Glimepiride-Vertex, tablets 3 mg 30 pcs

Glimepiride is an oral hypoglycemic drug – a sulfonylurea derivative of new (third) generation. Glimepiride acts mainly by stimulating the secretion and release of insulin from the beta cells of the pancreas (pancreatic action). As with other sulfonylurea derivatives, this effect is based on increasing the response of pancreatic beta cells to physiologic glucose stimulation, and the amount of insulin secreted is significantly lower than with traditional sulfonylurea derivatives.

The least stimulating effect of glimepiride on insulin secretion also provides a lower risk of hypoglycemia. In addition, glimepiride has extrapancreatic action – the ability to improve the sensitivity of peripheral tissues (muscle, fat) to the action of its own insulin, reduce insulin uptake by the liver; it inhibits the production of glucose in the liver. Glimepiride selectively inhibits cyclooxygenase and reduces the conversion of arachidonic acid to thromboxane A2, which promotes platelet aggregation, thus having an antithrombotic effect.

Glimepiride promotes normalization of lipids, reduces the level of low aldehyde in blood, which leads to a significant decrease in lipid peroxidation, this promotes the antiatherogenic effect of the drug.

Glimepiride increases the level of endogenous α-tocopherol, catalase activity, glutathione peroxidase and superoxide dismutase which helps to decrease the intensity of oxidative stress in patient’s organism that is constantly present in type 2 diabetes.

Indications

The drug is indicated for the treatment of type 2 diabetes mellitus when the previously prescribed diet and exercise are ineffective.

If Glimepiride monotherapy is ineffective, it may be used in combination therapy with metformin or with insulin.

Active ingredient

Composition

One tablet contains:
The active ingredient

glimepiride – 3 mg

Excipients:

Lactose (milk sugar),

Microcrystalline cellulose,

Pregelatinized starch,

sodium lauryl sulfate,

magnesium stearate.

How to take, the dosage

The drug is administered orally. The initial and maintenance doses of Glimepiride-Teva are established individually on the basis of the results of regular monitoring of blood glucose concentration.

The initial dose and dose selection

At the beginning of treatment, 1 mg of Glimepiride is prescribed once daily. When optimal therapeutic effect is achieved, it is recommended to take this dose as a maintenance dose. If there is no glycemic control, the daily dose should be gradually increased under regular monitoring of blood glucose concentration (at intervals of 1-2 weeks) to 2 mg, 3 mg or 4 mg per day. Doses over 4 per day are effective only in exceptional cases. The maximum recommended daily dose is 6 mg. Use in combination with metformin
In the absence of glycemic control in patients taking metformin, concomitant therapy with Glimepiride may be initiated. If the dose of metformin is maintained at the same level, treatment with Glimepiride is started with the minimum dose, and then the dose is gradually increased depending on the desired level of glycemic control, up to the maximum daily dose. Combination therapy should be conducted under close medical supervision.

Use in combination with insulin

. In cases where glycemic control cannot be achieved by taking the maximum dose of Glimepiride-, in monotherapy or in combination with the maximum dose of metformin, a combination of Glimepiride with insulin is possible. In this case, the last dose of Glimepiride prescribed to the patient remains unchanged. In this case, treatment with insulin begins with a minimum dose, with a possible subsequent gradual increase in its dose under the control of blood glucose concentrations. Combined treatment requires close monitoring by a physician.
Time and frequency of administration the daily dose is determined by the doctor, taking into account the patient’s lifestyle. As a rule, it is sufficient to prescribe a daily dose in one dose immediately before or during a solid breakfast or the first main meal. Glimepiride tablets are taken whole, without chewing, with enough fluid (about 0.5 glasses). It is very important not to skip meals after taking Glimepiride.

Length of treatment

Long-term treatment with Glimepiride, as a rule.

Transferring a patient from another oral hypoglycemic drug to glimepiride.

The starting daily dose of Glimepiride should be 1 mg when transferring from another oral hypoglycemic drug to Glimepiride (even if the patient is transferred to Glimepiride from the maximum dose of another oral hypoglycemic drug). Any increase in the dose of Glimepiride should be made in stages according to the above recommendations. It is necessary to take into account the effectiveness, dose and duration of action of the used hypoglycemic agent. In some cases, especially when taking hypoglycemic drugs with a long elimination half-life (e.g., chlorpropamide), it may be necessary to temporarily (for several days) discontinue treatment to avoid additive effects that increase the risk of hypoglycemia.

Transferring a patient from insulin to Glimepiride

. In exceptional cases of insulin therapy in patients with type 2 diabetes mellitus, with compensation for the disease and with preserved secretory function (3-cells of the pancreas), insulin may be replaced with Glimepiride. The transfer should be carried out under the close supervision of a physician. In this case, transfer of the patient to Glimepiride is started with a minimum dose of 1 mg.

