standards of fitness to drive)
 during periods of illness
 before, during and after sport
 when planning pregnancy, during pregnancy and while breastfeeding (see the NICE guideline on diabetes
in pregnancy)
 if there is a need to know blood glucose levels more than 4 times a day for other reasons (for example,
impaired awareness of hypoglycaemia, high-risk activities).
Additional blood glucose testing (more than 10 times a day) should be considered for adults with type 1 diabetes if
this is necessary because of the person's lifestyle (for example, driving for a long period of time, undertaking
high-risk activity or occupation, travel) or if the person has impaired awareness of hypoglycaemia.
Blood glucose targets
Advise adults with type 1 diabetes to aim for:
 a fasting plasma glucose level of 5–7 mmol/litre on waking and
 a plasma glucose level of 4–7 mmol/litre before meals at other times of the day.
Adults with type 1 diabetes who choose to test after meals should aim for a plasma glucose level of 5–9 mmol/litre
at least 90 minutes after eating. (This timing may be different in pregnancy – for guidance on plasma glucose
targets in pregnancy, see the NICE guideline on diabetes in pregnancy) .
Agree bedtime target plasma glucose levels that take into account timing of the last meal and its related insulin
dose, and are consistent with the recommended fasting level on waking.
Non-insulin treated patients:
 When the procedure may be a potential tool for life style modification
 Patients on maximum dose of oral hypoglycaemic drugs and approaching insulin conversion
 Patients with symptomatic hyperglycaemia or a history of hypoglycaemia
 Patients new to sulphonylureas or insulin secretagogues where tight glycaemic control is aimed for
 Patients who drive and are taking insulin secretagogues or sulphonylureas who may therefore experience
hypoglycaemia
 Patients choosing this method of monitoring following appropriate discussion with a diabetes specialist
healthcare professional.
 During illness.
Which method?
There are numerous meters available on the market all with comparable accuracy. They all have different features,
which may suit different patients. The following points must be observed.
 Ensure the patient is taught the correct use of the meter, including quality control tests
 Set glycaemic targets agreed with the patient
 Ensure the patient is made aware of how to interpret and act upon the results of the tests
Urine testing
Urine testing is no longer considered to be accurate enough for managing diabetes and is not appropriate for most
patients.
Home capillary blood glucose monitoring is not a substitute for laboratory testing eg: not to be used for diagnosis.
For testing in type 2 diabetes see NG 28 (December 2015) Type 2 diabetes in adults: management
Urinalysis
Ketostix®

1x 50 strips
It is important to measure urinary ketones if blood glucose levels >15mmol/litre and the patient is at risk of
ketoacidosis
First line drugs
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 9 of 22
Specialist only drugs
6.2 Thyroid and antithyroid drugs
6.2.1 Thyroid hormones
 Tablets 25 micrograms, 50 micrograms, 75 micrograms, 100 micrograms
Levothyroxine
 Injection 20 micrograms
Liothyronine
 Tablets 20 micrograms
Note:
Liothyronine may be suitable for a small number of patients who are unable to tolerate thyroxine. It may also be
useful for replacement for patients undergoing a blocking-replacement regimen.
6.2.2. Anti-thyroid drugs
 Tablets 5mg, 20mg
Carbimazole
 Tablets 50mg
Propylthiouracil
1. CSM warning: Neutropenia and agranulocytosis
Doctors are reminded of the importance of recognising bone marrow suppression induced by carbimazole and
the need to stop treatment promptly.
 Patients should 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.
 Carbimazole should be stopped promptly if there is clinical or laboratory evidence of neutropenia.
2. Propylthiouracil is used where there is a known sensitivity to carbimazole or in pregnancy. (Both propyluracil
and carbimazole cross the placenta and in high doses may cause foetal goitre and hypothyroidism. The lowest
dose to control the disease should be used)
Example of information which may be useful for patients:
Patient information leaflet for carbimazole / propylthiouracil tablets
You are about to start taking carbimazole/ propylthiouracil tablets
Carbimazole / Propylthiouracil is a drug used to control an overactive thyroid gland. It has been used for many years in thousands of
patients. It is unlikely that you will have any side effects from this drug.
However
Rarely the drug can cause
 rashes
 pain in the joints
 jaundice (a yellow discolouration of the skin)
 a blood condition resulting in reduced resistance to infection
You should see your family doctor if you develop any of these problems.
The effect of the drug on the blood is the most serious

You should see you doctor immediately if you develop fever, sore throat, mouth ulcers or excessive tiredness (this may mean
calling the on-call service at night or weekends)

If you develop these symptoms you will need to have a blood test without delay. You should not take any more carbimazole/
propylthiouracil until advised by your doctor

If you cannot see your GP immediately, you should go to the local hospital accident and emergency department for a blood test
6.3 Corticosteroids
6.3.1 Replacement therapy (mineralocorticoid)
Fludrocortisone

