Sugril

White, oblong and flat tablet with "
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" on one side and scored on the other.
Each tablet contains Glibenclamide 5 mg.

Pharmacology: Pharmacodynamics: Glibenclamide is a sulfonylurea antidiabetic agent (second generation). Glibenclamide appears to lower blood glucose concentration principally by stimulating secretion of insulin from beta cells of the pancreas, an effect dependent upon functioning beta cells. Glibenclamide reduces glucose output from the liver and increases insulin sensitivity at peripheral target sites. In addition to its blood glucose lowering actions, Glibenclamide produces a mild diuresis by enhancement of renal free water clearance.
Pharmacokinetics: Absorption: Glibenclamide is readily absorbed from the gastrointestinal tract and peak plasma concentrations usually occur within 2 to 4 hours. Serum insulin levels begin to increase 15-60 minutes after a single dose. The hypoglycemic action may persist for up to 24 hours. Food apparently does not affect the absorption of Glibenclamide.
Distribution: In vitro, Glibenclamide is more than 99% bound to serum proteins and its major metabolite, 4-trans-hydroxyglibenclamide, is more than 97% bound to serum proteins. The protein binding of Glibenclamide is principally nonionic. Glibenclamide does not accumulate.
Metabolism: Glibenclamide appears to be completely metabolized in the liver. The drug is metabolized at the cyclohexyl ring principally to 4-trans-hydroxyglibenclamide. Glibenclamide is also metabolized to the 3-cis-hydroxy derivative. The hypoglycemic activity of Glibenclamide metabolites is generally considered clinically unimportant.
Excretion: About 50% of a dose is excreted in the urine and 50% via the bile into feces. The terminal half-life has averaged about 10 hours.

Non-insulin-dependent (type 2) diabetes mellitus, whenever blood glucose levels cannot be controlled adequately by diet, physical exercise and weight reduction alone.

In principle, the dosage of Glibenclamide is governed by the desired blood glucose level. The dosage of Glibenclamide must be the lowest possible dose which is effective.
Treatment with Glibenclamide must be initiated and monitored by a doctor. The patients must take Glibenclamide at the times and in the doses prescribed by the doctor.
Mistakes, e.g. forgetting to take a dose, must never be corrected by subsequently taking a large dose.
Measures for dealing with such mistakes (in particular forgetting a dose or skipping a meal) or in the event a dose cannot be taken at the prescribed time must be discussed and agreed between doctor and patient beforehand.
If it is discovered that too high a dose or an extra dose of Glibenclamide has been taken, doctor must be notified immediately.
Initial dose and dose titration: The usual initial dosage is ½ to 1 tablet Glibenclamide once daily.
It is recommended that treatment be started with the smallest possible dose. This applies in particular to patients who are prone to hypoglycemia or who weigh less than 50 kg.
If necessary, the daily dose can be raised. It is recommended that the dose be increased gradually, i.e. in increments of not more than ½ tablet and at intervals of one to two weeks, and that the increase be guided by regular blood glucose monitoring.
Dose range in patients with well controlled diabetes; maximum doses: The usual single dose is ½ - 2 tablets Glibenclamide. A single dose of 2 tablets Glibenclamide must not be exceeded. Large daily doses must be divided into at least two separate single doses.
The usual daily dose is 1 to 2 tablets Glibenclamide. Exceeding a total daily dose of 3 tablets Glibenclamide is not recommended because higher daily doses of up to 4 tablets Glibenclamide are more effective only in exceptional cases.
Distribution of doses: Timing and distribution of doses are to be decided by the doctor. Taking into consideration the patient's current life-style. Normally a single daily dose of Glibenclamide is sufficient. It is recommended that daily doses of up to 2 tablets. Glibenclamide be taken before a substantial breakfast or before the first main meal and any remaining portions of the total daily dose before the evening meal. It is very important not to skip meals after the tablets have been taken.
Secondary dosage adjustment: Glibenclamide requirements may fall as treatment proceeds. To avoid hypoglycemia timely dose reduction or cessation of Glibenclamide therapy must therefore be considered. Correction of dosage must also be considered, whenever: the patient's weight changes; or the patient's life-style changes; or other factors arise which cause an increased susceptibility to hypoglycemia or hyperglycemia.
Duration of treatment: Treatment with Glibenclamide is normally a long-term therapy.
Changeover from other oral antidiabetics to Glibenclamide and other oral antidiabetics: When substitution Glibenclamide and other oral antidiabetics for other oral antidiabetics (drugs to lower blood glucose), it is recommended that the procedure be the same as for initial dosage starting with daily doses of ½ to 1 tablet Glibenclamide. This applies even on cases where the patient is being switched from the maximum dose of another oral antidiabetic.
Consideration must be given to the potency and duration of action of the previous antidiabetic agent. A break from medication may be required to avoid any summation of effects entailing a risk of hypoglycemia.
Administration: Glibenclamide tablets must be swallowed whole with sufficient amounts of liquid, e.g. with roughly half to one glass of water.

