Generics: Glimepiride + Metformin.
Dosage Form: Tablet.
This tablet is indicated as an adjunct to diet and exercise in type 2 diabetes mellitus patients-
- In case that the monotherapy with glimepiride or metformin does not result in adequate glycemic control.
- Replacement of combination therapy of glimepiride and metformin.
- Glimepiride may be a sulfonylurea antidiabetic operator which diminishes blood glucose concentration. The essential instrument of activity of Glimepiride shows up to be subordinate on invigorating the discharge of affront from working pancreatic beta cells. Glimepiride acts in concert with glucose by making strides the affectability of beta cells to physiological glucose jolt, coming about in affront emission. In expansion, extrapancreatic impacts like lessening of basal hepatic glucose generation, expanded fringe tissue affectability to affront and glucose take-up may too play part within the movement of Glimepiride. In non-fasting diabetic patients, the hypoglycaemic activity of a single dosage of Glimepiride endures for 24 hours.
- Metformin Hydrochloride is an antihyperglycemic medication of the biguanide class that is used to treat type 2 diabetes. Both baseline and postprandial plasma glucose levels are reduced. It has a different mode of action than sulfonylureas and does not cause hypoglycemia. Metformin Hydrochloride reduces hepatic glucose synthesis and glucose absorption in the intestine.
Dose dependent on Physicians instruction.
In principle, the dosage of Glimepiride 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 check of glucose in blood and urine. Monitoring of glucose levels in blood and urine also serves to detect either primary or secondary failure of therapy.
Initial dose and dose titration: the usual initial dose is 1 mg once daily, if necessary, the daily dose can be increased. Any increase can be based on regular blood sugar monitoring, and should be gradual, i.e., at intervals of 1 to 2 weeks, and carried out stepwise, as follows: 1 mg -> 2 mg -> 3 mg -> 4 mg -> 6 mg.
Dose in patients with well controlled diabetes: the usual dose range in patients with well controlled diabetes is 1 to 4 mg daily.
Distribution of doses: Timing and distribution of doses are decided by the physician, in consideration of the patient’s current life-style. Normally, a single daily dose is sufficient. This should be taken immediately before a substantial breakfast or if none is taken immediately before the first main meal. It is very important not to skip meals after taking the drug.
Secondary dosage adjustment: As control of diabetes improves, sensitivity to insuiin increases; therefore, Glimepiride requirement may fall as treatment proceeds. To avoid hypoglycaemia, timely dose reduction or cessation of Glimepiride therapy must be considered. A dose adjustment must also be considered whenever the patient’s weight or life-styie changes, or other factors arise which cause an increased susceptibility to hypo or hyperglycaemia.
Changeover from other oral antidiabetics to Glimepiride: There is no exact dosage relationship between Glimepiride and other oral blood sugar lowering agents. When substituting Glimepiride for other such agents, the initial daily dose is 1 mg; this applies even in changeover from maximum dose of other oral blood sugar lowering agents. Any dose increase should be in accordance with guideline given above in ‘initial dose and dose titration’. Consideration must be given to the potency and duration of action of the previous blood sugar lowering agent. It may be necessary to interrupt treatment to avoid additive effects which would increase the risk of hypoglycaemia.
- The dosage of this tablet is governed by the desired blood glucose level. The dosage of this tablet must be the lowest which is sufficient to achieve the desired metabolic control. During treatment with this tablet glucose levels in blood and urine must be measured regularly.
- Mistakes, e.g. forgetting to take a dose, must never be corrected by subsequently taking a larger dose.
- As an improvement in control of diabetes is, in itself, associated with higher insulin sensitivity, glimepiride requirements may fall as treatment proceeds. To avoid hypoglycaemia timely dose reduction or cessation of this tablet therapy must therefore be considered.
- The highest recommended dose per day should be 8 mg of glimepiride and 2000 mg of metformin.
- In order to avoid hypoglycaemia the starting dose of this tablet should not exceed the daily doses of glimepiride or metformin already being taken.
- When switching from combination therapy of glimepiride plus metformin as separate tablets, this combination should be administered on the basis of dosage currently being taken.
Route of administration: Orally.
- Glimepiride is metabolized by cytochrome P450 2C9 (CYP2C9). This ought to be taken under consideration when glimepiride is coadministered with inducers (e.g. rifampicin) or inhibitors (e.g. fuconazole) of CYP 2C9.
