Glizid MV

Gliclazide (Glizid MV) is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It belongs to the sulfonylurea class of insulin secretagogues, which act by stimulating β cells of the pancreas to release insulin. Sulfonylureas increase both basal insulin secretion and meal-stimulated insulin release. Medications in this class differ in their dose, rate of absorption, duration of action, route of elimination and binding site on their target pancreatic β cell receptor. Sulfonylureas also increase peripheral glucose utilization, decrease hepatic gluconeogenesis and may increase the number and sensitivity of insulin receptors. Sulfonylureas are associated with weight gain, though less so than insulin. Due to their mechanism of action, sulfonylureas may cause hypoglycemia and require consistent food intake to decrease this risk. The risk of hypoglycemia is increased in elderly, debilitated and malnourished individuals. Gliclazide (Glizid MV) has been shown to decrease fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels (reflective of the last 8-10 weeks of glucose control). Gliclazide (Glizid MV) is extensively metabolized by the liver; its metabolites are excreted in both urine (60-70%) and feces (10-20%).

Metformin (Glizid MV) is a biguanide antihyperglycemic agent used for treating non-insulin-dependent diabetes mellitus (NIDDM). It improves glycemic control by decreasing hepatic glucose production, decreasing glucose absorption and increasing insulin-mediated glucose uptake. Metformin (Glizid MV) may induce weight loss and is the drug of choice for obese NIDDM patients. Use of Metformin (Glizid MV) is associated with modest weight loss. When used alone, Metformin (Glizid MV) does not cause hypoglycemia; however, it may potentiate the hypoglycemic effects of sulfonylureas and insulin. Its main side effects are dyspepsia, nausea and diarrhea. Dose titration and/or use of smaller divided doses may decrease side effects. Metformin (Glizid MV) should be avoided in those with severely compromised renal function (creatinine clearance < 30 ml/min), acute/decompensated heart failure, severe liver disease and for 48 hours after the use of iodinated contrast dyes due to the risk of lactic acidosis. Lower doses should be used in the elderly and those with decreased renal function. Metformin (Glizid MV) decreases fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Metformin (Glizid MV) may also have a positive effect on lipid levels. In 2012, a combination tablet of linagliptin plus Metformin (Glizid MV) hydrochloride was marketed under the name Jentadueto for use in patients when treatment with both linagliptin and Metformin (Glizid MV) is appropriate.

Voglibose (Glizid MV) (INN and USAN) is an alpha-glucosidase inhibitor used for lowering post-prandial blood glucose levels in people with diabetes mellitus. It is made in India by Ranbaxy Labs and sold under the trade name Voglibose (Glizid MV).

30-mg: Non-insulin dependent diabetes (type 2) in adults when dietary measures, physical exercise and weight loss alone are not sufficient to control blood glucose.

80-mg: Gliclazide (Glizid MV) (Gliclazide (Glizid MV)) is a sulphonylurea hypoglycemic agent which is given by mouth in the treatment of non-insulin dependent diabetes mellitus. It is used to supplement treatment by diet modification when such modification has not proved effective on its own. Its duration of action is 12 hours or more. Gliclazide (Glizid MV) (Gliclazide (Glizid MV)) may be used in place of chlorpropamide in elderly patients.

In maturity onset (non-insulin-dependent) obese diabetics and juvenile diabetics in whom diet alone has failed as monotherapy or in combination with insulin, glitazones or sulfonylureas. Also as an adjunct to diet and exercise to improve glycemic control in patients with type-2 diabetes.

Glitazones are used in combination with Metformin (Glizid MV) HCl when glycemic control is poor on Metformin (Glizid MV) HCl monotherapy and maximum tolerated dose (preferable) of Metformin (Glizid MV) HCl has been tried. The combination of glitazone plus Metformin (Glizid MV) HCl is preferred to glitazone plus sufonylurea, particularly for obese patients.

Improvement of postprandial hyperglycemia in diabetes mellitus when sufficient effect has not been obtained in patients already undergoing dietary treatment and/or exercise therapy, or when sufficient effect has not been obtained in patients who have been using oral hypoglycemic drugs or insulin preparations, in addition to dietary treatment and/or exercise therapy.

