Glurenorm® [Glycidone]

Pharmacological properties

mechanism of action. glycidone stimulates the secretion of endogenous insulin by pancreatic β-cells.

Pharmacodynamic effects. The effect of lowering blood glucose levels begins 60–90 minutes after oral administration and reaches a maximum 2-3 hours after administration, the duration of the effect is about 8-10 hours. Glycvidone can be considered a short-acting drug, therefore it is recommended for the treatment of patients with diabetes Type II with an increased risk of hypoglycemia, for example, elderly patients and patients with renal failure. Since renal elimination of glycidone is negligible, glurenorm can be prescribed mainly to patients with renal failure or diabetic nephropathy. The efficacy and safety of treatment with glycvidone has been proven in a limited number of patients with diabetes who are shown sulfonylurea therapy and have concomitant liver diseases. Only the elimination of metabolically inactive metabolites was inhibited. However, a severe degree of liver failure is a contraindication (see CONTRAINDICATIONS).

Pharmacokinetics Absorption. After oral administration of a single dose of 30 mg, glycidone is rapidly and almost completely absorbed (80–95%) in the gastrointestinal tract with_max in blood plasma - 0.65 μg / ml (ranging from 0.12 to 2.14 μg / ml). WITH_max in plasma reached after 2.25 hours (ranging from 1.25 to 4.75 hours).

Based on the two-chamber model, the average C_max in glycidone plasma under AUC_0-∞ is 5.1 μg • h / ml (ranging from 1.5 to 10.1 μg • h / ml). There were no differences in plasma levels between diabetic patients and healthy volunteers.

Distribution. Glycvidone is actively associated with plasma proteins (99%). There is no clinical data on the penetration of glycidone or its metabolites through the BBB or placenta. Preclinical data indicate that glycidone and its metabolites do not penetrate these barriers. There is no data on the ability of glycidone to pass into breast milk.

Metabolism. Glycvidone is completely metabolized, mainly by hydroxylation and demethylation in the liver. Glycvidone metabolites show a very low pharmacological activity or its absence compared with the original drug.

Elimination. Glycvidone is excreted mainly in the form of metabolites through the biliary system with feces. Regardless of the method of application and quantity, only a small portion of the dose of glycidone is excreted by the kidneys and is determined in the form of metabolites in the urine (about 5%). Even after applying repeated doses of glycidone, renal excretion remains minimal. Based on the two-chamber model, the average main T_½α glycidone is 1.2 hours (ranging from 0.4 to 3.0 hours), while the average final T_½β is about 8 hours (ranging from 5.7 to 9.4 hours).

Special groups of patients

Elderly patients. Pharmacokinetic characteristics in the elderly and middle-aged people are equivalent.

Patients with renal / liver failure.It was found that in patients with liver failure, glycidone metabolism is supported. Glycvidone can be safely used in patients with liver disease. People with kidney failure do not accumulate drugs, given the fact that most drugs are excreted through the biliary system with feces. The drug can be safely used in patients at risk of chronic nephropathy.

Indications

Treatment of type II diabetes mellitus in middle-aged and elderly patients, when carbohydrate metabolism cannot be positively controlled only by diet therapy.

Application

The doctor’s recommendations regarding dosing and diet, adapted to the individual metabolism of each patient, should be strictly observed. the patient should not interrupt treatment without consulting a doctor.

Initial therapy. Typically, the initial dose of Glenrenorm is ½ tablets (15 mg). It is taken during breakfast. Glurenorm should be taken at the beginning of a meal. After taking the pill, do not skip meals. With the ineffectiveness of using ½ tablet during breakfast, the dose can be gradually increased. Provided that no more than 2 tablets (60 mg) are prescribed, the daily dose of Glurenorm can be taken once during breakfast. However, when used in higher doses, the best control is provided by 2-3 times a daily dose. In this case, the maximum dose should be taken at breakfast time. It should be noted that increasing the dose to 4 tablets (120 mg) per day usually does not lead to a further increase in the therapeutic effect. Therefore, the maximum recommended daily dose is 4 tablets (120 mg).

