Miaryl

Miaryl

glimepiride

Manufacturer:

Jin Yang

Distributor:

Propharm
Full Prescribing Info
Contents
Glimepiride.
Action
3rd generation oral hypoglycaemic agent.
Pharmacology: Glimepiride is a blood-sugar-lowering agent belonging to the sulfonylurea group. The primary mechanism of action in blood-glucose lowering is stimulation of the release of insulin from functioning pancreatic β-cells. Miaryl augments the normal action of insulin on peripheral glucose uptake. It also mimics such action as well as the glucose output of the liver. Good metabolic control over 24 hrs can be achieved with a single dose of Miaryl. In patients with insufficient response to the maximum dose, combined use with an additional oral antidiabetic containing metformin or with insulin improves metabolic control.
Pharmacokinetics: Absorption: The bioavailability of glimepiride after oral administration is complete. Food intake has no relevant influence on absorption, only absorption rate is slightly diminished. Maximum serum concentrations (Cmax) are reached approximately 2.5 hrs after oral intake (mean 0.3 mcg/mL during multiple dosing of 4 mg daily) and there is a linear relationship between dose and both Cmax and area under the time/concentration curve (AUC).
Distribution: 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 48 mL/min). In animals, glimepiride is excreted in milk. Glimepiride is transferred to the placenta. Passage of the blood-brain barrier is low.
Biotransformation and Elimination: 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 faeces. No unchanged substance was detected in the urine. Two metabolites, most probably resulting from hepatic metabolism (major enzyme is CYP2C9), were identified both in urine and faeces: The thyroid derivative and the carboxy derivative. 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 accumulation.
Pharmacokinetics were similar in males and females, as well as in young 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 the 2 metabolites was impaired. Overall, no additional risk of accumulation is to be assumed in such patients.
Indications/Uses
As an adjunct to diet and exercise in non-insulin dependent (type II) diabetes, whenever blood sugar levels cannot be controlled adequately by diet, physical exercise and weight reduction alone. Miaryl may be used in combination with an oral antidiabetic containing metformin or with insulin.
Dosage/Direction for Use
Recommended Dosage: In principle, the dosage of Miaryl is governed by the desired blood sugar level. The dosage of glimepiride must be the lowest which is sufficient to achieve the desired metabolic control.
The initial and the maintenance doses are set based on the results of regular checks of glucose in blood and urine.
Initial Dose: 1 mg once daily. If necessary, the daily dose can be increased. Any increase should be based on regular blood sugar monitoring, and should be gradual ie, at intervals of 1-2 weeks, and carried out stepwise as follows: 1 mg-2 mg-3 mg-4 mg-6 mg and in exceptional cases, 8 mg.
Patients with Well-Controlled Diabetes: Usual Dosage Range: 1-4 mg daily. Only some patients benefit from daily doses of >6 mg.
Distribution of Doses: Timing and distribution of doses are to be decided by the doctor, taking into consideration the patient's current lifestyle. Normally, a single daily dose of Miaryl is sufficient. This dose should be taken immediately before a substantial breakfast or, if none is taken, immediately before the 1st main meal. It is very important not to skip meals after taking Miaryl.
Duration of Treatment: Treatment with Miaryl is normally a long-term therapy.
Changeover from Oral Antidiabetics to Miaryl: When substituting Miaryl for other agents, the initial daily dose is 1 mg; this applies even in changeovers from the maximum dose of another oral blood sugar-lowering agent. Any Miaryl dose increase should be in accordance with guidelines given previously in Initial Dose.
Use in Combination with Insulin: Whenever blood sugar levels cannot be controlled adequately with the maximum daily dose of Miaryl, insulin may be given concomitantly. In this case, the current dose of Miaryl remains unchanged. Insulin treatment is started at a low dose, which is subsequently increased stepwise according to the desired blood sugar level. Combined treatment should be initiated under close medical supervision.
Overdosage
