Glimendide-kv

I N S T R U C T I O N for medical use of the medicinal product GLIMEPIRIDE-KV (GLIMEPIRIDE-KV)

Composition:

Active substance: glimepiride;

1 tablet contains 2 mg, 3 mg, or 4 mg of glimepiride;

Excipients: lactose monohydrate, microcrystalline cellulose, povidone, sodium lauryl sulfate, crospovidone, magnesium stearate.

Dosage form. Tablets.

Main physicochemical properties:

2 mg tablets – round, biconvex, with a score line, white or almost white. Slight roughness and marbling on the tablet surface are acceptable;

3 mg tablets – flat cylindrical in shape, bevelled edges, white or almost white. Slight roughness and marbling on the tablet surface are acceptable;

4 mg tablets – round, biconvex, with a score line, white or almost white. Slight roughness and marbling on the tablet surface are acceptable.

Pharmacotherapeutic group. Oral hypoglycemic agents, excluding insulin. Sulfonamides, urea derivatives. ATC code A10BB12.

Pharmacological properties.

Pharmacodynamics.

Glimepiride is an orally active hypoglycemic agent belonging to the sulfonylurea group. It can be used in insulin-independent (type 2) diabetes mellitus.

Glimepiride acts primarily by stimulating insulin release from pancreatic beta cells.

As with other sulfonylurea agents, this effect is based on increasing the sensitivity of pancreatic cells to physiological glucose stimulation. In addition, glimepiride exerts a pronounced extrapancreatic effect, which is also characteristic of other sulfonylurea agents.

Insulin release. Sulfonylurea agents regulate insulin secretion by closing ATP-dependent potassium channels located in the membrane of pancreatic beta cells. Closure of the potassium channel leads to depolarization of the beta cell and, via opening of calcium channels, increases calcium influx into the cell, thereby triggering insulin release through exocyt游戏副本

Clinical characteristics.

Indications.

Type 2 diabetes mellitus in adults when blood glucose levels cannot be controlled by diet, physical activity, and weight reduction alone.

Contraindications.

Glimipiride-KV is not indicated for the treatment of insulin-dependent diabetes mellitus, diabetic ketoacidosis, or diabetic coma. The use of this medicinal product is contraindicated in patients with severe impairment of renal or hepatic function. In cases of severe renal or hepatic dysfunction, patients should be switched to insulin therapy.

Glimipiride-KV must not be administered to patients with hypersensitivity to glimepiride or to any excipient contained in the medicinal product, or to other sulfonylurea derivatives or sulfonamide drugs (risk of developing hypersensitivity reactions).

Interaction with other medicinal products and other forms of interaction.

Concomitant use of Glimipiride-KV with certain drugs may either reduce or enhance the hypoglycemic effect of glimepiride. Therefore, other medicinal products should be taken only with the consent (or prescription) of a physician. Glimepiride is metabolized via cytochrome P450 2C9 (CYP2C9). It is known that co-administration of inducers (e.g., rifampicin) or inhibitors of CYP2C9 (e.g., fluconazole) may alter this metabolism. Results from in vivo interaction studies have shown that fluconazole, one of the most potent inhibitors of CYP2C9, increases the AUC of glimepiride approximately twofold.

The following types of interactions are supported by clinical experience with Glimipiride-KV and other sulfonylurea derivatives.

Enhancement of glucose-lowering effect, and thus, in some cases, hypoglycemia, may occur when glimepiride is taken concomitantly with the following agents: phenylbutazone, azapropazone, and oxyphenbutazone; sulfinpyrazone; insulin and oral antidiabetic agents (such as metformin); certain long-acting sulfonamides; tetracyclines; salicylates and p-aminosalicylic acid; monoamine oxidase inhibitors (MAO); anabolic steroids and male sex hormones; quinolone antibiotics and clarithromycin; chloramphenicol; probenecid; coumarin anticoagulants; miconazole; fenfluramine; disopyramide; pentoxifylline (high parenteral doses); fibrates; troglitazone; angiotensin-converting enzyme (ACE) inhibitors; fluconazole; fluoxetine; allopurinol; sympatholytics; cyclo-, tro-, and ifosfamide.

Reduction of glucose-lowering effect, and consequently, increased blood glucose levels, may occur when the patient is taking the following medicinal products concomitantly: estrogens and progestogens; saluretics, thiazide diuretics; thyroid-stimulating agents; glucocorticoids; phenothiazine derivatives, chlorpromazine; epinephrine and sympathomimetics; nicotinic acid (high doses) and its derivatives; laxatives (with prolonged use); phenytoin; diazoxide; glucagon; barbiturates and rifampicin; acetazolamide.