Special groups of patients

Patients with impaired renal function. Based on pharmacokinetic data, after the application of Glurenorm, only 5% of the metabolites are excreted by the kidneys. Dose adjustment for patients with impaired renal function is not required.

Patients with impaired liver function. The daily dose of Glyrenorm 75 mg requires careful medical supervision. Since 95% of Glurenorm is metabolized by the liver and, probably, by the biliary system, the drug should not be used in patients with severe hepatic impairment (see CONTRAINDICATIONS).

Children. Glurenorm is not recommended for use in children due to insufficient safety and efficacy data.

When replacing another oral hypoglycemic agent with a similar mechanism of action. The initial dose is determined depending on the course of the disease at the time of administration of the drug. When replacing another antidiabetic agent with Glurenorm, it should be remembered that the action of 1 tablet of Glurenorm (30 mg) is approximately equivalent to 1000 mg of tolbutamide.

Combination therapy If monotherapy with Glurenorm does not provide sufficient control of diabetes, the additional appointment of metformin alone should be considered.

Contraindications

Insulin-dependent type I diabetes mellitus, diabetic coma and precoma; diabetes complicated by acidosis and ketosis; pancreatic resection; period of severe infections; period before surgery; serious impaired liver function; intermittent acute (hepatic) porphyria; allergy to sulfonamides.

The use of the drug is contraindicated in hereditary disorders in which its inactive components can have a negative effect (seeSPECIAL INSTRUCTIONS).

Side effects

The frequency of adverse reactions is determined: very often (≥1 / 10), often (≥1 / 100, 1/10); infrequently (≥1 / 1000, 1/100), rarely (≥1 / 10,000, 1/1000), very rarely (1/10 000); unknown (cannot be established according to available data).

On the part of the blood system and lymphatic system: rarely - agranulocytosis, leukopenia, thrombocytopenia.

From the side of metabolism: often - hypoglycemia; rarely - loss of appetite.

Neurological disorders: infrequently - drowsiness, dizziness, headache; rarely - paresthesia.

From the side of the organ of vision: infrequently - violation of accommodation.

Cardiac disorders: rarely - angina pectoris, extrasystoles.

Vascular disorders: rarely - cardiovascular failure, arterial hypotension.

From the digestive tract: infrequently - diarrhea, vomiting, abdominal discomfort, nausea, constipation, dry mouth.

From the hepatobiliary system: rarely - cholestasis.

From the skin and subcutaneous tissue: infrequently - rash, itching; rarely - Stevens-Johnson syndrome, photosensitivity reactions, urticaria.

General disorders: rarely - chest pain, fatigue.

special instructions

Treatment for diabetes requires regular medical supervision. special caution should be exercised when selecting a dose or when replacing a drug (see ability to influence the reaction rate when driving vehicles and working with other mechanisms).

Although only 5% of Glurenorm is excreted by the kidneys and is usually well tolerated in patients with renal failure, in patients with severe renal failure, treatment should be carried out under close medical supervision. In case of signs of hypoglycemia, such as fever, skin rash, nausea, you should immediately consult your doctor.

If pregnancy is established, the reception of Glurenorm must be stopped as soon as possible and consult a doctor.