Polyethylene glycol electrolyte solution is a laxative solution that increases the amount of water in the intestinal tract to stimulate bowel movements. This medication also contains potassium, sodium, and other minerals to replace electrolytes that are passed from the body in the stool.

Polyethylene glycol electrolyte solution is used to clean the bowel before colonoscopy, a barium x-ray, or other intestinal procedures.

Polyethylene glycol electrolyte solution may also be used for purposes not listed in this medication guide.

Metformin (Glizid MV) is used to treat high blood sugar levels that are caused by a type of diabetes mellitus or sugar diabetes called type 2 diabetes. With this type of diabetes, insulin produced by the pancreas is not able to get sugar into the cells of the body where it can work properly. Using Metformin (Glizid MV) alone, with a type of oral antidiabetic medicine called a sulfonylurea, or with insulin, will help to lower blood sugar when it is too high and help restore the way you use food to make energy.

Many people can control type 2 diabetes with diet and exercise. Following a specially planned diet and exercise will always be important when you have diabetes, even when you are taking medicines. To work properly, the amount of Metformin (Glizid MV) you take must be balanced against the amount and type of food you eat and the amount of exercise you do. If you change your diet or exercise, you will want to test your blood sugar to find out if it is too low. Your doctor will teach you what to do if this happens.

Metformin (Glizid MV) does not help patients does not help patients who have insulin-dependent or type 1 diabetes because they cannot produce insulin from their pancreas gland. Their blood glucose is best controlled by insulin injections.

Metformin (Glizid MV) is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although this use is not included in product labeling, Metformin (Glizid MV) is used in certain patients with the following medical conditions:

• Polycystic ovary syndrome.

The daily dose of Gliclazide (Glizid MV) may vary from ½-2 tablets daily (ie, from 30-120 mg) taken orally in a single intake at breakfast.

If a dose is missed, there must be no increase in the dose the following day.

As with any hypoglycaemic agent, the dose should be adjusted according to the individual patient's metabolic response (blood glucose, HbA1c).

Initial Dose: Recommended Starting Dose: 30 mg daily (½ Gliclazide (Glizid MV) tablet). If blood glucose is effectively controlled, this dose may be used for maintenance treatment. If blood glucose is not adequately controlled, the dose may be increased to 60, 90 or 120 mg daily, in successive steps. The interval between each dose increment should be at least 1 month, except in patients whose blood glucose was not reduced after 2 weeks of treatment.

In such cases, the dose may be increased at the end of the 2nd week of treatment.

Maximum Recommended Daily Dose: 120 mg.

One Gliclazide (Glizid MV) modified-release tablet is equivalent to 2 Diamicron 30 mg modified-release tablet. The breakability of the Gliclazide (Glizid MV) modified-release tablet enables flexibility of dosing to be achieved.

Switching from Diamicron 80 mg Tablet to Gliclazide (Glizid MV) Modified-Release Tablet: 1 tablet of Diamicron 80 mg is comparable to 30 mg of the modified-release formulation (ie, ½ Gliclazide (Glizid MV) tablet). Consequently, the switch can be performed with careful blood monitoring.

Switching from Another

Oral Antidiabetic Agent to Gliclazide (Glizid MV):

The dosage and the half-life of the previous antidiabetic agent should be taken into account when switching to Gliclazide (Glizid MV).

A transitional period is not generally necessary. A starting dose of 30 mg should be used and this should be adjusted to suit the patient's blood glucose, as previously described.

When switching from a hypoglycaemic sulfonylurea with a prolonged half-life, a treatment-free period of a few days may be necessary to avoid an additive effect of the 2 antidiabetic agents, which might cause hypoglycaemia. The procedure described for initiating treatment should also be used when switching to treatment with Gliclazide (Glizid MV) ie, a starting dose of 30 mg daily, followed by a stepwise increase in dose, depending on the metabolic response.

Combination Treatment with Other Antidiabetic Agents: Gliclazide (Glizid MV) can be given in combination with biguanides, α-glucosidase inhibitors or insulin.

In patients inadequately controlled with Gliclazide (Glizid MV), concomitant insulin therapy can be initiated under close medical supervision.

Elderly (>65 years): Same dosing regimen as the one recommended for patients <65 years.

Patients with Renal Impairment: Same dosing regimen as the one recommended for patients with normal renal function with careful patient monitoring. These data have been confirmed in clinical trials.