Miaryl overdose may lead to severe and sometimes life-threatening hypoglycaemia and may require hospitalization even as a precautionary measure. Significant overdose with severe reactions is a medical emergency and will necessitate immediate treatment and hospitalization. Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dosage, meal patterns or physical activity may be necessary. More severe episodes with coma, seizure or neurologic impairment may be treated with glucagons (IM or SC) or concentrated glucose solution (IV). If life-threatening amounts have been ingested, detoxification (by gastric lavage, activated charcoal) will be necessary. Sustained administration of carbohydrates and observation may be necessary because hypoglycaemia may recur after apparent clinical recovery.
Contraindications
Not suitable for the treatment of insulin-dependent (type I) diabetes mellitus (eg, for the treatment of diabetics with a history of ketoacidosis), of diabetic ketoacidosis, or of diabetic precoma or coma. Miaryl must not be used in patients hypersensitive to glimepiride, other sulphonylureas, other sulfonamides or any of the excipients (risk of hypersensitivity reactions). No experience has been gained concerning the use of Miaryl in patients with severe impairment of liver function and in dialysis patients. In patients with severe impairment of renal or hepatic function, a changeover to insulin is indicated to achieve optimal metabolic control.
Use in pregnancy & lactation: To avoid risk of harm to the child, Miaryl must not be taken during pregnancy; a changeover to insulin is necessary. Patients planning a pregnancy must inform their doctor and should change over to insulin.
Ingestion of glimepiride with breast milk may harm the child. Therefore, Miaryl must not be taken by breastfeeding women and a changeover to insulin or discontinuation of breastfeeding is necessary.
Warnings
Special Warning on Increased Risk of Cardiovascular Mortality: The administration of oral hypoglycaemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin.
Special Precautions
To achieve optimal control of blood sugar, a correct diet, regular and sufficient physical exercise and, if necessary, reduction of body weight are just as important as regular intake of Miaryl. Clinical signs of hyperglycaemia are eg, increased urinary frequency, intense thirst, dryness of the mouth and dry skin. In the initial weeks of treatment, the risk of hypoglycaemia may be increased and necessitates careful monitoring. Factors favouring hypoglycaemia include: Unwillingness or incapacity of the patient to cooperate; undernutrition, 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; severe impairment of liver function; overdosage with Miaryl; certain uncompensated disorders of the endocrine system affecting carbohydrate metabolism or counter-regulation of hypoglycaemia (eg, in certain disorders of thyroid function and in anterior pituitary or adrenocortical insufficiency); concurrent administration of certain other medicines.
If such risk factors for hypoglycaemia are present, it may be necessary to adjust the dosage of Miaryl or the entire therapy. This also applies whenever illness occurs during therapy or the patient's lifestyle changes. Those symptoms of hypoglycaemia which reflect the body's adrenergic counter-regulation may be milder or absent in those situations where hypoglycaemia develops gradually, in the elderly, and in patients with a certain type of nervous disease (autonomic neuropathy) or those receiving concurrent treatment with β-blockers, clonidine, reserpine, guanethidine or other sympatholytic medicines.
It is known from other sulfonylureas that, despite initially successful countermeasures, hypoglycaemia may recur. Continued close observation is necessary.
In exceptional stress situations (eg, trauma, surgery, infections with fever) blood sugar control may deteriorate, and a temporary change to insulin may be necessary.
During treatment with Miaryl, glucose levels in blood and urine must be checked regularly, as should, the proportion of glycated haemoglobin.
Effects on the Ability to Drive or Operate Machinery: Alertness and reactions may be impaired due to hypo- or hyperglycaemia, especially when beginning or after altering treatment, or when Miaryl is not taken regularly. Such impairment may affect the ability to operate a vehicle or machinery.
Use In Pregnancy & Lactation
To avoid risk of harm to the child, Miaryl must not be taken during pregnancy; a changeover to insulin is necessary. Patients planning a pregnancy must inform their doctor and should change over to insulin.
Ingestion of glimepiride with breast milk may harm the child. Therefore, Miaryl must not be taken by breastfeeding women and a changeover to insulin or discontinuation of breastfeeding is necessary.
Side Effects
Hypoglycemia: As a result of the blood-sugar-lowering action of Miaryl, hypoglycaemia may occur and may also be prolonged.