Signs and symptoms: Acute overdose as well as long-term treatment with too high a dose of Glibenclamide may lead to severe, protracted, life-threatening hypoglycemia.
Management: As soon as an overdose of Glibenclamide has been discovered, a physician must be notified without delay. The patient must immediately take glucose, if possible in the form of glucose, unless a physician has already undertaken responsibility for treating the overdose.
Careful monitoring is essential until the physician is confident that the patient is out of danger. It must be remembered that hypoglycemia and its clinical signs may recur after initial recovery.
Admission to hospital may sometimes be necessary-even as precautionary measure. In particular, significant overdoses and severe reactions with signs such as loss of consciousness or other serious neurological disorders are medical emergencies and require immediate treatment and admission to hospital.
If, for example, the patient is unconscious, an intravenous injection of concentrated glucose solution is indicated (for adults starting with 40 ml of 20% solution, for example). Alternatively in adults, administration of glucagon, e.g. in doses of 0.5 to 1 mg i.v., s.c. or i.m. may be considered.
In particular when treating hypoglycemia in infants and young children, the dose of glucose given must be very carefully adjusted in view of the possibility of producing dangerous hyperglycemia, and must be controlled by close monitoring of blood glucose.
Patients who have ingested life-threatening amounts of Glibenclamide require of detoxification (e.g. by gastric lavage and medicinal charcoal).
After acute glucose replacement has been completed, it is usually necessary to give an intravenous glucose infusion in lower concentration so as to ensure that the hypoglycemia does not recur. The patient's blood glucose level should be carefully monitored for at least 24 hours. In severe cases with a protracted course, hypoglycemia, or the danger of slipping back into hypoglycemia, may persist for several days.

Glibenclamide must not be used for: Patients with insulin-dependent (type 1) diabetes mellitus; Treatment of diabetic ketoacidosis; Treatment of diabetic precoma or coma; Patients with serious renal dysfunction; Patients with serious hepatic or adrenocortical dysfunction; Patients hypersensitive to Glibenclamide, other sulfonylureas, any sulfonamide derivative, or any other ingredient of the product; Pregnant women; Breast-feeding women; Patients treated with bosentan.

Based on the Ministry of Public Health's Announcement: This medicine is contraindicated in patients with known hypersensitivity or allergy.
This medicine is contraindicated in patients with type 1 diabetes mellitus, diabetic ketoacidosis, severe infection and trauma.
This medicine should be avoided in the pregnancy and used with caution in breast-feeding.
While using this medicine, should not drink alcohol.
Use with caution as this medicine can cause hypoglycemia, such as hunger, palpitation, sweating.
If erythema multiforme, bullous eruptions, exfoliative dermatitis such as oral cavity, throat, nose, genital and conjunctivitis occur, this medicine should be discontinued and consult a doctor as it may be Stevens-Johnson syndrome.
Use with caution in patients with renal impairment.