Patients at Risk of Hypoglycaemia: In undernourished or malnourished patients; patients with severe or poorly compensated endocrine disorders (hypopituitarism, hypothyroidism, adrenocorticotrophic insufficiency); withdrawal of prolonged and/or high-dose corticosteroid therapy; severe vascular disease (severe coronary heart disease, severe carotid impairment, diffuse vascular disease), it is recommended that the minimum starting dose of 30 mg is used.

Administration: For oral use. It is recommended to swallow the dose without crushing or chewing.

If a dose is missed, there must be no increase in the dose taken the following day.

There is no fixed dosage regimen for the management of hyperglycemia in patients with type 2 diabetes with Metformin (Glizid MV) or Metformin (Glizid MV) XR or any other pharmacologic agent. Dosage of Metformin (Glizid MV) or Metformin (Glizid MV) XR must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses. The maximum recommended daily dose of Metformin (Glizid MV) is 2550 mg in adults and 2000 mg in pediatric patients (10-16 years of age); the maximum recommended daily dose of Metformin (Glizid MV) XR in adults is 2000 mg.

Metformin (Glizid MV) should be given in divided doses with meals while Metformin (Glizid MV) XR should generally be given once daily with the evening meal. Metformin (Glizid MV) or Metformin (Glizid MV) XR should be started at a low dose, with gradual dose escalation, both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient.

During treatment initiation and dose titration, fasting plasma glucose should be used to determine the therapeutic response to Metformin (Glizid MV) or Metformin (Glizid MV) XR and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately 3 months. The therapeutic goal should be to decrease both fasting plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of Metformin (Glizid MV) or Metformin (Glizid MV) XR, either when used as monotherapy or in combination with sulfonylurea or insulin.

Monitoring of blood glucose and glycosylated hemoglobin will also permit detection of primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication, and secondary failure, i.e., loss of an adequate blood glucose lowering response after an initial period of effectiveness.

Short-term administration of Metformin (Glizid MV) or Metformin (Glizid MV) XR may be sufficient during periods of transient loss of control in patients usually well-controlled on diet alone.

Metformin (Glizid MV) XR tablets must be swallowed whole and never crushed or chewed. Occasionally, the inactive ingredients of Metformin (Glizid MV) XR will be eliminated in the feces as a soft, hydrated mass.

Recommended Dosing Schedule

In general, clinically significant responses are not seen at doses below 1500 mg per day. However, a lower recommended starting dose and gradually increased dosage is advised to minimize gastrointestinal symptoms.

The usual starting dose of Metformin (Glizid MV) Tablets is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. Patients can also be titrated from 500 mg twice a day to 850 mg twice a day after 2 weeks. For those patients requiring additional glycemic control, Metformin (Glizid MV) may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given 3 times a day with meals.

The usual starting dose of Metformin (Glizid MV) XR (Metformin (Glizid MV) hydrochloride) Extended-Release Tablets is 500 mg once daily with the evening meal. Dosage increases should be made in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal. If glycemic control is not achieved on Metformin (Glizid MV) XR 2000 mg once daily, a trial of Metformin (Glizid MV) XR 1000 mg twice daily should be considered. If higher doses of Metformin (Glizid MV) are required, Metformin (Glizid MV) should be used at total daily doses up to 2550 mg administered in divided daily doses, as described above.

In a randomized trial, patients currently treated with Metformin (Glizid MV) were switched to Metformin (Glizid MV) XR. Results of this trial suggest that patients receiving Metformin (Glizid MV) treatment may be safely switched to Metformin (Glizid MV) XR once daily at the same total daily dose, up to 2000 mg once daily. Following a switch from Metformin (Glizid MV) to Metformin (Glizid MV) XR, glycemic control should be closely monitored and dosage adjustments made accordingly.

Pediatrics

The usual starting dose of Metformin (Glizid MV) is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses. Safety and effectiveness of Metformin (Glizid MV) XR in pediatric patients have not been established.

Transfer From Other Antidiabetic Therapy

When transferring patients from standard oral hypoglycemic agents other than chlorpropamide to Metformin (Glizid MV) or Metformin (Glizid MV) XR, no transition period generally is necessary. When transferring patients from chlorpropamide, care should be exercised during the first 2 weeks because of the prolonged retention of chlorpropamide in the body, leading to overlapping drug effects and possible hypoglycemia.

