Maninil of 5 tab. of 5 mg No. 120

Pharmacological properties

Pharmacodynamics. glibenclamide has gipoglikemiziruyushchy effect as at patients with diabetes іі type, and at healthy people as it increases insulin secretion by pancreas β-cells due to their stimulation. this action depends on concentration of glucose in the environment surrounding β-cells.

Pharmacokinetics. After oral administration, glibenclamide is quickly and almost completely soaked up. The concomitant use of food significantly does not influence glibenclamide absorption. Linking with proteins of blood plasma — 98%. The C _max in blood serum is reached in 1–2 h at use of Maninil 3.5 and in 2.5 h at use of Maninil 5 and makes 100 ng/ml. In 8–10 h the concentration in blood serum decreases depending on the entered dose by 5–10 ng/ml at use of Maninil 3.5 and by 10–20 ng/ml Maninil 5 use. The t _½ in/in introductions makes later 2 h, after oral administration of Maninil of 3.5 — 2-5 h and 7 h at Maninil 5 use. However some researches indicate that this time at patients with diabetes can increase to 8–10 h. In a liver glibenclamide is almost completely transformed to several metabolites which do not play an essential role in gipoglikemiziruyushchy effect of glibenclamide. Metabolites are completely brought out of an organism in equal quantities with urine and bile during 45–72 h. At patients with an abnormal liver function the removal of glibenclamide from blood plasma is slowed down. In a renal failure, depending on degree of a renal failure, removal of metabolites with urine kompensatorno increases. At moderate insufficiency of kidneys (clearance of creatinine of ≥30 ml/min.) the total elimination remains without changes; in a heavy renal failure the cumulation is possible.

Indication

Non-insulin-dependent diabetes at adults (type ii diabetes), if other measures as, for example, strict observance of a diet, reduction of excess body weight, sufficient physical activity did not lead to satisfactory correction of level of glucose in blood.

Use

Drug is appointed by the doctor. correction of a diet is obligatory. the dosage depends on results of a research of level of glucose in blood and urine. a pill should be taken before food, without chewing, washing down with enough liquid (it is better 1 glass of water). when assigning a dose, component a day, all quantity of tablets (dose) on one reception in the morning and one — in the evening in the ratio 2:1 is recommended to distribute more than 2 tablets of drug. it is very important to use medicament every time at the same time. if the patient missed one reception, then it is never impossible to compensate it by reception of higher dose in the following reception. duration of treatment depends on the course of the disease. during treatment it is necessary to carry out regular control of a condition of a metabolism.

Therapy is begun, whenever possible, with the minimum doses, first of all it concerns patients with the increased tendency to a hypoglycemia and with a body weight of 50 kg. Therapy it is reasonable to begin with appointment ½–1 Maninil 3.5 tablets (1.75-3.5 mg of glibenclamide) or ½–1 Maninil 5 tablets (2.5-5 mg of glibenclamide) of 1 times a day. At insufficient correction of a metabolism the dose is gradually raised with an interval of several days to 1 week, the necessary therapeutic dose which makes 15 mg/days (3 tablets of Maninil 5) or 10.5 mg of the micronized glibenclamide (3 tablets of Maninil 3.5) will not be reached yet.

Convertion of the patient from use of other anti-diabetic drugs. Convertion on intake of Maninil is carried out very carefully and begin with ½–1 Maninil 3.5 tablets (1.75-3.5 mg of glibenclamide a day) or ½–1 Maninil 5 tablets (2.5-5 mg of glibenclamide a day).

Selection of a dose. To patients of advanced age, astenizirovanny patients or at malnutrition and also in a renal failure or a liver it is necessary to lower an initial and maintenance dose in view of risk of development of a hypoglycemia. Besides, at degrowth of a body of the patient or at change of lifestyle it is necessary to resolve an issue of dose adjustment.

Combination with other anti-diabetic means. Maninil it is possible to appoint as monotherapy or in a combination with metformin. In reasonable cases at intolerance of metformin the additional use of medicaments of group of a glitazon can be shown (roziglitazon, pioglitazon). Maninil can also be combined with oral anti-diabetic medicaments which do not stimulate emission of endogenous insulin by β-cells of endogenous insulin (guary or acarbose). At secondary resistance to glibenclamide (decrease in products of insulin as a result of exhaustion of β-cells) combination therapy with insulin can be used. However at complete cessation of secretion of own insulin in an organism the monotherapy is shown by insulin.

Route of administration and duration of therapy. A pill should be taken before food, without chewing, washing down with enough liquid (it is better a glass of water). The daily dose which makes no more than 2 tablets of medicament should be accepted before a breakfast. At a daily dose which makes more than 2 tablets of medicament it is recommended to distribute all quantity on one morning and one evening receptions in the ratio 2:1. It is very important to use medicament every time at the same time. If the patient missed one reception, then it is never impossible to compensate it by reception of higher dose. Duration of treatment depends on a course of the disease. During treatment it is necessary to carry out regular control of level of glucose in blood plasma and urine; it is recommended to determine in addition the level of glikozilirovanny hemoglobin (HbA1c) and/or fructosamine and also other indicators (for example the level of lipids in blood).