The administration of Glibenclamide is associated with an increased risk of cardiovascular mortality, when compared to treatment with metformin or gliclazide, especially in patients with diagnosed coronary disease.
Clinical signs of hyperglycemia are: increased urinary frequency, intense thirst, dryness of the mouth and dry skin.
In exceptional stress situation (e.g., trauma, surgery, febrile infections), blood glucose regulation may deteriorate, and a temporary change to insulin may be necessary to maintain good metabolic control.
Persons allergic to sulfonamide derivatives may develop an allergic reaction to Glibenclamide as well.
To achieve the goal of treatment with Glibenclamide optimal control of blood glucose-adherence to correct diet, regular and sufficient physical exercise and reduction of body weight (if necessary) are just as necessary as regular intake of Glibenclamide.
During treatment with Glibenclamide, glucose levels in blood and urine must be measured regularly. In addition, it is recommended that regular determinations of the proportion of glycated hemoglobin (HbA1C) be carried out.
When starting treatment the patient must be informed about the effects and risks of Glibenclamide and about its interaction with dietary measures and physical exercise the importance of adequate cooperation must also be stressed.
As is necessary during treatment with any blood-glucose-lowering drug, the patient and the doctor must be aware of the risk of hypoglycemia (excessive reduction in blood glucose). Factors that cause hypoglycemia include: Unwillingness or (more commonly in older patients) incapacity of the patient to cooperate; Undernutrition, irregular mealtimes or missed meals; Alternations of diet or unaccustomed physical exertion; Impaired renal function; Serious liver dysfunction; Overdose with Glibenclamide; Uncompensated disorders of the endocrine system affecting carbohydrate metabolism or counter-regulation of hypoglycemia (as for thyroid function and in anterior pituitary gland or adrenocortical insufficiency); Concurrent administration of certain other medicines.
The patients must inform the doctor about such factors and about hypoglycemia episodes since they may indicate the need or particularly careful monitoring, if necessary, the dosage of Glibenclamide or the entire therapy must be modified. This is also applies, whenever illness occurs during therapy or the patient's life-style changes.
Those symptoms of hypoglycemia (excessive reduction blood glucose) which reflect the body's adrenergic counter-regulation where hypoglycemia develops gradually, where there is autonomic neuropathy (disorder of part of the nervous system) or where the patient is receiving concurrent treatment with beta-blockers, clonidine, reserpine, guanidine or other sympatholytic drugs may be milder or absent.
Hypoglycemia can, almost always, be promptly controlled by immediate intake of carbohydrates (glucose or sugar, e.g., in the form of sugar lumps, sugar sweetened fruit juice or tea). For this purpose patients must carry a minimum of 20 grams of glucose with them at all times. They may require the assistance of other person to avoid complications. Artificial sweeteners are ineffective in controlling hypoglycemia.
Despite initially successful countermeasures, hypoglycemia may recur. Patients must, therefore, remain under close observation. Severe hypoglycemia or a protracted episode, which can only be temporarily controlled by usual amounts of sugar, further requires immediate treatment and follow-up by a doctor and in some circumstances, in-patient hospital care. If treated by different doctors (e.g., hospital stay, after an accident, illness while on holiday), the patients must inform them of their diabetic condition and previous treatment.
Sulfonylurea therapy in patients with G6PD deficiency can result in hemolytic anemia. Glibenclamide should be used with caution in patients with G6PD deficiency, and a non-sulfonylurea alternative should be considered.
Effects on ability to drive and use machine: Glibenclamide may produce severe hypoglycemia. The patient's ability to concentrate and react may be impaired as a result of hypoglycemia. These impairments may present a risk in situations where these abilities are especially important, such as driving or operating other machinery. Patients need to be particularly careful to avoid hypoglycemia and should be warned of the problem.
Use in the Elderly: Elderly patients are particularly susceptible to hypoglycemic action of glucose-lowering drugs but difficult to recognize. The initial and maintenance dosing should be conservative to avoid hypoglycemic reactions.

Pregnancy: Glibenclamide crosses the placenta. Use of Glibenclamide in pregnant women should generally be avoided because of the risk of neonatal hypoglycemia. Women with type 2 diabetes who planning a pregnancy or during pregnancy should be treated with insulin.
Lactation: Glibenclamide may be present in breast milk. Because of the potential for hypoglycemia in the breastfeeding infant, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother. If Glibenclamide is discontinued, administration of insulin should be considered.

