GLIBEN 5 mg Coated Tablet

GLIBEN 5 mg tablets
GLIBENCLAMIDE

Pharmacotherapeutic category
Oral hypoglycemic agent

Therapeutic indications
Symptomatic diabetes mellitus in adults

Contraindications
Gliben is contraindicated:

• In patients with hypersensitivity to the active substance or to any of the excipients.
• In patients with insulin-dependent diabetes mellitus, type 1 (e.g. diabetics with a history of ketoacidosis)
• In the treatment of diabetic ketoacidosis
• In the treatment of diabetic coma or precoma
• In patients with severe renal dysfunction
• In patients with severe hepatic dysfunction
• During pregnancy (see “Pregnancy and breastfeeding”)
• During breastfeeding (see “Pregnancy and breastfeeding”))
• In patients with adrenal insufficiency
• In patients treated with bosentan (see “Interactions”).

Precautions for use
The use of oral hypoglycemic agents of the sulfonylurea group should be limited to patients with symptomatic
diabetes mellitus that has developed in adulthood and is not ketotic and that cannot be controlled with diet, and
in whom the administration of insulin is not indicated.
The clinical signs of hyperglycemia include: increased frequency of urination, intense thirst, dryness of the
mouth and dry skin.
To achieve the goal of Gliben therapy – namely optimal blood glucose control – in addition to the regular
intake of Gliben, factors such as a correct diet, sufficient and regular physical exercise and, if necessary, also
a reduction in body weight are equally important.
During therapy with Gliben, blood and urine glucose levels should be checked regularly.
Periodic assessments of glycated hemoglobin concentration are also recommended.
Monitoring blood and urine glucose levels also serves to identify therapeutic failure – primary or secondary.
At the beginning of therapy, the patient should be informed about the effects and risks of Gliben and its
interaction with dietary measures and physical exercise; the importance of adequate collaboration should also be
emphasized.
Therefore, in the case of treatment with any hypoglycemic drug, both the patient and the doctor must be aware
of the risk of hypoglycemia.
Factors that favor hypoglycemia are:

• lack of willingness or, more frequently in elderly patients, the patient's inability to cooperate;
• poor nutrition, irregular meal times or skipped meals;
• imbalance between physical exertion and carbohydrate intake;
• changes in diet;
• impaired renal function;
• severe hepatic dysfunction;
• overdosage (of Gliben);
• uncompensated endocrine diseases that affect carbohydrate metabolism or the counter-regulation of
  hypoglycemia (such as, for example, in some disorders of thyroid function and hypopituitarism or
  adrenocortical insufficiency);
• concomitant administration of certain drugs (see “Interactions”);
• Gliben therapy in the absence of indication.

The patient must inform the doctor of these factors and of hypoglycemic episodes, as these indicate the need
for particularly careful monitoring. If necessary, the dosage of Gliben or the entire therapy must be modified.
This is also true in cases of illnesses that occur during therapy or changes in the patient's lifestyle.
The symptoms of hypoglycemia that represent adrenergic counter-regulation (see “Undesirable effects”) may be
milder or absent when hypoglycemia develops slowly, when there is autonomic nervous system neuropathy or
when the patient is taking beta-blockers, clonidine, reserpine, guanethidine or other sympatholytic drugs.
In case of hypoglycemic manifestations (see “Undesirable effects”), administer carbohydrates (glucose or
sugar, e.g. as sugar cubes, tea or sugary fruit juices); in more severe cases, which can rarely lead to loss of
consciousness, a slow i.v. infusion of glucose solution is necessary.
For this reason, the patient must always carry at least 20 grams of glucose with them. Patients may need help
from other people to avoid complications.
Artificial sweeteners are not effective in controlling hypoglycemia.
Hypoglycemia may recur despite the success of initial countermeasures. Therefore, patients must remain
under observation.
Severe hypoglycemia, or a prolonged episode of hypoglycemia, which can only be controlled temporarily with
normal amounts of sugar, requires immediate treatment and monitoring by a doctor and, in some cases, hospital
admission.
If patients are treated by a doctor who is not their usual doctor (e.g. during a hospital stay, after an accident,
for an illness during a vacation), patients must inform the doctor of their diabetic condition and the therapy
previously implemented.
In concomitance with trauma, surgery, infectious diseases and fever, it may be necessary to temporarily
initiate insulin therapy to maintain adequate metabolic control.
ELDERLY
Patients aged 65 years or over are particularly sensitive to the hypoglycemic action of glibenclamide and are
therefore at greater risk of hypoglycemia. In the elderly, low blood sugar levels can be difficult to recognize.
The initial and maintenance dose of glibenclamide must be defined by the doctor with caution in order to avoid
hypoglycemic reactions.
It is known that the drug is excreted mainly by the kidneys and the risk of toxic reactions to this drug may be
greater in patients with impaired renal function. Since elderly patients may have reduced renal function, care
should be taken in dose selection, and it may be useful to monitor renal function. (see “Dosage, method and
time of administration”)