- Potentiation of the blood-glucose-lowering efect and, in this way, in a few occasions hypoglycaemia may happen when one of the taking after drugs is taken, for illustration: affront and other, verbal antidiabetics; Pro inhibitors; anabolic steroids and male sex hormones; chloramphenicol; coumarin subordinates; cyclophosphamide; disopyramide; fenfuramine; fenyramidol; fbrates; fuoxetine; guanethidine; ifosfamide; MAO inhibitors; miconazole; fuconazole; para-aminosalicylic corrosive; pentoxifylline (tall dosage parenteral); phenylbutazone; azapropazone; oxyphenbutazone; probenecid; quinolones; salicylates; sulfnpyrazone; clarithromycin; sulfonamide anti-microbials; tetracyclines; tritoqualine; trofosfamide.
- Weakening of the blood-glucose-lowering efect and, thus raised blood glucose levels may occur when one of the following drugs is taken, for example: acetazolamide; barbiturates; corticosteroids; diazoxide; diuretics; epinephrine (adrenaline) and other sympathomimetic agents; glucagon; laxatives (after protracted use); nicotinic acid (in high doses); oestrogens and progestogens; phenothiazines; phenytoin; rifampicin; thyroid hormones.
- H2 receptor antagonists, beta-blockers, clonidine and reserpine may lead to either potentiation or weakening of the blood-glucose-lowering efect. Under the infuence of sympatholytic drugs such as beta-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-glucose-lowering action of glimepiride in an unpredictable fashion.
- The efect of coumarin derivatives may be potentiated or weakened.
- Bile acid sequestrant: Colesevelam binds to glimepiride and reduces glimepiride absorption from the gastrointestinal tract. Glimepiride should be administered at least 4 hours prior to colesevelam.
For Metformin: Concomitant use not recommended:
Alcohol: Alcohol intoxication is associated with an increased risk of lactic acidosis, particularly in case of fasting, malnutrition or hepatic insufciency. Avoid consumption of alcohol and alcohol-containing medications.
Iodinated contrast agents: Metformin must be discontinued prior to, or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable.
Combinations requiring precautions for use: Some medicinal products can adversely afect renal function which may increase the risk of lactic Acidosis. When starting or using such products in combination with metformin, close monitoring of renal function is necessary. Glucocorticoids, beta-2-agonists, and diuretics have intrinsic hyperglycemic activity. Inform the patient and perform more frequent blood glucose monitoring. ACE-inhibitors may decrease the blood glucose levels. Metformin may decrease the anticoagulant efect of phenprocoumon. Therefore, a close monitoring of the INR is recommended. Levothyroxine can reduce the hypoglycemic efect of metformin. Monitoring of blood glucose levels is recommended, especially when thyroid hormone therapy is initiated or stopped, and the dosage of metformin must be adjusted if necessary.
Glimepiride is not suitable for the treatment of insulin dependent (type I) diabetes mellitus, or for the treatment of diabetic ketoacidosis, nor for the treatment of diabetic coma. Glimepiride must not be used in patients hypersensitive to Glimepiride, other sulfonylureas, other sulfonamides, severe hepatic dysfunction, severe impairment of renal function and dialysis patients. Also-
- In patients hypersensitive to glimepiride, metformin, other sulfonylureas, other sulfonamides, or any of the excipients of Amaryl M.
- In pregnant women.
- In breastfeeding women.
- 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 hepatic function, change-over to insulin is indicated, not least to achieve optimal metabolic control.
- Hypersensitivity to metformin or any of the excipients.
- Any type of acute metabolic acidosis such as lactic acidosis Diabetic ketoacidosis, diabetic pre-coma.
- Severe Renal failure or renal disfunction (e.g., serum creatine levels >135 μmol/L in males and >110 μmol/L in females), GFR < 30 mL/min.
- Acute conditions with the potential to alter renal function such as Dehydration, severe infection, intravascular administration of iodinated contrast agents etc.
- Acute or chronic disease which may cause tissue hypoxia such as cardiac or respiratory failure, recent myocardial infarction, shock
- Hepatic insufciency.
- Acute alcohol intoxication, alcoholism.