Endocrine and metabolism disorders: Very common frequency: hypoglycemia, which may be severe and has occasionally been fatal, may occur in patients receiving Glibenclamide.
Symptoms of hypoglycemia include headache, ravenous, hunger, nausea, vomiting, lassitude, sleepiness, disordered sleep, restlessness, aggressive, impaired concentration, alertness and reactions, depression, confusion, difficulty in speaking and even speech loss, visual disorders, tremor, paresis, sensory disturbances, dizziness, helplessness, loss of self-control, delirium, cerebral convulsion, somnolence and loss of consciousness up to and including coma, shallow respiration and slow heart rate (bradycardia).
Signs of adrenergic counter-regulation include sweating, clammy skin, anxiety, rapid heart rate (tachycardia), hypertension, palpitations, angina pectoris, and cardiac arrhythmias.
The clinical picture of a severe hypoglycemia attack may resemble that of a stroke. The symptoms nearly always subside when hypoglycemia is corrected.
Common frequency: weight gain.
Unknown frequency: sodium concentration in the serum may decrease.
Eye disorder: Unknown frequency: temporary visual impairment due to the change in blood glucose levels.
Gastrointestinal disorders: Common frequency: nausea, abdominal pain, diarrhea.
Uncommon frequency: sensations of pressure or fullness in the epigastrium.
Unknown frequency: vomiting.
However, despite continued treatment, these often subside and usually do not necessitate discontinuing Glibenclamide.
Hepatobiliary disorders: Unknown frequency: hepatitis, elevation of liver enzyme levels and/or cholestasis and jaundice which may progress to life-threatening liver failure but can regress after withdrawal of Glibenclamide.
Blood and lymphatic system disorders: Unknown frequency: mild to severe thrombocytopenia (e.g. presenting as purpura), hemolytic anemia, erythrocytopenia, leukopenia, granulocytopenia, agranulocytosis, pancytopenia.
These reactions are reversible once Glibenclamide has been withdrawn.
Immune system disorders: Unknown frequency: hypersensitivity reactions, allergic or pseudoallergic reactions may occur. Allergy to sulphonamide derivatives may also be responsible for allergic reaction to Glibenclamide. Mild reactions in the form of urticaria may develop into serious and even life-threatening reactions with dyspnea and fall in blood pressure, sometimes progressing to shock.
Skin and subcutaneous disorders: Common frequency: rashes.
Unknown frequency: itching, bullous reactions, erythema multiforme, dermatitis exfoliative, hypersensitivity of skin to light, allergic vasculitis.

An increased incidence of elevated liver enzymes was observed in patients receiving Glibenclamide concomitantly with bosentan. Both Glibenclamide and bosentan inhibit the bile salt export pump, leading to intracellular accumulation of cytotoxic bile salts. Therefore this combination should not be used (see Contraindications).
Glibenclamide is mainly metabolized by CYP2C9 and a lesser extent by CYP3A4. This should be taken into account when Glibenclamide is administered with inducers or inhibitors of CYP2C9.
Potentiation of the blood-glucose lowering effect and, thus, in some instances hypoglycemia may occur when taking other drugs, including insulin and other (oral) antidiabetics, ACE inhibitors, anabolic steroids and male sex hormones, chloramphenicol, coumarin derivatives, cyclophosphamide, disopyramide, fenfluramine, fenyramidol, fibrates, fluoxetine, ifosfamide, MAO inhibitors, miconazole, para-aminosalicylic acid, pentoxifylline (high dose parenteral), phenylbutazone, azapropazone, oxyphenbutazone, probenecid, quinolones, salicylates, sulfinpyrazone, sulphonamides, sympatholytic agents (such as beta blockers and guanethidine), clarithromycin, tetracyclines, tritoqualine, trofosfamide.
Weakening of the blood-glucose lowering effect and, thus, raised blood-glucose levels may occur when taking other drugs, including acetazolamide, barbiturates, corticosteroids, diazoxide, diuretics, epinephrine (adrenaline) and other sympathomimetic agents, glucagon, laxatives (after protracted use), nicotinic acid (in high dose), estrogens and progestogens, phenothiazines, phenytoin, thyroid hormones, rifampicin.
H2 antagonists, clonidine and reserpine may lead to either potentiation or weakening of the blood glucose lowering effect.
Under the influence of sympatholytic drugs such as beta blockers, clonidine, guanethidine, and reserpine, the signs of adrenergic counter-regulation to hypoglycemia may be reduced or absent.
Both acute and chronic alcohol intake may potentiate or weaken the blood glucose-lowering action of Glibenclamide in an unpredictable fashion.
Glibenclamide may either potentiate or weaken the effect of coumarin derivatives.
Glibenclamide may increase cyclosporine plasma concentration and potentially lead to its increased toxicity. Monitoring and dosage adjustment of cyclosporine are therefore recommended when both drugs are coadministered.
Colesevelam binds to Glibenclamide and reduces Glibenclamide absorption from the gastro-intestinal tract. No interaction was observed when Glibenclamide was taken at least 4 hours before colesevelam. Therefore, Glibenclamide should be administered at least 4 hours prior to colesevelam.

Store below 30°C.

Antidiabetic Agents

A10BB01 - glibenclamide ; Belongs to the class of sulfonylureas. Used in the treatment of diabetes.

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