Insulin Glargine

Registered South African indications:

• Diabetes mellitus

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients 
• Children <6 years of age

Cautions

• Pregnancy
• Severe renal impairment
• Severe hepatic impairment
• Elderly
• Diabetic ketoacidosis
• Patients at risk of cardiac complications of hypoglycaemia
• Patients at risk of cerebral complications of hypoglycaemia
• Proliferative retinopathy, particularly if not treated with photocoagulation
• Autonomic neuropathy
• Long history of diabetes
• Psychiatric illness
• Driving and the ability to operate machinery
• Intercurrent illness (e.g. vomiting, diarrhoea)
• Inadequate food intake
• Missed meals
• Unaccustomed, increased or prolonged physical activity
• Improved insulin sensitivity
• Alcohol consumption
• Certain uncompensated endocrine disorders (e.g. hypothyroidism and in anterior pituitary or adrenocortical insufficiency)
• Patients with risk factors for development of cardiac heart failure

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

Insulin-dependent diabetes mellitus 

• See link: General prescribing points on the principles of insulin dosing

The dosage should be determined by the healthcare professional, according to the requirements of the patient

See Additional Prescribing Points

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

Insulin-dependent diabetes mellitus

• See link: General prescribing points on the principles of insulin dosing

Not registered for use in South Africa for children below 6 years

The dosage should be determined by the healthcare professional, according to the weight and requirements of the patient

Pregnancy 

• Caution
• The human pregnancy experience with insulin glargine demonstrates that the risk to the embryo or foetal harm is low, if it exists at all
• As with all insulins, the primary concern is severe maternal hypoglycaemia
• It is not known if insulin glargine crosses the human placenta. Human insulin does not cross the placenta in clinically significant amounts
• Because of the close similarity between insulin glargine and human insulin, and its high molecular weight (6063), insulin glargine probably does not cross either
• In animal studies, the effects of insulin glargine did not generally differ from those resulting from human insulin
• Several reports have described the use of insulin glargine in human pregnancy. These reports concluded that the insulin analogue had maternal efficacy and safety similar to other insulins. No embryo-foetal adverse effects related to the drug were observed

Breastfeeding

• Compatible
• Insulin is a naturally-occurring constituent of the blood and is excreted into breast milk
• In a study, milk samples were obtained from breastfeeding mothers, the results showed that insulin, both endogenous and exogenous, are actively transported from the blood into milk and is protected from degradation and, presumably, has a functional developmental role in the infant
• No metabolic effects of ingested insulin glargine on the breastfed newborn/infant are anticipated since insulin glargine as a peptide is digested into aminoacids in the human gastrointestinal tract
• Breastfeeding women may require adjustments in insulin dose 

Renal impairment

• eGFR >30-89 ml/min/1.73 m²: No dose adjustment recommended
• eGFR <29 ml/min/1.73 m²: Caution; dose adjustment recommended
  Adjust insulin dose according to blood glucose ranges

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 ranges

Elderly

• Caution; dose adjustment recommended
  The dose of insulin glargine should be adjusted according to blood glucose measures

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Prohibited - At all times

Central Nervous System Disorders

• Dysgeusia

Endocrine and Metabolic Disorders

• Hypoglycaemia
• Sodium retention

Musculoskeletal Disorders

• Myalgia

Skin and Subcutaneous Tissue Disorders

• Lipohypertrophy
• Lipoatrophy
• Cutaneous amyloidosis
• Injection site redness, pain, itching, swelling or inflammation
• Hives

Immune, Blood and Lymphatic System Disorders

• Allergic reactions
• Immediate-type allergic reactions:
  - Generalised skin reactions
  - Angio-oedema
  - Bronchospasm
  - Hypotension
  - Shock
  - Death
• Formation of neutralising insulin antibodies