Concomitant Metformin (Glizid MV) or Metformin (Glizid MV) XR and

Oral Sulfonylurea Therapy in Adult Patients

If patients have not responded to 4 weeks of the maximum dose of Metformin (Glizid MV) or Metformin (Glizid MV) XR monotherapy, consideration should be given to gradual addition of an oral sulfonylurea while continuing Metformin (Glizid MV) or Metformin (Glizid MV) XR at the maximum dose, even if prior primary or secondary failure to a sulfonylurea has occurred. Clinical and pharmacokinetic drug-drug interaction data are currently available only for Metformin (Glizid MV) plus glyburide (glibenclamide).

With concomitant Metformin (Glizid MV) or Metformin (Glizid MV) XR and sulfonylurea therapy, the desired control of blood glucose may be obtained by adjusting the dose of each drug. In a clinical trial of patients with type 2 diabetes and prior failure on glyburide, patients started on Metformin (Glizid MV) 500 mg and glyburide 20 mg were titrated to 1000/20 mg, 1500/20 mg, 2000/20 mg, or 2500/20 mg of Metformin (Glizid MV) and glyburide, respectively, to reach the goal of glycemic control as measured by FPG, HbA1c, and plasma glucose response. However, attempts should be made to identify the minimum effective dose of each drug to achieve this goal. With concomitant Metformin (Glizid MV) or Metformin (Glizid MV) XR and sulfonylurea therapy, the risk of hypoglycemia associated with sulfonylurea therapy continues and may be increased. Appropriate precautions should be taken.

If patients have not satisfactorily responded to 1 to 3 months of concomitant therapy with the maximum dose of Metformin (Glizid MV) or Metformin (Glizid MV) XR and the maximum dose of an oral sulfonylurea, consider therapeutic alternatives including switching to insulin with or without Metformin (Glizid MV) or Metformin (Glizid MV) XR.

Concomitant Metformin (Glizid MV) or Metformin (Glizid MV) XR and Insulin Therapy in Adult Patients

The current insulin dose should be continued upon initiation of Metformin (Glizid MV) or Metformin (Glizid MV) XR therapy. Metformin (Glizid MV) or Metformin (Glizid MV) XR therapy should be initiated at 500 mg once daily in patients on insulin therapy. For patients not responding adequately, the dose of Metformin (Glizid MV) or Metformin (Glizid MV) XR should be increased by 500 mg after approximately 1 week and by 500 mg every week thereafter until adequate glycemic control is achieved. The maximum recommended daily dose is 2500 mg for Metformin (Glizid MV) and 2000 mg for Metformin (Glizid MV) XR. It is recommended that the insulin dose be decreased by 10% to 25% when fasting plasma glucose concentrations decrease to less than 120 mg/dL in patients receiving concomitant insulin and Metformin (Glizid MV) or Metformin (Glizid MV) XR. Further adjustment should be individualized based on glucose-lowering response.

Specific Patient Populations

Metformin (Glizid MV) or Metformin (Glizid MV) XR are not recommended for use in pregnancy. Metformin (Glizid MV) is not recommended in patients below the age of 10 years. Metformin (Glizid MV) XR is not recommended in pediatric patients (below the age of 17 years).

The initial and maintenance dosing of Metformin (Glizid MV) or Metformin (Glizid MV) XR should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Any dosage adjustment should be based on a careful assessment of renal function. Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of Metformin (Glizid MV) or Metformin (Glizid MV) XR.

Monitoring of renal function is necessary to aid in prevention of lactic acidosis, particularly in the elderly.

Adults: Normal Dose: Usually, Voglibose (Glizid MV) tablets are orally administered in a single dose of 0.2 mg, 3 times a day, before each meal. If the effect is not sufficient, the quantity of a single dose may be increased up to 0.3 mg.

Elderly: Since elderly patients generally have a physiological hypo function, it is desirable that such caution be taken as starting the administration at a low dose (eg, 0.1 mg at a time). Furthermore, Voglibose (Glizid MV)/Voglinorm-0.3 should be carefully administered under close observation through the course of the disease condition, with careful attention to the blood sugar level and the onset of gastrointestinal symptoms.