Interaction

Glimepiride is metabolized by cytochrome Р450 2С9 (CYP2C9). Concomitant use with inducers of CYP2C9 isoenzyme, such as rifampicin, may reduce the hypoglycemic effect of glimepiride and increase the risk of hypoglycemia in case of their withdrawal without adjusting the dose of glimepiride.

Concomitant use with CYP2C9 isoenzyme inhibitors, such as fluconazole, may increase the hypoglycemic effect of glimepiride and increase the risk of hypoglycemia and side effects of glimepiride, and may also decrease its hypoglycemic effect when they are discontinued without adjusting the dose of glimepiride.

. Increased hypoglycemic action and the associated possible development of hypoglycemia may be observed with the simultaneous use of glimepiride with insulin or other oral hypoglycemic drugs, metformin, angiotensin-converting enzyme inhibitors (ACE), allopurinol, anabolic steroids and male sex hormones, chloramphenicol, coumarin derivatives, cyclo-, tro- and isophosphamides, fenfluramine, disopyramide, fibrates, fluoxetine, sympatholytic drugs (guanethidine), monoamine oxidase inhibitors (MAOIs), miconazole, fluconazole, pentoxifylline (when given parenterally in high doses), phenylbutazone, azapropazone, oxyphenbutazone, probenicid, quinolones, salicylates and aminosalicylic acid, sulfinpyrazone, some long-acting sulfonamides, tetracyclines, tritoqualine. Weakening of hypoglycemic action and the associated increase in blood glucose concentration may be observed during concomitant use of glimepiride with acetazolamide, barbiturates, glucocorticosteroids, glucagon, laxatives (with prolonged use), nicotinic acid (in high doses) and nicotinic acid derivatives, estrogens and progestogens, phenothiazines, chlorpromazine, phenytoin, rifampicin, thyroid hormones, lithium salts. H2-histamine receptor blockers, clonidine and reserpine, can both potentiate and weaken the hypoglycemic effect of glimepiride.

Under the influence of sympatholytic drugs such as beta-adrenoblockers, clonidine, guanethidine and reserpine, the clinical signs of hypoglycemia may be weakened or absent. Against the background of glimepiride administration, enhancement or weakening of coumarin derivatives may be observed. When concomitant use with drugs that inhibit bone marrow hematopoiesis, the risk of myelosuppression increases. Single or chronic use of alcohol may both enhance and weaken the hypoglycemic effect of glimepiride.

Special Instructions

Glimepiride should be taken in the recommended doses and at the prescribed time. Mistakes in the use of the drug, e.g. skipping a dose, should never be corrected by taking a higher dose at a later time. The physician and the patient should agree in advance on the measures to be taken in case of such errors (e.g. skipping a dose or eating) or in situations in which the next dose cannot be taken at the prescribed time. The patient should inform the physician immediately if the dose of the drug is too high.
If a patient develops a hypoglycemic reaction when taking 1 mg of Glimepiride per day, this indicates that in this patient the normalization of blood glucose levels can be achieved with a single diet.

When compensation for type 2 diabetes is achieved, insulin sensitivity increases. Because of this, the need for Glimepiride may decrease during treatment. In order to avoid the development of hypoglycemia, the dose should be temporarily reduced or Glimepiride should be stopped. Dose adjustment should also be made if the patient’s body weight changes, if the patient’s lifestyle changes or if there are other factors contributing to the risk of hypo- or hyperglycemia. Adequate diet, regular and sufficient exercise and, if necessary, weight reduction are as important in achieving optimal blood glucose control as regular Glimepiride administration.

Clinical symptoms of hyperglycemia (insufficient decrease in blood glucose levels) are: increased frequency of urination, extreme thirst, dry mouth and dry skin. During the first weeks of treatment, the risk of hypoglycemia may increase, which requires special close monitoring of the patient. During treatment with Glimepiride, if meals are not taken regularly or if meals are missed, hypoglycemia may develop.

Its possible symptoms are: Headache, hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggressiveness, concentration, attention and reaction disorders, depression, confusion, speech and visual disturbances, aphasia, tremor, paresis, sensory disturbances, dizziness, delirium, cerebral convulsions, confusion or loss of consciousness, including coma, shallow breathing, bradycardia. In addition, sweating, restlessness, tachycardia, elevated blood pressure, angina, and heart rhythm disturbances may occur as a result of the adrenergic feedback mechanism. Factors contributing to hypoglycemia include:

The physician should be informed about the above factors and about episodes of hypoglycemia, because these require particularly close monitoring of the patient. If there are such factors that increase the risk of hypoglycemia, the dose of Glimepiride or the entire treatment regimen should be adjusted. This should also be done in the case of an intercurrent disease or changes in the patient’s lifestyle.

