Glurenorm^® (Tablets) Instructions for Use

Marketing Authorization Holder

Boehringer Ingelheim International, GmbH (Germany)

Manufactured By

Boehringer Ingelheim Ellas, A.E. (Greece)

ATC Code

A10BB08 (Gliquidone)

Active Substance

Gliquidone (Rec.INN registered by WHO)

Dosage Form

Glurenorm®

Tablets 30 mg: 30, 60, or 120 pcs.

Dosage Form, Packaging, and Composition

Tablets are white, smooth, round, with beveled edges, with a score on one side and an engraving “57C” on both sides of the score; on the other side, the company logo is engraved.

Excipients: lactose monohydrate – 134.6 mg, dried corn starch – 70 mg, soluble corn starch – 5 mg, magnesium stearate – 0.4 mg.

10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (6) – cardboard packs.
10 pcs. – blisters (12) – cardboard packs.

Clinical-Pharmacological Group

Oral hypoglycemic drug

Pharmacotherapeutic Group

Hypoglycemic agent for oral administration of the second-generation sulfonylurea group

Pharmacological Action

Glurenorm^® is a hypoglycemic drug for oral administration, a second-generation sulfonylurea derivative. It has pancreatic and extrapancreatic effects. It stimulates insulin secretion by potentiating the glucose-mediated pathway of insulin formation. In animal experiments, it was shown that Glurenorm^® reduces insulin resistance in the liver and adipose tissue by increasing insulin receptors, as well as by stimulating the post-receptor mechanism mediated by insulin.

The hypoglycemic effect develops 60-90 minutes after oral administration, the maximum effect occurs after 2-3 hours and lasts about 8-10 hours.

Pharmacokinetics

Absorption

After oral administration of a single dose of gliquidone (15 mg or 30 mg), the drug is rapidly and almost completely (80-95%) absorbed from the gastrointestinal tract, reaching a plasma concentration of 0.65 µg/ml (range 0.12-2.14 µg/ml). The mean time to reach C_max of the drug in plasma is 2 hours 15 minutes (range: 1.25-4.75 hours). The AUC_0-∞ value is 5.1 µg×h/ml (range: 1.5-10.1 µg×h/ml).

There are no differences in pharmacokinetic parameters between patients with diabetes mellitus and healthy individuals.

Distribution

Gliquidone has a high affinity for plasma proteins (>99%). There are no data on the possible passage of gliquidone or its metabolites through the blood-brain barrier or placenta. There are no data on the possibility of gliquidone penetration into breast milk.

Metabolism

Gliquidone is completely metabolized by the liver, mainly by hydroxylation and demethylation. Gliquidone metabolites have no or weakly expressed pharmacological activity compared to the parent substance.

Excretion

The main part of the metabolites is excreted through the intestines. Only a small part of the metabolites is excreted by the kidneys. Studies have shown that after oral administration, about 86% of the isotopically labeled drug (¹⁴C) is excreted through the intestines. Regardless of the dose and route of administration, about 5% (in the form of metabolites) of the administered amount of the drug is excreted by the kidneys. The level of excretion of Glurenorm^® by the kidneys remains minimal even with regular administration.

T_1/2 is 1.2 hours (in the range – 0.4-3.0 hours), the terminal T_1/2 is approximately 8 hours (in the range – 5.7-9.4 hours).

Pharmacokinetics in special clinical cases

In elderly patients and middle-aged patients, the pharmacokinetic parameters are similar.

The main part of the drug is excreted through the intestines. There is evidence that the metabolism of the drug does not change in patients with hepatic insufficiency. The excretion of gliquidone by the kidneys is insignificant; in patients with impaired renal function, the drug does not accumulate.

Indications

• type 2 diabetes mellitus in middle-aged and elderly patients (when diet therapy is ineffective).

ICD codes

Dosage Regimen

The drug is taken orally. It is necessary to follow the doctor’s recommendations regarding the dose of the drug and diet. Do not stop taking the drug without consulting a doctor.

The initial dose of Glurenorm^® is usually 1/2 tab. (15 mg) during breakfast. The drug must be taken at the beginning of a meal. After taking Glurenorm^®, a meal should not be skipped.

If taking 1/2 tab. (15 mg) does not lead to adequate improvement, after consulting a doctor, the dose should be gradually increased. If the daily dose of Glurenorm^® does not exceed 2 tablets. (60 mg), it can be prescribed in one dose, during breakfast.