Tablets 100 micrograms
Fludrocortisone may be given as a mineralocorticoid in combination with hydrocortisone in adrenocortical
insufficiency.
6.3.2 Glucocorticoid therapy
Notes:
1. Following concern about severe chickenpox associated with systemic corticosteroids, the CSM has issued
notice that every patient prescribed a systemic corticosteroid should receive the patient information leaflet
supplied by the manufacturer.
2. Steroid treatment cards should also be issued where appropriate.
First line drugs
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 10 of 22
Specialist only drugs
Prednisolone
Hydrocortisone
Dexamethasone
Methyl-prednisolone





Tablets 1mg, 5mg, 25mg
EC tablets 2.5mg, 5mg
Soluble tablets 5mg
Tablets 10mg, 20mg
Injection (as sodium succinate) 100mg





Tablets 500 microgram, 2mg
Dexamethasone sodium phosphate injection 3.3mg in 1ml
Oral solution 2mg/5ml
Injection (as sodium succinate) 125mg, 500mg, 1g, 2g.
Injection (as acetate) 40mg in 1ml, 80mg in 2ml (intramuscular depot)
Notes:
1. Equivalent doses of glucocorticoid activity:
5mg Prednisolone = Dexamethasone 750 micrograms
Hydrocortisone 20mg
Methylprednisolone 4mg
2. Different preparations of dexamethasone contain different salts. Therefore, care is needed to ensure that
patients receive equivalent doses when transferring from tablets to injections. The equivalent doses are
1mg dexamethasone (tablets)
1.2mg dexamethasone phosphate (injections)
1.3mg dexamethasone sodium phosphate (injections and oral solutions)
3. Patients receiving long-term oral corticosteroids should be assessed for risk of long-term side effects e.g.
osteoporosis or steroid cataract.
4. Prednisolone is the standard glucocorticoid steroid. The link with peptic ulceration and standard formulation
of prednisolone is weak and therefore E/C and soluble tablets offer no additional benefit.
5. Soluble tablets are included for the treatment of acute asthma in children.
6. Hydrocortisone is included as a first line drug for adrenocortical insufficiency and hypersensitivity reactions
only. If adrenocortical insufficiency is diagnosed the usual maintenance dose is 10mg in the morning,
5mg at midday and 5mg in the early evening. A daily profile of cortisol levels should be performed to check
the adequacy of replacement.
7. Dexamethasone has very high glucocorticoid activity and low mineralocorticoid activity therefore is suited to
treat those conditions where additional fluid retention or oedema may be a problem e.g. cerebral oedema.
The 100-microgram dose has been included for the management of patients with congenital hyperplasia.
8. Methylprednisolone is used intravenously for specific conditions requiring high dose, short-term treatment.
9. The DTB (March 99) has concluded that until there is clear evidence of the advantages of triamcinolone depot
injections (e.g. Kenolog®) over other hay fever treatments, including oral prednisolone, its use is no longer
acceptable.
6.4 Sex hormones
6.4.1 Female sex hormones
6.4.1.1 Oestrogens for HRT
The benefits and risks of Hormone Replacement Therapy:
Prescribing HRT requires careful analysis of the risks and benefits, and should be individualised.
preference must play an essential part in the decision to commence or continue HRT.
Patient
The decision to use HRT should be discussed with each woman on an individual basis, taking into consideration
her history, risk factors and personal preferences.
An individual’s risks and benefits should be regularly appraised (e.g. at least yearly) with continued HRT use.
Further information about the long-term risks and benefits of HRT can be found in NICE guidelines
NG23: Menopause: diagnosis and management (Nov 2015)
1.
2.
3.
4.
5.
Oral preparations, which are cheaper and widely used, tend to be first line therapy (DTB – November 96).
Patches should only be given if there is a need to bypass liver metabolism and patient preference.
Do not offer patches routinely. Only prescribe for patient preference or if compliance is poor.
Where patches are included in the formulary their strengths are expressed as dose delivered per 24 hours.
Prior to prescribing, patients may wish to know that conjugated oestrogens (Premarin®, Prempak-C® and
Premique®) are derived from urine of farmed horses.
First line drugs
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 11 of 22
Specialist only drugs
Sequential
combined
therapy
Elleste Duet®

Tablets estradiol (1mg, 2mg) with norethisterone acetate (1mg)
Femoston®

Tablets estradiol with dydrogesterone 1/10 and 2/10
Nuvelle®

Tablets estradiol valerate (2mg) with levonorgestrel (75micrograms)
Prempak-C®

Evorel Sequi®

Tablets conjugated estrogens (625micrograms, 1.25mg) with norgestrel
(150micrograms)
Patches estradiol (50micrograms) and norethisterone acetate (170micrograms)
Continuous
combined
therapy
Kliovance®
Climese®
Kliofem®
Premique®
Evorel Conti®
Unopposed
oestrogen
Elleste solo®
Premarin®
Women with uterus
Women with uterus

