Instructions Glurenorm tablets 30 mg blister No. 60
Composition
active ingredient: gliquevidone;
1 tablet contains gliquevidone 30 mg;
Excipients: lactose monohydrate; corn starch; magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: white, round, flat tablets on both sides, with beveled edges; on one side – a notch and marking “57C” on both sides of the notch; on the other side – the company symbol.
Pharmacotherapeutic group
Hypoglycemic drugs, except insulin. Sulfonylurea drugs. Gliquevidone.
ATX code A10V B08.
Pharmacological properties
Pharmacodynamics.
Mechanism of action: Gliquevidone stimulates the secretion of endogenous insulin by pancreatic beta cells.
Pharmacodynamic effects. The blood sugar-lowering effect begins 60–90 min after oral administration and reaches a maximum 2–3 hours after administration, the duration of the effect is about 8–10 hours. Gliquevidone can be considered a short-acting drug, therefore it is recommended for the treatment of patients with type 2 diabetes mellitus with an increased risk of hypoglycemia, such as the elderly and patients with renal insufficiency. Since the renal elimination of gliquevidone is insignificant, GLURENORM can be mainly prescribed to patients with renal insufficiency or diabetic nephropathy. The efficacy and safety of treatment with gliquevidone has been proven in a limited number of diabetic patients who respond to sulfonylurea therapy and have concomitant liver disease. Only the elimination of metabolically inactive metabolites was delayed. However, severe hepatic insufficiency is a contraindication (see section "Contraindications").
Pharmacokinetics. Absorption. After oral administration of a single dose of 30 mg, gliquevidone is rapidly and almost completely (80-95%) absorbed from the gastrointestinal tract with a maximum plasma concentration of 0.65 μg/ml (range 0.12 to 2.14 μg/ml). The maximum plasma concentration of the drug is reached after 2.25 hours (range 1.25 to 4.75 hours). Considering the two-compartment model, the average maximum plasma concentration of gliquevidone under the concentration-time curve from zero to infinity (AUC0-∞) is 5.1 μg/h/ml (range 1.5 to 10.1 μg/h/ml). No differences were observed between plasma concentration levels in diabetic patients and healthy volunteers.
Distribution. Gliquevidone is highly bound to plasma proteins (> 99%). There are no clinical data on the penetration of gliquevidone or its metabolites across the blood-brain barrier or placenta. Preclinical data indicate that gliquevidone and its metabolites do not penetrate these barriers. There are no data on the ability of gliquevidone to penetrate into breast milk.
Metabolism: Gliquevidone is completely metabolized, mainly by hydroxylation and demethylation in the liver. The metabolites of gliquevidone show very low or no pharmacological activity compared to the parent drug.
Elimination. Gliquevidone is mainly excreted as metabolites via the biliary system with feces. Regardless of the route of administration and the amount, only a small part of the gliquevidone dose is excreted by the kidneys and is found in the urine as metabolites (about 5%). Even after repeated doses of gliquevidone, renal excretion remains minimal. Based on the two-compartment model, the mean basal half-life (t½α) of gliquevidone is 1.2 hours (range 0.4 to 3 hours), while the mean terminal half-life (t½β) is about 8 hours (range 5.7 to 9.4 hours).
Special groups of patients.
Elderly patients: Pharmacokinetic characteristics in elderly and middle-aged patients are equivalent.
Patients with renal/hepatic insufficiency. It has been found that the metabolism of gliquevidone is maintained in patients with hepatic insufficiency. Gliquevidone can be safely used in patients with liver disease. In patients with renal insufficiency, drug accumulation does not occur, given that most drugs are excreted via the biliary system with feces. The drug can be safely used in patients at risk of chronic nephropathy.
Indication
Treatment of type 2 diabetes mellitus in middle-aged and elderly patients when carbohydrate metabolism is not successfully controlled by diet therapy alone.
Contraindication
Hypersensitivity to the active substance or to sulfonylurea derivatives, sulfonamides and other components of the drug; insulin-dependent type I diabetes mellitus; diabetic coma and precoma; metabolic disorders complicated by acidosis and ketosis; pancreatic resection; period of severe infections; period before surgery; severe liver dysfunction; intermittent acute (hepatic) porphyria.
GLURENORM should not be used during pregnancy and breastfeeding (see section “Use during pregnancy or breastfeeding”).
Interaction with other medicinal products and other types of interactions
Pharmacokinetic and pharmacodynamic interactions with GLURENORM may alter the hypoglycemic effect. Sulfonylureas are highly protein bound and may therefore be substituted by drugs with higher affinity.
