Glimep

Glimepiride.

Each tablet contains: Glimepiride 2mg.

Pharmacology: Pharmacokinetics: The absolute bioavailability of glimepiride is complete. Food intake has no relevant influence on the absorption. Maximum serum concentration (Cmax) are reached approximately 2.5 hrs after oral intake (309mg/mL during multiple dosing of 4 mg daily) and there's a linear relationship between dose and both Cmax and AUC (area under the time-concentration curve). Glimepiride has a very low distribution volume (approximately 8.8 L) which is roughly equal to the albumin distribution space, high protein binding (>99%) and a low clearance (approximately 48mL/min). Mean dominant serum half-life which is of relevance for the serum concentrations under multiple-dose conditions is about 5-8 hrs. After high doses, slightly longer half-lives were noted.
After a single dose of radiolabelled glimepiride, 58% of the radioactivity was recovered in the urine and 35% in the feces. No unchanged substance was detected in the urine. Two metabolites, most probably resulting from hepatic metabolism, were identified both in urine and feces. The hydroxy derivative and carboxy derivatives. After oral administration of glimepiride, the terminal half-lives of these metabolites were 3-6 and 5-6 hrs, respectively. Comparison of single and multiple once-daily dosing revealed no significant differences in pharmacokinetics and the intra individual variability was very low. There was no relevant cumulation. Pharmacokinetics were similar in males and females, as well as in young and elderly (>65 years) patients.
In patients with low creatinine clearance, there was a tendency for glimepiride clearance to increase and for average serum concentrations to decrease, most probably resulting from a more rapid elimination because of lower protein binding. Renal elimination of 2 metabolites was impaired. Overall, no additional risk of cumulation is to be assumed in such patients. Pharmacokinetics in 5 non-diabetic patients after bile duct surgery were similar to those in healthy persons. In animals, glimepiride is excreted into milk.

Use for the treatment of 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 Glimepiride is governed by the desired blood glucose level. The dosage of glimepiride must be the lowest which is sufficient to achieve the desired metabolic control.
During treatment with Glimepiride, glucose levels in blood and urine must be measured regularly. In addition, it is recommended that regular determinations of the proportion of glycated hemoglobin be carried out.
Mistake eg, forgetting to take a dose, must never be corrected by subsequently taking a larger dose. Measures for dealing with such mistakes (in particular, forgetting a dose or skipping a meal) or situations where a dose cannot be taken at the prescribed time must be discussed and agreed between physician and patient beforehand.
Doses 1 to 2mg daily by mouth initially may be increased if necessary to 4mg daily for maintenance. Daily Dose 1-4mg. Daily doses of more than 6mg are more effective only in minority of patients.
Administration: Glimepiride tablets must be swallowed without chewing with sufficient amount of liquid (approximately ½ glass).

Patients hypersensitive to glimepiride, other sulfonylureas, other sulfonamides, or any of the excipients of Glimepiride.
No experience has been gained concerning the use of glimepiride in patients with severe impairment of liver function and in dialysis patients.
In patients with severe impairment of renal or hepatic function, change over to insulin is indicated, not least to achieve optimal metabolic control.

In exceptional stress situation (eg, trauma, surgery, febrile infections), blood glucose regulation may deteriorate, and a temporary change to insulin may be necessary to maintain good metabolic control.

In the initial weeks of treatment, the risk of hypoglycemia may be increased and necessitate especially careful monitoring.
Factors favoring hypoglycemia include: Unwillingness or (more commonly in order patients) incapacity of the patient to cooperate; undernourishment, irregular mealtimes or skipped meals; imbalance between physical exertion and carbohydrate intake; alterations of diet; consumption of alcohol, especially in combination with skipped meals; impaired renal function; overdosage with glimepiride; certain uncompensated disorders of the endocrine system affecting carbohydrate metabolism or counter-regulation of hypoglycemia (eg, in certain disorders of thyroids function and in anterior pituitary or Corticoadrenal insufficiency); concurrent administration of certain other medicines.
Those symptoms of hypoglycemia which reflect the body's adrenergic counter-regulation may be milder or absent where hypoglycemia develops gradually, in the elderly, and where there is autonomic neuropathy or where the patient is receiving concurrent treatment with beta blockers, clonidine, reserpine, guanethidine or other sympatholytic drugs.
Hypoglycemia can almost always be promptly controlled by immediate intake of carbohydrates (glucose or sugar).
Effect on the Ability to Drive or Operate Machinery: Alertness and reactions may be impaired due to hypo- or hyperglycemia, especially when beginning or after altering treatment, or when glimepiride is not taken regularly. This way, for example, affect the ability to drive or operate machinery.

