Download Endocrine draft for consultation

NI Medicines Management Formulary
BNF Chapter 6 – Endocrine
(Adult)
1
Endocrine
BNF Chapter 6
6.1
6.1.1
6.1.2
6.1.4
6.1.6
6.2
6.2.1
6.2.2
(9.6.4)
6.3
6.4
6.4.1.1
6.4.2
6.5
6.5.1
6.5.2
6.6
(a)
(b)
(c)
6.7
6.7.1
6.7.4
Drugs used in diabetes
Insulins
Antidiabetic drugs
Treatment of hypoglycaemia
Diagnostic and monitoring agents for diabetes mellitus
Thyroid and antithyroid drugs, and parathyroid disease
Thyroid hormones
Antithyroid hormones
Parathyroid disease
Corticosteroids
Sex hormones
Hormone Replacement Therapy (HRT) for menopausal symptoms
Male sex hormones
Pituitary hormones and anti-oestrogens
Anterior pituitary hormones
Posterior pituitary hormones and antagonists
Drugs affecting bone metabolism
Prevention and treatment of post-menopausal osteoporosis
Corticosteroid-induced osteoporosis (prevention and treatment)
Male osteoporosis
Other endocrine drugs
Dopamine receptor agonists
Acromegaly
2
6.0 Endocrine
6.1 Drugs used in diabetes
6.1.1 Insulins
General advice
 Refer to NICE Guideline 17 for information on the management of
type 1 diabetes, NICE Guideline NG3 for information on diabetes
in pregnancy and NICE Guideline 28 for further information on the
management of type 2 diabetes
 Type of insulin, device and needle gauge and length 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
 Choice of insulin prescribed is guided by the duration of action and
regimen choice, and patient choice regarding device types. The
following table indicates preferred choices where all things are
equal regarding device choice
Formulary
Choices
Rapid
(analogue)
Immediate
with food
Short
15 to 30
mins
before
food
Intermediate
(isophane)*
Same time
every day
Long
(analogue)
Same time
every day
Apidra®
Actrapid®
Humulin I®
Humalog®
Humulin
S®
Abasaglar®** Humalog®
Mix 25
Lantus®
Humalog®
Mix 50
Levemir®
Novorapid®
Insulatard®
®
Insuman® Insuman
Basal
Rapid
Biphasic
Up to 15
mins
before
food
Novomix®
30
Biphasic
Isophane
Up to 30
mins
before
food
Humulin®
M3
Insuman®
Comb
(15, 25,
50)
*Human NPH (isophane and biphasic isophane) insulin is the preferred first-choice
insulin recommended by NICE for type 2 diabetes
**Insulin glargine is available as different branded products, some are biosimilars. It is
important they are prescribed by brand name to ensure the patient receives the intended
product. Abasaglar® is first choice insulin glargine on the formulary
3
Prescribing notes
 For most people with type 2 diabetes, long-acting insulin
analogues offer no significant advantage over NPH insulin
 Long-acting insulin analogues have a role in some patients, and
can be considered for those who fall into specific categories
including:
 those who require assistance from a carer or healthcare
professional to administer their insulin injections
 those who would otherwise need twice daily NPH insulin plus
oral hypoglycaemic drugs to control their diabetes
 those who experience significant hypoglycaemia on NPH
insulin irrespective of the level of HbA1c reached
 those who cannot use the device needed to inject NPH
insulin but who could administer their own insulin safely and
accurately if a switch to a long-acting insulin analogue were
made, or
 Clinicians should review and, where appropriate, revise prescribing
of long-acting insulin analogues in type 2 diabetes mellitus to
ensure that it is in line with NICE guidance
Insulin Pump Therapy
 Continuous subcutaneous insulin infusion (CSII) is an option for
people with type 1 diabetes meeting NICE TA151
recommendations (http://www.nice.org.uk/TA151)
 CSII therapy should be initiated by a trained specialist team
6.1.2 Antidiabetic drugs
General advice
 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 may need to
4
inform the DVLA and their vehicle insurance company. Advise
patients to check with their insurer and the GOV.UK website
 Women with type 2 diabetes who become pregnant whilst taking
antidiabetic medication should be referred urgently for specialist
advice. It is safe to continue metformin. See NICE NG3 on
diabetes in pregnancy
 See NG28 on type 2 diabetes for full advice
Cautions
Oral hypoglycaemics in elderly patients
 Certain aspects of type 2 diabetes in elderly patients require
special consideration. Drug-induced hypoglycaemia is one of the
most serious potential complications
 Risk of hypoglycaemia is increased when combination therapy is
used
 Risk of hypoglycaemia is increased with renal impairment.