When prescribing a higher dose, the best effect can be achieved by taking the daily dose divided into 2-3 doses. In this case, the highest dose should be taken at breakfast. Increasing the dose beyond 4 tablets. (120 mg)/day usually does not lead to a further increase in effectiveness.

The maximum daily dose is 4 tablets. (120 mg).

Patients with impaired renal function

About 5% of the drug’s metabolites are excreted by the kidneys. In patients with impaired renal function, dose adjustment is not required.

Patients with impaired liver function

Taking a dose exceeding 75 mg in patients with impaired liver function requires careful monitoring of the patient’s condition. The drug should not be prescribed to patients with severe liver dysfunction, since 95% of the dose is metabolized in the liver and excreted through the intestines.

Combination therapy

If the clinical effect of monotherapy with Glurenorm^® is insufficient, only additional prescription of metformin may be recommended.

Adverse Reactions

From the hematopoietic system thrombocytopenia, leukopenia, agranulocytosis.

From the metabolism hypoglycemia.

From the nervous system headache, dizziness, drowsiness, paresthesia, feeling of fatigue.

From the organ of vision accommodation disorders.

From the cardiovascular system: angina pectoris, extrasystole, cardiovascular insufficiency, hypotension.

From the digestive system decreased appetite, nausea, vomiting, constipation, diarrhea, feeling of discomfort in the abdomen, dry mouth, cholestasis.

From the skin and subcutaneous tissue rash, itching, urticaria, Stevens-Johnson syndrome, photosensitivity reaction.

Other chest pain.

Contraindications

• Type 1 diabetes mellitus;
• Diabetic acidosis, ketoacidosis, precoma and coma;
• Condition after pancreatic resection;
• Acute intermittent porphyria;
• Severe hepatic insufficiency;
• Some acute conditions (for example, infectious diseases or major surgical operations);
• Rare hereditary diseases, such as galactosemia, lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• Pregnancy;
• Lactation period (breastfeeding period);
• Age under 18 years (due to insufficient data on the efficacy and safety of the drug in this age group);
• Hypersensitivity to sulfonamides.

With caution

• Febrile syndrome;
• Thyroid diseases (with impaired function);
• Glucose-6-phosphate dehydrogenase deficiency;
• Alcoholism.

Use in Pregnancy and Lactation

There are no data on the use of gliquidone in women during pregnancy and breastfeeding.

It is unknown whether Gliquidone or its metabolites pass into breast milk. In pregnant women with diabetes mellitus, careful monitoring of plasma glucose concentration is necessary. The use of oral antidiabetic agents in pregnant women does not provide adequate control of carbohydrate metabolism. Therefore, the use of the drug Glurenorm^® during pregnancy and breastfeeding is contraindicated.

In case of pregnancy or planning pregnancy during the use of the drug Glurenorm^®, the drug should be discontinued and switched to insulin.

Use in Hepatic Impairment

The drug is contraindicated in acute hepatic porphyria, severe hepatic insufficiency.

Taking a dose exceeding 75 mg in patients with impaired liver function requires careful monitoring of the patient’s condition. The drug should not be prescribed to patients with severe liver dysfunction, since 95% of the dose is metabolized in the liver and excreted through the intestines. In clinical studies in patients with diabetes mellitus and liver dysfunction of varying severity (including acute liver cirrhosis with portal hypertension), Glurenorm^® did not cause further deterioration of liver function, the frequency of side effects did not increase, and hypoglycemic reactions were not detected.

Use in Renal Impairment

Since the main part of the drug is excreted through the intestines, in patients with impaired renal function, the drug does not accumulate. Therefore, Gliquidone can be safely prescribed to patients at risk of developing chronic nephropathy.

About 5% of the drug’s metabolites are excreted by the kidneys. In a clinical study – a comparison of patients with diabetes mellitus and impaired renal function of varying severity and patients with diabetes mellitus without impaired renal function, taking Glurenorm^® at a dose of 40-50 mg led to a similar effect on blood glucose levels. Accumulation of the drug and/or hypoglycemic symptoms were not noted. Thus, in patients with impaired renal function, dose adjustment is not required.

Pediatric Use

Contraindicated in children under 18 years of age (due to insufficient data on the efficacy and safety of the drug in this age group);

Geriatric Use

In elderly patients and middle-aged patients, the pharmacokinetic parameters are similar.

Special Precautions

Patients with diabetes mellitus must strictly follow the doctor’s recommendations. Particularly careful monitoring is needed when selecting the dose or when switching from another hypoglycemic drug.