Interactions
Associations not recommended
Bosentan:
An increased incidence of elevated liver enzyme values has been observed in patients receiving concomitant
therapy with bosentan and glibenclamide.
Both glibenclamide and bosentan inhibit the bile salt transport pump, leading to intracellular accumulation of
cytotoxic bile salts. Therefore, this combination should not be used.

To be considered
Patients who start or stop therapy while being treated with Gliben may have changes in glycemic control.
An enhancement of the hypoglycemic effect, and therefore in some cases hypoglycemia, may occur during
therapy with other drugs such as:
insulin and other oral antidiabetics, ACE inhibitors, anabolic steroids and male sex hormones, chloramphenicol,
coumarin derivatives, cyclophosphamide, disopyramide, fenfluramine, pheniramidol, fibrates, fluoxetine,
ifosfamide, MAO inhibitors, miconazole, para-aminosalicylic acid, pentoxifylline (parenterally at high doses),
phenylbutazone, azapropazone, oxyphenbutazone, probenecid, quinolones, salicylates, sulfinpyrazone,
sulfonamides, sympatholytic drugs such as beta-blockers and guanethidine, clarithromycin, tetracyclines,
tritoqualine, trofosfamide.
A reduction in the hypoglycemic effect, and therefore an increase in blood sugar, may occur during the
administration of other drugs such as:
acetazolamide, barbiturates, corticosteroids, diazoxide, diuretics, adrenaline and other sympathomimetic drugs,
glucagon, laxatives (after prolonged use), nicotinic acid (at high doses), estrogens and progestins, phenothiazines,
phenytoin, thyroid hormones, rifampicin.
H2 antagonists, clonidine and reserpine may lead to an enhancement or reduction of the hypoglycemic effect.
Occasional or chronic alcohol consumption may potentiate or reduce the hypoglycemic effect of glibenclamide in
an unpredictable manner.
Glibenclamide may potentiate or reduce the effect of coumarin derivatives.
Glibenclamide may increase plasma concentrations of cyclosporine and potentially lead to increased toxicity.
Therefore, monitoring and dose adjustment of cyclosporine are recommended when both drugs are administered
in combination.
Colesevelam binds to glibenclamide and reduces the absorption of glibenclamide from the gastrointestinal tract.
No interaction has been observed when glibenclamide was taken at least 4 hours before colesevelam.
Therefore, glibenclamide must be administered at least 4 hours before colesevelam.
In patients treated with sulfonylureas, the possibility of disulfiram-like reactions after ingestion of alcoholic
beverages must be considered.

Special warnings
Treatment with sulfonylureas in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency may lead to
hemolytic anemia.
Glibenclamide should therefore be used with caution in such patients and a therapeutic alternative should be
considered.
People allergic to other sulfonamide derivatives may experience allergic reactions also to glibenclamide.
ELDERLY
Age 65 years or over has been identified as a risk factor for hypoglycemia in patients treated with sulfonylureas.
Hypoglycemia may be difficult to recognize in the elderly. The initial and maintenance dose of glibenclamide
must be defined by the doctor with caution in order to avoid hypoglycemic reactions (see “Precautions for use”).
The medicine contains Lactose, so if you have a confirmed intolerance to sugars, contact your doctor before taking
the medicine.