Tablets estradiol (1mg) and norethisterone (500microgram)

Tablets estradiol (2mg) and norethisterone (0.7mg)

Tablets estradiol (2mg) and norethisterone (1mg)

Tablets conj. estrogens (625micrograms) and medroxyprogesterone acetate (5mg)

Patches estradiol (50micrograms) and norethisterone (170micrograms)
Women without uterus

Tablets estradiol (1mg, 2mg)

Tablets conj. estrogens (625micrograms, 1.25mg)
Elleste Solo®
MX
Evorel®

Patches estradiol (40micrograms, 80micrograms)

Estradiol
Implant

Patches estradiol (25micrograms, 50micrograms, 75micrograms,
100micrograms)
25mg, 50mg, 100mg
Notes:
1. Elleste Solo® is included as the cheapest brand. The 1mg preparation is licensed for menopausal symptoms
only; the 2mg preparation is licensed for both menopausal symptoms and osteoporosis prophylaxis.
2. Elleste Solo® MX 40micrograms patch is currently unlicensed for osteoporosis prophylaxis unlike the
80micrograms patch. The Evorel® range is included as an alternative.
Others:
Raloxifene
Tibolone
Ethinylestradiol

Tablets 60mg

Tablets 2.5mg

Tablets 10 micrograms, 50 micrograms, 1mg
Notes:
1. Ethinylestradiol is included for the specialist treatment of hereditary haemorrhagic telangiectasia.
2. Estradiol levels are rarely indicated. If it is thought necessary to perform such tests, please seek advice from
the biochemistry laboratory or a specialist as to which test to use.
3. Raloxifene is licensed for the treatment and prevention of postmenopausal osteoporosis. Does not reduce
menopausal vasomotor symptoms
6.4.1.2 Progestogens
Dydrogesterone
Medroxyprogesterone
acetate
First line drugs

Tablets 10mg

Tablets 5mg, 10mg
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 12 of 22
Specialist only drugs
Norethisterone
Progesterone
Ulipristal acetate▼

Tablets 1mg, 5mg



Pessaries 200mg, 400mg
Injection 50mg in 1ml, 100mg in 2ml
Esmya® tablets 5mg
Notes:
1. The norethisterone 5mg preparation is not licensed for HRT.
2. The Royal College of Obstetricians and Gynaecologists clinical audit unit (Feb 1999) has stated, “exogenous
progesterone should not be used in the treatment of recurrent miscarriage as it does not improve outcome”.
3. Ulipristal acetate can be used as an alternative to GnRH analogues for up to 3 months pre-operatively to treat
moderate to severe symptoms of uterine fibroids.
4. Related NICE guidance
NICE CG 44: Heavy menstrual bleeding: assessment and management (rev Aug 16)
Summary of those products included in the Formulary for Hormone Replacement Therapy (HRT).
Less androgenic progestogens
Androgenic progestogens



Use if androgenic problems e.g. skin problems: greasy / acne


Norethisterone
Levonorgestrel
Dydrogesterone
Medroxyprogesterone
Norgestrel
Brand(s)
Estrogen
Progestogen
No. of Rx Charges
Sequential combined therapy ~ Monthly Bleed
Tablets
Elleste Duet®
Estradiol (1mg, 2mg)
Norethisterone (1mg)
2
Prempak-C®
Conj. Estrogen (0.625mg, 1.25mg)
Norgestrel (150microgram)
2
Nuvelle®
Estradiol (2mg)
Levonogestrel (75micrograms)
2
Less androgenic / titration:
Femoston® 1/10
Estradiol (1mg, 2mg)
Femoston 2/10®
Estradiol (2mg)
Dydrogesterone (10mg)
2
Dydrogesterone (10mg)
2
Patches:
Estradiol (50micrograms)
Evorel Sequi®
Norethisterone (170micrograms)
2
Continuous combined therapy ~ No bleed
Tablets
Kliovance®
Estradiol (1mg)
Norethisterone (0.5mg)
1
Kliofem®
Estradiol (2mg)
Norethisterone (1mg)
1
Climesse®
Estradiol (2mg)
Norethisterone (0.7mg)
1
Premique®
Conj. Estrogen (0.625mg)
Less androgenic:
Medroxyprogesterone (5mg)
1
Patches:
Estradiol (50micrograms)
Evorel Conti®
Norethisterone (170micrograms)
1
Unopposed estrogen (if uterus is intact an adjunctive progestogen must be used)
Tablets
Elleste solo®
Estradiol (1mg, 2mg)
1
Premarin®
Conj. Estrogen (0.625mg, 1.25mg)
1
Patches:
Elleste Solo® MX
Estradiol (40, 80 microgram,)
1
Evorel®
Estradiol (25, 50,75,100
microgram)
1
Adjunctive progestogen
Tablets
First line drugs
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 13 of 22
Specialist only drugs
Duphaston HRT®
Dydrogesterone (10mg)
1
Micronor HRT®
Norethisterone (1mg)
1
Provera®
Medroxyprogesterone (10mg)
1
Patches – do not offer routinely. Only prescribe for patient preference or if compliance is poor.
6.4.2 Male sex hormones and antagonists
 Injection 250mg/ml (Nebido®)
Testosterone
Mesterolone


