Glimepiride, 2 mg, tablets, 30 pcs.
The drug is administered orally. The initial and maintenance doses of Glimepiride are set individually based on the results of regular monitoring of blood glucose concentrations.
Initial dose and dose selection At the beginning of treatment, 1 mg of Glimepiride is prescribed once a day. When the optimal therapeutic effect is achieved, it is recommended to take this dose as a maintenance dose. In the absence of glycemic control, the daily dose should be gradually increased under regular monitoring of blood glucose concentrations (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 case of lack of glycemic control in patients taking metformin, concomitant therapy with glimepiride can be started. While maintaining the dose of metformin at the same level, treatment with glimepiride begins with a 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 carried out under close medical supervision.
Use in combination with insulin In cases where it is not possible to achieve glycemic control 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 Glimepirida prescribed to the patient remains unchanged. In this case, insulin treatment begins with a minimum dose, with a possible subsequent gradual increase in its dose under the control of blood glucose concentrations. Combined treatment requires mandatory medical supervision.
The time and frequency of taking the daily dose is determined by the doctor, taking into account the patient’s lifestyle. As a rule, it is sufficient to administer the daily dose in one dose immediately before or during a large breakfast or the first main meal. Glimepiride tablets are taken whole, without chewing, with a sufficient amount of liquid (about 0.5 cups). It is very important not to skip meals after taking Glimepiride.
Duration of treatment As a rule, treatment with Glimepiride is long-term.
Transferring the patient from another oral hypoglycemic drug to glimepiride. When transferring a patient from another oral hypoglycemic drug to Glimepiride, the initial daily dose of the latter should be 1 mg (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 carried out in stages in accordance with the above recommendations. It is necessary to take into account the effectiveness, dose and duration of action of the hypoglycemic agent used. In some cases, especially when taking hypoglycemic drugs with a long half-life (for example, 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, when carrying out insulin therapy in patients with type 2 diabetes mellitus, with compensation of the disease and with preserved secretory function (3-cells of the pancreas, it is possible to replace insulin with Glimepiride. The transfer should be carried out under the close supervision of a physician. In this case transferring the patient to Glimepiride begins with a minimum dose of 1 mg.
Glimepiride
Glimepiride reduces blood glucose concentrations, mainly by stimulating the release of insulin from the beta cells of the pancreas. Its effect is primarily associated with improving the ability of pancreatic beta cells to respond to physiological stimulation with glucose.
Compared with glibenclamide, low doses of glimepiride cause the release of less insulin while achieving approximately the same reduction in blood glucose concentrations. This fact indicates that glimepiride has extrapancreatic hypoglycemic effects (increased tissue sensitivity to insulin and insulinomimetic effect).
Insulin secretion.
Like all other sulfonylureas, glimepiride regulates insulin secretion through interaction with ATP-sensitive potassium channels on beta cell membranes. Unlike other sulfonylurea derivatives, glimepiride selectively binds to a protein with a molecular weight of 65 kDa located in the membranes of pancreatic beta cells. This interaction of glimepiride with its binding protein regulates the opening or closing of ATP-sensitive potassium channels.
Glimepiride closes potassium channels. This causes depolarization of beta cells and leads to the opening of voltage-sensitive calcium channels and the entry of calcium into the cell. As a result, an increase in intracellular calcium concentration activates insulin secretion through exocytosis.
Glimepiride binds and is released from the binding protein much faster and, accordingly, more often than glibenclamide. It is assumed that this property of the high rate of exchange of glimepiride with the protein that binds to it determines its pronounced effect of sensitizing beta cells to glucose and protecting them from desensitization and premature exhaustion.
The effect of increasing tissue sensitivity to insulin
. Glimepiride enhances the effects of insulin on glucose uptake by peripheral tissues.
Insulinomimetic effect
. Glimepiride has effects similar to those of insulin on glucose uptake into peripheral tissues and glucose output from the liver. Glucose is absorbed by peripheral tissues by transporting it into muscle cells and adipocytes. Glimepiride directly increases the number of glucose transport molecules in the plasma membranes of muscle cells and adipocytes. An increase in the entry of glucose into cells leads to the activation of glycosylphosphatidylinositol-specific phospholipase C. As a result, the intracellular calcium concentration decreases, causing a decrease in the activity of protein kinase A, which in turn leads to stimulation of glucose metabolism.
Glimepiride inhibits the release of glucose from the liver by increasing the concentration of fructose-2,6-bisphosphate, which inhibits gluconeogenesis.