Pregnancy and breastfeeding
Gliben should not be administered during pregnancy.
The patient should switch to insulin therapy during pregnancy.
Patients who intend to become pregnant should inform their doctor. It is recommended that such patients
undergo insulin therapy.
Malformations have been found in children of women treated with glibenclamide during pregnancy.
A causal relationship with glibenclamide cannot be excluded. In this context, it is necessary to emphasize that it is
known that the incidence of malformations is increased in cases of uncontrolled diabetes - regardless of the type
of therapy used.
To prevent possible intake with breast milk, Gliben should not be administered to women during breastfeeding.
If necessary, the patient should switch to insulin therapy or discontinue breastfeeding.

Effects on ability to drive and operate machinery
Vigilance and reactions may be impaired by episodes of hypoglycemia or hyperglycemia, particularly at the
beginning of treatment, after changing the therapeutic regimen or when the drug is not taken regularly. This may
affect the ability to drive vehicles or operate machinery.

Dosage, method and time of administration
Gliben is available in 5 mg tablets, divisible into halves. The dosage must be established and adjusted by the
attending physician.
Generally, treatment will be started with one tablet a day. However, if the patient has never been treated with
other oral hypoglycemic agents, it is advisable to start with half a tablet. In any case, subsequent increases in the
daily dose will only be made after a new clinical examination.
When replacing Gliben with other sulfonylureas, it should be noted that the effect of one tablet (5 mg) corresponds
approximately to that of 1 g of tolbutamide. The tablets should be swallowed 30 minutes before meals with some
water.
Doses up to two tablets a day can be taken in one go, with breakfast; if this is light, they can be taken with lunch.
For higher doses, the rest will be taken with the evening meal.
ELDERLY
Patients aged 65 years or over: initial and maintenance doses of glibenclamide must be carefully adjusted to
reduce the risk of hypoglycemia. Treatment should be started with the lowest available dose and increased
gradually, if necessary (see “Precautions for use”).

Overdosage
Signs and symptoms
Acute overdosage, as well as long-term therapy with excessively high doses of
glibenclamide, can lead to severe, prolonged hypoglycemia, which can endanger the patient's life.
Treatment
When an overdose is identified, it is important to immediately inform a doctor. The patient should immediately take sugar, preferably as glucose, unless a doctor has already taken responsibility for treating the overdose.
Close monitoring is essential until the doctor deems the patient is out of danger. It should be noted that hypoglycemia and its symptoms can recur even after initial recovery.
Hospitalization may sometimes be necessary, even as a precautionary measure. In particular, significant overdose and severe reactions with signs such as loss of consciousness or other neurological disorders constitute a medical emergency and require immediate therapy and hospitalization.
For example, if a patient is unconscious, intravenous administration of a concentrated glucose solution (e.g., for adults starting with 40 mL of a 20% solution) is indicated. Alternatively, glucagon administration can be considered, e.g., at doses of 0.5 to 1 mg i.v., s.c. or i.m.
In particular, the treatment of hypoglycemia in newborns and children requires careful adjustment of the glucose dosage to be administered due to the possibility of causing dangerous hyperglycemia, constantly monitoring the same dosage by determining blood glucose levels.
For patients who have ingested dangerous amounts of Gliben, detoxification from the drug is necessary (e.g., gastric lavage or activated charcoal).
After the acute administration of glucose, an infusion of glucose at lower concentrations is usually necessary to ensure that hypoglycemia does not recur. The patient's blood glucose levels should be carefully monitored for 24 hours. In severe cases with a prolonged course of hypoglycemia, or the risk of returning to hypoglycemia, can persist for several days.

