Glimecomb, 40 mg+500 mg tablets 60 pcs

Glimecomb is a combined hypoglycemic drug for oral administration. Glimecomb® is a fixed combination of two oral hypoglycemic agents of the group of biguanides and the group of sulfonylurea derivatives.

It has pancreatic and extrapancreatic action.

Glicliquid is a sulfonylurea derivative. It stimulates insulin secretion by the pancreas and increases the sensitivity of peripheral tissues to insulin. Stimulates the activity of intracellular enzymes – muscle glycogen synthetase. Restores the early peak of insulin secretion, shortens the period from the moment of food intake to the beginning of insulin secretion, and reduces postprandial hyperglycemia.

. In addition to influence on carbohydrate metabolism, it influences the microcirculation, reduces adhesion and aggregation of platelets, delays the development of mural thrombosis, normalizes vascular permeability and prevents the development of microthrombosis and atherosclerosis, restores the process of physiological mural fibrinolysis, counteracts the increased response to adrenaline of vessels in microangiopathies.

Inhibits the development of diabetic retinopathy at the nonproliferative stage; in diabetic nephropathy during long-term use it is registered a significant reduction of proteinuria. It does not lead to weight gain, as it mainly influences the early peak of insulin secretion and does not cause hyperinsulinemia; it promotes weight loss in obese patients by following the proper diet.

Metformin belongs to the group of biguanides. Reduces blood glucose concentration by inhibiting gluconeogenesis in the liver, reducing absorption of glucose from the gastrointestinal tract and increasing its utilization in tissues. Reduces serum concentrations of triglycerides, cholesterol and LDL (determined on an empty stomach) and does not change the concentration of other density lipoproteins. Helps to stabilize or reduce body weight. There is no therapeutic effect in the absence of insulin in the blood. Does not cause hypoglycemic reactions. Improves blood fibrinolytic properties due to the inhibition of tissue-type inhibitor of profibrinolysin activator (plasminogen).

Pharmacokinetics

Glyclazid

Intake and distribution

After oral administration, absorption is high. With a dose of 40 mg, Cmax in plasma is reached after 2-3 hours and is 2-3 µg/ml. Binding to plasma proteins is 85-97%.

Metabolism and excretion

Metabolized in the liver. T1/2 is 8-20 hours. It is excreted mainly as metabolites by kidneys – 70%, through the intestines – 12%.

In elderly patients no clinically significant changes of pharmacokinetic parameters were observed.

Metformin

Absorption and distribution

After oral administration absorption is 48-52%. It is rapidly absorbed from the gastrointestinal tract. Absolute bioavailability (fasting) is 50-60%. Cmax in plasma is reached after 1.81-2.69 hours and does not exceed 1 µg/ml. Dietary intake decreases Cmax in plasma by 40% and delays its achievement by 35 min. Binding to plasma proteins is insignificant. Metformin is able to accumulate in erythrocytes.

T1/2 is 6.2 h. It is excreted by kidneys, mainly unchanged (glomerular filtration and tubular secretion) and through intestine (up to 30%).

Indications

Type 2 diabetes mellitus with ineffectiveness of diet therapy, exercise and prior therapy with metformin or gliclazide.

Substitution of prior therapy with two drugs (metformin and gliclazide) in patients with type 2 diabetes with stable and well-controlled blood glucose levels.

Active ingredient

Composition

How to take, the dosage

The drug Glimecomb is administered orally, during or immediately after a meal. The dose of the drug is determined by the doctor individually for each patient depending on the blood glucose level.

In general, the starting dose is 1 to 3 tablets daily with gradual dose adjustment until stable compensation of the disease is achieved.

The drug is usually taken 2 times a day (in the morning and in the evening). The maximum daily dose is 5 tablets.

