Glaritus

Insulin glargine.

Each Glaritus DispoPen-2 contains one 3 mL cartridge of Insulin Glargine injection.
Each mL contains Insulin Glargine 100 IU.
Glaritus contains insulin glargine for subcutaneous use. Insulin glargine is a recombinant human insulin analog that is a long-acting, parenteral blood-glucose-lowering agent. Insulin glargine has low aqueous solubility at neutral pH and completely soluble at pH 4. After injection into the subcutaneous tissue, the acidic solution is neutralized, leading to formation of microprecipitates from which small amounts of insulin glargine are slowly released, resulting in a relatively constant concentration/time profile over 24 hours with no pronounced peak. This profile allows once daily dosing as basal insulin.
Molecular formula: C₂₆₇H₄₀₄N₇₂O₇₈S₆.
Molecular weight: 6063.
Chemical name: 21^A-Gly-30^Ba-L-Arg-30³⁰b-L-Arg-human insulin.

Pharmacology: Mechanism of Action: The primary activity of insulin, including insulin glargine, is regulation of glucose metabolism. Insulin and its analogs lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis and proteolysis, and enhances protein synthesis.
Pharmacodynamics: The glucose-lowering effect on a molar basis (i.e., when given at the same doses) of intravenous insulin glargine is approximately the same as that for human insulin. Insulin Glargine differs because of its unique structure providing 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. The onset of action of Insulin Glargine is slower than NPH human Insulin.
The duration of action of insulin glargine after abdominal, deltoid, or thigh subcutaneous administration is reportedly similar. The time course of action of insulins, including Glaritus, may vary between individuals and within the same individual.
Comparative Pharmacodynamics of Glaritus with Lantus: Pharmacodynamics of insulin glargine from Glaritus was compared with that from Lantus in two separate studies - one in healthy volunteers (n=40 in two-way cross-over design) and second in patients of type 1 diabetes mellitus (n=111 in parallel group design) with successful achievement of bioequivalence of Glaritus to Lantus as displayed in the tables as follows. (See Tables 1 and 2.)


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Click on icon to see table/diagram/image


Pharmacokinetics: Absorption and Bioavailability: After subcutaneous injection of Insulin Glargine, the Insulin serum concentrations indicate a slower, more prolonged absorption and a lack of a peak in comparison to NPH human Insulin. Concentrations are thus consistent with the time profile of the pharmacodynamics activity of Insulin Glargine.
Metabolism and Elimination: A reported metabolism study in humans indicates that insulin glargine is partly metabolized at the carboxyl terminus of the B chain in the subcutaneous depot to form two active metabolites with in vitro activity similar to that of human insulin, M1 (21A-Gly-insulin) and M2 (21A-Gly-des-30B-Thr-insulin). Unchanged drug and these degradation products are also present in the circulation.
Special Populations: Age, Race, and Gender: Effect of age, race, and gender on the pharmacokinetics of Glaritus has not been evaluated. However, in reported clinical studies in adults and pediatric patients, subgroup analyses based on age, race, and gender did not show differences in safety and efficacy between insulin glargine and NPH insulin.
Obesity: Effect of Body Mass Index (BMI) on the pharmacokinetics of Glaritus has not been evaluated.

Glaritus is indicated for treatment of diabetes mellitus in adults, adolescents and children aged 2 years and above.

Glaritus contains insulin glargine an insulin analogue with a prolonged duration of action. It should be administered once daily at any time but at the same time each day.
The dosage and timing of dose of Glaritus should be individually adjusted. In patients with type 2 diabetes, Glaritus can also be given together with orally antidiabetic medicinal products.
Change-over to Glaritus: When changing from a treatment regimen with an intermediate- or another long-acting insulin to a regimen with Glaritus, the amount and timing of the short acting insulin or fast-acting insulin analogue or of the dose of any oral antidiabetic drugs may need to be adjusted.
Switch from twice daily NPH insulin to Glaritus: To reduce the risk of nocturnal and early morning hypoglycaemia, patients who are changing their basal insulin regimen from twice-daily NPH insulin to once-daily Glaritus should reduce their daily dose of basal insulin by 20-30% during the first weeks of treatment.
Switch from insulin glargine 300 unit/mL to Glaritus: Glaritus (100 IU/mL) and insulin glargine 300 U/mL are not bioequivalent and are not directly interchangeable. When switching from once daily insulin glargine 300 units/mL to once daily Glaritus, the dose should be reduced (approximately by 20%) to reduce the risk of hypoglycaemia.
During the first week the reduction should, at least partially, be compensated by an increase in mealtime insulin, after this period the regimen should be adjusted individually.
A program of close metabolic monitoring under medical supervision is recommended during transfer and in the initial weeks thereafter. As with all insulin analogues, this is particularly true for patients which, due to antibodies to human insulin, need high insulin doses and may experience an improved insulin response with insulin glargine.
With improved metabolic control and resulting increase in insulin sensitivity a further adjustment in dosage regimen may become necessary. Dose adjustment may also be required, for example, if the patient's weight or life-style changes, change of timing of insulin dose or other circumstances arise that increase susceptibility to hypo-or hyperglycaemia.
Method of administration: Glaritus is administered by subcutaneous tissue injection.
Glaritus is not intended for intravenous administration. The prolonged duration of action of insulin glargine is dependent on injection into the subcutaneous space. Intravenous administration of the usual subcutaneous dose could result in severe hypoglycaemia.
There are no clinically relevant differences in serum insulin or glucose levels after abdominal, deltoid or thigh administration of Glaritus. Injection sites must be rotated within a given injection area from one injection to the next.
Mixing, diluting: Glaritus must not be mixed with any other insulin or diluted. Mixing or diluting can change its time/action profile and mixing can cause precipitation.
Glaritus solution for injection in dispopen: Glaritus 100 IU/mL in dispopen is only suitable for subcutaneous injections.

