6: Endocrine system
Please select a topic:
6.1 Drugs used in diabetes / 6.2 Thyroid and antithyroid drugs6.3 Corticosteroids / 6.4 Sex hormones
6.5 Hypothalamic and pituitary hormones and anti-oestrogens / 6.6 Drugs affecting bone metabolism
6.7 Other endocrine drugs
Changes to the Formulary since previous version
(17.3.2014)
Section / Change / Reason for change6.1 – Diabetic Equipment. / REMOVED: Ketur / Discontinued
6.5 / ADDED: Merional® / Gateshead Medicines Management Committee approval
6.1 Drugs used in diabetes
Insulins
General notes
· Insulin should be initiated on specialist advice only. Choice depends on the particular needs of the individual patient, taking into account lifestyle, age, preference and capabilities.
· Type of insulin, device and needle size should be specified. Care should be taken to write the brand name in full to avoid errors such as, for example, administration of Humalog® in place of Humalog® Mix25 or Humalog® Mix50.
· Patients should not be changed from the insulin that they are currently receiving without specialist advice; ensure that the correct insulin has been prescribed.
· Insulin is available in 3mL cartridges, 10mL vials, and 3mL disposable pens. Not all insulin cartridges fit all pens.
· Pens are available on prescription.
· The B-D Safe-Clip® device snaps the needle off insulin syringes and stores the needle safely inside the clipper; this device is available on prescription.
Short-acting insulins
· Human Actrapid 10ml vial
· Human Novarapid 10ml vial, 3ml cartridges, 3ml flexpen
· Humulin S 10ml vial, 3ml cartridges
· Insulin Gluisline (Apidra®) 3ml solostar pen, 10ml vial, 3ml cartridges
· Insulin Lispro (Humalog) 10ml vial, 3ml cartridges, 3ml Kwik pen
Intermediate-acting insulins
· Humulin I 10ml vial, 3ml cartridges, 3ml Kwik pen
· Human Insulatard 10ml vial, 3ml cartridges, prefilled disposable pen
Long-acting insulins
· Insulin Glargine (Lantus) 10ml vial, 3ml cartridges, 3ml Solostar pen
· Insulin Detemir (Levemir®) 3ml cartridges, prefilled disposable pen(Flexpen)
Biphasic insulins
· Human Novomix 30 3ml cartridges, prefilled disposable pen(Flexpen)
· Humulin M3 10ml vial and 3ml cartridges, 3ml Kwik pen
· Humalog Mix 25 10ml vial, 3ml cartridges and prefilled disposable pens
· Humalog Mix 50
MHRA Drug Safety Update
Insulin glargine: studies of possible cancer link
Article date: September 2009
Summary
Recent observational studies have suggested a possible association between insulin glargine and an increased risk of cancer. The results are not entirely consistent, and can neither confirm nor exclude a relationship between insulin glargine and cancer. Therefore, the European Medicines Agency has advised that no change in recommendations for use is required at present.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087909
Antidiabetic drugs
· Acarbose 50mg tablets
· Exenatide 5microgram/dose and 10microgram/dose pen (Byetta®)
· Exenatide MR 2mg injection (Bydureon®)
· Liraglutide 18mg/3ml pen
· Lirxisenatide 10microgram and 20microgram injection
· Glibenclamide 2.5mg, 5mg tablets
· Gliclazide 30mg MR tablets
· Gliclazide 80mg tablets
· Glimepiride 1mg and 2mg tablets
· Glipizide 5mg tablets
· Metformin 500mg, 850mg tablets
· Metformin 500mg/5ml suspension
· Metformin SR 500mg and 1000mg tablets
· Metformin 500mg and 1000mg sachets
· Pioglitazone 15mg and 30mg tablets
· Sitagliptin 25mg, 50mg, 100mg tablets
· Linagliptin 5mg tablets
· Tolbutamide 500mg tablets
· Dapaglifozin 5mg and 10mg tablets
Dose
- Metformin tablets 500mg, 850mg: initially 500mg once or twice daily with meals; gradually increased to max 2g daily divided doses.
- Metformin SR tablets 500mg, 1000mg: initially 500mg once; gradually increased to max 2g once daily with evening meal.
- Metformin sachets 500mg: initially 500mg once; gradually increased to max 2g once daily with evening meal.
- Acarbose tablets 50mg: initially 50mg daily; gradually increased to max 200mg three times a day.
- Exenatide (Byetta®) injection 250micrograms/ml: initially 5micrograms twice daily within 1 hours before 2 main meals (at least 6 hours apart), increased if necessary after at least 1 month to max 10micrograms twice daily.
- Exenatide MR (Bydureon®) injection 2mg: 2mg once a week.
- Liraglutide injection 6mg/ml: initially 0.6mg once daily, increased after at least 1 week to 1.2mg once daily, increased if necessary after at least 1 week to max 1.8mg once daily.