Renal Impairment: Voglibose (Glizid MV) is poorly absorbed after oral doses and renal excretion is negligible, suggesting that no dose adjustment is required. However, pharmacokinetic studies in patients with renal insufficiency are not available.

See also:
What is the most important information I should know about Gliclazide (Glizid MV)?

Hypersensitivity to Gliclazide (Glizid MV), other sulfonylureas, sulfonamides or to any of the excipients of Gliclazide (Glizid MV).

Type I diabetes, diabetic ketoacidosis, diabetic pre-coma and coma; severe renal or hepatic insufficiency.

Treatment with miconazole.

Lactose Intolerance: Due to the presence of lactose in Gliclazide (Glizid MV), patients with rare hereditary problems of galactose intolerance, glucose galactose malabsorption or Lapp lactase deficiency should not take this medicinal product.

Use in pregnancy: Category C: It is important to achieve strict normoglycaemia during pregnancy.

Oral hypoglycaemic agents should be replaced by insulin. The sulfonylureas may enter the fetal circulation and cause neonatal hypoglycaemia. In animal studies, embryotoxicity and/or birth defects have been demonstrated with some sulfonylureas.

Gliclazide (Glizid MV) should not be used in pregnant women although animal studies of Gliclazide (Glizid MV) have not shown any teratogenic effect. From a clinical point of view, there are no adequate data to allow evaluation of the possible malformative or foetotoxic effects of Gliclazide (Glizid MV), when administered during pregnancy.

Use in lactation: In the absence of data on the transfer of Gliclazide (Glizid MV) into breast milk and given the risk of neonatal hypoglycaemia, breastfeeding is contraindicated during treatment with Gliclazide (Glizid MV).

See also:
What is the most important information I should know about Metformin (Glizid MV)?

Metformin (Glizid MV)® is contraindicated in patients with:

1. Renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels ≥1.5 mg/dL [males], ≥1.4 mg/dL [females] or abnormal creatinine clearance) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia.
2. Known hypersensitivity to Metformin (Glizid MV).
3. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin.

Metformin (Glizid MV)® should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function.

WARNINGS

Lactic Acidosis:

Lactic acidosis is a rare, but serious, metabolic complication that can occur due to Metformin (Glizid MV) accumulation during treatment with Metformin (Glizid MV)® (Metformin (Glizid MV) hydrochloride) Extended-Release Tablets; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/ L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When Metformin (Glizid MV) is implicated as the cause of lactic acidosis, Metformin (Glizid MV) plasma levels >5 μg/mL are generally found.

The reported incidence of lactic acidosis in patients receiving Metformin (Glizid MV) hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/ surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking Metformin (Glizid MV)® (Metformin (Glizid MV) hydrochloride) Extended-Release Tablets and by use of the minimum effective dose of Metformin (Glizid MV)®. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Metformin (Glizid MV)® treatment should not be initiated in patients ≥80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, Metformin (Glizid MV)® should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, Metformin (Glizid MV)® should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking Metformin (Glizid MV)®, since alcohol potentiates the effects of Metformin (Glizid MV) hydrochloride on lactate metabolism. In addition, Metformin (Glizid MV)® should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure.

The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient and the patient's physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur. Metformin (Glizid MV)® should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose and, if indicated, blood pH, lactate levels, and even blood Metformin (Glizid MV) levels may be useful. Once a patient is stabilized on any dose level of Metformin (Glizid MV)®, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease.

Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking Metformin (Glizid MV)® do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling.

Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia).

Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking Metformin (Glizid MV)®, the drug should be discontinued immediately and general supportive measures promptly instituted. Because Metformin (Glizid MV) hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated Metformin (Glizid MV). Such management often results in prompt reversal of symptoms and recovery.

ZAVESCA® is contraindicated in patients who have demonstrated hypersensitivity to the active substance or any of the excipients.

Pregnancy Category X.

