Glimepiride Stella

Glimepiride.

Active ingredient: Glimepiride 2 mg.
Excipients/Inactive Ingredients: Lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, povidone K30, sodium lauryl sulfate, magnesium stearate, indigo carmine lake.

Glimepiride STELLA 2 mg is indicated for the treatment of type 2 diabetes mellitus, when diet, physical exercise and weight reduction alone are not adequate.

Administration: For oral administration.
Tablets should be swallowed without chewing with some liquid.
The basis for successful treatment of diabetes is a good diet, regular physical activity, as well as routine checks of blood and urine. Tablets or insulin cannot compensate if the patient does not keep to the recommended diet.
Dosage: The dosage is determined by the results of blood and urinary glucose determinations.
The starting dose is 1 mg glimepiride per day. If good control is achieved, this dosage should be used for maintenance therapy.
For the different dosage regimens appropriate strengths are available.
If control is unsatisfactory, the dosage should be increased, based on the glycaemic control, in a stepwise manner with an interval of about 1 to 2 weeks between each step, to 2, 3, or 4 mg glimepiride per day.
A dosage of more than 4 mg glimepiride per day gives better results only in exceptional cases.
The maximum recommended dose is 6 mg glimepiride per day.
In patients not adequately controlled with the maximum daily dose of metformin, concomitant glimepiride therapy can be initiated. While maintaining the metformin dose, the glimepiride therapy is started with a low dose, and is then titrated up depending on the desired level of metabolic control up to the maximum daily dose. The combination therapy should be initiated under close medical supervision.
In patients not adequately controlled with the maximum daily dose of glimepiride, concomitant insulin therapy can be initiated if necessary. While maintaining the glimepiride dose, insulin treatment is started at a low dose and titrated up depending on the desired level of metabolic control. The combination therapy should be initiated under close medical supervision.
Normally a single daily dose of glimepiride is sufficient. It is recommended that this dose be taken shortly before or during a substantial breakfast or - if none is taken - shortly before or during the first main meal. If a dose is forgotten, this should not be corrected by increasing the next dose.
If a patient has a hypoglycaemic reaction on 1 mg glimepiride daily, this indicates that they can be controlled by diet alone.
In the course of treatment, as an improvement in control of diabetes is associated with higher insulin sensitivity, glimepiride requirements may fall. To avoid hypoglycaemia timely dose reduction or cessation of therapy must therefore be considered. Change in dosage may also be necessary if there are changes in weight or life style of the patient, or other factors that increase the risk of hypo- or hyperglycaemia.
Switch over from other oral hypoglycaemic agents to glimepiride: A switch over from other oral hypoglycaemic agents to glimepiride can generally be done. For the switch over to glimepiride the strength and the half-life of the previous medicinal product has to be taken into account. In some cases, especially in antidiabetics with a long half-life (e.g. chlorpropamide), a wash out period of a few days is advisable in order to minimise the risk of hypoglycaemic reactions due to the additive effect.
The recommended starting dose is 1 mg glimepiride per day. Based on the response the glimepiride dosage may be increased stepwise, as indicated previously.
Switch over from insulin to glimepiride: In exceptional cases, where type 2 diabetic patients are regulated on insulin, a changeover to glimepiride may be indicated. The changeover should be undertaken under close medical supervision.
Special populations: Patients with renal or hepatic impairment: See Contraindications.
Paediatric population: The available data on safety and efficacy are insufficient in the paediatric population and therefore such use is not recommended.
(Consider other sources for 1 mg and 3 mg dosage.)

Symptoms: After ingestion of an overdosage hypoglycaemia may occur, lasting from 12 to 72 hours, and may recur after an initial recovery. Symptoms may not be present for up to 24 hours after ingestion. In general observation in hospital is recommended. Nausea, vomiting and epigastric pain may occur. The hypoglycaemia may in general be accompanied by neurological symptoms like restlessness, tremor, visual disturbances, co-ordination problems, sleepiness, coma and convulsions.
Management: Treatment primarily consists of preventing absorption by inducing vomiting and then drinking water or lemonade with activated charcoal (adsorbent) and sodium-sulphate (laxative). If large quantities have been ingested gastric lavage is indicated, followed by activated charcoal and sodium-sulphate. In case of (severe) overdosage hospitalisation in an intensive care department is indicated. Start the administration of glucose as soon as possible, if necessary by a bolus intravenous injection of 50 ml of a 50% solution, followed by an infusion of a 10% solution with strict monitoring of blood glucose. Further treatment should be symptomatic.
In particular when treating hypoglycaemia due to accidental intake of glimepiride in infants and young children, the dose of glucose given must be carefully controlled to avoid the possibility of producing dangerous hyperglycaemia. Blood glucose should be closely monitored.