Use in pregnancy: Glimepiride must not be taken during pregnancy. Otherwise, there is risk of harm to the fetus. The patients must change over to insulin during pregnancy. Patients planning a pregnancy must inform their physician. It is recommended that such patients change over to insulin.
Use in Lactation: To prevent possible ingestion with the breast milk and possible harm to the child, glimepiride must not be taken by breastfeeding women. If necessary, the patient must change over to insulin, or must stop breastfeeding.

Hypoglycemia: As a result of blood glucose-lowering action of glimepiride, hypoglycemia may occur, which, based on what is known of other sulfonylureas, may also be prolonged.
Possible symptoms of hypoglycemia include headache, ravenous hunger, nausea, vomiting, lassitude, sleepiness, disordered sleep, restlessness, aggressiveness, impaired concentration, impaired alertness and reactions, depression, confusion, speech disorders, aphasia, visual disorder, tremor, pareses, sensory disturbances, dizziness, helplessness, loss of self-control, delirium, cerebral convulsion, somnolence and loss of consciousness up to and including coma, shallow, respiration and bradycardia.
In addition, signs of adrenergic counter-regulation may be present eg, sweating, clammy skin, anxiety, tachycardia, hypertension, palpitation, angina pectoris and cardiac arrhythmias.
Eyes: Especially at the start of treatment, there may be temporary visual impairment due to the change in blood glucose levels.
The cause is a temporary alteration in the turgidity and hence, the refractive index of the lens, this being dependent on blood glucose level.
Digestive Tract: Occasionally, gastrointestinal symptoms eg, nausea, vomiting, sensation of pressure or fullness in the epigastrium, abdominal pain, and diarrhea may occur.
In rare cases, there may be elevation of liver enzyme levels. Sulfonylureas, including glimepiride, may also, in isolated instances, cause impairment of liver function (eg, with cholestasis and jaundice) as well as hepatitis which may also lead to liver failure.
Blood: Changes in the blood picture may occur: Rarely, thrombopenia and, in isolated cases, leucopenia may develop. Based on what is known to other sulfonylureas, drugs of this class may, in isolated instances, cause in addition to the previously mentioned hemolytic anemia or eg, erythrocytopenia, granulocytopenia, agranulocytosis and (eg, due to myelosuppression) pancytopenia.
Others: Occasionally, allergic or pseudoallergic reactions may occur eg, in the form of itching, urticaria or rashes. Based on what is known of other sulfonylureas, such mild reactions may develop into serious reactions with dyspnea and a fall in blood pressure, sometimes progressing to shock. In the event of urticaria, a physician must therefore be notified immediately.
In isolated cases, a decrease in serum sodium concentration and, based on what is known of other sulfonylureas, allergic vasculitis or hypersensitivity of the skin to light may occur.

Numerous interactions have been reported with the sulfonylureas, largely representing either pharmacokinetics interactions (due to the displacement of the antidiabetic from plasma proteins or alteration in its metabolism or excretion) or pharmacological interactions with drugs having an independent effect on blood glucose.
A diminished hypoglycemic effect, possibly requiring an increased dose of sulfonylurea, has been seen or might be expected on theoretical grounds with adrenaline, aminogluthimide, chlorpromazine, corticosteroids, diazoxide, oral contraceptives, rifampicins, and thiazide diuretics.
An increased hypoglycemic effect has occurred or might be expected with ACE inhibitors, alcohol, allopurinol, some analgesics (notably azapropazone, phenylbutazone, and the salicylates), azole, antifungal, chloramphenicol, cimetidine, clofibrate and related compounds, coumarin, anticoagulants, heparin, MAOIs, octreotide, ranitidine, sulfinpyrazone, sulfonamides, tetracyclines, tricyclic antidepressants, and thyroids hormones. Beta blockers have been reported both to increase hypoglycaemia and to mask the typical sympathetic warning signs. There are sporadic and conflicting reports of a possible interactions with calcium-channel blockers, but overall any effect seems to be of little clinical significance. In addition to producing hypoglycemia alcohol can interact with chlorpropamide to produce an unpleasant flushing reaction. Such an effect is rare with other sulfonylureas and alcohol.

Store in a dry place at a temperatures not exceeding 30°C.
Protect from sunlight.

Antidiabetic Agents

A10BB12 - glimepiride ; Belongs to the class of sulfonylureas. Used in the treatment of diabetes.

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