Glukonorm plus, 5 mg+500 mg 30 pcs

Oral hypoglycemic agent (second generation sulfonylurea derivative + biguanide)

Indications

Type 2 diabetes mellitus in adults:

– when diet therapy, exercise therapy, and prior monotherapy with metformin or a sulfonylurea derivative are ineffective;

– to replace prior therapy with two drugs (metformin and a sulfonylurea derivative) in patients with stable and well-controlled glycemia levels.

Active ingredient

Composition

Active substances:

Glibenclamide – 5.00 mg,

metformin hydrochloride – 500 mg.

Auxiliary substances:

microcrystalline cellulose – 57.20 mg,

hyprolose (hydroxypropyl cellulose) – 13.80 mg,

croscarmellose sodium – 18.00 mg,

magnesium stearate – 6.00 mg.

Shell for dosage of 5 mg + 500 mg:

. VIVACOAT® PM-2P-050 [hypromellose(hydroxypropyl methylcellulose 6 cPs) – 9.00 mg, hyprolose (hydroxypropyl cellulose) – 0.90 mg, polyethylene glycol 3350 – 0.90 mg, gitan dioxide – 4,75 mg, talc – 1.80 mg, iron oxide yellow dye (E172) – 0.26 mg, quinoline yellow dye (E104) – 0.37 mg, sunset yellow dye (E110) – 0.02 mg] – 18.00 mg.

How to take, the dosage

The dose of the drug is determined by the doctor individually for each patient depending on the level of glycemia. The initial dose is 1 tablet of Glukonorm® Plus 2.5 mg + 500 mg once a day. To avoid hypoglycemia, the initial dose should not exceed the daily dose of glibenclamide (or the equivalent dose of another previously taken sulfonylurea drug) or metformin, if they were used as first-line therapy. It is recommended that the dose be increased by no more than 5 mg of glibenclamide + 500 mg of metformin per day every 2 or more weeks to achieve adequate blood glucose control.

Replacement of prior combination therapy with metformin and glibenclamide: The starting dose should not exceed the daily dose of glibenclamide (or the equivalent dose of another sulfonylurea drug) and metformin taken previously. Every 2 or more weeks after the start of treatment, the dose of the drug is adjusted according to the level of glycemia.

The maximum daily dose is 6 tablets of Gluconorm® Plus 2.5 mg + 500 mg.

The dosing regimen

The dosing regimen depends on the individual prescription:

For doses of 2.5 mg + 500 mg

– once daily, in the morning at breakfast, when prescribed 1 tablet per day;

– twice daily, in the morning and evening, when prescribed 2 or 4 tablets per day.

For doses of 2.5 mg + 500 mg

Three times daily, morning, afternoon, and evening, when prescribing 3, 5, or 6 pills per day.

The tablets should be taken with meals. Each ingestion of the drug should be accompanied by a meal that is high enough in carbohydrates to prevent hypoglycemia.

Elderly patients

The dose of the drug is adjusted according to the state of renal function. The initial dose should not exceed 1 tablet of Gluconorm® Plus 2.5 mg + 500 mg. Regular evaluation of renal function should be carried out.

Children

The drug Glukonorm® Plus is not recommended for use in children.

Interaction

Contraindicated combinations

Associated with glibenclamide

Miconazole may cause hypoglycemia (up to and including coma).

Injurious to metformin use

Iodine-containing contrast agents: Depending on renal function, the drug should be discontinued 48 hours before or after intravenous administration of iodine-containing contrast agents.

Unrecommended combinations

Related to the use of sulfonylurea derivatives

Alcohol: a disulfiram-like reaction (alcohol intolerance) is very rarely observed when alcohol and glibenclamide are taken simultaneously. Alcohol intake may increase the hypoglycemic effect (by inhibiting the compensatory reactions or delaying its metabolic inactivation), which may contribute to the development of hypoglycemic coma. During treatment with Gluconorm® Plus, alcohol and medicinal products containing alcohol should be avoided. Phenylbutazone increases the hypoglycemic effect of sulfonylurea derivatives (by replacing the sulfonylurea derivatives at the sites of their binding to the protein and/or reducing their elimination). It is preferable to use other anti-inflammatory agents detecting lower effects, or to warn the patient about the need for self-monitoring of glycemic levels; if necessary, the dose should be adjusted when co-administering the anti-inflammatory agent and after discontinuation.

