Insulin Detemir

Registered South African indications:

• Diabetes mellitus

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Intravenous administration
• Hypoglycaemia
• Children <2 years of age

Cautions

• Severe renal impairment or ESRD
• Severe hepatic impairment
• Elderly
• Inadequate dosing or discontinuation of treatment
• Changes to usual meal plan (e.g. skipped meals)
• Unplanned, strenuous physical exercise
• Changes in physical activity
• Greatly improved blood glucose control
• Concomitant illness (e.g. fever or infections)
• Concomitant diseases affecting the adrenal, pituitary or thyroid gland
• Transfer from other insulin medicinal products
• Visual impairment
• Long standing diabetes mellitus
• Driving and the ability to operate heavy machinery

Forms avail. in SA and covered in this monograph: inj

Insulin-dependent diabetes mellitus 

The dose of insulin should be individually adjusted

• SC (inj): Initial: 0.4-0.5 units/kg/day; Maintenance: 0.4-1.0 units/kg/day in divided doses
• See link:  General prescribing points on the principles of insulin dosing

For patients at higher risk of hypoglycaemia (on oral hypoglycaemic agents, malnutrition, elderly, and low cognitive status), conservative initial doses of 0.2-0.4 units/kg/day may be considered to avoid the potential for hypoglycaemia

Higher initial doses may be required in patients who are obese, sedentary, or presenting with ketoacidosis 

For individual dose adjustments, the following titration guidelines are recommended for adult type 2 diabetes:

^*Self-Monitored Plasma Glucose

The above-recommended dosages must be individual-titrated to achieve glucose control and avoid hypoglycaemia

When adjusting dose in order to improve glucose control, patients should be advised to be aware of the signs of hypoglycaemia

Insulin detemir can be given at any time during the day, but at the same time each day

Insulin detemir can be used alone as the basal insulin or in combination with bolus insulin. It can also be used in combination with oral antidiabetic medicines or as add-on therapy to GLP-1 receptor agonists (e.g. dulaglutide)

See Additional Prescribing Points

Paed. forms avail. in SA and covered in this monograph: inj

Insulin-dependent diabetes mellitus

The dose of insulin should be individually adjusted

• SC (inj): Maintenance: 0.5-1.0 units/kg/day in divided doses
• During puberty, maintenance doses may be increased to the range of 1.2-2.0 units/kg/day
• See link:  General prescribing points on the principles of insulin dosing

Not registered for use in South Africa for children below 2 years

Glucose monitoring should be intensified in children and adolescents

Care should be taken to match insulin doses (especially in basal-bolus regimens) with food intake and physical activities in order to minimise the risk of hypoglycaemia

Pregnancy

• Safe
• Treatment with insulin detemir can be considered during pregnancy, but any potential benefit must be weighed against a possibly increased risk of an adverse pregnancy outcome
• The human data presented by the manufacturer and other sources indicate that the effects of insulin detemir on the embryo and/or the fetus are similar to human insulin
• It is not known if insulin detemir crosses the human placenta. Human insulin does not cross the placenta in clinically significant amounts. Because of the close similarity between insulin detemir and human insulin, and its high molecular weight (~5917), insulin detemir probably does not cross either
• In general, intensified blood glucose control and monitoring of pregnant women with diabetes are recommended throughout pregnancy and when contemplating pregnancy
• Insulin requirements usually fall in the first trimester and increase subsequently during the second and third trimester. After delivery, insulin requirements normally return rapidly to pre-pregnancy values
• Post-marketing data from 250 outcomes from pregnant women exposed to insulin detemir indicate no adverse effects of insulin detemir on pregnancy and no malformative or foetal/neonatal toxicity of insulin detemir
• Animal data do not indicate reproductive toxicity

Breastfeeding

• Compatible 
• It is unknown whether insulin detemir is excreted in human milk
• No reports describing the use of insulin detemir during human lactation has been located. Insulin is a natural component of the blood and is excreted into breast milk. Insulin detemir is probably also present in milk
• No metabolic effects of ingested insulin detemir on the breastfed newborn/infant are anticipated since insulin detemir, as a peptide, is digested into amino acids in the human gastrointestinal tract
• Breastfeeding women may require adjustments in insulin dose and diet

Fertility

• Animal studies do not indicate harmful effects with respect to fertility

Renal impairment

• eGFR >30-89 ml/min/1.73m²: No dose adjustment recommended
• eGFR <29 ml/min/1.73m² or ESRD: Caution; dose adjustment recommended
  Reduce recommended dose by up to 20%. Monitor glucose target and renal function

Hepatic impairment

• Mild to moderate (Child-Pugh Classes A & B): No dose adjustment recommended
• Severe (Child-Pugh Class C): Caution; dose adjustment recommended
  Adjust insulin dose according to blood glucose target