Implant 100mg, 200mg
Testogel® 50mg in 5g Gel Sachets

Tablets 25mg
Notes:
1. Testosterone products are indicated on the formulary for male hypogonadism
2. Oral testosterone is often not sufficient to provide adequate testosterone replacement.
3. Nebido® is the preferred intramuscular preparation as it offers the advantage of less frequent dosing with
less inter-dose fluctuation of testosterone levels.
4. Gel is a cost-effective alternative for those patients who prefer the transdermal route
Anti-androgens
Cyproterone acetate

Tablets 50mg
Finasteride

Tablets 5mg
Notes:
1. Cyproterone acetate (Dianette®) is recommended for use in women only for the treatment of (a) severe
acne, refractory to prolonged oral antibiotic therapy; (b) moderately severe hirsutism.
2. Although Dianette also acts as an oral contraceptive, it should not be used in women solely for contraception,
but should be reserved for those women requiring treatment for the androgen-dependent conditions
described above.
3. HEPATOTOXICITY. Direct hepatic toxicity including jaundice, hepatitis and hepatic failure has been
reported (usually after several months) in patients treated with cyproterone acetate 200-300 mg daily.
Liver function tests should be performed before treatment and whenever symptoms suggestive of
hepatotoxicity occur and if confirmed cyproterone should normally be withdrawn.
4. Finasteride results in shrinkage of prostatic glandular tissue. The evidence suggests that it can reduce the
risk of acute urinary retention and need for surgery, although such events are relatively uncommon. It may be
useful in men whose prostates are particularly large where TURP/surgery is not indicated or desired.
Improvement may take 6 months to be observed.
6.5 Hypothalamic and pituitary hormones and anti-oestrogens
Note:
The use of all preparations in this section requires detailed prior investigation and should be reserved for
specialist care.
6.5.1 Hypothalamic and anterior pituitary hormones and anti-oestrogens
Anti-oestrogen
Note:
IVF is provided by specialist centres and no drugs should be prescribed in primary care.
Anterior pituitary hormones
Tetracosactide  Injection 250 micrograms in 1ml, 1mg in 1ml
(depot)
(Synacthen®)
Note:
Tetracosactrin test – measure plasma cortisol immediately before and at exactly 30 and 60 minutes after an
IM/IV dose of 250micrograms. If inconclusive the 5-hour test may be used by injecting 1mg IM (depot). Plasma
cortisol should be measured immediately before the injection, after exactly 30 minutes and then at 1,2,3,4 and 5
hours.
Gonadotrophins
First line drugs
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 14 of 22
Specialist only drugs
Note:
IVF is provided by specialist centres and no drugs should be prescribed in primary care.
Growth
hormone
Somatropin






Genotropin® injection 5.3mg, 12mg
MiniQuick® injection 0.2mg, 0.4mg. 0.6mg,
0.8mg, 1mg, 1.2mg, 1.4mg, 1.6mg, 1.8mg,
2mg
Humatrope® cartridge 6mg, 12mg, 24mg
Norditropin® SimpleXx injection
5mg in 1.5ml, 10mg in 1.5ml, 15mg in 1.5ml
Omnitrope 5mg in 1.5ml, 10mg in 1.5ml
Saizen 8mg click.easy
For use in Genotropin pen or mixer
Single dose syringes
For use in pen device
For use in Nordipen device
For use in Omnitrope pen device
For use in one.click auto-injector, cool.click
needle free auto-injector or easypod autoinjector
NICE TA188 : Human growth hormone (somatropin) for the treatment of growth failure in children (May
2010)
Somatropin (recombinant human growth hormone) is recommended as a treatment option for children with
growth failure associated with any of the following conditions:

growth hormone deficiency

Turner syndrome

Prader–Willi syndrome

chronic renal insufficiency

born small for gestational age with

subsequent growth failure at 4 years of age or later

short stature homeobox-containing gene
A paediatrician (a doctor who specialises in treating children) who is an expert in treating children with a growth
hormone disorder should always be responsible for starting and checking the progress of growth hormone
treatment.
The choice of product should be made on an individual basis after informed discussion between the responsible
clinician and the patient and/or their carer about the advantages and disadvantages of the products available,
taking into consideration therapeutic need and the likelihood of adherence to treatment. If, after that discussion,
more than one product is suitable, the least costly product should be chosen.
Treatment with somatropin should be discontinued if any of the following apply:

growth velocity increases less than 50% from baseline in the first year of treatment

final height is approached and growth velocity is less than 2 cm total growth in 1 year

there are insurmountable problems with adherence
 final height is attained.
Growth hormone can be prescribed for the above uses under shared care arrangements in primary care. It is the
responsibility of the tertiary centre to select the product most appropriate for the patient.
NICE guidance TA64 : somatropin in adults with growth failure
Growth hormone deficiency (adults) - human growth hormone (Nov 2003)
NICE has recommended that recombinant human growth hormone should be used only for adults with severe
growth hormone deficiency that is severely affecting their quality of life. To be apart of this group, NICE says a
person should:

have a peak growth hormone response of less than 9 mU/litre in the ‘insulin tolerance test’ for growth
hormone deficiency or a similar low result in another reliable test, and

have an impaired quality of life because of their growth hormone deficiency (judged using a specific
questionnaire called the 'Quality of life assessment of growth hormone deficiency in adults’ designed to
assess the quality of life in people with growth hormone deficiency; a person should score at least 11 in
this questionnaire), and

already be receiving replacement hormone treatment for any other deficiencies of pituitary hormones if
he or she has one or more other deficiencies.
NICE has also said that people who have recombinant human growth hormone should have their quality of life
First line drugs
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 15 of 22
Specialist only drugs
checked again 9 months after starting the treatment. This is so that treatment can be stopped if it isn’t having a
positive effect, which is judged to be the case if the person’s score on the quality of life questionnaire hasn’t
improved by at least 7 points.
NICE has made the following recommendation for the treatment of people who develop growth hormone
deficiency in early adulthood (before 25 years of age), after their growth has slowed down (that is they grow less
than 2 cm in a year). The level of growth hormone should be checked. If the peak growth hormone response is
less than 9 mU/litre in the insulin tolerance test for growth hormone deficiency or there is a similar low result in
another reliable test, then growth hormone treatment should be given until what is known as ‘adult peak bone
mass’ is achieved (this happens at around age 25 years). After adult peak bone mass has been achieved an
assessment of whether it is appropriate to continue with the human growth hormone treatment should be made,
in line with the three measures described above.
Finally, NICE has recommended that the first stages of growth hormone treatment (starting treatment,
adjusting the dose to suit the person, and assessing how well it is working) should be carried out by a
consultant endocrinologist who has a special interest in growth hormone disorders (a consultant
endocrinologist is a doctor who has specialised in disorders involving hormones). If, after the first stages, the
growth hormone is to be prescribed by the person’s GP, then the GP and consultant should ‘share’ the person’s
care.
6.5.2 Posterior pituitary hormones and antagonists
Posterior pituitary hormones
Desmopressin  Desmotabs 200micrograms

DesmoMelt 120 and 240 micrograms




DDAVP® tablets 100 and 200 micrograms
Nasal solution 100mcg/ml
nasal spray 10 micrograms per metered spray
Injection 4 micrograms in 1ml
Notes:
1. The oral tablet and the oral lyophilisate formulations of desmopressin (Desmotab® and DesmoMelt®) are
now the only formulations licensed for use in primary nocturnal enuresis.
2. Other brands and formulations are licensed mainly for cranial diabetes insipidus.
3. CSM warning: Hyponatraemic convulsions: Patients being treated for primary nocturnal enuresis should be
warned to avoid fluid overload (including during swimming) and to stop taking desmopressin during an
episode of vomiting or diarrhoea (until fluid balance normal). The risk of hyponatraemia convulsions can also
be minimised by keeping to the recommended starting doses and by avoiding concomitant use of drugs that
increase secretion of vasopressin (e.g. tricyclic antidepressants).
4. In nocturia and nocturnal enuresis, limit fluid intake to minimum from 1 hour before dose until 8 hours
afterwards.
5. In nocturia, periodic blood pressure and weight checks are needed to monitor for fluid overload.
6. NICE clinical guidelines (CG111) on the management of nocturnal enuresis in children and young
people
Terlipressin
Vasopressin

Injection 1mg in 5ml

Injection 20 units/ml
Antidiuretic hormone antagonists
Demeclocycline  Capsules 150mg
Tolvaptan