Undesirable Effects
Hypoglycemia
Hypoglycemic phenomena may occur, although rarely, during therapy with sulfonylureas, especially in debilitated subjects, in old age, in case of unusual physical exertion, irregular feeding or consumption of alcoholic beverages, impaired renal and/or hepatic function.
The first symptoms of hypoglycemia are generally headache, irritability and nervous depression, sleep disturbances, tremor, profuse sweating. In these cases, it is advisable to promptly inform the doctor, who must also be informed in case of febrile illnesses or intercurrent digestive disorders.
As a consequence of the hypoglycemic effect of Gliben, hypoglycemia can occur, sometimes prolonged, which also endangers the patient's life. This occurs when there is an imbalance between the dosage of Gliben and the intake of carbohydrates in the diet, physical exercise and other factors that affect metabolism.
Elderly patients are particularly sensitive to the blood glucose-lowering action of hypoglycemic drugs (see “Precautions for use”).
Possible symptoms of hypoglycemia include: headache, uncontrollable hunger, nausea, vomiting, fatigue, disturbed sleep, agitation, aggressiveness, impaired concentration, alertness and reactions, depression, confusion, speech disorders, aphasia, visual disturbances, tremors, paresis, sensory disturbances, dizziness, feeling of powerlessness, loss of self-control, delirium, seizures, drowsiness and loss of consciousness to coma, shallow breathing and bradycardia.
In addition, there may be signs of adrenergic counterregulation such as sweating, moist skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmias.
The clinical picture of a severe hypoglycemic attack can resemble that of a stroke.
The symptoms of hypoglycemia usually disappear with its correction.
Eye disorders
Particularly at the beginning of therapy, there may be a temporary visual disturbance due to changes in blood glucose levels. The cause of this is a temporary alteration of the turbidity, and therefore of the refractive index of the lens, which depends on blood glucose levels.
Gastrointestinal disorders
Occasionally, gastrointestinal disturbances such as nausea, vomiting, a feeling of pressure or fullness in the epigastrium, abdominal pain and diarrhea may occur.
However, despite continued therapy, these symptoms often disappear and generally do not require discontinuation of Gliben treatment.
In isolated cases, there may be an increase in liver enzymes and also impairment of liver function (e.g. with cholestasis and jaundice) and hepatitis which can regress after discontinuation of Gliben, even if they can lead to liver failure which can endanger the patient's life.
Hematopoietic system disorders
Alterations of the blood picture can occur which can endanger the patient's life. These may include, rarely, thrombocytopenia from mild to severe (e.g. presenting with purpura) and in isolated cases hemolytic anemia, erythrocytopenia, leukopenia, granulocytopenia, agranulocytosis and pancytopenia (e.g. due to myelosuppression). In principle, these reactions are reversible upon discontinuation of Gliben.
Immune system disorders
Allergic or pseudo-allergic reactions may occasionally occur, e.g. in the form of itching or skin rash. In isolated cases, mild reactions in the form of urticaria and angioedema can transform into severe reactions, endangering the patient's life, with dyspnea and hypotension which sometimes progresses to shock. Therefore, in case of urticaria and angioedema, the doctor must be informed immediately.
A hypersensitivity reaction may be due to glibenclamide, but may also be caused by one of the excipients. An allergy to sulfonamide derivatives may also be responsible for an allergic reaction to glibenclamide.
In isolated cases, allergic vasculitis may manifest, which, in some cases, can endanger the patient's life. In isolated cases, hypersensitivity of the skin to light may occur and concentrations of sodium in the serum may decrease.
Skin and subcutaneous tissue disorders
Rash, pruritus, urticaria, angioedema, erythema, maculopapular rashes, bullous reactions, erythema multiforme and exfoliative dermatitis may occur with unknown frequency.
It is important to inform the doctor or pharmacist of any adverse effects, even if not described in the

Shelf Life and Storage
Shelf life: see the expiration date printed on the packaging.
The expiration date indicated refers to the product in intact packaging, stored correctly.

WARNING:do not use the medicine beyond the expiration date printed on the packaging.
Medicines should not be disposed of via drains or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep the medicine out of the sight and reach of children.

Composition
Each tablet contains:

Active ingredient
Glibenclamide 5 mg

Excipients
Corn starch, microcrystalline cellulose, lactose monohydrate, magnesium stearate, talc.

Pharmaceutical form and content
Tablets. 30 tablets

Marketing Authorisation Holder and Manufacturer
ABIOGEN PHARMA S.p.A.
Via Meucci, 36 – Ospedaletto - Pisa