H2-receptor antagonists, beta-blockers, clonidine, and reserpine may either enhance or reduce the glucose-lowering effect.

Under the influence of sympatholytic agents such as beta-blockers, clonidine, guanethidine, and reserpine, symptoms of adrenergic counter-regulation during hypoglycemia may be diminished or absent.

Alcohol consumption may unpredictably enhance or reduce the hypoglycemic effect of glimepiride.

Glimepiride may either increase or decrease the effect of coumarin derivatives.

Colesevelam binds to glimepiride and reduces its absorption from the gastrointestinal tract. No interactions were observed when glimepiride was administered at least 4 hours prior to colesevelam. Therefore, glimepiride should be taken at least 4 hours before colesevelam administration.

Special precautions for use.

Glimipiride-KV should be taken shortly before or during a meal.

In case of irregular eating habits or missed meals, treatment with Glimipiride-KV may cause hypoglycemia. Possible symptoms of hypoglycemia include: headache, intense feeling of hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, increased motor activity, aggression, difficulty concentrating, anxiety and delayed reaction time, depressive state, confusion, speech and visual disturbances, aphasia, tremor, paresis, sensory disturbances, dizziness, helplessness, loss of self-control, delirium, convulsions, somnolence and loss of consciousness up to coma, shallow breathing and bradycardia. In addition, signs of adrenergic counter-regulation may occur, such as sweating, cold and clammy skin, anxiety, tachycardia, arterial hypertension, palpitations, angina pectoris and cardiac arrhythmias.

The clinical picture of a severe hypoglycemic attack may resemble that of a stroke.

Symptoms of hypoglycemia can almost always be rapidly relieved by immediate intake of carbohydrates (sugar). Artificial sweeteners are ineffective.

Based on experience with other sulfonylurea derivatives, it is known that despite initial effectiveness of measures to correct hypoglycemia, it may recur.

Severe or prolonged hypoglycemia, which is only temporarily corrected by usual amounts of sugar, requires immediate treatment and sometimes hospitalization.

Factors predisposing to the development of hypoglycemia include:

• unwillingness or (especially in elderly patients) inability of the patient to cooperate with the physician;
• inadequate food intake, irregular eating, skipped meals or periods of fasting;
• dietary disturbances;
• imbalance between physical exertion and carbohydrate intake;
• alcohol consumption, especially when combined with skipped meals;
• impaired renal function;
• severe impairment of liver function;
• overdose of Glimipiride-KV;
• certain decompensated endocrine disorders affecting carbohydrate metabolism or counter-regulation of hypoglycemia (e.g., certain thyroid dysfunction, or deficiency of anterior pituitary or adrenal cortex function);
• concomitant use of certain other medicinal products (see section "Interaction with other medicinal products and other forms of interaction").

Treatment with Glimipiride-KV requires regular monitoring of blood and urine glucose levels. Additionally, determination of glycosylated hemoglobin levels is recommended.

During treatment with Glimipiride-KV, liver function tests and hematological parameters (especially leukocyte and platelet counts) should be monitored regularly.

In stressful situations (e.g., trauma, unplanned surgical procedures, infections accompanied by fever), temporary transition to insulin therapy may be indicated.

Experience with the use of Glimipiride-KV in patients with severe hepatic impairment or in patients undergoing dialysis is lacking. Patients with severe renal or hepatic dysfunction should be switched to insulin therapy.

Treatment with sulfonylurea drugs in patients with glucose-6-phosphate dehydrogenase deficiency may lead to the development of hemolytic anemia. Since glimepiride belongs to the sulfonylurea class of drugs, it should be used with caution in patients with glucose-6-phosphate dehydrogenase deficiency. Alternative non-sulfonylurea agents should be considered for such patients.

Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Use during pregnancy or breastfeeding.

Pregnancy.

Risk associated with diabetes mellitus.

Abnormal blood glucose levels during pregnancy may increase the risk of congenital malformations and perinatal mortality. Therefore, careful monitoring of blood glucose levels in pregnant women is essential to avoid teratogenic risk.

Pregnant women with diabetes should be switched to insulin therapy. Women with diabetes should inform their physician about a planned pregnancy to allow timely adjustment of treatment and transition to insulin.