Children. Not to apply glibenclamide to children.

Contraindication

Hypersensitivity to active ingredient, to ponso 4r or to any component of drug. hypersensitivity to other medicaments of sulphonylurea, sulfonamides, diuretics derivative of sulfonamide and a probenetsid — cross-reactions are possible. insulin-dependent diabetes mellitus (і type), full secondary inefficiency of therapy by glibenclamide in diabetes іі type, a metabolic acidosis, a diabetic prekoma or a coma, a state after pancreatectomy. heavy abnormal liver functions. heavy renal failures. period of pregnancy and feeding by a breast. use along with bosentany.

Side effects

Disbolism and food. increase in body weight, a hypoglycemia which can accept long character and lead to a heavy hypoglycemia with a coma which threatens the patient's life. at the erased hypoglycemia course, in autonomous neuropathy or the accompanying therapy sympatholytic means typical symptoms harbingers of a hypoglycemia can be weakened or be absent. symptoms harbingers of a hypoglycemia are, sudden sweating, the strengthened heartbeat, a shiver, feeling of hunger, concern, feeling of crawling of goosebumps in an oral cavity, pallor of skin, a headache, drowsiness, sleep disorders, sensation of fear, uncertainty of movements, reversible neurologic symptoms (for example disturbance of the speech and sight, the phenomenon of paralysis or disturbance of sensitivity).

from an organ of sight. Visual disturbances and accommodations, especially in an initiation of treatment.

from a digestive tract. Nausea, feeling of overflow/swelling in a stomach, vomiting, an abdominal pain, diarrhea, an eructation, metal taste in a mouth. These complaints have passing character and in general do not demand medicament withdrawal.

from a liver and a gall bladder. Passing increase in AsAT and AlAT, SF, medicamentous hepatitis, intra hepatic cholestasia, perhaps, caused by allergic reaction of giperergichesky type of cells of a liver. These disturbances have reversible character after medicament withdrawal, but can lead to a liver failure, life-threatening.

from skin and hypodermic cellulose. Itching, urtikarny rash, erythema nodosum, korepodobny or makulopapulezny dieback, purpura, photosensitization. These phenomena of hypersensitivity reactions have reversible character, but very seldom can pass into the life-threatening states which are followed by an asthma and considerable decrease in the ABP up to development of shock. Reactions of hypersensitivity, including rash, arthralgias, fever, a proteinuria and jaundice; the allergic vasculitis, poses a threat of life. At emergence of skin reactions it is necessary to see a doctor.

from the system of blood and lymphatic system. Thrombocytopenia, a leukopenia, an erythropenia, a granulocytopenia up to development of an agranulocytosis, aplastic anemia, an eosinophilia. In some cases: pancytopenia, hemolytic anemia. The specified changes of a picture of blood have reversible character after medicament withdrawal, but very seldom can pose a threat for life.

Other side effects. Weak diuretic action, a reversible proteinuria, a hyponatremia, disulfiramopodobny reaction, a cross allergy with the sulfonamides derivative of sulfonamides and probenetsidy, a syndrome of inadequate secretion of antidiuretic hormone. Ponso 4R can cause allergic reactions.

Special instructions

needs to be remembered that at simultaneous use of maninil with a clonidine, blockers of β-adrenoceptors, guanetidiny and reserpine perception by the patient of symptoms — hypoglycemia harbingers can be broken.

In a renal failure or a liver, reduced function of a thyroid gland, a hypophysis or bark of adrenal glands needs extra care.

patients of advanced age have a danger of development of the prolonged hypoglycemia therefore glibenclamide is appointed with extra care and under constant observation in an initiation of treatment; administration of medicaments of sulphonylurea with shorter period of action is reasonable in the beginning. At the complicated contact with the patient (for example in cerebral atherosclerosis) risk of development of a hypoglycemia increases. Considerable intervals between meals, insufficient amount of the consumed carbohydrates, unusual physical activity, diarrhea or vomiting can increase risk of development of a hypoglycemia. Intake of the medicines operating on central nervous system and blockers of β-adrenoceptors and also autonomous neuropathy symptoms can mask gipoglekimiya harbingers.

Alcohol at the single use in a significant amount and at its constant use can strengthen or weaken unexpectedly effect of Maninil. Constant abuse of depletive can lead to deterioration in a metabolism. At the non-compliance with the scheme of treatment insufficient gipoglikemiziruyushchy effect of medicament or during stressful situations the glucose level in blood plasma can increase. Hyperglycemia symptoms: a polydipsia, dryness in a mouth, frequent urination, an itching and xeroderma, fungus or infectious diseases of skin, decrease in working capacity. At the expressed stressful situations (injury, operation, an infectious disease which is followed by fervescence) the metabolism can worsen that leads to a hyperglycemia, sometimes so expressed that there can be a need for temporary transfer of the patient on therapy by insulin. The patient has to be informed that during treatment by Maninil he should report about development of other diseases to the doctor immediately.