Jinarc® tablets 15mg,30mg,45mg,60mg, 90mg
Note:
Demeclocycline may be used in the treatment of hyponatraemia resulting from inappropriate secretion of
antidiuretic hormone.
NICE has approved tolvaptan for treating autosomal dominant polycystic kidney disease in patients with chronic
kidney disease stage 2 or 3 at the start of treatment where there is evidence of rapidly progressing disease.
Further information can be found at NICE TA358 (Oct 2015)
First line drugs
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 16 of 22
Specialist only drugs
6.6 Drugs affecting bone metabolism
NICE CG 146. Osteoporosis: Assessing the risk of fragility fracture (August 2012)
This gives guidance on the selection and use of risk assessment tools in people who may be at risk of fragility
fractures.
NICE Technology Appraisal Guidance 160: Alendronate, etidronate, risedronate, raloxifene and strontium
ranelate for the primary prevention of osteoporotic fragility fractures in postmenopausal women (Updated
January 2011)
This guidance relates only to treatments for the primary prevention of fragility fractures in postmenopausal women
who have osteoporosis. Osteoporosis is defined by a T-score of −2.5 standard deviations (SD) or below on dualenergy X-ray absorptiometry (DXA) scanning. However, the diagnosis may be assumed in women aged 75 years or
older if the responsible clinician considers a DXA scan to be clinically inappropriate or unfeasible.
This guidance assumes that women who receive treatment have an adequate calcium intake and are vitamin D
replete. Unless clinicians are confident that women who receive treatment meet these criteria, calcium and/or
vitamin D supplementation should be considered.
This guidance does not cover the following:
 The treatment of women who have sustained a clinically apparent osteoporotic fragility fracture (for
recommendations for the treatment of women with a prior osteoporotic fragility fracture, see the accompanying
NICE technology appraisal, ‘Alendronate, etidronate, risedronate, raloxifene, strontium ranelate and teriparatide
for the secondary prevention of osteoporotic fragility fractures in postmenopausal women.
 The use of alendronate, etidronate, risedronate, raloxifene or strontium ranelate for the primary prevention of
osteoporotic fragility fractures in women with normal bone mineral density (BMD) or osteopenia (that is, women
with a T-score between −1 and −2.5 SD below peak BMD).
First line drugs
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 17 of 22
Specialist only drugs


The use of these drugs for the primary prevention of osteoporotic fragility fractures in women who are on longterm systemic corticosteroid treatment.
The treatment of osteoporosis in men
NICE Technology Appraisal Guidance 161: Alendronate, etidronate, risedronate, raloxifene and strontium
ranelate for the secondary prevention of osteoporotic fragility fractures in postmenopausal women
(Updated January 2011) This guidance relates only to treatments for the secondary prevention of fragility fractures
in postmenopausal women who have osteoporosis and have sustained a clinically apparent osteoporotic fragility
fracture. Osteoporosis is defined by a T-score of −2.5 standard deviations (SD) or below on dual-energy X-ray
absorptiometry (DXA) scanning. However, the diagnosis may be assumed in women aged 75 years or older if the
responsible clinician considers a DXA scan to be clinically inappropriate or unfeasible.
This guidance assumes that women who receive treatment have an adequate calcium intake and are vitamin D
replete. Unless clinicians are confident that women who receive treatment meet these criteria, calcium and/or
vitamin D supplementation should be considered.
This guidance does not cover the following:
 The use of alendronate, etidronate, risedronate, raloxifene, strontium ranelate or teriparatide for the secondary
prevention of osteoporotic fragility fractures in women with normal bone mineral density (BMD) or osteopenia
(that is, women with a T-score between −1 and −2.5 SD below peak BMD).
 The use of these drugs for the secondary prevention of osteoporotic fragility fractures in women who are on
long-term systemic corticosteroid treatment.
 The treatment of osteoporosis in men
Note: NICE guidance is based on the cost-effectiveness of individual treatments. Patients who fall outside
the criteria specified in NICE Guidance should not be considered for NHS treatment.
For the approved treatment pathway agreed across East Sussex see below:
MHRA Drug Safety Update April 2009
The available data suggest that long-term use of carbamazepine, phenytoin, primidone and sodium valproate
is associated with decreased bone mineral density that may lead to osteopenia, osteoporosis and increased
fractures in the following at-risk patients:

Those who are immobilised for long periods

Those who have inadequate sun exposure

Those with inadequate dietary calcium intake
Vitamin D supplementation should be considered for at-risk patients who are taking these medicines long term.
SECONDARY PREVENTION: Osteoporotic women (T-score of – 2.5 or lower) and having sustained a
clinically apparent fragility fracture
Alendronate 70mg weekly. Prescribe generically

Contraindication to alendronate
OR

Intolerance to alendronate
(persistent upper GI disturbance
requiring discontinuation of
treatment) OR

Unable to comply with
administration instructions

Contraindications to oral
bisphosphonates OR
Risendronate 35mg weekly
OR
Ibandronate 150mg monthly
Prescribe generically
In accordance with age, T-score and number of independent clinical
risk factors (see table below).
NB: X = no treatment recommended.
Age
No. risk factors for fracture
1
2
50- 54
X
- 3.0
55–59
- 3.0
– 3.0
60–64
– 3.0
– 3.0
65–69
– 3.0
– 2.5
70 or older
– 2.5
– 2.5
1 2 First line drugs
Second line drugs
3
- 2.5
– 2.5
– 2.5
– 2.5
– 2.5

