Glysolin G

Insulin glargine.

Each mL of cartridge contains: Insulin Glargine (rDNA) 100 IU, m-Cresol (as preservative) 0.27% w/v and Water for Injection q.s.
Insulin Glargine Injection (rDNA) origin is a recombinant human insulin analogue produced by Recombinant DNA technology. Insulin Glargine differs from human insulin in that the amino acid asparagine at position A2t is replaced by glycine and two arginines are added to the C-terminus of the B chain.
Chemically it is a 21^-Gly-30a-L-Arg-30b-Arg human insulin and has the empirical formula of C₂₆₇H₄₀₄N₇₂O₇₈S₆ and a molecular weight of 6063.
Insulin Glargine is an insulin analogue, equipotent to human insulin, with a peakless glucose lowering profile and a prolonged duration of action that permits once daily dosing.
Excipients/ Inactive Ingredients: Active: Insulin Glargine (rDNA).
Inactive: m-Cresol (as preservative), Water for Injection.

Pharmacotherapeutic Group: Antibdiabetic.
Pharmacology: Pharmacodynamics: The primary activity of insulin, including Insulin Glargine, is the regulation of glucose metabolism. Insulin and its analogues lower blood glucose levels by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis in the adipocyte, inhibits proteolysis and enhances protein synthesis.
Insulin Glargine differs from other insulins because its unique structure provides a smooth and peakless profile with a prolonged duration of action of 24 hours (end of observation period) compared to 14.5 hours for NPH Human Insulin.
In clinical studies, intravenous Insulin Glargine and human insulin have been shown to be equipotent when given at the same doses. The onset of action of Insulin Glargine is slower than NPH human insulin. The effect profile of Insulin Glargine is smooth and peakless, and the duration of its effect is prolonged compared to NPH human insulin.
Pharmacokinetics: After subcutaneous injection of Insulin Glargine, the insulin serum concentrations indicate a slower, more prolonged absorption and a lack of peak in comparison to NPH human Insulin. Concentrations are thus consistent with the time profile of the pharmacodynamics activity of Insulin Glargine.
Insulin Glargine is a human Insulin analogue that has been designed to have a low solubility at neutral pH. At pH 4, the pH of Insulin Glargine injection solution, it is completely soluble. After injection to subcutaneous tissue, the acidic solution is neutralized, leading to formation of microprecipitates from which small amounts of Insulin Glargine are continuously released, providing a smooth, peakless predictable time/concentration profile and a prolonged duration of action. This allows once daily dosing to meet a patient's basal insulin needs.
Insulin glargine is partly degraded in the subcutaneous depot at the carboxyl terminus of the B chain to form the active metabolites, with similar in vitro activity to insulin.

Insulin Glargine is an insulin analogue indicated for once-daily subcutaneous administration in the treatment of Type 1 or Type 2 diabetes mellitus patients who require insulin for the control of hyperglycemia.

Insulin Glargine is given subcutaneously once a day. It may be administered at any time during the day. However, at the same time every day. It is not intended for intravenous administration.
The desired blood glucose levels as well as the doses and timing of Insulin Glargine, must be determined and adjusted individually by the physician.
With insulin, it is important to use a syringe that is marked for the desired strength, e.g.U-40. Failure to use the proper syringe can lead to a mistake in dosage, causing serious problems such as severe hypoglycaemia.
Insulin is usually administered in the abdominal wall, the thigh, the gluteal region or the deltoid region. Although absorption of Insulin Glargine does not differ between the injection sites, as with all insulins, injection sites must be rotated from one injection to the next to avoid lipodystrophy.
The average range of total daily insulin requirement for maintenance in type 1 diabetic patients ranges between 0.5 and 1.0 IU/kg. Further, in insulin resistance, the daily requirement of insulin may be substantially higher. In patients with type 2 diabetes, the requirements of insulin are lower i.e. approximately 0.3-0.6 IU/kg/day.
Dose adjustment may be required, if patients undertake increased physical activity or change their usual diet or if the patient’s weight or lifestyle change or other circumstances arise that increase susceptibility to hypoglycaemia or hyperglycemia. Any change of insulin dose should be made cautiously and only under medical supervision.
Changeover to Insulin Glargine: The initial dose of Insulin Glargine should be determined individually, depending on the desired blood glucose levels. When changing from a treatment regimen with intermediate- or long-acting insulin to a regimen with Insulin Glargine, the amount and timing of short-acting insulin or fast-acting insulin analogue or the dose of any oral antidiabetic drug may need to be adjusted.
A close metabolic monitoring under medical supervision is recommended during changeover and in the initial weeks thereafter. With improved metabolic control and resultant increase in insulin sensitivity (reduced insulin requirements), further adjustment of the dose of Insulin Glargine and other insulin or oral antidiabetic agents in the regimen may become necessary.
Internationally accepted label of Insulin Glargine suggest that on transferring patient from twice daily NPH human insulin to Insulin Glargine Injection once daily, to reduce the risk of hypoglycaemia the initial dose (IU) was usually reduced by approximately 20% (compare to total daily IU of NPH human insulin) and then adjusted based on patient response.
Pediatric Use: Insulin Glargine can be administered to children aged 6 years and older. Administration to children less than 6 years of age has not been studied.