Voglibose (Glizid MV) may cause fetal harm when administered to a pregnant woman. In female rats given miglustat by oral gavage at doses of 20, 60, 180 mg/kg/day beginning 14 days before mating and continuing through gestation day 17 (organogenesis), decreased live births including complete litter loss and decreased fetal weight was observed in the mid and high-dose groups (systemic exposures ³2 times the human therapeutic systemic exposure based on body surface area comparison). In pregnant rats given miglustat by oral gavage at doses of 20, 60, 180 mg/kg/day from gestation day 6 through lactation (postpartum day 20), dystocia and delayed parturition were observed in the mid- and high-dose groups (systemic exposures ³2 times the human therapeutic systemic exposure, based on body surface area comparison), in addition decreased live births and pup body weights were observed at >20 mg/kg/day (systemic exposures less than the human therapeutic systemic exposure, based on body surface area comparison).

In pregnant rabbits given miglustat by oral gavage at doses of 15, 30, 45 mg/kg/day during gestation days 6-18 (organogenesis), maternal death and decreased body weight gain were observed at 15 mg/kg/day (systemic exposures less than the human therapeutic systemic exposure, based on body surface area comparisons).

ZAVESCA® is contraindicated in women who are or may become pregnant. If this drug is administered to a woman with reproductive potential, the patient should be apprised of the potential hazard to a fetus.

Use Metformin (Glizid MV) extended-release tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Metformin (Glizid MV) extended-release tablets. Talk to your pharmacist if you have questions about this information.
• Take Metformin (Glizid MV) extended-release tablets by mouth with the evening meal unless your doctor tells you otherwise.
• Swallow Metformin (Glizid MV) extended-release tablets whole. Do not break, crush, or chew before swallowing.
• Take Metformin (Glizid MV) extended-release tablets on a regular schedule to get the most benefit from it. Taking Metformin (Glizid MV) extended-release tablets at the same time each day will help you remember to take it.
• Continue to take Metformin (Glizid MV) extended-release tablets even if you feel well. Do not miss any doses.
• If you miss a dose of Metformin (Glizid MV) extended-release tablets, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Metformin (Glizid MV) extended-release tablets.

Gliclazide (Glizid MV) is used to lower the blood sugar levels in type 2 diabetes mellitus when diet, physical exercise and weight reduction alone are not adequate.

Use: Labeled Indications

Diabetes mellitus, type 2: Management of type 2 diabetes mellitus when hyperglycemia cannot be managed with diet and exercise alone.

Note: If not contraindicated and if tolerated, Metformin (Glizid MV) is the preferred initial pharmacologic agent for type 2 diabetes management (ADA 2020).

Off Label Uses

Antipsychotic-induced weight gain

Data from multiple meta-analyses of randomized controlled trials with varying degrees of heterogeneity (primarily in patients with schizophrenia and schizoaffective disorder) support the use of Metformin (Glizid MV) in promoting modest weight loss and preventing weight gain associated with second-generation antipsychotics in adult patients

Voglibose (Glizid MV) is used to reduce high post meal glucose level in diabetes mellitus in patients who have been using other diabetic medications.

See also:
What other drugs will affect Gliclazide (Glizid MV)?

Gliclazide (Glizid MV): Drugs which may increase the hypoglycemic effect of Gliclazide (Glizid MV) include phenylbutazone, salicylates, sulfonamides, coumarin derivatives, clofibrate, monoamine oxidase inhibitors (MAOIs), β-adrenergic blocking drugs, cimetidine, disopyramide, miconazole, tetracycline compounds and chloramphenicol.

Drugs which may reduce the effectiveness of Gliclazide (Glizid MV) include corticosteroids, oral contraceptives, thiazide diuretics, thyroid hormones, phenothiazine derivatives and abuse of laxatives.

Care should be taken with any other drugs which may affect the diabetic condition.

Gliclazide (Glizid MV)-OD: Hepatic enzyme inhibitors eg, sulfonamides, tuberculostatics, clarithromycin, phenylbutazone, clofibrate, coumarin derivatives, salicyclates, nonsteroidal anti-inflammatory agents (NSAIDs), probenecid, β-blockers (eg, propranolol), tetracycline compounds, chloramphenicol, azole antifungal agents (eg, miconazole, ketoconazole, itraconazole), H₂-receptor antagonists (eg, cimetidine), disopyramide and angiotensin-converting enzymes (ACE) inhibitors (eg, captopril and enalapril), and MAOIs may increase Gliclazide (Glizid MV)’s hypoglycemic effect.

Inducers of hepatic enzymes eg, rifampicin, barbiturates, thyroid hormones and phenytoin may lower Gliclazide (Glizid MV)’s plasma concentration.