- Lixisenatide injection 10microgram, 20microgram: initially 10 micrograms once daily, increased after at least 14 days to 20 micrograms once daily.
- Sitagliptin tablets 100mg: 100mg once daily.
- Linagliptin tablets 5mg: usual dose is 5mg once daily.
- Tolbutamide tablets 500mg: 500mg to 1g (max 2g) daily in divided doses with or immediately after breakfast.
- Glimepiride tablets 1mg and 2mg: initially 1mg daily with meals; adjusted according to response up to usual max 4mg daily.
- Glibenclamide tablets 2.5mg and 5mg: initially 5mg daily with or immeditately after breakfast; adjusted according to response up to max 15mg daily.
- Gliclazide tablets 80mg: initially 40-80mg daily, max 320mg daily; doses above 160mg daily should be divided.
- Glipizide tablets 2.5mg, 5mg: initially 2.5-5mg daily, max 20mg daily; doses above 10mg daily can be divided.d to usual maintenance dose 1g twice daily; max 3g daily in divided doses.
- Pioglitazone tablets 15mg, 30mg: in combination with metformin or a sulphonylurea, 15-30mg once daily.
- Dapaglifozin tablets 5mg, 10mg: usual dose is 10mg once daily.
Prescribing notes
General notes
· First-line treatment for management of type 2 diabetes is usually a trial of dietary therapy unless there is intercurrent infection, severe hyperglycaemia or severe osmotic symptoms.
· Patients commencing blood glucose lowering agents should inform the DVLA and their car insurance company.
· Those with type 2 diabetes may require treatment with insulin, either alone or in combination with oral agents.
· Newer hypoglycaemic agents are substantially more expensive than the older hypoglycaemic agents.
Biguanides and sulphonylureas
· Metformin is the first choice oral hypoglycaemic drug. It is the only oral antidiabetic drug which has a proven survival advantage. It does not need to be limited to overweight patients.
· Due to the rare but serious risk of lactic acidosis, metformin must be avoided in patients with: significant renal impairment (estimated glomerular filtration rate (eGFR) less than 30mL/min); alcoholism with previous pancreatitis; severe cardiac/respiratory disease producing tissue hypoxia; severe liver disease with potential for hepatic failure.
· The precipitant of a lactic acid crisis is often in the eGFR range 30 to 45mL/min when the patient develops what would have been a trivial illness (such as diarrhoea and vomiting) which compromises renal function and causes acute renal failure. This is compounded if the patient is also taking diuretics and/or ACE inhibitors in combination with metformin. Unlike acute illnesses in type 1 diabetes (where insulin treatment MUST be continued) stopping the above cocktail of drugs for a day or two will NOT cause any immediate problem for the patient and will protect renal function until the patient improves. Blood glucose estimation should be used to assess any glycaemic deterioration. In circumstances where renal impairment is suspected, NSAIDs should NOT be used as they can further compromise renal function.
· Metformin may cause gastro-intestinal adverse effects; it should be started at low dose and taken after meals, and the dose gradually increased every 10-15 days if tolerated. Hypoglycaemia is not a problem with metformin monotherapy.
· Metformin prolonged release tablets (Glucophage SR®) are restricted for use in patients who are unable to tolerate immediate release metformin, and in whom the continued use of metformin offers a clinically significant benefit. They are more expensive than the immediate release tablets but les expensive than other newer oral agents.
· Sulphonylureas should be taken before meals
· Gliclazide 30mg m/r (Diamicron® MR) should be reserved for patients with demonstrable compliance problems.
· Patients should be informed that sulphonylureas can cause hypoglycaemia. The risk of hypoglycaemia increases with age.
Dapagliflozin
· Dapagliflozin reversibly inhibits sodium-glucose co-transporter 2 in the kidneys to reduce glucose reabsorption and increase glucose excretion.
Glitazones (thiazolidinediones)
· Pioglitazone can be used in combination with insulin in patients with type 2 diabetes mellitus, who have insufficient glycaemic control on insulin, in whom metformin is inappropriate because of contraindications or intolerance.
· Glitazones can cause weight gain and fluid retention. They must not be used in patients with heart failure or history of heart failure.
· Glitazones reduce bone mineral density in post-menopausal women with a subsequent increase in fracture risk. They should be avoided in elderly women with high fracture risk, irrespective of cardiovascular risk.
· Liver function should be checked before initiating glitazones and periodically thereafter based on clinical judgement. Glitazones should not be used in patients with hepatic impairment.
· There is an increased risk of hypoglycaemia when combined with a sulphonylurea.