Related to glibenclamide use

Bozentan in combination with glibenclamide increases the risk of hepatotoxic effects. It is recommended to avoid concomitant administration of these drugs. The hypoglycemic effect of glibenclamide may also be reduced.

Risk of lactoacidosis is increased in acute alcohol intoxication, especially in case of starvation or poor nutrition, or liver failure. Alcohol and medicinal products containing ethanol should be avoided during treatment with Gluconorm® Plus.

Combinations requiring caution

Related to the use of all hypoglycemic agents

Chlorpromazine: at high doses (100 mg/day) causes increased glycemia (reducing insulin release).

Precautionary measures: the patient should be advised to monitor blood glucose levels independently; if necessary, the dose of the hypoglycemic agent should be adjusted during concomitant use of the neuroleptic and after discontinuation of the drug.

Glucocorticosteroids (GCS) and tetracosactide: increase in blood glucose, sometimes accompanied by ketosis (GCS cause reduced glucose tolerance).

Precautionary measures: the patient should be advised to monitor blood glucose alone; if necessary, the dose of hypoglycemic agent should be adjusted during concomitant use of GCS and after stopping their use.

Danazolol has a hyperglycemic effect. It is necessary to adjust the dose of Glukonorm® Plus under glycemic control if treatment with danazolol and discontinuation of danazol is necessary.

β2-adrenomimetics: by stimulating the β2-adrenoreceptors they increase the concentration of glucose in the blood.

Precautionary measures: the patient should be warned and blood glucose control should be established; transfer to insulin therapy is possible.

Diuretics: increase blood glucose levels.

Precautionary measures: the patient should be warned about the need for self-monitoring of blood glucose; it may be necessary to adjust the dose of hypoglycemic agent during concomitant use with diuretics and after discontinuation of their use.

Angiotensin-converting enzyme (ACE) inhibitors (captopril, enalapril): the use of ACE inhibitors helps to reduce blood glucose. If necessary, the dose of the drug Glukonorm® Plus should be adjusted during concomitant use with ACE inhibitors and after discontinuation of their use.

Associated with metformin use

Diuretics: Lactoacidosis occurring when taking metformin against the background of functional renal failure caused by taking diuretics, especially “loop” diuretics.

The glibenclamide-associated β-adrenoblockers, clonidine, reserpine, guanethidine, and sympathomimetics mask some symptoms of hypoglycemia: palpitations and tachycardia; most non-selective β-adrenoblockers increase the frequency and severity of hypoglycemia.

Patients should be advised to self-monitor blood glucose, especially at the start of treatment.

Fluconazole: prolongation of the elimination half-life of glibenclamide with possible occurrence of hypoglycemia. The patient should be cautioned about the need for self-monitoring of blood glucose; it may be necessary to adjust the dose of hypoglycemic drugs during concomitant treatment with fluconazole and after discontinuation of its use.

Cholic acid sequestrants: Concomitant use with Gluconorm® Plus decreases the plasma concentration of glibenclamide, which may lead to a decrease in hypoglycemic effect. Glukonorm® Plus should be taken at least 4 hours before taking bile acid sequestrants.

Other interactions: combinations to be considered

Involved with glibenclamide

Desmopressin: Glibenclamide may decrease the antidiuretic effect of desmopressin.

Sulfonamide antibacterial drugs, fluoroquinolones, anticoagulants (coumarin derivatives), monoamine oxidase inhibitors (MAOIs), chloramphenicol, pentoxifylline, hypolipidemic drugs from the group of fibrates, disopyramide – risk of hypoglycemia with glibenclamide.