Possible symptoms of hypoglycaemia include headache, ravenous hunger, nausea, vomiting, lassitude, sleepiness, disordered sleep, restlessness, aggressiveness, impaired concentration, alertness and reactions, depression, confusion, difficulty in speaking and even speech loss, visual disorders, tremor, pareses, sensory disturbances, dizziness, helplessness, loss of self-control, delirium, cerebral convulsions, somnolence and loss of consciousness up to and including coma, shallow respiration and slow heart rate (bradycardia). In addition, signs of adrenergic counter-regulation may be present eg, sweating, clammy skin, anxiety, rapid heart rate (tachycardia), hypertension, palpitations, angina pectoris and cardiac arrhythmias. The clinical picture of a severe hypoglycaemic attack may resemble that of a stroke. The symptoms of hypoglycaemia nearly always subside when hypoglycaemia is corrected.
Eyes: Especially at the start of treatment, temporary visual impairment may occur due to the change in blood sugar levels.
Digestive Tract: Occasionally, gastrointestinal symptoms eg, the following may occur: Nausea, vomiting, sensations of pressure of fullness in the epigastrium, abdominal pain and diarrhea. In rare cases, liver enzyme levels may increase. In isolated cases, impairment of liver function (eg, with cholestasis and jaundice) and hepatitis may develop, possibly leading to liver failure.
Blood: Severe changes in the blood picture may occur: Rarely, thrombocytopenia, and, in isolated cases, leucopenia, haemolytic anaemia or erythrocytopenia, granulocytopenia, agranulocytosis and pancytopenia (eg, due to myelosuppression) may develop.
Others: Occasionally, allergic or pseudoallergic reactions may occur eg, in the form of itching, urticaria or rashes. Such reactions may be mild, but also may become more serious and may be accompanied by dyspnoea and a fall in blood pressure, sometimes progressing to shock. If urticaria occurs, a doctor must be notified immediately. In isolated cases, a decrease in serum sodium, inflammation of blood vessels (allergic vasculitis) and hypersensitivity of the skin to light may occur.
Since some adverse effects (eg, severe hypoglycaemia, certain changes in the blood picture, severe allergic or pseudoallergic reactions or liver failure) may, under certain circumstances, become life-threatening. It is essential that, if sudden or severe reactions do occur, to inform a doctor at once, and on no account, continue taking Miaryl without a doctor's expressed guidance.
Drug Interactions
Patients who take or discontinue taking certain medicines while undergoing treatment with Miaryl may experience changes in blood sugar control.
Potentiation of blood-sugar-lowering and thus, hypoglycaemia may occur with one of the following medicines: Insulin and other oral antidiabetics, ACE inhibitors, allopurinol, anabolic steroids and male sex hormones, chloramphenicol, coumarin derivatives, cyclophosphamide, disopyramide, fenfluramine, fenyramidol, fibrates, fluoxetine, guanethidine, ifosfamide, MAO inhibitors, miconazole, para-aminosalicylic acid, pentoxifylline (high dose parenteral), phenylbutazone, azapropazone, oxyphenbutazone, probenecid, quinolones, salicylates, sulfinpyrazone, sulfonamides, tetracyclines, tritoqualine, trofosfamide.
Weakening of the blood-sugar-lowering effect and thus, raised blood sugar levels may occur with one of the following medicines: Acetazolamide, barbiturates, corticosteroids, diazoxide, diuretics, adrenaline and other sympathomimetic agents, glucagons, laxatives (after protracted use), nicotinic acid (in high doses), oestrogens and progestogens, phenothiazines, phenytoin, rifampicin, thyroid hormones.
H2-receptor antagonists, clonidine and reserpine may lead to either potentiation or weakening of the blood-sugar-lowering effect. β-blockers decrease glucose tolerance. In patients with diabetes mellitus, this may lead to deterioration of metabolic control.
Under the influence of sympatholytic medicines eg, β-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation to hypoglycaemia may be reduced or absent.
Both acute and chronic alcohol intake may potentiate or weaken the blood-sugar-lowering action of Miaryl unpredictably.
The effect of coumarin derivatives may be potentiated or weakened.
Storage
Store at room temperature of not >25°C, in airtight containers.
Shelf-Life: 3 years.
MIMS Class
ATC Classification
A10BB12 - glimepiride ; Belongs to the class of sulfonylureas. Used in the treatment of diabetes.
Presentation/Packing
Tab 2 mg (grayish-green, oblong-shaped with a score) x 30's.
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