MHRA Drug Safety Update
Pioglitazone: risk of bladder cancer
Article date: August 2011
Summary
Use of pioglitazone is associated with a smallincreased risk of bladder cancer. Healthcare professionals should be aware of new warnings and precautions for use in at-risk patients.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON125962
MHRA Drug Safety Update
Insulin combined with pioglitazone: risk of cardiac failure
Article date: January 2011
Summary
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for the development of cardiac failure. If the combination is used, patients should be observed for signs and symptoms of heart failure, weight gain, and oedema.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON105746
Dipeptidyl peptidase-4 inhibitor (DDP-4 inhibitor)
· Sitagliptin is approved for use by prescribers with a special interest in diabetes. It should be used in combination with metformin where the addition of a sulphonylurea is not appropriate.
· Linagliptin should be reserved for use in patients with moderate to severe renal impairment.
· DDP-4 inhibitors are considered to be weight neutral.
· DPP-4 inhibitors have been shown to reduce Hb1Ac levels but there is not data on morbidity, mortality, or long-term adverse effects.
MHRA Drug Safety Update
Dipeptidylpeptidase-4 inhibitors (gliptins): risk of acute pancreatitis
Article date: September 2012
Summary
There have been reports of acute pancreatitis associated with drugs in the dipeptidylpeptidase-4 (DPP-4) inhibitor class of antidiabetic agents (‘gliptins’). Patients should be informed of the characteristic symptoms of acute pancreatitis – persistent, severe abdominal pain (sometimes radiating to the back) – and encouraged to tell their healthcare provider if they have such symptoms. If pancreatitis is suspected, the DPP-4 inhibitor and other potentially suspect medicinal products should be discontinued.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON185628
Incretin mimetic
· Exenatide should only be used as a 3rd line option. All new patients requiring a GLP-1 should be prescribed lixisenatide or liraglutide.
· 10-20% of patients experience upper gastro-intestinal side effects with exenatide. Acute pancreatitis has been reported with exenatide, patients should be informed of the warning signs to look for.
· Liraglutide may be an option in those experiencing excessive side-effects with exenatide/lixisenatide. It is administered once a day independent of food intake, which may suit those with irregular working patterns.
· There is an increased risk of hypoglycaemia when combined with a sulphonylurea.
· Long term studies are needed to determine the effects of exenatide and liraglutide on disease related morbidity and mortality.
· Gastric emptying may be delayed, therefore the rate and extent of absorption of other drugs administered at the same time may be affected. For oral drugs that require threshold concentrations for efficacy, patients should take these medicines at least 1 hour before.
MHRA Drug Safety Update
Exenatide (Byetta®): risk of severe pancreatitis and renal failure
Article date: March 2009
Summary
Suspected adverse reaction reports of necrotising and haemorrhagic pancreatitis have been received in association with exenatide. Some of these reports had a fatal outcome. If pancreatitis is diagnosed, exenatide should be permanently discontinued. Reports of renal impairment, including acute renal failure and worsened chronic renal failure have also been received. Exenatide is not recommended for use in patients with end-stage renal disease or severe renal impairment.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON088117
Treatment of hypoglycaemia
· Glucagon 1mg syringe
· Glucose 40% gel 25g
Dose
- Glucagon 1mg vial: subcutaneous, intramuscular or intravenous injection, adult and child over 25kg- 1 mg.
Prescribing notes
· Following administration of glucagon, it is important to give supplementary carbohydrate to restore liver glycogen and prevent secondary hypoglycaemia.
· Although intravenous glucose is the more effective treatment where intravenous access is readily available, intramuscular glucagon may be more appropriate.
· Glucagon injection may be repeated once after 10 minutes if necessary, but intravenous glucose is preferable. If there is no response, then hospital admission should be considered.
Diabetic equipment
· Insulin syringes 100 units
· Microfine + needles 5mm, 8mm, 12.7mm
· Accu-check advantage II Test strips
· Accu-check Aviva blood test strips
· Diabur 5000 strips
· Ketodiastix test strips
· BD Optimus Lancer, Microfine + lancets, BD safe clip
· Penfine needles Sizes 6mm, 12mm
· Novofine needles sizes 6mm, 8mm, 12mm
· Humapen Ergo
· Accu-check Fastclix lancets
Choice of meter depends on experience and patient preference and capabilities e.g. visual acuity, manual dexterity. Meters are not available on prescription. Patients may purchase any meter but should do so only following expert advice from a suitably trained person. Strips may be prescribed and can also be bought over-the-counter.
Prescribing notes
· Home blood glucose monitoring in non-insulin treated Type 2 diabetes should routinely be undertaken:
* where treatment change is indicated
* to monitor a treatment change
* where hypoglycaemia is suspected
* where control is poor
· In such cases, blood glucose monitoring should not require to be performed routinely on more than 2 days in the week or more than twice in the day. The timing of the samples will depend on the particular case but a fasting value is useful. Correct meter care and quality control are essential when meters are used.
· Patients must be aware of how to interpret the results.