Decreased renal function in elderly subjects is frequent and
asymptomatic. Special caution should be exercised in situations
where renal function may become impaired, for example when
initiating antihypertensive therapy or diuretic therapy and when
starting therapy with a non-steroidal anti-inflammatory drug
(NSAID)
a) Biguanides
Formulary choice Metformin tablets
500mg (immediate
release)
Dose:
Initially 500mg with breakfast
for at least 1 week, then
500mg with breakfast and
evening meal for at least 1
week, then 500mg with
breakfast, lunch and evening
5
meal; usual max. 2g daily in
divided doses
Caution in renal impairment
(see notes below)
Prescribing Notes
 Metformin is the first choice oral antidiabetic drug. It is the only oral
antidiabetic drug which has a proven survival advantage. It does
not need to be limited to overweight patients
 Metformin may cause gastro-intestinal adverse effects; it should be
started at low dose and taken with or after meals. A slow increase
in dose may improve gastrointestinal tolerability. Hypoglycaemia is
not a problem with metformin monotherapy
 Metformin prolonged release tablets are more expensive than
immediate release tablets, but less expensive than other newer
oral agents. They should be reserved for patients:
o unable to tolerate immediate release metformin, or
o with demonstrable compliance problems (once daily
dosing)
 Metformin is a useful drug and can be safely used in CKD. It is
associated with lactic acidosis, however this is rare and the risk
may be overstated. It is reasonable for GPs to use in people with
Stage 3 CKD (eGFR >30mL/min). However, dose reduction and
specialist involvement should be considered as renal function
declines towards this level
 Continuing metformin during periods of dehydration or acute
illness (such as diarrhoea and vomiting) can increase the risk of
lactic acidosis. 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 drugs for a day or two will not
cause any immediate problem for the patient and will protect renal
function until the patient improves
6
b) Sulfonlyureas
Formulary choice Gliclazide tablets
80mg
Dose:
Initially 40-80mg daily before
main meal, max 320mg daily;
doses above 160mg daily
should be divided
Renal impairment – see BNF
Prescribing Notes
 Gliclazide modified release tablets should be reserved for patients
with demonstrable compliance problems
 Patients should be informed that sulfonylureas can cause
hypoglycaemia. The risk of hypoglycaemia increases with age
 Driving requirements and advice for monitoring of blood glucose in
people with type 2 diabetes differ depending on medication and
license group. Information may be accessed on the GOV.UK
website
c) Other anti-diabetic drugs
(i)
Dipeptidyl peptidase-4 inhibitor (DPP-4 inhibitors)
Alogliptin
tablets 25mg
Formulary
choices
Dose:
25mg once daily
Reduce dose to:
12.5mg once daily if eGFR 30-50mL/min
6.25mg once daily if eGFR <30mL/min
Or
Sitagliptin
Dose:
tablets 100mg 100mg once daily
Reduce dose to:
50mg once daily if eGFR 30-50mL/min
25mg once daily if <30mL/min or End
Stage Renal Disease
7
Prescribing Notes
 DPP-4 inhibitors have been shown to have a modest impact on
HbA1c with mean reduction of 0.6-0.8%, but there is no data on
morbidity, mortality or long-term adverse effects
 The DPP-4 inhibitors differ in terms of their licensed indications /
combinations
 Prescribe as per NICE Guideline NG28 recommendations. See
also NICE Algorithm for blood glucose lowering therapy in adults
with type 2 diabetes
 Fixed dose combination products containing metformin and a
DPP4 should be reserved for patients with demonstrable
compliance problems
 A small increased risk of acute pancreatitis has been identified for
all licensed DPP-4 inhibitors. 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. Refer to MHRA advice for full details
(ii)
Glitazones (thiazolidinediones)
Formulary
choice
Pioglitazone tablets
15mg, 30mg, 45mg
Dose:
Initially 15–30mg once daily,
increased to 45mg once daily
according to response
Prescribing Notes
 Prescribe as per NICE Guideline NG28 recommendations. See
also NICE Algorithm for blood glucose lowering therapy in adults
with type 2 diabetes
 Do not commence or continue a thiazolidinedione in people who
have heart failure, or who are at higher risk of fracture
 Liver function should be checked before initiating pioglitazone and
periodically thereafter based on clinical judgement. It should not be
8
initiated in anyone with ALT > 2.5 times the upper limit of normal or
with other evidence of liver disease
 The balance of risks and benefits should be considered both
before initiating and during treatment. Prescribers should review
patients after three to six months (and regularly thereafter) to
ensure only patients who are benefiting from treatment continue
 Competact® (pioglitazone and metformin) should be reserved for
patients with demonstrable compliance problems. It is
significantly more expensive than prescribing pioglitazone and
metformin separately
Cautions
 Pioglitazone can cause significant weight gain and fluid retention.
