Pharmacological properties
Glimepiride-Teva is an orally active hypoglycemic substance that belongs to the group of sulfonylurea derivatives and can be used for non-insulin-dependent diabetes mellitus.
The drug acts mainly by stimulating the release of insulin from pancreatic β-cells. As with other sulfonylureas, this effect is based on an increase in the response of pancreatic β-cells to physiological glucose stimulation. In addition, Glimepiride-Teva has a pronounced effect not only on the pancreas, which is also characteristic of other sulfonylureas.
Insulin release. Sulfonylureas regulate insulin secretion by closing the ATP-sensitive potassium channel in the β-cell membrane. Closing the potassium channel induces depolarization of the β-cell and leads to the opening of calcium channels and increased calcium influx into the cell, which in turn leads to insulin release by exocytosis.
Glimepiride binds with a high rate of substitution to a β-cell membrane protein associated with the ATP-sensitive potassium channel, but the location of the binding site differs from the usual binding site of sulfonylurea derivatives.
The drug's action in locations other than the pancreas is to improve the sensitivity of peripheral tissues to insulin and reduce insulin utilization by the liver.
The utilization of blood glucose by peripheral muscle tissues and adipose tissue occurs with the help of special transport proteins located on the cell membrane. The transport of glucose into these tissues is an intermediate stage in glucose metabolism. Glimepiride-Teva very quickly increases the number of active molecules transporting glucose on the plasma membranes of muscle and adipose tissue cells, which leads to stimulation of glucose uptake.
General characteristics. In healthy individuals, the minimum effective dose when taken orally is about 0.6 mg. The effect of the drug Glimepiride-Teva is dose-dependent and reproducible. The physiological response to acute physical exertion, i.e. a decrease in insulin secretion, is preserved under the action of glimepiride.
Pharmacokinetics. The bioavailability of Glimepiride-Teva after oral administration is 100%. Food intake does not significantly affect absorption, although it slightly reduces its rate. C max in blood plasma is achieved 2.5 hours after oral administration.
T ½ with multiple doses is about 58 hours.
Indication
Type 2 diabetes mellitus in cases where diet, exercise, and weight loss do not produce a positive result.
Application
The basis of successful diabetes treatment is a proper diet, regular exercise, and regular blood and urine tests. Medications cannot provide adequate glycemic control if the patient does not follow the recommended diet.
The dose of Glimepiride-Teva is determined based on the results of metabolic tests (measurement of glucose levels in the blood and urine). In the first weeks of treatment, there may be an increased risk of hypoglycemia, so particularly careful monitoring is necessary.
For adults: The initial dose is 1 mg of the drug per day. If this dose allows to achieve adequate glucose control, it should be used for maintenance treatment.
If satisfactory glucose control is not achieved, the dose should be gradually increased based on glycemic control data, with an interval of about 1-2 weeks for each dose increase, by 2 or 3 or 4 mg of glimepiride-Teva per day.
A dose of the drug above 4 mg/day gives better results only in exceptional cases. The maximum recommended dose is 6 mg/day.
If the maximum daily dose of metformin does not provide adequate glucose control, concomitant treatment with Glimepiride-Teva can be initiated. While maintaining the metformin dose, Glimepiride-Teva treatment should be initiated at a low dose, which should then be gradually increased depending on the desired level of glycemic control to the maximum daily dose. Combination therapy should be initiated under close medical supervision.
If the maximum daily dose of Glimepiride-Teva does not achieve adequate glycemic control, concomitant insulin treatment can be initiated if necessary. While maintaining the dose of Glimepiride-Teva, insulin treatment should be started with a low dose, which should be gradually increased depending on the desired level of glycemic control to the maximum daily dose. Combination therapy should be initiated under close medical supervision.
Usually, one dose of Glimepiride-Teva per day is sufficient. It is recommended to take the drug shortly before or during a hearty breakfast. Otherwise, shortly before or during the first main meal.
If the patient forgets to take the next dose of the drug, the next dose should not be increased.
The tablets should be taken whole with a small amount of water.
During treatment with Glimepiride-Teva, the required dose may be reduced as a result of improved glycemic control due to increased sensitivity to insulin action. In order to avoid hypoglycemia, it is necessary to reduce the dose in a timely manner or discontinue treatment with the drug. The need to change the dose may also arise due to changes in body weight, the patient's lifestyle or the effects of other factors that increase the risk of hypo- or hyperglycemia.
Transferring a patient from other oral antidiabetic agents to Glimepiride-Teva. In general, such a transfer is possible. When transferring to Glimepiride-Teva, the dose and T ½ of the drug used previously should be taken into account. In some cases, especially if antidiabetic agents with a long T ½ (for example, chlorpropamide) were used, it is recommended to take into account T ½ for several days to minimize the risk of hypoglycemic reactions due to an additive effect. The recommended initial dose is 1 mg of the drug per day. Based on data on the effect on blood glucose levels, the dose of Glimepiride-Teva can be increased as indicated above.