Special Instructions

Contraindications

– Hypersensitivity to metformin, glibenclamide or other sulfonylurea derivatives or excipients;

– type 1 diabetes mellitus;

– diabetic ketoacidosis, diabetic precoma, diabetic coma;

– renal insufficiency or impaired renal function (creatinine clearance less than 60 ml/min);

– acute conditions that may lead to changes in renal function: dehydration, severe infection, shock, intravascular administration of iodine-containing contrast agents (see “

– acute or chronic diseases that are accompanied by tissue hypoxia: cardiac or respiratory failure, recent myocardial infarction, shock;

– hepatic failure;

– porphyria;

– pregnancy, period of breastfeeding;

– concomitant use of miconazole;

– major surgical operations;

– chronic alcoholism, acute alcohol intoxication;

– lactoacidosis (including a history of

– adherence to a hypocaloric diet (less than 1000 calories per day).

The drug is not recommended for persons older than 60 years of age who perform heavy physical work, because of the increased risk of lactoacidosis in them.

With caution:

Fever syndrome, adrenal insufficiency, hypofunction of the anterior pituitary gland lobe, thyroid disease with uncompensated impaired thyroid function.

Side effects

The following side effects may occur during treatment with Gluconorm® Plus.

The side effects are presented according to the effect on organs and organ systems.

The following adverse events noted with Glukonorm® Plus are distributed by frequency of occurrence according to the following gradation: Very common (≥ 1/10), common (≥ 1/100 to 1/10), infrequent (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000).

In each group, adverse effects are presented in decreasing order of severity.

In metabolic and nutritional aspects:

Hypoglycemia (see “Overdose,” “Special Precautions”).

Rarely: episodes of hepatic porphyria and cutaneous porphyria.

Very rare: lactoacidosis (see “Special Precautions”).

A decrease in absorption of vitamin B12, accompanied by a decrease in its concentration in the blood serum with long-term use of metformin. If megaloblastic anemia is detected, the possibility of this etiology must be considered. Disulfiram-like reaction with alcohol use.

Laboratory findings:

Infrequent: moderate to moderate increases in serum urea and creatinine concentrations.

Very rare: hyponatremia.

The blood and lymphatic system:

Rarely: leukopenia, thrombocytopenia.

very rarely: agranulocytosis, hemolytic anemia, bone marrow aplasia and pancytopenia.

These adverse events disappear after discontinuation of the drug.

Nervous system disorders:

Often: taste disorder (metallic taste in the mouth).

Visually: at the beginning of treatment there may be temporary visual impairment due to decreased blood glucose levels.

Gastrointestinal tract:

Very common: nausea, vomiting, diarrhea, abdominal pain and lack of appetite. These symptoms are more common at the beginning of treatment and in most cases go away on their own. To prevent these symptoms, it is recommended that the drug be taken in 2 or 3 doses; increasing the dose slowly also improves tolerability.

Some skin reactions, such as itching, urticaria, maculopapular rash.

Very rare: cutaneous or visceral allergic vasculitis, erythema polymorphicum, exfoliative dermatitis, photosensitization.

The immune system:

Very rare: anaphylactic shock.

Cross-sensitivity reactions to sulfonamides and their derivatives may occur.

Hepatic and biliary tract disorders:

Very rare: impaired liver function or hepatitis requiring discontinuation of treatment.

Overdose

In case of overdose, hypoglycemia may occur due to the presence of the sulfonyl urea derivative in the drug (see “Special Precautions”).

Mild to moderate symptoms of hypoglycemia without loss of consciousness and neurological manifestations may be corrected by immediate consumption of sugar. It is necessary to perform a dose adjustment and/or change the diet. The occurrence of severe hypoglycemic reactions in patients with diabetes mellitus, accompanied by coma, paroxysm or other neurological disorders, requires emergency medical care. It is necessary to administer intravenous dextrose solution immediately after establishing the diagnosis or suspicion of hypoglycemia until the patient is hospitalized. After recovery of consciousness, the patient should be given food rich in easily digestible carbohydrates (to avoid the recurrence of hypoglycemia).

Long-term overdose or concomitant risk factors can provoke lactoacidosis because the drug contains metformin (see Special Precautions).

Lactoacidosis is a condition requiring urgent medical care; treatment of lactoacidosis should be performed in the clinic. Hemodialysis is the most effective treatment to eliminate lactate and metformin.

The plasma clearance of glibenclamide may increase in patients with liver disease. Since glibenclamide actively binds to blood proteins, the drug is not eliminated by dialysis.

Pregnancy use

Similarities