Sensory Disorders

• Visual impairment
• Retinopathy
• Transient amaurosis

Others

• Oedema

• Pioglitazone
• Beta blockers
• Clonidine
• Lithium salts
• Alcohol
• Pentamidine
• Guanethidine
• Reserpine
• Oral antidiabetic medicinal products
• Angiotensin converting enzyme (ACE) inhibitors
• Disopyramide
• Fibrates
• Fluoxetine
• Monoamine oxidase (MAO) inhibitors
• Pentoxifylline
• Propoxyphene
• Salicylates
• Somatostatin analogues
• Sulphonamide antibiotics
• Corticosteroids
• Danazol
• Diazoxide
• Diuretics
• Glucagon
• Isoniazid
• Oestrogens and progestogens
• Protease inhibitors
• Atypical antipsychotic medications
• Olanzapine
• Clozapine
• Phenothiazine derivatives
• Somatropin
• Sympathomimetic agents
• Epinephrine
• Salbutamol
• Terbutaline
• Thyroid hormones

Diabetes mellitus

• Blood glucose
• HbA1c
• Renal function
• Hepatic function

Gestational diabetes mellitus

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

Storage instructions

• Store between 2^oC and 8^oC, away from direct light
• Do not freeze. Ensure that the container is not directly touching the freezer compartment or freezer packs
• Once in use the cartridge, vial or disposable pen may be stored up to 30^oC for 4 weeks. The reusable pen containing a cartridge must not be stored in the refrigerator. The unused portion must be discarded
• Keep vial in the original carton. It is recommended that the date of the first withdrawal from the vial be noted on the label

Method of administration

• Insulin glargine is administered subcutaneously
• Insulin glargine should not be administered intravenously. The prolonged duration of action of insulin glargine is dependent on its injection into subcutaneous tissue. Intravenous administration of the usual subcutaneous dose could result in severe hypoglycaemia
• There are no clinically relevant differences in blood insulin or glucose levels after abdominal, deltoid or thigh administration of insulin glargine. Injection sites must be rotated within a given injection area from one injection to the next
• Insulin glargine must not be mixed with any other insulin or diluted. Mixing or diluting can change its time/action profile and mixing can cause precipitation

Special precautions for disposal and other handling

Insulin Pen 

• The pen should be used as recommended in the information provided with the device
• The instructions for using the pen must be followed carefully for loading the cartridge, attaching the needle and administering the injection
• If the pen is damaged or not working properly (due to mechanical defects) it has to be discarded, and a new pen has to be used

Cartridge

• Inspect the cartridge before use
• It must only be used if the solution is clear, colourless, with no solid particles visible, and if it is of water-like consistency
• Before insertion into the pen, the cartridge must be stored at room temperature for 1 to 2 hours
• Air bubbles must be removed from the cartridge before injection 
• Empty cartridges must not be refilled and must be properly discarded. Insulin label must always be checked before each injection to avoid medication errors between insulin glargine and other insulins

Pre-filled pen (KwikPen)

• Inspect the cartridge before use
• It must only be used if the solution is clear, colourless, with no solid particles visible, and if it is of water-like consistency
• Insulin glargine must not be mixed with any other insulin or diluting. Mixing or diluting can change its time/action profile and mixing can cause precipitation
• Empty pens must never be reused and must be properly discarded
• To prevent possible transmission of disease, each pen must be used by one patient only
• Insulin label must always be checked before each injection to avoid medication errors between insulin glargine and other insulins
• The patient should be advised to read the instructions for use included in the package leaflet carefully before use

Insulin glargine is a human insulin analogue designed to have a low solubility at a neutral pH. It is completely soluble at the acidic pH of the injection solution. After injection into the subcutaneous tissue, the acidic solution is neutralised leading to the formation of micro-precipitates from which small amounts of insulin glargine are continuosly released resulting in a prolonged duration of action.

Injection (per ml) 100u

• Basaglar (Eli Lilly) 
• Endulin Select (Mylan)
• Lantus (Sanofi Aventis) originator
• Optisulin (Sanofi Aventis)

Injection (per ml) 300u

• Toujeo (Sanofi Aventis) originator