Symptoms: An excess of insulin, may lead to severe and sometimes long-term and life-threatening hypoglycaemia.
Management: Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dosage of the medicinal product, meal patterns, or physical activity may be needed.
More severe episodes culminating in coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycaemia may recur after apparent clinical recovery.

Glaritus is contraindicated: During episodes of hypoglycemia.
In patients with hypersensitivity to Glaritus or one of its excipients.

General: Glaritus is not the insulin of choice for the treatment of diabetic ketoacidosis. Instead, regular insulin administered intravenously is recommended in such cases.
In case of insufficient glucose control or a tendency to hyper-or hypoglycaemic episodes, the patient's adherence to the prescribed treatment regimen, injection sites and proper injection technique and all other relevant factors must be reviewed before dose adjustment is considered.
Patients must be instructed in the skills necessary for the self-management of diabetes, such as blood sugar monitoring, proper injection technique, measures for recognising and managing reduced or increased blood sugar levels (hypo-or hyperglycaemia) as described as follows. In addition, they must learn how to handle special situations such as skipped, inadequate or increase insulin doses, inadequate food intake or missed meals. Moreover, patients and their relatives must learn how to recognize the signs and symptoms of hypo-or hyperglycaemia, what corrective actions need to be taken and when they must speak with their doctor.
Hypoglycaemia: The time of occurrence of hypoglycaemia depends on the action profile of the insulins used and may, therefore, change when the treatment regimen is changed. Due to more sustained basal insulin supply with Glaritus, less nocturnal but more early morning hypoglycaemia can be expected.
Hypoglycaemia is more likely to occur at the start of insulin treatment, following transfer to a different insulin preparation, where metabolic control is unstable, or in severe kidney or liver diseases.
Symptoms that may indicate the onset of hypoglycaemia may be, e.g., sweating, clammy skin, anxiety, fast heartbeat, high blood pressure, palpitations and irregular heartbeat, chest pain (angina pectoris). In many patients, these signs and symptoms often develop before those of a low sugar level in the brain. The latter include headache, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensation (paraesthesiae) numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after oneself, convulsions, and loss of consciousness.
The initial symptoms pointing to the onset of hypoglycaemia ("warning symptoms") may change be milder, or be entirely absent, e.g., in the following circumstances: Markedly improved blood sugar control, slow-developing hypoglycaemia, advanced age, a certain type of nervous disease (autonomic neuropathy), long-standing diabetes, a psychiatric illness, or concurrent use of other medicines [see Interactions]. In such circumstances severe hypoglycaemia (and even loss of consciousness) may develop without the patients noticing it. Affected patients should try to keep familiar at all times with their individual warning symptoms. More frequent blood sugar testing can help to identify mild hypoglycaemic episodes which otherwise might be overlooked. Patients not confident of recognizing their warning symptoms should avoid situations (e.g. driving) that might result in danger to themselves or others.
As with all insulins, particular caution should be exercised, and intensified blood glucose monitoring is advisable, in patients in whom hypoglycaemic episodes might be of particular clinical relevance. For example, these could be patients with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of cardiac of cerebral complications of hypoglycaemia) as well as in patients with proliferative retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following hypoglycaemia).
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be absent in certain risk groups. These include patients: In whom glucaemic control is markedly improved; in whom hypoglycaemia develops gradually; who are elderly; after transfer from animal insulin to human insulin; in whom an autonomic neuropathy is present; with a long history of diabetes; suffering from psychiatric illness; receiving concurrent treatment with certain other medicinal products.
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the patient's awareness of hypoglycaemia.
The prolonged effect of subcutaneous insulin glargine may delay recovery from hypoglycaemia.
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, unrecognized (especially nocturnal) episodes of hypoglycaemia must be considered.