Concomitant use of the following medicinal products may enhance the hypoglycaemic effect of Glurenorm: ACE inhibitors, allopurinol, analgesics and non-steroidal anti-inflammatory drugs (e.g. salicylates, phenylbutazone), antifungals, chloramphenicol, clarithromycin, clofibrates, coumarin anticoagulants, fluoroquinolones, heparin, MAO inhibitors, sulfinpyrazones, sulfonamides, tetracyclines and tricyclic antidepressants, cyclophosphamide and derivatives, insulin and other oral antidiabetic agents - with or without a significant risk of hypoglycaemia.
Beta-blockers, other sympatholytics (e.g. clonidine), reserpine and guanethidine may possibly enhance the hypoglycaemic effect of Glurenorm and may also mask the symptoms of hypoglycaemia.
Concomitant use of the following medicinal products may reduce the hypoglycaemic effect of Glurenorm: aminoglutethimide, corticosteroids, diazoxide, oral contraceptives, sympathomimetics, rifampicin, thiazide or loop diuretics, thyroid hormones, glucagon, phenothiazines and nicotinic acid.
Barbiturates, rifampicin, phenytoin and similar substances may possibly reduce the hypoglycemic effect of Glurenorm by stimulating liver enzymes.
Reduced or increased hypoglycemic effect of Glurenorm is observed when taken simultaneously with H2-receptor antagonists (cimetidine, ranitidine) and alcohol.
When GLURENORM is used simultaneously with alcohol, patients' tolerance to alcohol decreases and metabolism worsens. In addition, excessive use of laxatives leads to metabolic disorders.
Application features
Treatment of diabetes requires regular medical supervision. Particular care should be taken when adjusting the dose or when changing the drug.
Although only 5% of Glurenorm is excreted by the kidneys, patients with severe renal insufficiency should be treated under close medical supervision. If signs of hypoglycemia such as tachycardia, shock, hyperthermia, clammy skin, motor agitation and hyperreflexia occur, a doctor should be consulted immediately, as hypoglycemia can lead to life-threatening conditions such as coma (see section "Overdose"). In studies with GLURENORM, fever, skin rashes and nausea were also observed in hypoglycemia. In the case of potentially prolonged hypoglycemia, temporary improvement of the hypoglycemic state with the next dose of the drug may be accompanied by a new hypoglycemic episode.
Treatment of patients with glucose-6-phosphate dehydrogenase deficiency with sulfonylureas may cause hemolytic anemia. Since GLURENORM belongs to the sulfonylurea class, caution should be exercised when using the drug in patients with glucose-6-phosphate dehydrogenase deficiency and consideration should be given to alternative non-sulfonylurea therapy.
Oral antidiabetic therapy should not replace a therapeutic diet, which allows you to control the patient's body weight and is mandatory regardless of the use of a particular drug prescribed by a doctor.
As with all oral medications used to treat diabetes, missing meals or not taking the dosage regimen recommended by your doctor may result in a significant drop in blood glucose levels or loss of consciousness, for example, if the tablet is taken before a meal instead of at the beginning. The effect on blood glucose levels always increases the risk of hypoglycemia more significantly. If clinical signs of hypoglycemia develop, food containing sugar should be consumed immediately. If hypoglycemia persists, treatment should be intensified immediately and a doctor consulted.
Exercise may enhance the hypoglycemic effects. Alcohol or stress may enhance or weaken the hypoglycemic effect of sulfonylureas.
Particular attention should be paid to the simultaneous use of GLURENORM and other drugs, especially those that enhance the hypoglycemic effect of GLURENORM (see section "Interaction with other drugs and other types of interactions").
One 30 mg tablet contains 134.6 mg of lactose, and at the maximum recommended dose 538.4 mg of lactose is ingested. Therefore, this medicine is not recommended for patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
One GLURENORM tablet contains 0.1346 g of carbohydrates, which corresponds to 0.011 XO.
Use during pregnancy or breastfeeding
Pregnancy. Studies of the use of GlurenormU during pregnancy or breastfeeding have not been conducted. Therefore, the use of GlurenormU should be avoided in women during pregnancy or breastfeeding. If pregnancy is established, GlurenormU should be discontinued and replaced with insulin treatment.
Breastfeeding: It is not known whether gliquevidone or its metabolites are excreted in human milk.
Fertility: There are no clinical or preclinical data on the effects of GLURENORM on fertility.