It must not be used in patients with heart failure or history of heart
failure
 Macular oedema has also been associated with use of
pioglitazone
 Pioglitazone should not be used in patients with current or a
history of bladder cancer or in patients with uninvestigated
macroscopic haematuria. See EMA advice
 Do not commence/continue in people with a high risk of fracture
(refer FRAX or QFracture to assess risk)
(iii)
Sodium-glucose co-transporter 2 (SGLT-2) inhibitors
Canagliflozin 100mg,
300mg tablets
Dose:
100mg once daily; increased
if tolerated to 300mg once
daily if required, dose to be
taken preferably before
breakfast
Renal impairment – see BNF
Or
Formulary
choices
Dapagliflozin 10mg
Dose:
9
tablets
10mg once daily
Avoid if eGFR<60mL/min
(ineffective)
Or
Empagliflozin 10mg,
25mg tablets
Dose:
10mg once daily, increased
to 25mg once daily if
necessary and tolerated
Renal impairment – see BNF
Prescribing Notes
 Empagliflozin is recommended as first choice in patients with
established cardiovascular disease
 Prescribe as per NICE Guideline NG28 recommendations. See
also NICE Algorithm for blood glucose lowering therapy in adults
with type 2 diabetes
 SGLT-2 inhibitors as monotherapies should be prescribed in line
with NICE TA 390
 Serious cases of diabetic ketoacidosis have been reported in
patients taking an SGLT-2 inhibitor. See MHRA Drug Safety
Update April 2016 for advice
 A signal of increased lower limb amputation in people taking
canagliflozin is currently under investigation. See MHRA advice for
healthcare professionals
10
(iv)
GLP-1 mimetic (injectable)
1st choice
Liraglutide injection
6mg/mL
2nd choice
(where weekly
injection is
preferred)
Dulaglutide
1.5mg/0.5ml solution
for injection
Dose:
Initially 0.6mg once daily,
increased after at least 1
week to 1.2mg once daily
Liraglutide 1.8mg daily is
not recommended by NICE
for the treatment of people
with type 2 diabetes
Renal impairment – see BNF
Dose:
Add-on therapy: 1.5mg once
weekly
Renal impairment – see BNF
Prescribing Notes
 Prescribe as per NICE Guideline NG28 recommendations. See






also NICE Algorithm for blood glucose lowering therapy in adults
with type 2 diabetes
Please avoid prescribing large quantities to prevent waste, GLP-1
agonists require refrigeration and are expensive. One month’s
supply should be adequate for most patients
Stopping rules with GLP-1 mimetics: NICE state only continue
GLP‑1 mimetic therapy if the person with type 2 diabetes has had
a beneficial metabolic response (a reduction of at least 11
mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of
initial body weight in 6 months)
Gastric emptying may be delayed. Therefore the rate and extent of
absorption of other oral drugs administered at the same time may
be affected
Doses of concomitant sulfonylurea may need to be reduced when
a GLP-1 mimetic is started
Upper gastrointestinal side effects such as nausea are common
with GLP-1 mimetic therapy
There are rare reports of acute pancreatitis in patients using these
drugs. GLP-1 mimetics should be avoided in patients considered
11
to be at high risk of pancreatitis. Patients and their carers should
be told how to recognise signs and symptoms of pancreatitis
 Thyroid adverse events, including increased blood calcitonin,
goitre and thyroid neoplasm, have been reported in clinical trials
with liraglutide, particularly in patients with pre-existing thyroid
disease
6.1.4 Treatment of hypoglycaemia
Formulary
choices
Glucose (oral)
Dose:
Initially, glucose 15-20g is
given by mouth usually in
liquid form
See attached leaflet for further
details on management of ‘hypos’
– ADD LINK to regional leaflet
Or
Glucagon 1mg vial
(GlucaGen® HypoKit)
Dose:
Subcutaneous, intramuscular
or intravenous injection, adult
and child (over 25kg) 1mg
Or
Glucose intravenous
infusion
As per local trust policy
Prescribing Notes
Prevention and management of hypoglycaemia
Acute management:
 Hypoglycaemia is defined as blood glucose of less than 4mmol/L
(if not < 4mmol/L but the patient is symptomatic, give a small
carbohydrate snack for symptom relief)
 If the patient is conscious, capable and co-operative, give 15-20g
12
quick acting carbohydrate of the patient’s choice where possible.
Examples are given in the ‘hypo’ leaflet – ADD LINK when
available
 If the patient is conscious but not capable and/or co-operative, give
2 tubes of oral glucose gel (squeezed into mouth between teeth
and gums) OR Glucagon 1mg IM
 Once Capillary Blood Glucose (CBG) is above 4mmol/L give 20g
of long acting carbohydrate, e.g. 2 digestive biscuits or a slice of
bread or next meal if due. If IM glucagon has been used give 40g
of long acting carbohydrate in order to replenish glycogen stores
 Adults with decreased level of consciousness due to
hypoglycaemia who are unable to take oral treatment safely should
be:
 given intramuscular glucagon by a trained user (intravenous
glucose may be used by professionals skilled in obtaining
intravenous access)
 monitored for response at 10 minutes, and then given
intravenous glucose if the level of consciousness is not
improving significantly
 then be given oral carbohydrate when it is safe to administer
it, and placed under continued observation by a third party
who has been warned of the risk of relapse
6.1.6 Diagnostic and monitoring agents for diabetes mellitus
To be updated
Refer to HSC Board Regional Prescribing Policy - Guidance on Self
Monitoring of Blood Glucose in People with Type 2 Diabetes
(ADD LINK once updated)
13
6.2 Thyroid and antithyroid drugs and parathyroid disease
6.2.1 Hypothyroidism
Formulary
choice
Levothyroxine tablets
25micrograms,
50micrograms, 100
micrograms
Dose:
Initially 100 micrograms
(50micrograms if elderly)
daily, adjusted in steps of 2550micrograms every 6 weeks
until TSH is within normal
reference range. Usual dose
100–150micrograms daily.