Interaction

Strengthening of hypoglycemic action of the drug Glimecomb is observed when concomitant use with ACE inhibitors (captopril, enalapril), blockers of histamine H2-receptors (cimetidine), antifungal drugs (miconazole, fluconazole), NSAIDs (phenylbutazone, azapropazone, oxyphenbutazone), with fibrates (clofibrate, besafibrate), anti-tuberculosis drugs (etionamide), salicylatesCoumarin-type anticoagulants, anabolic steroids, beta-adrenoblockers, MAO inhibitors, long-acting sulfonamides, with cyclophosphamide, chloramphenicol, fenfluramine, fluoxetine, guanethidine, pentoxifylline, tetracycline, theophylline, tubule secretion blockers, reserpine, bromocriptine, disopyramide, pyridoxine, with other hypoglycemic drugs (incl.including acarbose, biguanides, insulin), allopurinol, oxytetracycline.

. Decrease of hypoglycemic action of Glimecomb preparation is observed when concomitant use with barbiturates, GCS, adrenomimetics (epinephrine, clonidine), antiepileptic drugs (phenytoin), slow calcium channel blockers, carbohydrase inhibitors (acetazolamide), thiazide diuretics, Chlorthalidone, furosemide, triamterene, asparaginase, baclofen, danazol, diazoxide, isoniazid, morphine, ritodrine, salbutamol, terbutaline, glucagon, rifampicin, thyroid hormones, lithium salts, high-dose nicotinic acid, chlorpromazine, oral contraceptives and estrogens.

Increases the risk of ventricular extrasystole on a background of cardiac glycosides.

Drugs that depress medullary hematopoiesis increase the risk of myelosuppression.

Ethanol increases the likelihood of lactacidosis.

Pharmacokinetic interaction

Metformin decreases Cmax in plasma and T1/2 of furosemide by 31 and 42.3%, respectively.

Furosemide increases Cmax of metformin by 22%.

Nifedipine increases absorption, increases plasma Cmax, and slows metformin excretion.

The cationic drugs (amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene and vancomycin) that are secreted in the tubules compete for tubular transport systems and can increase Cmax of metformin in plasma by 60% with long-term therapy.

Contraindications

The drug is not recommended for patients older than 60 years of age who perform heavy physical work, because of the increased risk of lactacidosis.

The drug should be used with caution in febrile syndrome, adrenal insufficiency, hypothyroidism, and thyroid disease with impaired thyroid function.

Side effects

Endocrine system: hypoglycemia (in case of violation of the dosing regimen and inadequate diet) – headache, fatigue, hunger, excessive sweating, sudden weakness, palpitation, dizziness, impaired coordination of movements, temporary neurological disorders; with progression of hypoglycemia loss of self-control, loss of consciousness is possible.

Metabolic disorders: in some cases – lactacidosis (weakness, myalgia, respiratory disorders, drowsiness, abdominal pain, hypothermia, decreased BP, bradyarrhythmia).

Digestive system disorders: dyspepsia (nausea, diarrhea, feeling of heaviness in epigastrium, “metal” taste in mouth), decreased appetite (intensity of these reactions decreases if the drug is taken with food); rarely – hepatitis, cholestatic jaundice (drug withdrawal is required), increased liver transaminase activity, ALP.

With the hematopoietic system: rarely – inhibition of medullary hematopoiesis (anemia, thrombocytopenia, leukopenia).

Allergic reactions: itching, urticaria, maculopapular rash.

Others: visual impairment.

In cases of side effects, the dose should be reduced or the drug temporarily stopped.

General side effects of sulfonylurea derivatives: erythropenia, agranulocytosis, hemolytic anemia, pancytopenia, allergic vasculitis, life-threatening liver failure.

Overdose

Symptoms: lactacidosis is possible (because the drug contains metformin), hypoglycemia.

Treatment: if symptoms of lactacidosis occur, the drug should be stopped. Lactacidosis is a condition requiring emergency medical care; treatment is carried out in a hospital. The most effective method of treatment is hemodialysis.

In case of mild or moderate hypoglycemia, glucose (dextrose) or sugar solution is taken orally. In cases of severe hypoglycemia (loss of consciousness), a 40% solution of dextrose (glucose) or glucagon is administered by IV, IM or p/u. After recovery of consciousness, the patient should be given food rich in carbohydrates, in order to avoid the recurrence of hypoglycemia.