Risk associated with glimepiride.

There are no data on the use of glimepiride in pregnant women. Animal studies indicate reproductive toxicity, likely related to the pharmacological effect of glimepiride (hypoglycemia).

Therefore, glimepiride must not be used at any time during pregnancy.

If a patient taking glimepiride plans a pregnancy or becomes pregnant, she should be switched to insulin therapy as soon as possible.

Breastfeeding period.

It is unknown whether the drug is excreted in human breast milk. In rats, glimepiride is excreted in breast milk. Since other sulfonylurea derivatives are excreted in breast milk and there is a risk of hypoglycemia in breastfed infants, breastfeeding is not recommended during treatment with glimepiride.

Ability to affect reaction speed when driving or operating machinery.

Studies on the effect of the medicinal product on the ability to drive vehicles or operate machinery have not been conducted.

The ability to concentrate and reaction speed may be impaired due to hypoglycemia or hyperglycemia or, for example, due to visual disturbances. This may pose a risk in situations where such abilities are particularly important (e.g., driving a car or operating machinery).

Patients should be warned not to allow hypoglycemia to develop while driving. This is especially important for individuals who have poor or no awareness of the warning signs of hypoglycemia and for those who experience frequent hypoglycemic episodes. Serious consideration should be given to whether driving or operating machinery is appropriate under such circumstances.

Method of Administration and Dosage

The medicinal product is intended for oral administration.

Successful treatment of diabetes mellitus depends on the patient adhering to an appropriate diet, regular physical activity, and continuous monitoring of glucose levels in blood and urine. Failure to follow the prescribed diet cannot be compensated by taking tablets or using insulin.

The dosage is determined based on blood and urine glucose test results.

The initial dose is 1 mg (½ of a 2 mg tablet) of glimepiride per day. If this dose effectively controls the disease, it should be used for maintenance therapy.

If glycemic control is not optimal, the dose should be gradually increased to 2, 3, or 4 mg of glimepiride per day in stepwise increments (with intervals of 1–2 weeks).

Doses exceeding 4 mg per day provide better results only in individual cases.

The maximum recommended dose is 6 mg of Glimepiride-KV per day.

If the maximum daily dose of metformin does not provide adequate glycemic control, concomitant therapy with glimepiride may be initiated.

While maintaining the previous metformin dosage, glimepiride therapy should begin with a low dose, which can then be gradually increased up to the maximum daily dose, depending on the desired level of metabolic control. Combination therapy must be conducted under strict medical supervision.

If the maximum daily dose of Glimepiride-KV does not provide adequate glycemic control, concomitant insulin therapy may be initiated if necessary. While maintaining the previous glimepiride dosage, insulin treatment should begin with a low dose, which can then be gradually increased based on the desired level of metabolic control.

Combination therapy must be conducted under strict medical supervision.

Usually, a single daily dose of glimepiride is sufficient. It is recommended to take it shortly before or during a substantial breakfast or, if breakfast is not consumed, shortly before or during the first main meal of the day.

Errors in drug administration, such as missing a scheduled dose, should never be corrected by taking a higher dose subsequently.

The tablet should be swallowed whole, without chewing, with liquid.

If a hypoglycemic reaction occurs in a patient receiving 1 mg of glimepiride per day, this indicates that diabetes mellitus may be controlled solely by dietary adherence.

Improved diabetes control is associated with increased insulin sensitivity; therefore, during the course of treatment, the need for glimepiride may decrease. To avoid hypoglycemia, the dose should be gradually reduced or therapy discontinued altogether. Re-evaluation of dosage may also be necessary if the patient's body weight or lifestyle changes, or if other factors affecting the risk of hypo- or hyperglycemia arise.

Transition from other oral hypoglycemic agents to Glimepiride-KV.

Transition from other oral hypoglycemic agents to Glimepiride-KV is generally possible. During such a transition, the potency and half-life of the previous agent should be considered. In some cases, especially when the previous antidiabetic agent has a long half-life (e.g., chlorpropamide), it is recommended to wait several days before starting Glimepiride-KV. This helps reduce the risk of hypoglycemic reactions due to additive effects of the two agents.

The recommended initial dose is 1 mg of glimepiride per day. As noted above, the dose may be gradually increased according to the patient's response to the drug.

Transition from insulin to Glimepiride-KV.