Glimepiride is contraindicated in patients with the following conditions: hypersensitivity to glimepiride, other sulfonylureas or sulfonamides or to any of the excipients listed in Description; insulin dependent diabetes; diabetic coma; ketoacidosis; severe renal or hepatic function disorders.
In case of severe renal or hepatic function disorders, a change over to insulin is required.

Glimepiride must be taken shortly before or during a meal.
When meals are taken at irregular hours or skipped altogether, treatment with glimepiride may lead to hypoglycaemia. Possible symptoms of hypoglycaemia include: headache, ravenous hunger, nausea, vomiting, lassitude, sleepiness, disordered sleep, restlessness, aggressiveness, impaired concentration, alertness and reaction time, depression, confusion, speech and visual disorders, aphasia, tremor, paresis, sensory disturbances, dizziness, helplessness, loss of self-control, delirium, cerebral convulsions, somnolence and loss of consciousness up to and including coma, shallow respiration and bradycardia. In addition, signs of adrenergic counter-regulation may be present such as sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmias.
The clinical picture of a severe hypoglycaemic attack may resemble that of a stroke.
Symptoms can almost always be promptly controlled by immediate intake of carbohydrates (sugar). Artificial sweeteners have no effect.
It is known from other sulfonylureas that, despite initially successful countermeasures, hypoglycaemia may recur.
Severe hypoglycaemia or prolonged hypoglycaemia, only temporarily controlled by the usual amounts of sugar, require immediate medical treatment and occasionally hospitalisation.
Factors favouring hypoglycaemia include: unwillingness or (more commonly in older patients) incapacity of the patient to cooperate; undernutrition, irregular mealtimes or missed meals or periods of fasting; alterations in diet; imbalance between physical exertion and carbohydrate intake; consumption of alcohol, especially in combination with skipped meals; impaired renal function; serious liver dysfunction; overdosage with glimepiride; certain uncompensated disorders of the endocrine system affecting carbohydrate metabolism or counter regulation of hypoglycaemia (as for example in certain disorders of thyroid function and in anterior pituitary or adrenocortical insufficiency); concurrent administration of certain other medicinal products.
Treatment with glimepiride requires regular monitoring of glucose levels in blood and urine. In addition determination of the proportion of glycosylated haemoglobin is recommended.
Regular hepatic and haematological monitoring (especially leucocytes and thrombocytes) are required during treatment with glimepiride.
In stress-situations (e.g. accidents, acute operations, infections with fever etc.) a temporary switch to insulin may be indicated.
No experience has been gained concerning the use of glimepiride in patients with severe impairment of liver function or dialysis patients. In patients with severe impairment of renal or liver function change over to insulin is indicated.
Treatment of patients with G6PD-deficiency with sulfonylurea agents can lead to hemolytic anaemia. Since glimepiride belongs to the class of sulfonylurea agents, caution should be used in patients with G6PD-deficiency and a non-sulfonylurea alternative should be considered.
Fatalities associated with the administration of sulfonamides, although rare, have occurred due to severe reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
The product contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed.
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or operating machinery).
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is particularly important in those who have reduced or absent awareness of the warning symptoms of hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is advisable to drive or operate machinery in these circumstances.

Pregnancy: Risk related to the diabetes: Abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities and perinatal mortality. So the blood glucose level must be closely monitored during pregnancy in order to avoid the teratogenic risk. The use of insulin is required under such circumstances. Patients who consider pregnancy should inform their physician.
Risk related to glimepiride: There are no adequate data from the use of glimepiride in pregnant women. Animal studies have shown reproductive toxicity which likely was related to the pharmacologic action (hypoglycaemia) of glimepiride.
Consequently, glimepiride should not be used during the whole pregnancy. In case of treatment by glimepiride, if the patient plans to become pregnant or if a pregnancy is discovered, the treatment should be switched as soon as possible to insulin therapy.
Lactation: The excretion in human milk is unknown. Glimepiride is excreted in rat milk. As other sulfonylureas are excreted in human milk and because there is a risk of hypoglycaemia in nursing infants, breast-feeding is advised against during treatment with glimepiride.