Concomitant administration with anticoagulants (warfarin and other anticoagulants) may lead to potentiation of anticoagulation. Adjustment of anticoagulant dosage may be necessary.

Drugs that induce hyperglycemia leading to a loss of control of blood sugar: diuretics (thiazides, furosemide), corticosteroids and tetracosactrin, danazol, chlorpromazine, ritodrine/salbutamol/terbutaline (IV), oral contraceptives (estrogens plus progestogens, and nicotinic acid in pharmacologic doses.

Acute or chronic alcohol intake may unpredictably potentiate or reduce the activity of Gliclazide (Glizid MV).

See also:
What other drugs will affect Metformin (Glizid MV)?

Drug Interactions (Clinical Evaluation Of Drug Interactions Conducted With Immediate-Release Metformin (Glizid MV))

Glyburide

In a single-dose interaction study in type 2 diabetes patients, co-administration of Metformin (Glizid MV) and glyburide did not result in any changes in either Metformin (Glizid MV) pharmacokinetics or pharmacodynamics. Decreases in glyburide AUC and Cmax were observed, but were highly variable. The single-dose nature of this study and the lack of correlation between glyburide blood levels and pharmacodynamic effects, makes the clinical significance of this interaction uncertain.

Furosemide

A single-dose, Metformin (Glizid MV)-furosemide drug interaction study in healthy subjects demonstrated that pharmacokinetic parameters of both compounds were affected by co-administration. Furosemide increased the Metformin (Glizid MV) plasma and blood Cmax by 22% and blood AUC by 15%, without any significant change in Metformin (Glizid MV) renal clearance. When administered with Metformin (Glizid MV), the Cmax and AUC of furosemide were 31% and 12% smaller, respectively, than when administered alone, and the terminal half-life was decreased by 32%, without any significant change in furosemide renal clearance. No information is available about the interaction of Metformin (Glizid MV) and furosemide when co-administered chronically.

Nifedipine

A single-dose, Metformin (Glizid MV)-nifedipine drug interaction study in normal healthy volunteers demonstrated that co-administration of nifedipine increased plasma Metformin (Glizid MV) Cmax and AUC by 20% and 9%, respectively, and increased the amount excreted in the urine. Tmax and half-life were unaffected. Nifedipine appears to enhance the absorption of Metformin (Glizid MV). Metformin (Glizid MV) had minimal effects on nifedipine.

Cationic Drugs

Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with Metformin (Glizid MV) by competing for common renal tubular transport systems. Such interaction between Metformin (Glizid MV) and oral cimetidine has been observed in normal healthy volunteers in both single- and multiple-dose, Metformin (Glizid MV)-cimetidine drug interaction studies, with a 60% increase in peak Metformin (Glizid MV) plasma and whole blood concentrations and a 40% increase in plasma and whole blood Metformin (Glizid MV) AUC. There was no change in elimination half-life in the single-dose study. Metformin (Glizid MV) had no effect on cimetidine pharmacokinetics. Although such interactions remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment of Metformin (Glizid MV)® and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system.

Other

Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving Metformin (Glizid MV)®, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving Metformin (Glizid MV)®, the patient should be observed closely for hypoglycemia.

In healthy volunteers, the pharmacokinetics of Metformin (Glizid MV) and propranolol, and Metformin (Glizid MV) and ibuprofen were not affected when coadministered in single-dose interaction studies.

Metformin (Glizid MV) is negligibly bound to plasma proteins and is, therefore, less likely to interact with highly protein-bound drugs such as salicylates, sulfonamides, chloramphenicol, and probenecid, as compared to the sulfonylureas, which are extensively bound to serum proteins.

Concomitant use of Voglibose (Glizid MV) with derivatives of sulfonylamide, sulfonylurea, biguanide derivatives, insulin preparations and agents improving insulin resistance causes hypoglycemia. Therefore, whenever Voglibose (Glizid MV) is used in combination with these drugs, it should be initiated at a lower dose.

Caution should be taken while concomitantly using Voglibose (Glizid MV) with drugs enhancing the hypoglycemic action of antidiabetic drugs including beta blockers, salicylic acid preparations, monoamine oxidase inhibitors, fibrate derivatives and warfarin.