Where there is cardiac
disease, initially
25micrograms daily, adjusted
in steps of 25micrograms
Prescribing Notes
 Prior to treatment, it is important to establish that Thyroid
Stimulating Hormone (TSH) is elevated, thus confirming primary
hypothyroidism. A normal or low TSH may suggest pituitary or
hypothalamic disease for which specialist referral is necessary
 TSH should be checked 6 weeks after starting levothyroxine or
after any change in dose, then annually once stable
 Alteration in thyroxine absorption may occur with introduction of
other medication such as iron and calcium preparations or drugs
altering gastric acid, such as proton pump inhibitors. Thyroid
function should be checked 6 weeks after starting such treatment
 Pregnant women with hypothyroidism should be seen by a
specialist for titration of levothyroxine regimens, although it is
recommended that upon confirmation of pregnancy, due to the
early increase in thyroxine requirements, thyroxine dosage is
doubled on Saturdays and Sundays until early review by a
specialist
 There is insufficient evidence to support the use of liothyronine for
the treatment of hypothyroidism. See PrescQIPP for further details
14
6.2.2 Hyperthyroidism
General advice
 Radioactive iodine is increasingly used as first choice for
thyrotoxicosis. Treatment should be under specialist care
a) Antithyroid drugs
Formulary
choice
Carbimazole tablets
5mg, 20mg
To be initiated on
specialist advice
Dose:
20-60mg (BNF states 1540mg) daily until euthyroid
(usually 4-8 weeks), then
progressively reduced to a
maintenance dose, typically
5-15mg, daily usually for 1218 months
Prescribing Notes
 Carbimazole should be initiated under specialist advice to ensure
the correct diagnosis is made and that treatment is appropriate.
Carbimazole can be given by titration method or in a blockingreplacement regimen
 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 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 and similar advice regarding
neutropenia should be given when using this drug
 Severe hepatic reactions have been reported with propylthiouracil,
including fatal cases and cases requiring liver transplant. Liver
function should be monitored and propylthiouracil discontinued if
significant liver-enzyme abnormalities develop
15
 All pregnant women with thyrotoxicosis should be seen by a
specialist endocrine team early in gestation. Propylthiouracil is the
drug of choice during early pregnancy and breastfeeding
b) Beta-blockers
Formulary choice Propranolol tablets
10mg, 40mg
Dose:
Thyrotoxicosis (adjunct),
orally 10-40mg 3-4 times
daily
Or
Propranolol MR
capsules 80mg,
160mg
Dose:
A dose of 80mg, taken either
morning or evening, may be
sufficient to provide adequate
control in many patients. The
dose may be increased to
160mg, and then if
necessary further increased
to 240mg per day
Prescribing Notes
 Beta blockade can be withdrawn once hyperthyroidism is
controlled (2-6 weeks), and the patient maintained on carbimazole
 Diltiazem may be considered as an alternative if a beta-blocker is
contraindicated (under specialist advice)
9.6.4 Parathyroid disease
a) Hyperparathyroidism
Prescribing Notes
 Primary hyperparathyroidism: Parathyroid surgery is the treatment
16
of choice in most symptomatic patients. Medical management is
used for those for whom surgery is not suitable. Cinacalcet is
occasionally used under specialist supervision only
 Secondary hyperparathyroidism: Medical management is the
mainstay of treatment and the underlying condition needs to be
treated
 Cinacalcet is approved for specialist use in renal patients with
secondary hyperparathyroidism, who have uncontrolled plasma
levels of parathyroid hormone (greater than 85 picomol/litre), that
is refractory to standard therapy and in whom surgical
parathyroidectomy is not suitable. A shared care guideline for
cinacalcet is available here:
 All patients with severe hypercalcaemia (>3mmol/l) should be
referred for urgent specialist input
b) Hypoparathyroidism
Formulary
choice
Alfacalcidol (1α–
hydroxycholecalciferol)
capsules
250nanograms,
500nanograms,
1microgram; oral
drops
2micrograms/mL
Dose:
Orally, initially 1microgram
daily (elderly 500nanograms)
adjusted to avoid
hypercalcaemia;
maintenance, usually 0.251microgram daily
Prescribing Notes
 If hypercalcaemia occurs, alfacalcidol should be stopped and
restarted when plasma calcium is normal (usually within a week)
 Supplemental calcium (usual dose 1-2g daily) may be required in
addition to alfacalcidol. Care should be taken to avoid
hypercalcaemia
6.3 Corticosteroids
a) Replacement therapy
17
Formulary choices
Replacement therapy Dose:
(mineralocorticoid) - Usual dose 50-300
Fludrocortisone tablets micrograms daily
100 micrograms
Glucocorticoid
therapyHydrocortisone tablets
10mg, 20mg
Dose:
15-30mg daily in
divided doses
Prescribing Notes