Elderly

• Caution; dose adjustment recommended
  Conservative initial dose is required to avoid risk for hypoglycaemia. Reduce the initial recommended dose by 10-20%. Avoid intensive glucose control (risk for hypoglycaemia and CVS-related mortality)
  Control of geriatric patient's blood glucose needs to be individualised. In cases of severe hypoglycaemia, dosage reductions of 20-40% have been recommended

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Prohibited - At all times

Endocrine and Metabolic Disorders

• Hypoglycaemia

Musculoskeletal Disorders

• Peripheral neuropathy

Skin and Subcutaneous Tissue Disorders

• Urticaria
• Rash
• Eruptions
• Injection site lipodystrophy
• Injection site reactions
  - Pain
  - Redness
  - Hives
  - Inflammation
  - Bruising
  - Swelling
  - Itching

Immune, Blood and Lymphatic System Disorders

• Anaphylactic reactions
  - Generalised skin rash
  - Itching
  - Sweating
  - Gastrointestinal upset
  - Angioneurotic oedema
  - Difficulties breathing
  - Palpitation
  - Reduction in blood pressure

Sensory Disorders

• Transient refraction anomalies
• Diabetic retinopathy

Others

• Oedema

• Pioglitazone
• Beta-blockers
• Octreotide
• Lanreotide
• Alcohol
• Oral antidiabetic medicinal products
• GLP-1 receptor agonists
• Dulaglutide
• Monoamine oxidase inhibitors (MAOIs)
• Angiotensin converting enzyme (ACE) inhibitors
• Enalapril
• Angiotensin receptor blockers (ARBs)
• Losartan
• Renin antagonists
• Aliskiren
• Salicylates
• Anabolic steroids
• Sulphonamides
• Oral contraceptives
• Thiazides
• Glucocorticoids 
• Thyroid hormones
• Sympathomimetics
• Epinephrine
• Growth hormone
• Danazol

Diabetes mellitus 

• Blood glucose 
• Electrolytes
• HbA1c
• Renal function
• Hepatic function
• Weight

Gestational diabetes mellitus

• Blood glucose 4 times daily (1 fasting and 3 after meals)

Overdose

• A specific overdose for insulin cannot be defined, however, hypoglycaemia may develop over sequential stages if too high doses relative to the patient's requirement are administered
• Mild hypoglycaemic episodes can be treated by oral administration of glucose or sugary products. It is therefore recommended that the diabetic patient always carries sugar-containing products
• Severe hypoglycaemic episodes, where the patient becomes unconscious, can be treated with glucagon (0.5 to 1mg) given intramuscularly or subcutaneously by a trained person, or with glucose given intravenously by a healthcare professional. Glucose must be given intravenously if the patient does not respond to glucagon within 10 to 15 minutes. Upon regaining consciousness, administration of oral carbohydrates is recommended for the patient in order to prevent a relapse
• Beta-blockers may also mask the symptoms of hypoglycaemiaand delay recovery from hypoglycaemia

Special precautions for use

• Insulin detemir should not be mixed with other insulins
• Insulin detemir is not to be used in insulin infusion pumps
• Substances added to insulin detemir may cause degradation of insulin detemir itself e.g. if the additive contains thiols or sulphites
• Insulin detemir should not be added to infusion fluids

Dosing precautions

• Insulin detemir is administered subcutaneously by injection in the thigh or abdominal wall. Injection sites should be alternated within the same region
• Insulin detemir should not be administered intravenously as it may result in severe hypoglycaemia
• Insulin detemir should be administered once or twice daily depending on the patient's needs
• The insulin detemir injection can be given at any time during the day, provided it is at the same time each day
• For patients who require twice daily dosing of insulin detemir to optimise their blood glucose control, the evening dose can be administered either with the evening meal, at bedtime, or 12 hours after the morning dose
• Transferring patients from intermediate or long-acting insulins to insulin detemir may require adjustment of dose and timing of administration, close glucose monitoring is recommended during the transition and thereafter

Travelling

• Before travelling between different time zones, the patient should seek the doctor's advice since this may mean that the patient has to take the insulin and meals at different times

Storage and handling 

• Store in a refrigerator between 2°C-8°C. Keep away from the cooling element
• Do not freeze - insulin detemir that has been frozen must not be used
• Do not use if the solution is not clear, colourless and aqueous
• The patient should be advised to discard the needle after each injection
• Any unused insulin detemir should be disposed of in accordance with local requirements
• Needles, cartridges and pre-filled pens must not be shared
• Cartridges must not be refilled

Insulin detemir is a soluble, long-acting insulin analogue with a prolonged duration of effect used as a basal insulin. The prolonged action of insulin detemir is mediated by the strong self-association of insulin detemir molecules at the injection site and albumin binding via the fatty acid side chain. The blood glucose lowering effect of insulin detemir is due to the facilitated uptake of glucose following binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver.

Injection (per ml) 100u

• Levemir (Novo Nordisk) originator