Glimepiride, metformin hydrochloride.
Each uncoated bilayered tablet contains: Glimepiride USP 2 mg; Metformin Hydrochloride USP (in sustained-release form) 500 mg.
Excipient/Inactive Ingredients: Hypromellose, Sodium carboxymethyl cellulose, Methacrylic acid copolymer dispersion, Macrogol, Povidone, Magnesium stearate, Purified water, Sodium starch glycolate, Lactose, Titanium dioxide, Microcrystalline cellulose, Magnesium stearate, Pregelatinized starch.
Colors: Ferric oxide (Yellow) and Titanium Dioxide.
Pharmacokinetics: Glimepiride: Single oral dose of Glimepiride, 1 and 8 mg results in a Cmax of 103.2 and 550.8 μg/L. The Tmax is found to be between 2.4 to 3.75 hours in Type II diabetic patients. The volume of distribution is low as the plasma protein binding is very high (99%). Accumulation does not occur after multiple doses of Glimepiride. Glimepiride is metabolized mainly in the liver to active metabolites 37-52% of Glimepiride is found in urine as metabolites within 48 hours. T½ is about 5 hours after the first dose, which increases up to 9.2 hours after multiple doses.
Metformin: Following a single oral dose of Metformin HCl Extended Release, Cmax is achieved with a median value of 7 hours and a range of 4 to 8 hours. Metformin has an absolute oral bioavailability of 50 to 60%. Although the extent of Metformin absorption (as measured by AUC) from the extended release Metformin tablet increased by approximately 50% when given with food, there was no effect of food on Cmax and Tmax. Both high and low fat meals had the same effects on the pharmacokinetics of extended release Metformin. Following absorption, Metformin is rapidly distributed and does not bind to plasma proteins. It does not undergo hepatic metabolism or biliary excretion. The drug undergoes renal excretion and has a plasma elimination half life of 6.2 hours after oral administration. In patients with decreased renal functions, the plasma and blood half life of Metformin is prolonged and the renal clearance is decreased in proportion to the decrease in creatinine clearance.
Diabetes mellitus type 2, whenever blood sugar levels cannot be controlled adequately by diet, physical exercise and weight reduction. Also, it is for replacement therapy in diabetic patients stabilized on glimepiride (1 or 2 mg) with metformin (500 mg SR). Indicated for patients of 18 years of age and older.
Glimepiride 2 mg/Metformin hydrochloride 500 mg: 1 tablet once daily or as directed by the physician.
Dosage must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily dose.
The maximum recommended daily dose of metformin in adults is 2000 mg and glimepiride is 8 mg once daily.
Do not crush or chew the tablet; the whole tablet has to be taken with water. Start with one tablet per day. The aim should be to decrease both fasting plasma glucose and glycosylated hemoglobin levels to normal by using the lowest effective dose of the drug.
Hemodialysis may be useful for removal of accumulated metformin from patients in whom overdosage is suspected.
This combination is not suitable for the treatment of diabetes mellitus type 1 (e.g. for the treatment of diabetics with a history of ketoacidosis), or of diabetic precoma or coma.
It must not be used in patients hypersensitive to metformin hydrochloride, glimepiride, sulfonylureas, other sulfonamides, or any of the excipients (risk of hypersensitivity reactions).
Impaired renal function; acute complications (severe infections, major operations and trauma); before x-ray examinations with iodinated contrast materials; liver damage; alcoholism; deficiencies of vitamin B12, folic acid and iron; ketosis-prone diabetes; severe cardiovascular or respiratory disease; general ill health (malnutrition, dehydration, etc); diabetes with significant late complications (nephropathy, retinopathy).
Glimepiride: If risk factors for hypoglycemia are present, it may be necessary to adjust the dosage of glimepiride or the entire therapy. This also applies whenever illness occurs during therapy or the patient's lifestyle changes.
Symptoms of hypoglycemia may be milder or absent in those situations where hypoglycemia develops gradually, in the elderly and in the patients with autonomic neuropathy or those 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, e.g. in the form of sugar lumps, sugar-sweetened fruit juice or sugar sweetened tea). For this purpose, patients must carry a minimum of 20 grams of glucose with them at all times. They may require assistance of other persons to avoid complication. Artificial sweeteners are ineffective in controlling hypoglycemia.
Continued close observation is necessary. Severe hypoglycemia requires immediate treatment and follow-up by a physician and in some circumstances, hospitalization.
In exceptional stress situations (e.g. trauma, surgery, infections with fever) blood sugar control may deteriorate, and temporary change to insulin may be necessary.
During treatment with glimepiride, glucose levels in blood and urine must be checked regularly, as should, additionally, the proportion of glycated hemoglobin. Alertness and reactions may be impaired due to hypoglycemia or hyperglycemia, especially when beginning or after altering treatment, or when glimepiride is not taken regularly. This may affect the ability to operate vehicle or machinery.
Metformin: Lactic Acidosis: Metformin can provoke lactic acidosis; however, the reported incidence is very low. Conditions like impaired hepatic function, renal dysfunction, hypoxemia, dehydration, sepsis, excessive alcohol intake can increase the risk of lactic acidosis. The risk can be decreased by regular monitoring of renal function and by use of minimum effective dose. In a patient with lactic acidosis, who is on metformin treatment, the drug should be discontinued immediately. Supportive measures and prompt hemodialysis should be started.