 In Addison’s disease (primary adrenal failure), hydrocortisone
(glucocorticoid) and fludrocortisone (mineralocorticoid) are given in
combination
 In acute adrenocortical insufficiency, intravenous hydrocortisone
sodium succinate 100mg is given every 6-8 hours in sodium
chloride intravenous infusion 0.9%
 In secondary adrenal failure (hypopituitarism), hydrocortisone is
given alone, as a mineralocorticoid is not usually required
 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. They should
all be encouraged to wear a Medi-Alert bracelet. More serious
illnesses or gastro-intestinal disturbances necessitate prompt
parenteral hydrocortisone
b) Glucocorticoid therapy
Formulary
choices
Prednisolone tablets
1mg, 5mg, 25mg;
gastro-resistant
Dose:
Dependent on condition
being treated (refer to BNF
18
tablets 2.5mg, 5mg;
chapter 6). Preferably taken
in the morning after breakfast
Or
Dexamethasone
tablets
500micrograms, 2mg;
injection 3.8mg/mL;
injection 3.3mg/mL
Dose:
Dependent on condition
being treated (refer to BNF
chapter 6)
Or
Hydrocortisone
injection (SoluCortef®)
hydrocortisone (as
sodium succinate)
100mg vial with 2mL
amp water for
injections
Dose:
Dependent on condition
treated (refer to BNF)
Or
Methylprednisolone
Dose:
tablets 2mg, 4mg,
Dependent on condition
16mg, 100mg;
treated (refer to BNF)
Methylprednisolone
sodium succinate
(Solu-Medrone®) vials
40mg, 125mg,
500mg, 1g, 2g;
Intramuscular depot:
Methylprednisolone
acetate (DepoMedrone®) vials
40mg/mL, 80mg/2mL,
120mg/3mL
19
Prescribing Notes
 Corticosteroids are used in the treatment of a wide range of
conditions. Doses of corticosteroids used vary widely in different
diseases and in different patients. Refer to relevant section of BNF
 Patients receiving 7.5mg or more of prednisolone daily (or
equivalent, see BNF chapter 6) for longer than 3 months should
receive osteoporosis prophylaxis. No osteoporosis prophylaxis is
indicated when corticosteroids are used as replacement therapy.
See BNF chapter 6
 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 750
micrograms dexamethasone. See BNF chapter 6
The table below shows equivalent anti-inflammatory doses:
Equivalent anti-inflammatory doses of corticosteroids
This table takes no account of mineralocorticoid effects, nor does it take account of
variations in duration of action
Prednisolone 5mg
≡ Betamethasone 750 micrograms
≡ Deflazacort 6mg
≡ Dexamethasone 750 micrograms
≡ Hydrocortisone 20mg
≡ Methylprednisolone 4mg
≡ Prednisone 5mg
≡ Triamcinolone 4mg
20
6.4 Sex hormones
6.4.1.1 Hormone replacement therapy (HRT) for menopausal symptoms
General advice
 See NICE NG23 Menopause: diagnosis and management
 See CKS Menopause for practical guidance on best practice
 In most women with troublesome symptoms the benefits of
HRT outweigh the risks. Discuss risks and benefits prior to
starting (refer to links above)
 Women with a premature menopause (<40 years of age) should
be referred to a specialist HRT clinic. HRT is normally
recommended until the average age of the natural menopause (52
years of age).
 HRT preparations should be brand prescribed to aid product
identification
 For use of HRT in osteoporosis prophylaxis refer to (ADD JUMP to
6.6 (c))
21
For PDF click here (add link )
a) Women who have not had a hysterectomy
Sequential combined (oral)
1st choice Elleste-Duet® 1mg,
2mg tablets
(estradiol and
norethisterone)
Dose:
Elleste-Duet® 1mg tablets –
menopausal symptoms, 1 white tablet
daily for 16 days starting on day 1 of
menstruation (or at any time if cycles
have ceased or are infrequent), then 1
green tablet daily for 12 days;
subsequent courses are repeated
without interval
Elleste-Duet® 2mg tablets –
menopausal symptoms and
osteoporosis prophylaxis (see section
22
6.6), 1 orange tablet daily for 16 days,
starting on day 1 of menstruation (or at
any time if cycles have ceased or are
infrequent) then 1 grey tablet daily for
12 days; subsequent courses are
repeated without interval
Or
Femoston® 1/10,
2/10 tablets
(estradiol and
dydrogesterone)
Dose:
Femoston® 1/10 tablets – menopausal
symptoms and osteoporosis
prophylaxis (see section 6.6), in women
with a uterus, 1 white tablet daily for 14
days, starting within 5 days of onset of
menstruation (or any time if cycles have
ceased or are infrequent) then 1 grey
tablet daily for 14 days; subsequent
courses repeated without interval
Femoston® 2/10 tablets - menopausal
symptoms and osteoporosis
prophylaxis (see section 6.6), in women
with a uterus, 1 red tablet daily for 14
days, starting within 5 days of onset of
menstruation (or any time if cycles have
ceased or are infrequent) then 1 yellow
tablet daily for 14 days; subsequent
courses repeated without interval;
where therapy required for menopausal
symptoms alone, Femoston® 1/10 given
initially and Femoston® 2/10 substituted
if symptoms not controlled
23