Intolerance to 2 or more oral
Specialist
only drugs
bisphosphonates
(persistent
upper GI disturbance requiring
Page 18 of 22
discontinuation of treatment) OR
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
//
Zoledronic acid 5mg IV every 12 months
Supply and administration in secondary care only
Teriparatide 20mcg SC daily
Supply via secondary care for 18 months only
In accordance with age, T-score and number of fractures (see table
below).
Age
< 2 fractures
> 2 fractures
55 - 64
X
– 4.0
65 or older
– 4.0
– 3.5
Independent clinical risk factors for
fracture are



parental history of hip fracture
alcohol intake of 4 or more units
per day
rheumatoid arthritis.
PRIMARY PREVENTION: Post-menopausal and osteoporotic women (confirmed T-score of – 2.5 or lower)
with no history of fragility fractures
Alendronic acid 70mg weekly. Prescribe generically
Eligibility for treatment is dependent on age and the presence of indictors for low bone mineral density (BMD) and
risk factors for fracture (see below).
Indicators of low BMD
Independent clinical risk factors for fracture
low body mass index (defined as less than 22 kg/m2)
medical conditions such as Ankylosing spondylitis,
Crohn’s disease
conditions that result in prolonged immobility
untreated menopause
parental history of hip fracture
alcohol intake of 4 or more units per day
rheumatoid arthritis
Age 70+ - any one from the above table
Age 65-69 – one independent clinical risk factor for fracture
Age <65 – one independent clinical risk factor for fracture and one indicator of low BMD



Contraindication to alendronate OR
Intolerance to alendronate (persistent upper GI disturbance requiring discontinuation of treatment) OR
Unable to comply with administration instructions
First line drugs
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 19 of 22
Specialist only drugs
Risendronate 35mg weekly or Ibandronic acid 150mg monthly
Prescribe generically in accordance with age, T-score and number of independent clinical risk factors (see table
below).
NB: X = no treatment recommended.
Age
No. risk factors for fracture
1
2
3
65–69
X
– 3.5
– 3.0
70 - 74
– 3.5
– 3.0
– 2.5
75 or older
– 3.0
– 3.0
– 2.5
Independent clinical risk factors for fracture: see above



Contraindications to oral bisphosphonates OR
Intolerance to 2 or more oral bisphosphonates (persistent upper GI disturbance requiring discontinuation of treatment) OR
Unable to comply with administration instructions
Denosumab 60mg SC every 6 months on specialist recommendation. Suitable for prescribing and
administration in primary care.
OR
Strontium ranelate 2g daily
In accordance with age, T-score and number of independent clinical risk factors (see table below).
NB: X = no treatment recommended.
Age
No. risk factors for fracture
1
2
65–69
X
– 4.5
– 4.0
70–74
– 4.5
– 4.0
– 3.5
75 or older
– 4.0
– 4.0
– 3.0
Independent clinical risk factors for fracture: see above
3
6.6.1 Calcitonin and parathyroid hormone

Teriparatide
Injection 250microgram/ml 2.4ml pre-filled pen for 28 doses
6.6.2 Bisphosphonates and other drugs affecting bone metabolism
Alendronic acid (alendronate)


Tablets 10mg, for once daily doses
Tablets 70mg, for once a week doses
Risedronate


Tablets 5mg, 35mg (see notes below)
Tablets 30mg
Ibandronic acid (ibandronate)

Tablets 150mg
Strontium ranelate

Granules 2g/sachet
Denosumab (Prolia®)