Transferring a patient from insulin to glimepiride-Teva. In exceptional cases, transfer to glimepiride-Teva may be indicated in patients with type 2 diabetes who have been using insulin. The transfer should be carried out under close medical supervision.
Contraindication
Insulin-dependent diabetes; diabetic coma; diabetic ketoacidosis; severe renal or hepatic impairment; hypersensitivity to glimepiride-Teva, other sulfonylurea derivatives or sulfonamides, or any component of the drug. In severe renal or hepatic impairment, the patient should be transferred to insulin.
Side effects
Based on experience with glimepiride-Teva and other sulfonylurea derivatives, the following side effects have been identified.
On the part of the immune system: leukocytoclastic vasculitis, mild hypersensitivity reactions, which may progress to serious reactions with shortness of breath, decreased blood pressure and sometimes shock; allergic vasculitis.
Cross-allergy with sulfonylurea derivatives, sulfonamides or related substances is possible.
Blood and lymphatic system disorders: thrombocytopenia, leukopenia, erythrocytopenia, granulocytopenia, agranulocytosis, hemolytic anemia and pancytopenia. These phenomena usually disappear after discontinuation of treatment.
Metabolism and nutrition disorders: hypoglycemic reactions after taking Glimepiride-Teva.
Such reactions are usually immediate, may be severe and are not always easily reversible. The occurrence of such reactions, as with other antidiabetic agents, depends on individual factors such as dietary habits and dosage (see Precautions). The clinical presentation of a severe hypoglycaemic attack may resemble that of a stroke.
On the part of the organ of vision: temporary visual disturbances due to changes in blood glucose levels, especially at the beginning of treatment.
On the part of the digestive system: bloating, feeling of discomfort in the stomach and abdominal pain, nausea, vomiting and diarrhea, in which cases it is sometimes necessary to discontinue use of the drug.
Hepatobiliary system: possible increase in liver enzymes, liver dysfunction (e.g. with cholestasis and jaundice); hepatitis, which may progress to liver failure.
Skin and subcutaneous tissue disorders: Allergic and pseudoallergic reactions may occur, including itching, rash, urticaria, and photosensitivity.
Others: decreased plasma sodium concentration.
Special instructions
Glimepiride-Teva should be taken immediately before or during meals.
If the patient eats irregularly or forgets to eat at all, treatment with the drug may lead to hypoglycemia. Possible symptoms of hypoglycemia include headache, severe hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, increased motor activity, aggression, impaired concentration, anxiety and delayed reactions, depression, confusion, speech and visual disturbances, aphasia, tremor, paresis, sensory disturbances, dizziness, helplessness, loss of self-control, delirium, cerebral convulsions and loss of consciousness, including coma, shallow breathing and bradycardia.
In addition, signs of adrenergic repulsion may be present, such as increased sweating, cold and clammy skin, restlessness, tachycardia, hypertension, palpitations, angina pectoris, and arrhythmia.
The clinical presentation of a severe hypoglycemic attack can be similar to that of a stroke. Symptoms of hypoglycemia will almost always be adequately controlled by immediate ingestion of carbohydrates (sugar). Artificial sweeteners are ineffective.
From the experience of using other sulfonylureas, it is known that, despite the initial effectiveness of measures to eliminate hypoglycemia, it may occur again.
Factors that may contribute to the development of hypoglycemia:
unwillingness or (more often in elderly patients) inability of the patient to cooperate with the doctor; malnutrition, irregular meal intake, fasting; dietary disorders; imbalance between physical activity and carbohydrate intake; alcohol consumption, especially in the absence of meals; impaired renal function; severe liver function disorders; overdose of glimepiride; uncompensated endocrine disorders affecting carbohydrate metabolism or counterregulatory hypoglycemia (for example, certain disorders of the thyroid gland, adenohypophysis or adrenal cortex); simultaneous administration of other drugs (see Interaction with other drugs).
Treatment with Glimepiride-Teva requires regular monitoring of blood and urine glucose levels. In addition, determination of glycosylated hemoglobin in the blood is recommended.
During treatment, liver function tests and hematological parameters (especially leukocyte and platelet counts) should be monitored regularly.
In stressful situations (e.g. accidents, unplanned surgeries, infections with fever) temporary transfer of the patient to insulin may be indicated.
There is no experience with the use of Glimepiride in patients with severe hepatic impairment or patients on dialysis. In patients with severe renal or hepatic impairment, a switch to insulin is indicated.