Oral antidiabetic therapy should not replace a therapeutic diet that allows you to control the patient’s body weight, and it is mandatory regardless of the use of a drug prescribed by a doctor. As with the oral forms of all drugs used in the treatment of diabetes mellitus, untimely food intake or non-compliance with the dosage regimen recommended by the doctor can lead to a significant decrease in blood glucose level or loss of consciousness, for example, if a pill is taken before meals instead of beginning of meal. The effect on blood glucose levels always more markedly increases the risk of hypoglycemia. With the development of clinical signs of hypoglycemia, food containing sugar should be taken immediately. Exercise can enhance the hypoglycemic effect. Alcohol or stress can enhance or weaken the hypoglycemic effect of sulfonylurea. Treatment with sulfonylurea in patients with glucose-6-phosphate dehydrogenase deficiency can cause hemolytic anemia.Since glurenorm belongs to the class of sulfonylurea preparations, it should be used with caution in patients with glucose-6-phosphate dehydrogenase deficiency and consider the possibility of alternative therapy. Particular attention should be paid to the simultaneous use of Glurenorm and other drugs, especially those that enhance the hypoglycemic effect of Glurenorm (see INTERACTIONS).

1 30 mg tablet contains 134.6 mg of lactose and when using the maximum recommended dose, 538.4 mg of lactose enters the body. Therefore, the drug is not recommended for patients with rare hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose or galactose.

During pregnancy and breastfeeding. A study of the use of Glurenorm during pregnancy and lactation was not performed. Therefore, it is necessary to avoid the use of Glurenorm for the treatment of women during this period. If pregnancy is established, you should stop taking Glurenorm as soon as possible and replace it with insulin treatment.

Children. There is no data on the use of the drug in children.

Influence on the ability to drive vehicles and work with mechanisms. No studies have been conducted. Patients should be warned about the possibility of drowsiness, dizziness and disturbance of accommodation or the appearance of other clinical signs of hypoglycemia during treatment with Glyrenorm. Care must be taken when driving vehicles or operating machinery. When developing a hypoglycemic effect, patients should avoid potentially dangerous activities.

Interactions

Possible interactions with drugs that affect glucose metabolism must be taken into account.

Pharmacokinetic and pharmacodynamic interactions with Glyrenorm can change the hypoglycemic effect. Sulfonylurea binds to a large extent to blood proteins and therefore can be replaced by drugs with high affinity.

The simultaneous use of the following drugs can enhance the hypoglycemic effect of Glurenorm: ACE inhibitors, allopurinol, analgesics and NSAIDs, antifungal agents, chloramphenicol, clarithromycin, clofibrate, coumarin anticoagulants, fluoroquinolones, heparin sulfin cyclides, antioxidants, cyclin cyclides, anti-cyclin cyclin cyclides, and anti-cyclin cyclin cyclides, antioxidants, anti-cyclin cyclin cyclides, anti-cyclin cyclin antiphosphonides, antioxidants, antimycid inhibitors, cyclofenders, antimycid inhibitors, and antimycid inhibitors; and derivatives, insulin and other oral antidiabetic agents with / without a significant risk of hypoglycemia.

Β-adrenergic receptor blockers, other sympatholytics (e.g. clonidine), reserpine and guanethidine are likely to enhance the hypoglycemic effect of Glyrenorm, as well as mask the symptoms of hypoglycemia.

The simultaneous use of the following drugs can reduce the hypoglycemic effect of Glurenorm: aminoglutetimide, GCS, diazoxide, oral contraceptives, sympathomimetics, rifampicin, thiazide or loop diuretics, thyroid hormones, glucagon, phenothiazines and nicotinic acid.

Barbiturates, rifampicin, phenytoin and similar substances are likely to reduce the severity of the hypoglycemic effect of Glurenorm by stimulating liver enzymes.

A decrease or increase in the severity of the hypoglycemic effect of Glurenorm is noted with simultaneous use with N antagonists₂receptors (cimetidine, ranitidine) and alcohol.

Overdose

An overdose of sulfonylurea can cause hypoglycemia.

Symptoms: possible development of hypoglycemic reactions (prolonged), such as fainting, tachycardia, wet skin, motor arousal and hyperreflexia, disorders of the stomach.

Treatment: urgent oral or iv administration of glucose. Control of the concentration of glucose in the blood plasma is required, it may be necessary to further prescribe glucose.

Storage conditions

At a temperature not exceeding 25 ° C.