At patients with insufficiency in an organism glyukozo-6-fosfatdegidrogenazy treatment with sulphonylurea drugs, including glibenclamide, can cause hemolytic anemia therefore it is necessary to resolve an issue of their conversion to the medicaments alternative to sulphonylurea derivatives. Patients with hereditary intolerance have galactoses, insufficiency of lactase or a syndrome of glyukozo-galaktozny malabsorption Maninil should not be applied.

Use during pregnancy and feeding by a breast. Glibenclamide is contraindicated.

, therapy by oral hypoglycemic means needs to be postponed before pregnancy planning. Control of diabetes insulin is therapy of the choice during pregnancy or feeding by a breast.

Ability to influence speed of response at control of vehicles or work with mechanisms. At a hypoglycemia the ability to concentration of attention and speed of response can decrease that it is necessary to consider and take security measures for elimination of a hypoglycemia at control of vehicles and work with other mechanisms. It is especially important in cases of frequent emergence of hypoglycemic states or lack of adequate perception of symptoms — hypoglycemia harbingers, at the same time it is necessary to resolve an issue of expediency of control of vehicles.

At simultaneous use of maninil with other medicines its action can amplify or be weakened by

Interaction

Strengthening of effect of glibenclamide (development of hypoglycemic states is possible) can arise at simultaneous use with other oral anti-diabetic medicaments and insulin, APF inhibitors, anabolic steroids and medicaments of male sex hormones, antidepressants (fluoxetine, MAO inhibitors), blockers of β-adrenoceptors, derivatives of a hinolon, chloramphenicol, Clofibratum and its analogs, coumarin derivatives, Disopyramidum, fenfluraminy, Miconazolum, PASK, pentoksifilliny (at parenteral administration in a high dose), perhexiliny, pyrazyl ketone derivatives, probenetsidy, salicylates, sulfonamides, medicaments of a tetracycline row, tritokvaliny, cytostatics of group of cyclophosphamide. Reception of blockers of β-adrenoceptors, a clonidine, guanetidin and reserpine can reduce perception of early symptoms of a hypoglycemia.

Decrease in effect of glibenclamide (development of hyper glycemic reactions is possible) can arise at simultaneous use with acetazoleamide, blockers of β-adrenoceptors, barbiturates, diazoxide, diuretics, a glucagon, an isoniazid, GKS, nikotinata, derivatives of a fenotiazin, Phenytoinum, rifampicin, hormones of a thyroid gland, medicaments of female sex hormones (gestagena, are oestrogenic), sympathomimetics.

Blockers of N ₂ - receptors, the clonidine and reserpine can both weaken, and to strengthen gipoglikemiziruyushchy effect of drugs. In some cases pentamidine can lead to heavy hypo - or a hyperglycemia. Action of derivatives of coumarin can both amplify, and to be weakened.

Bosentan. At patients who received glibenclamide along with bosentany growth of frequency of increase in level of liver enzymes was observed. And glibenclamide, and bosentan suppress function of the pump which brings bilious salts out of a cell. It leads to intracellular accumulation of bilious salts which have cytotoxic effect therefore such combination should not be used.

Single overdose or use of slightly raised doses can lead

for a long time to the heavy prolonged hypoglycemia which poses a threat for life. at intentional overdose there is a danger of the prolonged hypoglycemia with tendency to a recurrence after several days of successful treatment.

Symptoms of overdose (hypoglycemia): a sudden hyperhidrosis, the strengthened heartbeat, a shiver, feeling of hunger, concern, paresthesias in a mouth, pallor of integuments, a headache, drowsiness, sleep disorders, fearfulness, uncertainty of movements, reversible neurologic deficit (disturbance of the speech and sight, appearance of paralysis or disturbance of sensitivity). At the progressing hypoglycemia the loss of consciousness (hypoglycemic coma) is possible. In such cases the integuments to the touch damp and cold, are noted tachycardia, a hyperthermia, motive excitement, hyperreflexia, paresis and a positive Babinski's reflex, spasms can develop.

Treatment: easy or moderate severity the patient is capable to eliminate a hypoglycemia independently, having eaten sugar or carbohydrate-rich food. Therefore they have to carry always with themselves 20 g of glucose. Patients have to tell the doctor when there was a hypoglycemia, for dose adjustment if it is necessary. At a heavy hypoglycemia it is necessary to ask immediately for the help the doctor.

At accidental overdose and in the presence of contact with the patient needs to cause vomiting, to carry out gastric lavage (in the absence of convulsive readiness) and in/in to enter glucose solution. If the patient fainted, it is necessary to begin immediately in/in administration of glucose (bolyusno 40–80 ml of 40% of solution of glucose with the subsequent infusion of 5-10% of solution of glucose). If necessary it is possible to enter in addition 1 mg of a glucagon in oil or in / century. If the patient does not recover consciousness, the above-stated actions are repeated, if necessary carry out intensive care. At the prolonged hypoglycemia the observation of a condition of the patient with regular control of a glycemia within several days and, if necessary — performing infusional therapy is required.

Storage conditions

In original packing at a temperature below 25 °C.