The use of sulfonylureas in patients with glucose-6-phosphate dehydrogenase deficiency may lead to hemolytic anemia. Since glimepiride belongs to the sulfonylurea class, caution should be exercised in patients with glucose-6-phosphate dehydrogenase deficiency and consideration should be given to switching to alternative non-sulfonylurea therapy.
Patients with hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not use Glimepiride-Teva, as the drug contains lactose.
Use during pregnancy or breastfeeding
Pregnancy. Risk associated with diabetes. Violation of normal blood glucose levels during pregnancy is highly likely to lead to congenital malformations and perinatal mortality. In this regard, in order to avoid teratogenic effects, blood glucose levels should be carefully monitored during pregnancy. In such circumstances, insulin should be prescribed. Patients planning a pregnancy should inform their doctor about this.
Risk associated with glimepiride. There are no adequate data on the use of glimepiride during pregnancy. Animal studies have shown reproductive toxicity, which is likely to be due to the pharmacological action (hypoglycemia) of glimepiride.
Therefore, the drug should not be used during pregnancy.
In cases of early pregnancy planning or detection of pregnancy during glimepiride treatment, insulin therapy should be switched to as soon as possible.
Breastfeeding. It is not known whether glimepiride is excreted in human milk. Since other sulfonylurea drugs are excreted in human milk and there is a risk of hypoglycemia in newborns, the use of the drug during breastfeeding is not recommended.
Children. Do not use the drug to treat children.
Ability to influence the speed of reaction when driving a car or working with other mechanisms. The patient's ability to concentrate and react quickly may be impaired as a result of hypo- or hyperglycemia, or as a result of visual impairment. This may pose a risk in situations where these qualities are especially important (for example, driving a car or using mechanisms).
Patients should be advised to take precautions to avoid hypoglycemia while driving. This is especially true for those who have poor or no ability to recognize the warning signs of hypoglycemia and those who have frequent episodes of hypoglycemia. It is necessary to seriously consider whether to drive or operate machinery under these circumstances.
Interactions
If the drug is taken simultaneously with some other drugs, an undesirable increase or decrease in the severity of the hypoglycemic effect of the drug Glimepiride-Teva may occur. Therefore, other drugs should be used only as prescribed by a doctor.
Glimepiride is metabolized by cytochrome P450 2C9 (CYP 2C9). The metabolism is known to be affected by concomitant administration of inducers (e.g. rifampicin) or inhibitors of CYP 2C9 (e.g. fluconazole).
The results of an in vivo study showed that the AUC of glimepiride is doubled with simultaneous use of fluconazole (a CYP 2C9 inhibitor).
The hypoglycemic effect of Glimepiride-Teva may be reduced, leading to worsening of glycemic control, if the drug is taken simultaneously with drugs containing the following active ingredients: estrogens and gestagens, saluretics, thiazide diuretics, thyroid stimulating agents, glucocorticoids, phenothiazine derivatives, chlorpromazine, adrenaline and sympathomimetics, nicotinic acid (high doses) and nicotinic acid derivatives, laxatives (long-term use), phenytoin, diazoxide, glucagon, barbiturates and rifampicin, acetazolamide.
H2 receptor antagonists, β-blockers, clonidine and reserpine may lead to potentiation or reduction of the hypoglycemic effect.
Under the influence of sympatholytic drugs such as β-blockers, clonidine and reserpine, signs of adrenergic reversibility in hypoglycemia may be reduced or absent.
Alcohol consumption may increase or decrease the hypoglycemic effect of glimepiride in an unpredictable manner.
The drug may enhance or weaken the effects of coumarin derivatives.
Overdose
Hypoglycemia may develop, lasting 12-72 hours and may recur after initial improvement. Symptoms may persist for approximately 24 hours after administration of Glimepiride. Hospitalization for observation is generally recommended. Nausea, vomiting, and epigastric pain may occur. Hypoglycemia may usually be accompanied by neurological symptoms such as increased motor activity, tremor, restlessness, visual disturbances, impaired coordination, drowsiness, coma, and convulsions.
Treatment consists mainly in preventing absorption by inducing vomiting followed by drinking water or lemonade with activated charcoal (adsorbent) and sodium sulfate (laxative). If the drug was taken in a high dose, gastric lavage is indicated followed by the use of activated charcoal and sodium sulfate. In case of severe overdose, hospitalization in the intensive care unit is indicated. Glucose administration should be started as soon as possible. If necessary, use a bolus i/v injection of 50 ml of 50% glucose, then 10% glucose solution with careful monitoring of blood glucose levels. Further treatment is symptomatic.
Glucose should be administered very carefully, while monitoring blood glucose levels, as there is a risk of dangerous hyperglycemia.
Storage conditions
At a temperature not exceeding 25 °C.