Compliance of the patient to the dosage and dietary regimen, correct insulin administration and awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Presence of factors increasing the susceptibility to hypoglycaemia require particularly close monitoring and may necessitate dose adjustment. These include: Change in the injection area; improved insulin sensitivity (by e.g., removal of stress factors); unaccustomed, increased or prolonged-physical activity; intercurrent illness (e.g. vomiting, diarrhoea); inadequate food intake; missed meals; alcohol consumption; certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or adrenocortical insufficiency); concomitant treatment with certain other medicinal products.
A hypoglycaemic attack can be corrected by immediately taking sugar, e.g., in the form of glucose, sugar cubes or sugar-sweetened beverages. In this regard, note that food or beverages containing artificial sweeteners (e.g. diet foods and drinks) are not suitable. Subsequently, some food having a long-acting blood-sugar-raising effect (e.g. bread) should be taken. The long action of Glaritus may delay recovery from hypoglycaemia. If hypoglycaemia recurs, another 10-20 g of sugar should be taken. If a hypoglycaemia attack cannot be corrected of if it recurs, speak to a doctor immediately.
Carry at least 20 g of sugar at all times, together with some information identifying the patient as a diabetic. Inability to swallow or unconsciousness will make necessary injections of glucose solution of glucagons (a medicine increasing blood sugar), even where the presence of hypoglycaemia is uncertain. Following intake of glucose, hypoglycaemia should be conformed by means of blood sugar testing.
Hyperglycaemia may occur under certain circumstances. These include: Omission of reduction of injections or decrease in insulin effectiveness (e.g. due to incorrect storage); pen malfunction; decreased physical activity, stress situations (emotional distress, excitement), injuries, operations, feverish illnesses or certain other diseases; concurrent use of other medicines [see Interactions].
Thirst, increased need to pass water, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heartbeat and high concentrations of sugar and ketone bodies in the urine may be signs of hyperglycaemia. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious metabolic condition (ketoacidosis) resulting from lack of insulin. Blood sugar testing or tests for ketones in urine must be carried out as soon as any such symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.
Intercurrent illness: Intercurrent illness requires intensified metabolic monitoring. In many cases urine tests for ketones are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often increased. Patients with type 1 diabetes must continue to consume at least a small amount of carbohydrate on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. and they must never omit insulin entirely.
Hepatic Impairment: In patients with hepatic impairment, insulin requirements may be diminished due to reduced capacity for gluconeogenesis and reduced insulin metabolism.
Renal Impairment: In patients with renal impairment, insulin requirements may be diminished due to reduced insulin metabolism.
Obesity: Subgroup analyses based on BMI in reported controlled clinical studies, did not show differences in safety and efficacy between insulin glargine and NPH.
Use in Children: The safety and effectiveness of insulin glargine have been established in pediatric patients aged >2 years in reported clinical studies. The safety and effectiveness of insulin glargine in pediatric patients younger than 2 years of age have not been established.
Use in the Elderly (≥65 years old): In the geriatric, progressive deterioration of renal function may lead to a steady decrease in insulin requirements.

Pregnancy: There are no well-controlled clinical studies of the use of Glaritus in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. All pregnancies have a background risk of birth defects, loss, or other adverse outcome regardless of drug exposure. This background risk is increased in pregnancies complicated by hyperglycemia and may be decreased with good metabolic control. It is essential for patients with diabetes or history of gestational diabetes to maintain good metabolic control before conception and throughout pregnancy. In patients with diabetes or gestational diabetes, insulin requirements may decrease during the first trimester, generally increase during the second trimester, and rapidly decline after delivery. Careful monitoring of glucose control is essential in these patients. Therefore, female patients should be advised to tell their physicians if they intend to become, or if they become pregnant while taking Glaritus.
Insulin requirements may decrease during the first trimester and generally increase during the second and third trimesters.
Nursing Mothers: Endogenous insulin is present in human milk; it is unknown whether insulin glargine is excreted in human milk. Because many drugs, including human insulin, are excreted in human milk, caution should be exercised when Glaritus is administered to a nursing woman. Use of Glaritus is compatible with breastfeeding, but women with diabetes who are lactating may require adjustments of their insulin doses.