Sequential combined (transdermal)
1st choice
Evorel® Sequi patches:
combination pack of 4
Evorel® 50 patches
(estradiol
50micrograms/24hours)
and 4 Evorel® Conti
patches (estradiol
50micrograms/24hours)
and norethisterone
acetate
170micrograms/24hours
Dose:
Menopausal symptoms and
osteoporosis prophylaxis (see
section 6.6), in women with a
uterus, 1 Evorel® 50 patch to be
applied twice weekly for 2 weeks,
starting within 5 days of onset of
menstruation (or at any time if
cycles have ceased or are
infrequent), followed by 1 Evorel®
Conti patch twice weekly for 2
weeks; subsequent courses are
repeated without interval
2nd choice
FemSeven Sequi®
patches: providing
estradiol 50micrograms
per 24 hours (phase 1);
estradiol 50micrograms
and levonorgestrel
10micrograms per 24
hours (phase 2)
Dose:
Menopausal symptoms in women
with a uterus,
one Phase 1 patch applied once a
week for 2 weeks followed by
one Phase 2 patch once a week
for 2 weeks; subsequent courses
are repeated without interval
Continuous combined (oral)
1st choice
Kliovance® tablets
(estradiol 1mg and
norethisterone
500micrograms)
Kliofem® tablets
(estradiol 2mg and
norethisterone 1mg)
Dose:
Menopausal symptoms and
osteoporosis prophylaxis (see
section 6.6) in women with a
uterus whose last menstrual period
occurred over 12 months
previously, 1 tablet daily
continuously; start at end of
scheduled bleed if changing from
cyclical HRT
24
2nd choice
Femoston® - conti
0.5mg/2.5mg tablets;
1mg/5mg tablets
(estradiol and
dydrogesterone)
Dose:
Femoston®-conti 0.5 mg/2.5 mg
tablets:
menopausal symptoms in women
with a uterus whose last menstrual
period occurred over 12 months
previously, 1 tablet daily
continuously (if changing from
cyclical HRT begin treatment the
day after finishing oestrogen plus
progestogen phase)
Femoston®-conti 1 mg/5 mg
tablets:
Menopausal symptoms and
osteoporosis prophylaxis (see
section 6.6) in women with a
uterus whose last menstrual period
occurred over 12 months
previously, 1 tablet daily
continuously (if changing from
cyclical HRT begin treatment the
day after finishing oestrogen plus
progestogen phase)
Continuous combined (transdermal)
1st choice
Evorel® Conti patches
(estradiol
50micrograms/24hours
and norethisterone
170micrograms/24hours
(matrix patch))
Dose:
Menopausal symptoms and
osteoporosis prophylaxis (see
section 6.6), in women with a
uterus, 1 patch to be applied
twice weekly continuously
Prescribing Notes
 HRT preparations should be brand prescribed to aid product
25





identification
It is recommended that the lowest dose of HRT based on relieving
menopausal symptoms should be prescribed
Women with an early menopause (<45 years), especially if
surgically induced, require the higher dose of oestrogen to control
their vasomotor symptoms and for bone protection
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
Progestagenic side effects (women typically describe symptoms
similar to ‘PMS’) may resolve within a few months. For persistent
or troublesome symptoms consider:
o Changing the progestogen type e.g. to a less androgenic one
such as dydrogesterone
o Changing the route of delivery e.g. oral to transdermal
o 3 monthly bleed preparation (Tridestra®)
o Using a Mirena® IUS as the progestogen component of HRT
b) Women who have had a hysterectomy or who have a Mirena® Intra
Uterine System (ISU) in situ
Unopposed oestrogens (oral)
1st choice
Elleste-Solo®
Dose:
1mg, 2mg
Elleste-Solo® 1mg tablets (estradiol) tablets menopausal symptoms, 1 mg daily
Elleste-Solo® 2mg tablets menopausal symptoms not controlled
with lower strength and osteoporosis
prophylaxis (see section 6.6), 2 mg
daily
26
Unopposed oestrogens (transdermal)
1st choice
Evorel® patches
50micrograms (or
25micrograms,
75micrograms,
100micrograms/24
hours) (estradiol)
Dose:
Menopausal symptoms and
osteoporosis prophylaxis (see section
6.6), 1 patch to be applied twice weekly
continuously
Therapy should be initiated with Evorel®
50 patch; subsequently adjust
according to response; dose may be
reduced to Evorel® 25 patch after first
month if necessary for menopausal
symptoms only
Unopposed oestrogens (gel)
1st choice
Oestrogel® 0.06%
gel
Dose:
Menopausal symptoms and
osteoporosis prophylaxis (see section
6.6), 2 measures (estradiol 1.5 mg) to
be applied over an area twice that of
the template provided once daily
continuously; for menopausal
symptoms may be increased if
necessary after 1 month to max. 4
measures daily
Prescribing Notes
 HRT preparations should be brand prescribed to aid product
identification
 It is recommended that the lowest dose of HRT based on relieving
menopausal symptoms should be prescribed
 Women with an early menopause (<45 years), especially if
27
surgically induced, require the higher dose of oestrogen to control
their vasomotor symptoms and for bone protection
 Mirena® is licensed for 4 years for endometrial protection during