Symptoms of hypoglycemia may be subdued or absent in elderly patients, in patients with autonomic neuropathy or receiving concomitant treatment with β-adrenoblockers, clonidine, reserpine, guanethidine or other sympatholytic agents. Hypoglycemia can almost always be quickly controlled by immediate intake of carbohydrates (glucose or sugar, e.g. in the form of a piece of sugar, sweet fruit juice or tea). The patient should therefore always carry at least 20 glucose (4 sugars). Sugar substitutes are ineffective in the treatment of hypoglycemia.

It is known from experience with other sulfonylurea drugs that despite the initial success of relief of hypoglycemia, its recurrence is possible. In this regard, continuous and careful monitoring of the patient is necessary. Severe hypoglycemia requires immediate treatment under medical supervision, and in certain circumstances, hospitalization of the patient.

If a patient with diabetes mellitus is treated by different doctors (for example, during a hospital stay after an accident, when the disease occurs on weekends), he must necessarily inform them about his disease and the previous treatment.
During treatment with Glimepiride, regular monitoring of liver function and peripheral blood picture (especially leukocyte and platelet counts) is required.

In stressful situations (e.g., trauma, surgery, infectious diseases accompanied by fever) it may be necessary to temporarily transfer the patient to insulin therapy.

There is no experience with Glimepiride in patients with severe hepatic and renal dysfunction or patients on hemodialysis. Patients with severe renal and hepatic dysfunction should be transferred to insulin therapy.

During treatment with Glimepiride, regular monitoring of blood glucose concentration as well as glycosylated hemoglobin concentration is necessary.

At the beginning of treatment, when changing from one drug to another, or when taking Glimepiride irregularly, there may be a decrease in the patient’s concentration and psychomotor reaction rate due to hypo- or hyperglycemia. This may adversely affect the ability to drive motor vehicles or operate various machines and mechanisms.

Contraindications

Type 1 diabetes mellitus; diabetic ketoacidosis, diabetic precoma and coma; hyperosmolar coma; hypersensitivity to glimepiride or to any inactive component of the drug, to other sulfonylurea derivatives or to sulfonamides (risk of hypersensitivity reactions); severe liver function impairment; severe renal function impairment (including hemodialysis patients).including patients on hemodialysis); lactose intolerance, lactase deficiency, glucose-galactose malabsorption; children under 18 years of age; insufficiency of glucose-6-phosphate dehydrogenase; pregnancy and breast-feeding.

With caution – conditions requiring transfer of the patient to insulin therapy (extensive burns, severe multiple trauma, extensive surgery); adrenal insufficiency; thyroid disease (hypothyroidism, thyrotoxicosis); disorders of food and drug absorption in the gastrointestinal tract, including intestinal obstruction, intestinal paresis; infectious fever; alcoholism; in the first days of treatment (increased risk of hypoglycemia); with increased risk of hypoglycemia; with intercurrent diseases during treatment or with changes in the patient’s lifestyle (change of diet and time of meals, increase or decrease of physical activity).

Side effects

Rarely:
Metabolic reactions: development of hypoglycemic reactions. These reactions mainly occur shortly after taking the drug, and they are not always easy to stop.

Visually: during treatment (especially at the beginning) there may be transient decrease in vision due to changes in blood glucose concentrations.

Digestive system disorders: increase in liver enzymes activity, cholestasis, jaundice, hepatitis (up to liver failure).

Blood system disorders: thrombocytopenia (moderate to severe), leukopenia, hemolytic or aplastic anemia, erythrocytopenia, granulocytopenia, agranulocytosis and pancytopenia.

Sometimes:

Digestive system: nausea, vomiting, feeling of heaviness or discomfort in the epigastrium, abdominal pain, diarrhea, very rarely leading to discontinuation of treatment.

Allergic reactions: the appearance of symptoms of urticaria (itching, skin rash). These reactions are usually moderate in severity, but may progress, accompanied by a drop in blood pressure, dyspnea, up to the development of anaphylactic shock. If symptoms of urticaria occur, seek medical attention immediately. Cross-allergy with other sulfonylurea derivatives, sulfonamides, or similar substances is possible; allergic vasculitis may also develop.

In exceptional cases:

Other adverse effects: possible development of photosensitization, hyponatremia.

Because certain side effects, such as: severe hypoglycemia, serious changes in blood picture, severe allergic reactions, liver failure, can under certain circumstances be life threatening, in case of development of adverse or severe reactions the patient should immediately inform the attending physician about them and under no circumstances continue taking the drug without his recommendation.

Overdose

Symptoms:

Hypoglycemia (nausea, vomiting and epigastric pain, restlessness, tremors, visual disturbances, coordination disorders, drowsiness, coma and seizures).

Treatment:

If the patient is conscious – induction of vomiting, copious drinking, activated charcoal and laxatives. In severe overdose – intravenous bolus injection of dextrose solution (50 ml of 40% solution), then – infusion of 10% solution. Continuous monitoring of the patient, maintenance of vital functions and blood glucose concentration control are necessary (recurrent episodes of hypoglycemia are possible). Further treatment is symptomatic.

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