The following adverse reactions are discussed elsewhere: Hypoglycaemia: Hypoglycaemia, in general the most frequent undesirable effect of insulin therapy, may occur if the insulin dose is too high in relation to the insulin requirement. Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. Prolonged or severe hypoglycaemic episodes may be life-threatening.
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more marked is the phenomenon of counter-regulation and its symptoms.
Eyes: A marked change in glycaemic control may cause temporary visual impairment, due to temporary alteration in the turgidity and refractive index of the lens.
Long-term improved glycaemic control decreases the risk of progression of diabetes retinopathy. However, intensification of insulin therapy with abrupt improvement in glycaemic control may be associated with temporary worsening of diabetic retinopathy. In patients with proliferative retinopathy, particularly if not treated with photocoagulation, severe hypoglycaemic episodes may result in transient amaurosis.
Lipodystrophy: As with any insulin therapy, lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation of the injection site within the given injection area may help to reduce or prevent these reactions.
Injection site and allergic reactions: Reactions at the injection site include redness, pain, itching, hives, swelling, or inflammation. Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks.
Immediate-type allergic reactions to insulin are rare. Such reactions to insulin (including insulin glargine) or the excipients may, for example, be associated with generalized skin reactions, angioedema, bronchospasm, hypotension and shock, and may be life-threatening.
Other reactions: Insulin administration may cause insulin antibodies to form. In clinical studies, antibodies that cross-react with human insulin and insulin glargine were observed with the same frequency in both NPH insulin and insulin glargine treatment groups. In rare cases, the presence of such insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to hyper-or hypoglycaemia. Rarely, insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is improved by intensified insulin therapy.

Drugs That May Increase the Risk of Hypoglycemia: Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, Disopyramide, Fibrates, Fluoxetine, Monoamine oxidase inhibitors, Pentoxifylline, Pramlintide, Propoxyphene, Salicylates, Somatostatin analogs (e.g., Octreotide), and Sulfonamide antibiotics.
Intervention: Dose reductions and increased frequency of glucose monitoring may be required when insulin glargine is co-administered with these drugs.
Drugs That May Decrease the Blood Glucose Lowering Effect of Glaritus: Drugs: Atypical antipsychotics (e.g., Olanzapine and Clozapine), Corticosteroids, Danazol, Diuretics, Estrogens, Glucagon, Isoniazid, Niacin, Oral contraceptives, Phenothiazines, Progestogens (e.g., in oral contraceptives), Protease inhibitors, Somatropin, Sympathomimetic agents (e.g., Albuterol, Epinephrine, Terbutaline), and Thyroid hormones.
Intervention: Dose increases, and increased frequency of glucose monitoring may be required when insulin glargine is co-administered with these drugs.
Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of Glaritus: Drugs: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.
Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when insulin glargine is co-administered with these drugs.
Drugs That May Blunt Signs and Symptoms of Hypoglycemia: Drugs: Beta-blockers, clonidine, guanethidine, and reserpine.
Intervention: Increased frequency of glucose monitoring may be required when insulin glargine is co-administered with these drugs.

Components: Dose dialer, Dose display window, Dose indicator, Glaritus DispoPen-2 body, Glaritus cartridge, Cartridge holder, Glaritus DispoPen-2 Cap, Needle, Outer Protective Flap, Outer Protective Cap, Plunger.
Getting Started: a) Remove the DispoPen cap and check that the DispoPen contains the correct type of Insulin, i.e. Insulin Glargine.
Priming & Injecting: b) Remove the outer protective cap of the needle and firmly screw it on to the threads at the end of the cartridge holder.
c) Remove the outer protective cap and the needle cap from the needle.
d) It is important to prime the DispoPen 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.
e) Hold Insulin Glargine DispoPen with the needle pointing upwards and tap the cartridge gently with the finger few times. Press the plunger all the way in. Repeat steps d and e till a drop of insulin appears at the needle tip, ensuring the expulsion of air. Insulin Glargine DispoPen is now ready for use.
f) Check that the dose dialer is set to zero. Dial the number of units that need to be injected.
g) Insert the needle at the site of injection using the technique recommended by the doctor.
h) Deliver the dose by pushing the plunger all the way in. The dose display windows reads 0, this confirms that the patient have injected the right amount of insulin.
i) Count till 10 and remove the needle from the skin. Reattach the white outer protective needle cap and remove the needle. Replace the DispoPen cap on to the DispoPen. Dispose off the needle in the recommended way.

Glaritus DispoPen-2 which is not in use should be stored in a refrigerator (2-8°C) but not allowed to freeze.
Once opened, Glaritus DispoPen-2 should be stored at temperature not above 30°C for up to 4 weeks.
Do not expose to excessive heat or direct sunlight.
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 Glaritus cartridges.

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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