SC Injection 60mg/ml in pre-filled syringe
Denosumab (XGEVA®)▼

SC Injection 70mg/ml vial
Notes:
1. Generic alendronic acid together with calcium and vitamin D is the recommended preferred option.
2. HRT should not be used purely to treat osteoporosis.
3. Calcium and vitamin D3 alone is probably not cost-effective unless there is proven deficiency, except for those
frail, elderly mobile patients in care homes.
4. Oral bisphosphonates are absorbed very poorly; therefore counselling should be given to the patient as to how
and when administration is most appropriate.
First line drugs
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 20 of 22
Specialist only drugs
5. Bisphosphonates can cause severe oesophageal reactions. Patients should be advised to discontinue
treatment and seek medical attention if they develop symptoms of oesophageal irritation, new or worsening
heartburn, pain on swallowing or retrosternal pain. Strict guidelines on administration should be followed.
6. Denosumab (Prolia®) is a novel monoclonal antibody treatment approved by NICE for the prevention of
osteoporotic fractures in post-menopausal women NICE TA 204 (Oct 2010) It should be initiated on the advice of
an appropriate specialist but is suitable for prescribing by GPs and administering by appropriately trained practice
and community nurses.
MHRA safety advice has been issued around the risk of severe symptomatic hypocalcaemia associated with the
use of denosumab and to inform about the risk of late onset of hypocalcaemia.
Pre-existing hypocalcaemia must be corrected prior to initiating denosumab, and supplementation of calcium
and vitamin D is required in all patients receiving the 120 mg dose unless hypercalcaemia is present.
Hypocalcaemia can occur at any time during treatment. Further MHRA safety guidance advises that prescribers
should check calcium levels:
 before each dose
 within two weeks after the initial dose in patients with risk factors for hypocalcaemia (eg, severe renal
impairment, creatinine clearance <30 ml/min)
 if suspected symptoms of hypocalcaemia occur.
Denosumab requires no special injection technique and can be administered by healthcare professionals trained
to give subcutaneous injections.
7. Denosumab (XGEVA®▼) has been approved by NICE as a treatment option for the prevention of skeletalrelated events in adults with bone metastases from solid tumours TA 265
8. Safety update - Osteonecrosis of the jaw
The MHRA has issued safety guidance for both bisphosphonates and denosumab. All patients with cancer
should have a dental check-up before treatment. All patients should be advised to maintain good oral hygiene
and have regular dental check-ups whilst on treatment and report any oral symptoms such as dental mobility,
pain, or swelling to a doctor and dentist.
9. Safety update – Atypical femoral fractures
Bisphosphonates and denosumab have been linked to rare cases of atypical femoral fracture with long-term use.
The need for treatment should be reviewed regularly particularly if treatment is extended beyond 5 years.
10. Safety advice for strontium ranelate indicates that it is now restricted to the treatment of severe osteoporosis in
postmenopausal women and adult men at high risk of fracture who cannot use other osteoporosis treatments due
to, for example, contraindications or intolerance.
The risk of developing cardiovascular disease should be assessed before starting treatment. Treatment should
not be started in people who have or have had:

ischaemic heart disease

peripheral arterial disease

cerebrovascular disease

uncontrolled hypertension
Cardiovascular risk should be monitored every 6–12 months
Treatment should be stopped if the individual develops ischaemic heart disease, peripheral arterial disease, or
cerebrovascular disease, or if hypertension is uncontrolled
Intravenous infusion
Disodium pamidronate
Zoledronic acid





Concentrate for intravenous infusion 3mg/ml: 5ml,10ml vials
Concentrate for intravenous infusion 6mg/ml: 10ml vial
Concentrate for intravenous infusion 9mg/ml: 10ml vial
Intravenous infusion 50 microgram/ml: 100ml
Cancer indications
Intravenous infusion 40 micrograms/ml: 100ml
Note:
These products should only be administered by staff trained to administer intravenous infusions in a hospital or
specialist centre.
6.7 Other endocrine drugs
6.7.1. Bromocriptine and other dopamine-receptor stimulants
 Tablets 1mg, 2.5mg
Bromocriptine
Cabergoline
First line drugs


Capsule 5mg, 10mg
Tablets 500 micrograms
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 21 of 22
Specialist only drugs
Notes:
1. CSM Advice: The ergot-derived dopamine-receptor agonists, bromocriptine, cabergoline, lisuride and
pergolide have been associated with pulmonary, retroperitoneal and pericardial fibrotic reactions. The CSM
has advised that before starting treatment with these ergot derivatives, investigations such as measurement of
ESR, U&Es and a chest X-ray may be appropriate. If long-term treatment is expected, then lung function tests
may be helpful. Patients should be monitored for progressive fibrotic disorders.
2. The above are included in this section for their inhibition of prolactin release. Refer to chapter 4, section 9.1 for
the treatment of Parkinson’s disease.
3. Bromocriptine has a known safety profile in pregnancy; cabergoline is contra-indicated in pregnancy
4. Cabergoline has an advantage of administration on a once weekly basis.
6.7.2. Drugs affecting gonadotrophins
Gonadorelin analogues
 Injection 3.6mg
Goserelin
 Injection 3.75mg
Leuprorelin
Notes:
1. Goserelin and leuprorelin are included in this section for endometriosis only. Please refer to chapter 8 for other
indications.
2. Gonadorelin analogues are contra-indicated for use longer than 6 months (do not repeat), where there is
undiagnosed vaginal bleeding, in pregnancy and in breast-feeding.
Breast Pain (mastalgia)
Note:
The product licences for Epogam® and Efamast® (gamolenic acid) where withdrawn as from 7 th October 2002
due to the lack of efficacy and are no longer prescribable.
6.7.3. Metyrapone and trilostane
Metyrapone

Capsules 250mg
Note:
Metyrapone is used for Cushing’s syndrome, often in a lower dose combination with aminoglutethamide to reduce
side effects.
First line drugs
Second line drugs
Specialist drugs
Adapted from the Plymouth Joint Formulary Chapter 6 Endocrine System
Page 22 of 22
Specialist only drugs