Hypoglycaemia may occur as a result of an excess of insulin relative to food intake, energy expenditure or both. Mild episodes of hypoglycaemia usually can be treated with oral glucose. It is therefore recommended that the diabetic patient constantly carry some sugar lump, sweets, biscuits or sugary fruit juice. Adjustments in drug dosage, meal patterns, or exercise may be needed. More severe episodes of hypoglycaemia with coma, seizure, or neurologic impairment may be treatment with intravascular/subcutaneous glucagon or concentrated intravenous glucose. Glucose must also be given intravenously. If the patient does not respond to glucagon within 10 to 15 minutes, sustained carbohydrates intake and observation may be necessary because hypoglycaemia may recur after apparent clinical recovery.

Insulin Glargine must not be used in patients hypersensitive to Insulin Glargine or any of its excipients.

Insulin Glargine is not intended for IV administration. Intravenous administration of the usual subcutaneous dose could result in severe hypoglycaemia.
Insulin Glargine is not the insulin of choice for the treatment of diabetic ketoacidosis. Instead, intravenous regular insulin is recommended in such cases.
Renal Impairment: In patients with renal impairment, insulin requirements may be diminished. In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin requirements.
Hepatic Impairment: In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced capacity for gluconeogenesis and reduced insulin metabolism.
Intercurrent conditions: Insulin requirements may be altered during intercurrent conditions such as illness, emotional disturbances or stress.
Effects on the Ability to Drive and Use Machines: The patient’s ability to concentrate and react may be impaired as a result of hypoglycemia. This may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or operating machinery).
Patients should therefore be advised to avoid hypoglycemia during driving. This is particularly significant in patients who have reduced awareness of the warning signs of hypoglycemia or have frequent episodes of hypoglycemia.
Use in Pregnancy & Lactation: To date, no relevant epidemiological data are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal or fetal development, parturition or postnatal development.
It is essential for parents with pre-existing or gestational diabetes to maintain good metabolic control throughout pregnancy. Insulin requirements may decrease during the first trimester, increase during the second and third trimesters and rapidly decline after delivery. Careful blood glucose control is essential in such patients.

To date, no relevant epidemiological data are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal or fetal development, parturition or postnatal development. It is essential for parents with pre-existing or gestational diabetes to maintain good metabolic control throughout pregnancy. Insulin requirements may decrease during the first trimester, increase during the second and third trimesters and rapidly decline after delivery. Careful blood glucose control is essential in such patients.