oestrogen replacement therapy (i.e. Mirena® provides the
progestogen component of HRT). In practice, it is used for up to 5
years, providing the woman is not experiencing bleeding
Preparations for vaginal atrophy
See section 7.2.1
6.4.2 Male sex hormones
Prescribing Notes
 Testosterone is an amber drug. A shared care guideline is
available here:
28
6.5 Pituitary hormones and anti-oestrogens
6.5.2 Posterior pituitary hormones and antagonists
(a) diabetes insipidus
1st choice
Desmopressin nasal
spray
10micrograms/metered
spray; intranasal
solution
100micrograms/mL
Dose:
Intranasally, diabetes
insipidus, treatment,
10-40micrograms
daily in 1-2 divided
doses
2nd choice
Desmopressin tablets
100micrograms,
200micrograms
Dose:
diabetes insipidus,
treatment, initially
300micrograms daily
in 3 divided doses;
maintenance 300–
600micrograms daily
in 3 divided doses;
range 0.2–1.2mg
daily
Or
Desmopressin
sublingual tablets 60
micrograms, 120
micrograms, 240
micrograms
Dose:
diabetes insipidus,
initially 180
micrograms daily in 3
divided doses; range
120-720 micrograms
daily
Prescribing Notes
 A single dose of desmopressin is also used as part of a test
29
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 1-4 micrograms daily by
subcutaneous, intramuscular or intravenous injection)
 Measurement of plasma sodium should be undertaken to guard
against excessive water intake which would be reflected by a
low plasma sodium. The frequency of monitoring should be
individualised and more frequent monitoring will be required
during the stabilisation phase
(b) antidiuretic hormone antagonists
Formulary choice
Demeclocycline
capsules 150mg
Dose:
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
 Tolvaptan may be used under specialist use for the treatment
of hyponatraemia secondary to syndrome of inappropriate
antidiuretic hormone secretion. MHRA has advised about safety
concerns with tolvaptan leading to an over-rapid increase in
serum sodium and risk of serious neurological events and risk
of liver injury
30
6.6 Drugs affecting bone metabolism
General Notes




Refer to NI Osteoporosis Care Pathway (when ready)
Refer to NICE Pathway – Osteoporosis
Consider risk assessment using FRAX or QFracture
Consider falls prevention measures. The greatest risk of
fracture in the elderly comes from falls, not osteoporosis
 For the management of glucocorticoid-induced osteoporosis,
refer to the Royal College of Physicians treatment algorithm.
Patients receiving 7.5mg or more of prednisolone daily for
longer than 3 months should receive osteoporosis prophylaxis
 Male osteoporosis is often secondary to other medical
conditions; specialist referral is recommended
Drugs for the treatment and management of Osteoporosis
(a) Calcium and Vitamin D
1st choice
Adcal-D3® Caplets
750mg/200IU
nd
2 choice
Calceos®
500mg/400IU
chewable tablets
Reserve (for patients Calfovit D3®
who cannot swallow 1200mg/800IU
caplets or take
powder for oral
chewable tablets)
suspension
Dose: Two tablets to be
taken twice a day
Dose: One tablet twice a
day
Dose: 1 sachet per day
(it is advised to take
during the evening meal)
Prescribing Notes
 Those with, or at risk of, osteoporosis should maintain adequate
supply of calcium and vitamin D. If deficiency is suspected, this
should be corrected by increasing dietary intake or taking
supplements. See National Osteoporosis Society website for
information on calcium rich food and a calcium calculator
 Supplementation with calcium and vitamin D alone has been
31
shown to reduce fracture rates in housebound elderly patients
without previous fracture. Evidence in other patient groups is
lacking
 There is no convincing evidence associating calcium
supplementation and cardiovascular disease. However, with the
introduction of licensed vitamin D preparations, many clinicians
are moving away from the use of combined calcium and vitamin
D preparations in favour of single agent vitamin D preparations
(in patients who are calcium replete)
 For vitamin D guidance, see section 9.6.4 add jumps
(b) Bisphosphonates
Formulary
choices
Risedronate
sodium tablets
35mg
Dose:
35mg once weekly. Take with a full
glass of water on an empty stomach at
least 30 minutes before breakfast and
other medication (e.g. calcium
supplements). Stand or sit upright for at
least 30 minutes and do not lie down
until after breakfast
Or
Alendronic acid
tablets 70mg
Dose:
70mg once weekly. Take with a full
glass of water on an empty stomach at
least 30 minutes before breakfast and
other medication (e.g. calcium
supplements). Stand or sit upright for at
least 30 minutes and do not lie down
until after breakfast
32
Prescribing Notes
 People receiving drug treatment for osteoporosis (unless
confident that the patient is receiving an adequate dietary
intake) should receive a vitamin D supplement (+/- calcium).