Metabolism and nutrition disorders
- As a result of the blood-glucose-lowering action of glimepiride, Hypoglycaemia which may also be prolonged.
- The clinical picture of a severe hypoglycaemic attack may resemble that of a stroke.
Eye disorders: 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.
- Occasionally, Gastrointestinal symptoms such as nausea, vomiting, sensations of pressure or fulness in the epigastrium, abdominal pain and diarrhea may occur.
- In isolated cases, there may be hepatitis, elevation of liver enzyme levels and/or cholestasis and jaundice, which may progress to life-threatening liver failure.
- Blood and lymphatic system disorders-
- Changes in the blood picture may occur: Rarely, thrombocytopenia and, in isolated cases, leucopenia, hemolytic anemia, erythrocytopenia, granulocytopenia, agranulocytosis or pancytopenia may develop. Cases of severe thrombocytopenia with platelet count less than 10,000/μl and thrombocytopenic purpura have been reported in post-marketing experience.
Skin and subcutaneous tissue disorders: Alopecia.
Occasionally, Allergic or pseudo allergic reactions may occur, e.g. in the form of itching, urticaria or rashes. Such mild reactions may develop into serious reactions with dyspnoea and a fall in blood pressure, sometimes progressing to shock.
In isolated cases, a decrease in serum sodium concentration and allergic vasculitis or hypersensitivity of the skin to light may occur.
Investigations: Glimepiride, like all sulfonylureas, can cause weight gain.
- Gastrointestinal symptoms such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite (>10%) are very common. These occur most frequently during initiation of therapy and resolve spontaneously in most cases.
- Metallic taste (3%) is common
- Decrease of vitamin B12 absorption with decrease of serum levels has been observed in patients treated long-term with metformin and appears generally to be without clinical signifcance (<0.01%). However, Cases of peripheral neuropathy in patients with vitamin B12 defciency have been reported in post-marketing experience.
- Lactic acidosis (0.03 cases/1000 patient-years) is very rare
- Hemolytic anemia.
- Reduction of thyrotropin level in patients with hypothyroidism.
- Hypomagnesemia in the context of diarrhea.
- Hepatobiliary disorders: Reports of liver function tests abnormalities and hepatitis resolving upon metformin discontinuation
Pregnancy & Lactation:
For Glimepiride: Glimepiride must not be taken during pregnancy. Otherwise, there is risk of harm to the child. The patient 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.
For Metformin: When the patient plans to become pregnant and during pregnancy, diabetes should not be treated with metformin but insulin should be used to maintain blood glucose levels as close to normal as possible in order to lower the risk of fetal malformations associated with abnormal blood glucose levels.
For Glimepiride: To prevent possible ingestion with the breast milk and possible harm to the child, glimepiride must not be taken by breast-feeding women. If necessary the patient must change over to insulin, or must stop breastfeeding.
For Metformin: Metformin is excreted into milk in lactating rats. Similar data is not available in humans and a decision should be made whether to discontinue nursing or to discontinue metformin, taking into account the importance of the compound to the mother.
Precautions & Warnings:
Within the introductory weeks of treatment, the chance of hypoglycemia may be expanded and requires particularly cautious observing. In case hazard components for hypoglycemia are show, it may be vital to alter the dosage of glimepiride or the complete treatment. This too applies at whatever point ailment happens amid treatment or the patient’s life-style changes. It is known from other sulfonylureas that, in spite of at first effective countermeasures, hypoglycaemia may repeat. Patients must, subsequently, stay beneath near perception. Extreme hypoglycaemia advance requires quick treatment and follow-up by a doctor and, in a few circumstances, in-patient clinic care. Treatment of patients with G6PD-defciency with sulfonylurea specialists can lead to hemolytic weakness. Since glimepiride has a place to the lesson of sulfonylurea specialists, caution ought to be utilized in patients with G6PD-defciency and a non-sulfonylurea elective ought to be considered.
In patients with hypothyroidism, regular monitoring of thyroid-stimulating hormone (TSH) levels is indicated. Long-term metformin medication has been linked to a drop in vitamin B12 serum levels, which can lead to peripheral neuropathy. Vitamin B12 levels should be checked on a regular basis.
Do not store at temperatures above 30°C. Keep out of the reach of youngsters and away from light.Keep out of the reach of children.
Manufactured by: Synovia Bangladesh ltd.