The most commonly seen adverse reaction with human insulin therapy include the following: Hypoglycemia: Hypoglycemia is one of the most common adverse effects seen with the use of any type of insulin including human insulin.
The incidence of hypoglycemia in regimens that include Insulin Glargine is significantly reduced compared with regimens containing NPH human insulin. The time of occurrence of hypoglycemia depends on the action profile of the insulin and may, therefore, change when the treatment regimen is changed. While switching from twice daily NPH to once daily Glargine the dose of Glargine should be adjusted to avoid hypoglycemia.
Oedema: Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is improved by intensified insulin therapy.
Allergy to insulin: Systemic Allergy: Less common, but potentially more serious, is generalized allergy to insulin, which may cause rash over the whole body, shortness of breath, wheezing, reduction in blood pressure, fast pulse or sweating. Severe cases of generalized allergy may be life threatening.
Local Allergy: Patients occasionally experience redness, swelling and itching at the site of injection of insulin. This condition called local allergy usually clears up in a few days to a few weeks. In some instances, this condition may be related to factors other than insulin, such as irritants in the skin cleansing agent.
Hyperglycemia and ketoacidosis: In patients with insulin-dependent diabetes, prolonged hyperglycemia can result in diabetic acidosis. If uncorrected, prolonged hyperglycemia or diabetic acidosis can result in loss of consciousness or death. Therefore it is important that one should obtain medical assistance immediately.
Injection site reactions: As with any insulin therapy, lipodystrophy may occur at the injection site and delay insulin absorption. Other injection site reactions with insulin therapy include redness, pain, itching, hives, swelling and inflammation. Most minor reactions to insulins usually resolve in a few days to a few weeks.
Insulin resistance: When insulin requirement is increased (>200 IU/day), insulin resistance is said to be developed.
Other: A marked change in glycemic control may cause temporary visual impairment, due to temporary alteration in the turgidity and refractive index of the lens. Intensification of insulin therapy with abrupt improvement in glycemic control may be associated with temporary worsening of diabetic retinopathy.

A number of substances affect glucose metabolism and may require insulin dose adjustment.
Substances that may enhance the blood glucose lowering effect and susceptibility to hypoglycemia include: oral antidiabetic agents, ACE inhibitors, pentoxifylline, perhexiline, disopyramide, fibrates, fluoxetine, MAO inhibitors, detropropoxyphene, salicylates, sulfonamide antibiotics.
Substances that may reduce the blood glucose lowering effect and susceptibility to hyperglycemia include: corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, oral contraceptives, phenothiazine derivatives, somatotrophin, sympathomimetic agents (e.g. epinephrine [aderenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic medications (e.g. olanzapine and clozapine).
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the blood glucose lowering effect of insulin. Pentamidine may cause hypoglycemia, which may be sometimes be followed by hyperglycemia.
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent.
Laboratory Tests: As with all insulins, the therapeutic response to human insulin should be monitored by periodic blood glucose tests. Periodic measurement of glycosylated haemoglobin is recommended for the monitoring of long term glycemic control.

Procedure for Insulin Administration: Getting Started: Remove the pen delivery cap and check that the pen delivery device contains the correct type of Insulin, i.e. Insuline Glargine.
Priming & Injecting: Remove the outer protective flap of the needle and firmly screw it onto the threads at the end of the cartridge holder.
Remove the outer protective cap and the needle cap from the needle. It is important to prime the pen delivery device before use to remove any air that may be inside the needle.
Dial 2 units with the help of Dose Dialer. The dose display window shows the units of insulin dialed.
Hold Insulin Glargine pen delivery device is now ready for use.
Check that dose dialer is set to zero. Dial the number of units that need to be injected.
Insert the needle at the site of injection using the technique recommended by the doctor.
Deliver the dose by pushing the plunger all the way in.
The dose display window reads 0, this confirms that you have injected the right amount of insulin. Count till 10 and remove the needle from the skin.
Reattach the white outer protective needle cap and remove the needle.
Replace the pen delivery device cap on to the pen delivery device.
Dispose off the needle in the recommended way.

Glysolin G Cartridge which is not in use should be stored in a refrigerator (2°C to 8°C) but not allowed to freeze. When in use, cartridge may be used in Glysolin G Pen or may be carried at room temperature (up to 25°C) for up to 4 weeks.
Do not expose to excessive heat or direct sunlight. Insulin Glargine pen delivery device must be kept out of reach of children.
Insulin Glargine must only be used if the solution is clear and colourless with no particles visible.
Insulin Glargine must not be mixed with any other insulin nor be diluted. Mixing or diluting can change its time/action profile and mixing can cause precipitation.
Remove the needle from the Pen after each injection, otherwise temperature changes may cause liquid to leak out of the needle and the insulin concentration may increase.
Do not refill the Insulin Glargine Pen delivery device.
Insulin Glargine pen delivery device should never be used after the expiry date.

Insulin Preparations

A10AE04 - insulin glargine ; Belongs to the class of long-acting insulins and analogues for injection. Used in the treatment of diabetes.

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