Click here for formulary choices – add jump
 Before starting treatment, calcium, phosphate, alkaline
phosphatase and renal function should be checked
 Due to concerns about these potential side effects of long-term
bisphosphonate therapy, patients should be assessed for
benefit and on-going need after 5 years of oral bisphosphonate
therapy. For those patients who are then deemed at continued
high risk of fracture and who continue to receive treatment, local
expert opinion is that no patient should receive continuous oral
bisphosphonate therapy for more than 10 years without referral
to a specialist
 GI Side Effects
o Bisphosphonates have complex administration
instructions. GI side effects are minimised by following
these instructions
o Oral bisphosphonates should be avoided in anyone with a
history of oesophageal stricture or severe oesophagitis
o Risedronate may be preferable in those patients that have
a history of (recent) proven peptic ulcer disease, active
GORD, or develop significant GI side effects on
alendronate
o PPIs are unlikely to be helpful as this is due to a local
irritant effect
 Long term adherence is poor and patients should be
encouraged to continue taking their bisphosphonate
 Monthly oral ibandronate is an alternative option for younger
patients who have predominantly spinal osteoporosis (no data
is available for hip fracture)
 The intravenous bisphosphonates zoledronic acid and
ibandronic acid are red list drugs for specialist use only
33
Cautions
 Renal impairment:
Alendronate should be avoided if eGFR <35mL/min
Risedronate should be avoided if eGFR < 30mL/min
 High dose IV bisphosphonate therapy is associated with
osteonecrosis of the jaw. It is rarely associated with oral
bisphosphonates. History of poor dentition is a risk factor. Refer
to MHRA advice
 Atypical femoral fracture has been reported rarely with
bisphosphonate treatment, mainly in patients receiving longterm treatment for osteoporosis. Patients should be advised to
report any thigh, hip or groin pain. The need to continue
bisphosphonate treatment for osteoporosis should be reevaluated periodically based on the benefits and potential risks
of bisphosphonate therapy for individual patients, particularly
after 5 or more years of use and should not exceed 10 years.
See MHRA warning for further details
 Osteonecrosis of the external auditory canal has been reported
very rarely with bisphosphonates. For full details see MHRA
warning
(c) Other drug therapies used in osteoporosis
Denosumab
 Denosumab is recommended in post-menopausal osteoporosis
where oral bisphosphonates are unsuitable due to contraindication (severe GORD), intolerance or compliance issues
 Denosumab is an amber list drug. Further details can be found in
the Shared Care Guideline:
Hormone Replacement Therapy (HRT) add jump to HRT section
 HRT should be considered for women who have experienced a
premature menopause to reduce their risk of osteoporotic fractures
and for relief of menopause symptoms
 HRT should not be considered first-line therapy for the long-term
34
prevention of osteoporosis in women over 50 years of age. It is an
option where other therapies are contraindicated, cannot be
tolerated, or if there is a lack of response. For most women the
benefits of HRT outweigh the small risks up to the age of 60 years
and women will gain bone protection if they are taking HRT for
symptom relief
Raloxifene
 Raloxifene is an alternative option for patients for the secondary
prevention of osteoporotic fractures in postmenopausal women in
line with NICE TA161. It is not recommended for primary
prevention
 Raloxifene has not been shown to prevent non-vertebral fractures
Strontium
 Strontium ranelate is restricted to patients with severe
osteoporosis who cannot use other treatments and should NOT be
started in people who have or have had:
o ischaemic heart disease
o peripheral arterial disease
o cerebrovascular disease
o uncontrolled hypertension
 See MHRA warnings for further information
Teriparatide
 Teriparatide is a red list drug and therefore for specialist use only
35
6.7 Other endocrine drugs
6.7.1 Dopamine-receptor agonists
Treatment of hyperprolactinaemia
1st choice
Cabergoline tablets
500 micrograms
Dose:
See BNF for dose
adjustment
2nd choices
Bromocriptine tablets
1mg, 2.5mg; capsules
5mg, 10mg
Dose:
Initial dose usually 1–
1.25mg at bedtime;
see BNF for dose
adjustment
Or
Quinagolide tablets 25
micrograms,
50micrograms,
75micrograms
Dose:
See BNF for dose
adjustment
Prescribing Notes
 Choice of drug therapy should be made by specialist depending on
individual patient circumstances
 A shared care guideline for cabergoline is available here:
 Bromocriptine is the drug of choice for hyperprolactinaemia if
pregnancy is sought
 For suppression of lactation, see BNF
 For Parkinson’s disease, see section 4.9.1 ADD JUMP
6.7.4 Acromegaly
The primary treatment of acromegaly is usually pituitary surgery.
Management and treatment requires specialist involvement.
36
Prescribing Notes
 Lanreotide and octreotide are indicated for the relief of symptoms
associated with acromegaly
 See BNF chapter 8 for the use of somatostatin analogues
(octreotide and lanreotide) in neuroendocrine tumours
 A shared care guideline for lanreotide is available here
 A shared care guideline for octreotide is available here
37