The following adverse reactions from clinical investigations were based on experience with glimepiride and other sulfonylureas, were listed as follows by system organ class and in order of decreasing incidence (very common: ≥1/10; common: ≥1/100 to <1/10; uncommon: ≥1/1,000 to <1/100; rare: ≥1/10,000 to <1/1,000; very rare: <1/10,000), not known (cannot be estimated from the available data).
Blood and lymphatic system disorders: Rare: thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, erythropenia, haemolytic anaemia and pancytopenia, which are in general reversible upon discontinuation of medication.
Not known: severe thrombocytopenia with platelet count less than 10,000/μl and thrombocytopenic purpura.
Immune system disorders: Very rare: Leukocytoclastic vasculitis, mild hypersensitivity reactions that may develop into serious reactions with dyspnoea, fall in blood pressure and sometimes shock.
Not known: Cross-allergenicity with sulfonylureas, sulfonamides or related substances is possible.
Metabolism and nutrition disorders: Rare: Hypoglycaemia. (These hypoglycaemic reactions mostly occur immediately, may be severe and are not always easy to correct. The occurrence of such reactions depends, as with other hypoglycaemic therapies, on individual factors such as dietary habits and dosage.)
Eye disorders: Not known: Visual disturbances, transient, may occur especially on initiation of treatment, due to changes in blood glucose levels.
Gastrointestinal disorders: Very rare: Nausea, vomiting, diarrhoea, abdominal distension, abdominal discomfort and abdominal pain, which seldom lead to discontinuation of therapy.
Hepato-biliary disorders: Very rare: Hepatic function abnormal (e.g. with cholestasis and jaundice), hepatitis and hepatic failure.
Not known: Hepatic enzymes increased.
Skin and subcutaneous tissue disorders: Not known: Hypersensitivity reactions of the skin may occur as pruritus, rash, urticaria and photosensitivity.
Investigations: Very rare: Blood sodium decrease.

If glimepiride is taken simultaneously with certain other medicinal products, both undesired increases and decreases in the hypoglycaemic action of glimepiride can occur. For this reason, other medicinal products should only be taken with the knowledge (or at the prescription) of the doctor.
Glimepiride is metabolized by cytochrome P450 2C9 (CYP2C9). Its metabolism is known to be influenced by concomitant administration of CYP2C9 inducers (e.g. rifampicin) or inhibitors (e.g. fluconazole).
Results from an in-vivo interaction study reported in literature show that glimepiride AUC is increased approximately 2-fold by fluconazole, one of the most potent CYP2C9 inhibitors.
Based on the experience with glimepiride and with other sulfonylureas, the following interactions have to be mentioned.
Potentiation of the blood-glucose-lowering effect and, thus in some instances hypoglycaemia may occur when one of the following medicinal products is taken, for example: phenylbutazone, azapropazone and oxyfenbutazone; insulin and oral antidiabetic products, such as metformin; salicylates and p-amino-salicylic acid; anabolic steroids and male sex hormones; chloramphenicol, certain long acting sulfonamides, tetracyclines, quinolone antibiotics and clarithromycin; coumarin anticoagulants; fenfluramine; disopyramide; fibrates; ACE inhibitors; fluoxetine, MAO-inhibitors; allopurinol, probenecid, sulfinpyrazone; sympatholytics; cyclophosphamide, trophosphamide and iphosphamides; miconazole, fluconazole; pentoxifylline (high dose parenteral); tritoqualine.
Weakening of the blood-glucose-lowering effect and, thus raised blood glucose levels may occur when one of the following medicinal products is taken for example: oestrogens and progestogens; saluretics, thiazide diuretics; thyroid stimulating agents, glucocorticoids; phenothiazine derivatives, chlorpromazine; adrenaline and sympathicomimetics; nicotinic acid (high dosages) and nicotinic acid derivatives; laxatives (long term use); phenytoin, diazoxide; glucagon, barbiturates and rifampicin; acetazolamide.
H2 antagonists, beta-blockers, clonidine and reserpine may lead to either potentiation or weakening of the blood-glucose-lowering effect.
Under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation to hypoglycaemia may be reduced or absent.
Alcohol intake may potentiate or weaken the hypoglycaemic action of glimepiride in an unpredictable fashion.
Glimepiride may either potentiate or weaken the effects of coumarin derivatives.
Colesevelam binds to glimepiride and reduces glimepiride absorption from the gastro-intestinal tract. No interaction was observed when glimepiride was taken at least 4 hours before colesevelam. Therefore, glimepiride should be administered at least 4 hours prior to colesevelam.

Store in a well-closed container, in a dry place. Do not store above 30°C.

Antidiabetic Agents

A10BB12 - glimepiride ; Belongs to the class of sulfonylureas. Used in the treatment of diabetes.

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