Effect on platelet aggregation
.
Glimepiride reduces platelet aggregation in vitro
and
in vivo
. This effect appears to be due to selective inhibition of cyclooxygenase, which is responsible for the formation of thromboxane A, an important endogenous platelet aggregation factor.
Antiatherogenic effect of the drug
. Glimepiride helps normalize lipid levels, reduces the content of malonaldehyde in the blood, which leads to a significant reduction in lipid peroxidation. In animals, glimepiride leads to a significant reduction in the formation of atherosclerotic plaques.
Reducing the severity of oxidative stress
, which is constantly present in patients with type 2 diabetes mellitus. Glimepiride increases the content of endogenous α-tocopherol, the activity of catalase, glutathione peroxidase and superoxide dismutase.
Cardiovascular effects
. Through ATP-sensitive potassium channels (see above), sulfonylureas also have effects on the cardiovascular system. Compared with traditional sulfonylurea derivatives, glimepiride has a significantly lesser effect on the cardiovascular system, which may be explained by the specific nature of its interaction with the ATP-sensitive potassium channel protein that binds to it.
In healthy volunteers, the minimum effective dose of glimepiride is 0.6 mg.
The effect of glimepiride is dose-dependent and reproducible. The physiological response to physical activity (decreased insulin secretion) is preserved when taking glimepiride.
There are no significant differences in the effect depending on whether the drug was taken 30 minutes before a meal or immediately before a meal. In patients with diabetes mellitus, sufficient metabolic control can be achieved within 24 hours with a single dose of the drug. In a clinical study, 12 of 16 patients with renal failure (creatinine clearance 4-79 ml/min) also achieved sufficient metabolic control.
Combination therapy with metformin
. In patients with insufficient metabolic control when using the maximum dose of glimepiride, combination therapy with glimepiride and metformin may be initiated. Two studies demonstrated improved metabolic control with combination therapy compared with either drug alone. Combination therapy with insulin.
In patients with insufficient metabolic control when using maximum doses of glimepiride, concomitant insulin therapy may be initiated. In two studies, this combination achieved the same improvement in metabolic control as insulin alone; however, combination therapy requires a lower dose of insulin.
Use in
children
. There is insufficient data on the long-term effectiveness and safety of the drug in children.
Instructions for use of GLIMEPIRIDE
The dose is set individually based on regular monitoring of blood glucose concentrations. It is recommended to take the minimum dose that can adequately control metabolism.
During treatment, it is necessary to regularly measure glucose concentrations in the blood and urine. In addition, it is recommended to regularly determine the proportion of glycosylated hemoglobin.
If the patient has forgotten to take the next dose, it should not be increased at the next dose. Such situations, when the patient forgets to take the next dose at the prescribed time, should be discussed and agreed upon with the attending physician before starting treatment.
In case of accidental intake of a dose exceeding the recommended one, you should immediately inform your doctor.
Initial dose and increase.
The usual starting dose is 1 mg once daily.
If necessary, the daily dose can be increased. When increasing the dose, it is necessary to take into account the concentration of glucose in the blood and increase the dose gradually, i.e. at intervals of one to two weeks as follows:
- 1 mg - 2 mg - 3 mg - 4 mg - 6 mg. Doses greater than 6 mg per day are effective in only a small number of patients. The maximum daily dose is 8 mg and it is not recommended to exceed it.
Dosage range for patients with well-controlled diabetes mellitus.
Typically, doses for patients with well-controlled diabetes mellitus range from 1 to 4 mg glimepiride per day.
Dosing frequency and time.
The time and frequency of doses is determined by the attending physician depending on the patient’s lifestyle. Usually one dose of the drug per day is enough.
It is recommended to take glimepiride before a large meal (usually before breakfast). It is very important not to skip meals after taking the drug.
Secondary dose adjustment
. During treatment, the need for glimepiride may decrease. To avoid hypoglycemia, dose reduction or discontinuation of treatment must be carried out in a timely manner. It is also worth considering dose adjustments based on changes in the patient's weight, lifestyle, or other factors that may increase susceptibility to hypoglycemia or hyperglycemia.
Duration of treatment.
Treatment with glimepiride is usually long-term.
Transfer from another oral hypoglycemic drug.
There is no direct relationship between the dose of glimepiride and another hypoglycemic agent, therefore the initial daily dose of glimepiride should be 1 mg, even when switching from the maximum dose of another drug.
Application.
The tablets are taken whole, without chewing, with a sufficient amount of liquid.