In exceptional cases, patients with type 2 diabetes who are receiving insulin may be candidates for switching to Glimepiride-KV. Such a transition must be conducted under strict medical supervision.

Children.

Currently, there is a lack of evidence-based data on the use of glimepiride in patients under 8 years of age. Limited evidence exists regarding the use of glimepiride as monotherapy in children aged 8 to 17 years (see sections "Pharmacodynamics" and "Pharmacokinetics"). Data on the safety and efficacy of the drug in children are insufficient; therefore, it is not recommended for use in this patient population.

Overdose

Overdose may lead to hypoglycemia lasting from 12 to 72 hours, which may recur after initial improvement. Symptoms may appear up to 24 hours after drug administration. Typically, such patients require clinical observation. Nausea, vomiting, and epigastric pain may occur. Hypoglycemia is often accompanied by neurological symptoms such as restlessness, tremor, visual disturbances, coordination disorders, drowsiness, coma, and seizures.

Treatment of overdose. Treatment primarily involves preventing drug absorption. To achieve this, vomiting should be induced, followed by drinking water or soda containing activated charcoal (adsorbent) and sodium sulfate (laxative). If a large amount of glimepiride has been ingested, gastric lavage is indicated, followed by administration of activated charcoal and sodium sulfate. In cases of severe overdose, hospitalization in a resuscitation unit is required. Glucose administration should be initiated as soon as possible: if necessary, initially a single intravenous injection of 50 mL of a 50% glucose solution, followed by infusion of a 10% glucose solution with continuous monitoring of blood glucose levels. Further treatment is symptomatic.

When treating hypoglycemia caused by accidental ingestion of Glimepiride-KV in infants and young children, the glucose dose must be carefully adjusted to avoid dangerous hyperglycemia, with blood glucose levels closely monitored.

Adverse Reactions

Below is a list of adverse reactions observed during clinical trials with glimepiride and other sulfonylurea derivatives. Adverse reactions are categorized by organ systems and frequency of occurrence: very common — ≥ 1/10; common — from ≥ 1/100 to < 1/10; uncommon — from ≥ 1/1000 to < 1/100; rare — from ≥ 1/10,000 to < 1/1000; very rare — < 1/10,000; frequency not known — cannot be estimated from available data.

Blood and lymphatic system disorders:
Rare – thrombocytopenia, leucopenia, granulocytopenia, agranulocytosis, erythropenia, haemolytic anaemia, and pancytopenia, which are usually reversible upon discontinuation of the drug; frequency not known – severe thrombocytopenia with platelet count less than 10,000/µL and thrombocytopenic purpura.

Immune system disorders:
Very rare – leukocytoclastic vasculitis, moderate hypersensitivity reactions which may progress to severe forms, accompanied by dyspnoea, hypotension and sometimes shock; frequency not known – possible cross-allergy with sulfonylureas, sulfonamides or related substances.

Metabolism and nutrition disorders:
Rare – hypoglycaemia. Hypoglycaemic reactions usually occur immediately, may be severe, and are not always easily corrected. The occurrence of such reactions, as with other hypoglycaemic agents, depends on individual factors such as dietary habits and dosage (see section "Special precautions for use" for details).

Eye disorders:
Frequency not known – transient visual disturbances, particularly at the beginning of treatment, due to changes in blood glucose levels.

Gastrointestinal disorders:
Very rare – nausea, vomiting, diarrhoea, abdominal distension, discomfort in the abdomen, abdominal pain, which rarely lead to the necessity of discontinuing treatment.

Hepatobiliary disorders:
Frequency not known – increased liver enzyme levels; very rare – liver function abnormalities (e.g., with cholestasis or jaundice), hepatitis, and hepatic failure.

Skin and subcutaneous tissue disorders:
Frequency not known – hypersensitivity reactions may occur, including pruritus, rash, urticaria, and photosensitivity.

Laboratory findings:
Very rare – decreased serum sodium levels.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after marketing authorization is an important procedure. It allows continuous monitoring of the benefit-risk ratio of the medicinal product. Healthcare professionals are required to report all suspected adverse reactions through the national pharmacovigilance system.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging.

Keep out of reach and sight of children.

Packaging. 10 tablets in a blister; 3 blisters in a carton.

Prescription status. Prescription only.

Manufacturer. JSC "KYIV VITAMIN PLANT".

Manufacturer's address and location of operations.

38 Kopilivska Street, Kyiv, 04073, Ukraine.

Web-site: www.vitamin.com.ua