The ability to influence the reaction speed when driving or working with other mechanisms
No studies have been conducted. Patients should be warned about the possibility of drowsiness, dizziness and accommodation disorders or other clinical signs of hypoglycemia during treatment with GLURENORM. Caution should be exercised when driving or operating machinery. If hypoglycemic effects develop, patients should avoid potentially hazardous activities.
Method of administration and doses
The doctor's recommendations regarding dosage and diet, adapted to the individual metabolism of each patient, should be strictly followed. The patient should not interrupt treatment without consulting a doctor.
Initial therapy.
The usual starting dose of GlurenormU is ½ tablet (15 mg), taken with breakfast. GLURENORM should be taken at the start of a meal. After taking the tablet, a meal should not be missed. If ½ tablet with breakfast is ineffective, the dose can be gradually increased. Provided that no more than two tablets (60 mg) are prescribed, the daily dose of GlurenormU can be taken once with breakfast. However, when prescribing higher doses, the best control is provided by using the daily dose in two or three doses. In this case, the highest dose should be taken with breakfast. 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 renal impairment.
GLURENORM is excreted mainly as metabolites via the biliary system with feces (see section "Pharmacological properties. Pharmacokinetics"). The elimination of GLURENORM does not affect renal function. However, daily doses of gliquevidone above 50 mg have not been studied in this group of patients. Given the available data, dose adjustment is not required in patients with impaired renal function (see section "Special instructions").
Patients with impaired liver function.
Daily doses of GLURENORM exceeding 75 mg require close medical supervision. Since 95% of GLURENORM is metabolized by the liver and biliary system, the drug is contraindicated in patients with severe hepatic impairment (see section "Contraindications").
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 prescribing the drug. When replacing another antidiabetic agent with Glurenorm, it should be remembered that the effect of 1 tablet of Glurenorm (30 mg) is approximately equivalent to the effect of 1000 mg of tolbutamide. Replacement usually begins with ½ tablet of Glurenorm.
Combination therapy.
If Glurenorm monotherapy does not provide sufficient control of diabetes, additional administration of metformin alone is recommended.
Duration of treatment.
GLURENORM is prescribed for long-term therapy. Dose adjustments, discontinuation of the drug, and replacement of therapy can only be carried out with the participation of a doctor.
Children
GLURENORM is not recommended for use in children due to insufficient data on safety and efficacy.
Overdose
Overdose of sulfonylureas can cause hypoglycemia.
Symptoms: Prolonged hypoglycaemic reactions may develop, which may lead to repeated episodes of hypoglycaemia despite successful first-line therapy. Patients may develop life-threatening hypoglycaemic shock characterised by symptoms such as fainting, tachycardia, clammy skin, motor agitation and hyperreflexia, gastrointestinal upset and skin reactions.
Therapy. In case of hypoglycemia, urgent oral or intravenous administration of glucose is necessary. Monitoring of plasma glucose concentration is necessary, further administration of glucose may be necessary. In case of allergic reactions, discontinue use of the drug and replace it with other oral antidiabetic drugs or insulin.
Side effects
The frequency of adverse reactions is defined as: very common (≥ 1/10); common (≥ 1/100 < 1/10); uncommon (≥ 1/1000 < 1/100); rare (< 1/10000); unknown (cannot be estimated from the available data).
From the blood and lymphatic system:
rare – agranulocytosis*, leukopenia, thrombocytopenia.
Metabolism:
frequent – hypoglycemia;
rare – decreased appetite;
unknown - weight gain.
Neurological disorders:
infrequently - drowsiness, dizziness, headache;
isolated – paresthesias.
On the part of the organs of vision:
uncommon – accommodation disorders.
Cardiac disorders:
isolated – angina pectoris, extrasystoles.
Vascular disorders:
rare – cardiovascular failure, arterial hypotension.
From the digestive tract:
Infrequent: diarrhea, vomiting, abdominal discomfort, nausea, constipation, dry mouth.
Hepatobiliary system disorders:
isolated cases – cholestasis.
From the skin and subcutaneous tissue:
infrequent – rash, itching;
rare – Stevens-Johnson syndrome, photosensitivity reactions, urticaria.
General violations:
*Adverse reactions not observed during clinical trials but reported during the post-marketing period.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 ºС in a place inaccessible to children.
Packaging
10 tablets in a blister, 6 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Boehringer Ingelheim Hellas Single Member SA/Boehringer Ingelheim Hellas Single Member SA
Location of the manufacturer and address of its place of business.
5th km Paiania-Markopoulo, Koropi Attiki, 19441, Greece/5th km Paiania-Markopoulo, Koropi Attiki, 19441, Greece.
