Glibenclamide (tablets 0.005 g)
Tabulettae Glibenclamidi 0.005
International Non-proprietary Name
Glibenclamide.
Glibenclamide.
Pharmacotherapeutic group
Oral hypoglycemic agents. Sulfonyl urea derivatives.
Composition
1 tablet contains 5 mg of glibenclamide.
Pharmacological action
Pharmacodynamics
Glibenclamide exhibits hypoglycemic action.
Specifically stimulates insular beta cells, increases insulin secretion by pancreas. Predominantly the action does not interfere with the insulin-synthetic function of the pancreas. It restores physiological sensitivity of beta-cells during glycemia. It potentiates the effect of insulin (endogenous and exogenous), as it increases the number of insulin receptors, enhances insulin-receptor interaction and restores the transduction of postreceptor signal. The increase of plasma insulin concentrations and decrease of glucose levels occur gradually, which reduces the risk of hypoglycemic conditions. Increases sensitivity of insulin receptors to insulin in peripheral tissues and causes extrapancreatic effects. It increases the utilization of glucose in the liver and muscles, stimulates glycogen formation. Favorable effects exchange processes, decrease non-esterified fatty acids plasma content. It exhibits antidiuretic effect, decreases thrombogenic blood properties.
The action starts within 2 h following administration, reaches maximum within 7-8 h and persists for 8-12 h.
Pharmacokinetics
Rapidly and practically completely absorbed from the gastrointestinal tract. Cmax following a single dose is reached within 1-2 h. Plasma protein binding is 99%. Practically does not cross placenta. Elimination half-life is 4-11 h. In completely converts into two inactive metabolites in the liver (approximately equal quantities are formed), one of which is excreted in urine and the other one - in bile.
Indications
Glibenclamide is used for the treatment of moderate diabetes mellitus, predominantly in patients above 40 years suffering from obesity, for whom adequate metabolic control can not be reached with the help of diet only; primary or secondary resistance to other sulfanilamides, possessing hypoglycemic properties; in patients, receiving insulin up to 30 units daily, in order to reach better normalization of carbohydrate metabolism, as well as to reduce insulin doses.
Glibenclamide can be administered in combination with biguanides or insulin.
Administration and dosing regimen
Preparation should be administered orally 1-3 times a day 20-30 minutes before food intake. The initial dose is chosen depending on individual. The dose depends on age, severity of diabetes mellitus, blood glucose concentrations after fasting and in 2 h after food. The initial dose for elderly patients is 1 mg (1/5 tablet) a day.
An average daily dose varies from 2.5 (1/2 tablet) to 15 mg (3 tablets). Doses above 15 mg daily do not increase the intensity of hypoglycemic effect. In case of the absence of diabetes mellitus compensation within 4-6 weeks it is necessary to consider the possibility of combined therapy with biguanides or insulin.
When changing hypoglycemic agents with similar activity glibenclamide is administered according to the scheme above and the preceding agent should be withdrawn immediately. When changing between biguanides the initial daily dose of glibenclamide is 2.5 mg (1/2 tablet), is necessary daily dose can be increased every 5-6 days on 2.5 mg (1/2 tablet) till the achievement of compensation.
Special indications
It is necessary to have food not later than in 1 h after the administration of the preparation. During therapy blood glucose levels should ne regularly monitored. Following physical and emotional overexertion, change if dietary regime the doses of the preparation should be adjusted.
During treatment with glibenclamide it is recommended not to consume alcohol (disulfiram-like reaction and marked hypoglycemia can occur) and to avoid a prolonged sunlight exposure.
Clinical manifestations of hypoglycemia can be masked when administered concomitantly with beta-blockers, clonidine, reserpine, guanethidine.
Influence on the ability to drive and work with mechanisms: during treatment it is advisable to exercise caution during driving and other potentially dangerous activities, requiring concentration and fast psychomotor reactions.
Side effects
Nervous system and sensory organs: headache, dizziness, taste alterations.
Gastro-intestinal tract: impaired hepatic function, cholestasis, dyspepsia.
Hemopoietic and hemostasis systems: rarely – thrombocytopenia, hypoplastic or hemolytic anemia, leucopenia, eosinophilia, agranulocytosis, pancytopenia.
Allergic reactions: skin rash, pruritus.
Others: hypoglycemia, proteinuria, late skin porphyria, pyrexia, arthralgia, polyuria, body weight increase, photosensitization.
Contraindications
Hypersensitivity (including to sulfanilamide preparations, thiazide diuretics), diabetic precomatose and comatose state, ketoacidosis, major burns, surgical intervention and traumas, ileus, stomach paresis, severe impairment of microcirculation, pronounced impairment hepatic and/or renal functions, leucopenia, diabetes mellitus type 1, pregnancy, breast-feeding, conditions accompanied by the impairment of food absorption, hypoglycemia (including infectious diseases).
Precautions
The periodicity of administration should be strictly followed. When determining dose levels sugar profile should be regularly monitored. During treatment dynamic monitoring of glucose levels (glycated hemoglobin) it required — not less than once in 3 months. Clinical manifestations of hypoglycemia can be masked when administered concomitantly with beta-blockers, clonidine, reserpine, guanethidine. During treatment it is recommended not to consume alcohol and to avoid a prolonged sunlight exposure. Fatty food should be limited.
Drug interactions
The preparation is a synergist of indirect anticoagulants.
Urine acidifying agents (ammonium chloride, calcium chloride, ascorbic acid in large doses) enhance glibenclamide effect.
Systemic antimycotic agents (azoles derivatives), fluoroquinolones, tetracycline, chloramphenicol, H2-blockers, beta-blockers, angiotensin-converting enzyme inhibitor, non-steroidal anti-inflammatory agents, monoamine oxidase inhibitors, clofibrate, bezafibrate, probenecid, paracetamol, ethionamide, anabolic steroids, pentoxifylline, allopurinol, cyclophosphamide, reserpine, sulfanilamides, insulin potentiate hypoglycemia.
Barbiturates, phenothiazines, diazoxide, glucocorticoids and thyroid hormones, oestrogens, gestagens, glucagon, adrenomimetic preparations, lithium salts, nicotinic acid derivatives and saluretics decrease hypoglycemic effect. Rifampicin accelerates inactivation and decreases the efficacy of glibenclamide.
Overdosage
Symptoms:hypoglycemia (hunger, diaphoresis, sudden weakness, palpitations, tremor, anxiety, headache, dizziness, insomnia, irritability, depression, brain edema, speech and vision impairment, impairment of consciousness), hypoglycemic coma.
Treatment:if the patient is conscious – administer sugar orally, in unconscious state – injection of 50% glucose solution (50 mL intravenously and orally), continuous intravenous infusion of 5-10% glucose solution, intramuscular injection of 1-2 mg of glucagon, 200 mg diazoxide orally every 4 h or 30 mg intravenously within 30 minutes, monitoring of glycemia level. In brain edema - mannite and dexamethasone.
Presentation
Tablets 5 mg. 10, 20 tablets in blisters, 50tablets in a jar.