Impaired renal function: Caution should be exercised with concomitant therapies that may affect renal function or interfere with the disposition of metformin (eg, cationic drugs).
Use of Iodinated Contrast Media: The drug should be stopped at least two days before X-ray examination with iodinated contrast material and reinstituted only after renal function has been re-evaluated and found to be normal.
Hypoxic States: Metformin therapy should be promptly discontinued when such events occur in patients.
Surgical Procedures: The drug should be temporarily discontinued and restarted only when the patient resumes oral intake and has normal renal function.
Alcohol Intake: Patients should be warned against excessive alcohol intake, acute or chronic, while receiving metformin.
Impaired hepatic function: The drug should be generally avoided in patients with hepatic disease.
Hypoglycemia: Hypoglycemia does not normally occur when the drug is given alone but has been observed when given in combination with sulfonylureas and/or alcohol.
Deficiencies of folic acid, iron and vitamin B12: Serum vitamin B12 concentrations should be measured annually during long-term treatment.
Laboratory Tests: Monitoring of response to therapy to be done periodically through measurement of fasting blood glucose and glycosylated hemoglobin levels.
During initial dose titration, fasting glucose can be used to determine the response. Subsequently, both glucose and glycosylated hemoglobin must be monitored, which may be useful in evaluating long-term control.
Additional Safety Information: As part of the Risk Minimization Measures for the Important Identified Risks "Coadministration of iodinated contrast media" and "Use in Perioperative period": Intravascular administration of iodinated contrast media may lead to kidney failure, resulting in metformin build up and a risk of lactic acid accumulation in the blood.
It is recommended to discontinue metformin treatment, 48 hours before elective surgery, involving general, spinal or peridural anesthesia.
Therapy may be started no earlier than 48 hours following surgery or resumption of eating normally, provided normal kidney function has.
Pregnancy: Pregnancy is generally regarded as a contraindication and insulin should be used in all pregnant diabetic women.
Nursing Mothers: The ingredients in the combination may enter breast milk and is best avoided in nursing mothers.
Hypoglycemia: As a result of the blood-sugar lowering action of glimepiride, hypoglycemia may occur and may also be prolonged.
Eyes: Especially at the start of treatment, temporary visual impairment may occur due to the change in blood sugar levels.
Digestive tract: Occasionally, nausea, vomiting, sensations of pressure or fullness in the epigastrium, abdominal pain and diarrhea may occur. In isolated cases, liver enzymes levels may increase, and impairment of liver function (e.g. with cholestasis and jaundice) and hepatitis may develop, possibly resulting in liver failure.
Blood: Rarely, thrombocytopenia and in isolated cases, leukopenia, hemolytic anemia, erythrocytopenia, granulocytopenia, agranulocytosis, and pancytopenia (e.g. due to myelosuppression) may develop.
Other adverse reactions: Allergic or pseudoallergic reactions like itching, urticaria or rashes may occur. Such reactions are mild but may become more serious and be accompanied by dyspnea, and a fall in blood pressure, sometimes progressing to shock. If urticaria occurs, a physician must be notified immediately. In isolated cases allergic vasculitis, hypersensitivity of the skin to light, and a decrease in serum sodium may occur.
Cimetidine: Metformin interacts with cimetidine. Therefore, the dose of metformin should be reduced if cimetidine is co-prescribed.
Hyperglycemic Agents: Drugs with hyperglycemic potential (e.g. thiazides, corticosteroids and others) may partly offset the anti-hyperglycemic action of metformin, and in such cases, the glycemic control should be closely monitored.
Alcohol: Alcohol potentiates the action of metformin on lactate metabolism as well as the anti-hyperglycemic effect. Hence, patients treated with metformin should preferably avoid alcohol and alcoholism is a definite contraindication.
Other Interactions: Studies with furosemide and nifedipine suggest a possible interaction by increasing plasma metformin levels. However no such changes were found with propranolol and ibuprofen.
The absorption of metformin may be reduced by acarbose and guar gum. Hypoglycemia due to interaction with glimepiride may occur when one of the following medicines is taken, for example: insulin and other oral antidiabetics, ACE inhibitors, allopurinol, anabolic steroids and male sex hormones, chloramphenicol, coumarin derivatives, cyclophosphamide, disopyramide, fenfluramine, fenyramidol, fibrates, fluoxetine, guanethidine, isofamide, MAO inhibitors, miconazole, para-aminosalicylic acid, pentoxifylline (high dose parenteral), phenylbutazone, azapropazone, oxyphenbutazone, probenecid, quinolones, salicylates, sulfinpyrazone, sulfonamides, tetracyclines, tritoqualine, trofosfamide.
Hyperglycemia due to interaction with glimepiride may occur when one of the following medicines is taken, for example: acetazolamide, barbiturates, corticosteroids, diazoxide, diuretics, epinephrine (adrenaline) and other sympathomimetic agents, glucagons, laxatives (after protracted use), nicotinic acid (in high doses), estrogens 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. Beta-blockers may increase the tendency to hypoglycemia.
The effect of coumarin derivatives may be potentiated or weakened.
Store at temperatures not exceeding 25°C. Protect from light and moisture.
Shelf-Life: 24 months.
A10BD02 - metformin and sulfonylureas ; Belongs to the class of combinations of oral blood glucose lowering drugs. Used in the treatment of diabetes.
Sign Out