Oral hypoglycemic agents should not replace the therapeutic diet, which allows controlling the patient’s body weight. Skipping a meal or not following the doctor’s recommendations can significantly reduce blood glucose concentration and lead to loss of consciousness. If the tablet is taken before meals, and not as recommended, at the beginning of a meal, the effect of the drug on blood glucose concentration is more pronounced, which increases the risk of developing hypoglycemia.

If symptoms of hypoglycemia appear, it is necessary to immediately take food containing sugar. In case of persistent hypoglycemic condition, you should immediately consult a doctor.

Physical activity can enhance the hypoglycemic effect.

Alcohol or stress can enhance or reduce the hypoglycemic effect of sulfonylurea derivatives.

The use of sulfonylurea derivatives in patients suffering from glucose-6-phosphate dehydrogenase deficiency can lead to hemolytic anemia. Since Glurenorm^® belongs to sulfonylurea derivatives, caution must be exercised when using the drug in patients with glucose-6-phosphate dehydrogenase deficiency and, if possible, a decision must be made to change the drug.

One tablet of the drug Glurenorm^® contains 134.6 mg of lactose (538.4 mg of lactose in the maximum daily dose). Patients with rare hereditary diseases, such as galactosemia, lactase deficiency, glucose-galactose malabsorption, should not take Glurenorm^®.

Gliquidone belongs to short-acting sulfonylurea derivatives and is therefore used in patients with type 2 diabetes mellitus with an increased risk of hypoglycemia, for example, in elderly patients and patients with impaired renal function.

Since the renal excretion of gliquidone is insignificant, Glurenorm^® can be used in patients with renal disorders and diabetic nephropathy. However, treatment of patients with severe renal insufficiency should be carried out under careful medical supervision.

There is evidence that the use of gliquidone in patients with type 2 diabetes mellitus who have concomitant liver diseases is effective and safe. Only the excretion of inactive metabolites in such patients is somewhat delayed. However, the drug is not recommended for patients with diabetes mellitus and concomitant severe liver dysfunction.

During clinical studies, it was revealed that the use of the drug Glurenorm^® for 18 and 30 months did not lead to an increase in body weight; even cases of body weight reduction by 1-2 kg were noted. In comparative studies with other sulfonylurea derivatives, it was proven that in patients taking Glurenorm^® for more than a year, there are no significant changes in body weight.

Effect on the ability to drive vehicles and mechanisms

There are no data on the effect of the drug on the ability to drive vehicles and mechanisms. However, patients should be warned about such manifestations of hypoglycemia as drowsiness, dizziness, accommodation disorders, which may occur while taking the drug. Caution must be exercised when driving vehicles and mechanisms. In hypoglycemic conditions, driving vehicles and mechanisms should be avoided.

Overdose

Overdose with sulfonylurea derivatives can lead to hypoglycemia.

Symptoms: tachycardia, increased sweating, feeling of hunger, palpitations, tremor, headache, insomnia, irritability, speech and vision disorders, motor restlessness and loss of consciousness.

Treatment in case of symptoms of hypoglycemia, glucose (dextrose) or carbohydrate-rich foods should be taken orally. In severe hypoglycemia (loss of consciousness, coma), dextrose is administered intravenously. After regaining consciousness – intake of easily digestible carbohydrates (to avoid recurrent hypoglycemia).

Drug Interactions

Enhancement of the hypoglycemic effect is possible with the simultaneous administration of gliquidone and ACE inhibitors, allopurinol, analgesics and NSAIDs, antifungal drugs, chloramphenicol, clarithromycin, clofibrate, coumarin derivatives, fluoroquinolones, heparin, MAO inhibitors, sulfinpyrazone, sulfonamides, tetracyclines and tricyclic antidepressants, cyclophosphamide and its derivatives, insulin and oral hypoglycemic agents.

Beta-blockers, sympatholytics (including clonidine), reserpine and guanethidine can enhance the hypoglycemic effect and simultaneously mask the symptoms of hypoglycemia.

A decrease in the hypoglycemic effect is possible with the simultaneous administration of gliquidone and aminoglutethimide, sympathomimetics, corticosteroids, thyroid hormones, glucagon, thiazide and “loop” diuretics, oral contraceptives, diazoxide, phenothiazine and drugs containing nicotinic acid.

Barbiturates, rifampicin and phenytoin can also reduce the hypoglycemic effect of gliquidone.

Enhancement or weakening of the hypoglycemic effect of gliquidone has been described when taking histamine H₂-receptor blockers (cimetidine, ranitidine) and ethanol.

Storage Conditions

The drug should be stored in a dry place, out of the reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 5 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.