Caution should be taken while concomitantly using Voglibose (Glizid MV) with drugs diminishing the hypoglycemic action of antidiabetic drugs eg, epinephrine, adrenocortical hormone, thyroid hormone, etc.

Incompatibilities: None reported.

See also:
What are the possible side effects of Gliclazide (Glizid MV)?

Good clinical acceptability of Gliclazide (Glizid MV), has been established in many studies as well as in medical practice.

The safety of a modified-release formulation of Gliclazide (Glizid MV) (30-120 mg) has been evaluated in controlled clinical trials in 955 patients, of which 728 patients were treated in long-term comparative trials, against a Gliclazide (Glizid MV) immediate-release formulation (80-320 mg), for up to 10 months. In these comparative trials, the overall incidence and type of adverse events were similar in both groups. Adverse events were generally mild and transient, not requiring discontinuation of therapy.

However, where patients did discontinue due to adverse events, the percentage was lower in the modified-release group (2.9%) than in the immediate-release group (4.5%).

Hypoglycaemia : As is the case with all sulfonylurea drugs, hypoglycaemic reactions have been reported following Gliclazide (Glizid MV) administration. However, a number of studies have shown that hypoglycaemia is less common with Gliclazide (Glizid MV) than with glibenclamide.

Possible symptoms of hypoglycaemia are: Headache, intense hunger, nausea, vomiting, lassitude, sleep disorders, agitation, aggression, poor concentration, reduced awareness and slowed reactions, depression, confusion, visual and speech disorders, aphasia, tremor, paresis, sensory disorders, dizziness, feeling of powerlessness, loss of seIf-control, delirium, convulsions, shallow respiration, bradycardia, drowsiness and loss of consciousness, possibly resulting in coma and/or death.

In addition, signs of adrenergic counter-regulation may be observed: Sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmia. Usually, symptoms disappear after intake of carbohydrate eg, sugar (artificial sweeteners have no effect). Experience with other sulfonylureas shows that hypoglycaemia can recur even when these measures are initially effective. If a hypoglycaemic episode is severe or prolonged and even if it is temporarily controlled by intake of sugar, immediate medical treatment or even hospitalisation is required.

In long-term comparative studies, the percentage of patients experiencing hypoglycaemic episodes was similar between patients treated with the modified-release formulation of Gliclazide (Glizid MV) (11.6%) and those treated with the immediate-release formulation of Gliclazide (Glizid MV) (11.1 %). However, the number of hypoglycaemic episodes/100 patient-months was lower in the modified-release group (3.5) than in the immediate-release group (4.8).

Analysis of elderly patients (>65 years old) showed less hypoglycaemia than in the general population, with a prevalence of hypoglycaemic episodes lower in the modified-release group (2.6 hypoglycaemic episodes for 100 patient-months) than in the immediate-release group (4.1).

The percentage of patients experiencing hypoglycaemic episodes in the sub-population with renal failure, was similar to that observed in the general population.

Other Adverse Events: Adverse events reported during controlled clinical trials with the modified-release formulation of Gliclazide (Glizid MV) were those expected in an ageing population with diabetes.

Adverse events that were reported in at least 2% of patients, in long-term controlled clinical studies, are presented in Table 2. The most frequent adverse events were not specifically related to the disease (eg, respiratory infections or back pain).

Analysis of adverse events in sub-populations showed a similar pattern to that seen in the general population. Gender, age and renal insufficiency had no significant influence on the safety profile of the modified-release formulation of Gliclazide (Glizid MV).

Gastrointestinal disturbances (reported with Gliclazide (Glizid MV)), including nausea, dyspepsia, diarrhoea, abdominal pain, vomiting and constipation may be avoided or minimised if Gliclazide (Glizid MV) is taken with breakfast.

The following adverse events have been rarely reported: Skin and mucosae reactions: Pruritus, urticaria, maculopapular rashes, rash, erythema and bullous reactions.

Haematological Disorders (As with Other Sulfonylurea Drugs): A few rare cases of anaemia, leucopenia, thrombocytopenia and agranulocytosis.

Occasional elevations of serum creatinine, blood urea nitrogen, serum bilirubin and hepatic enzymes (AST, ALT, alkaline phosphatase) levels and exceptionally, hepatitis. Treatment should be discontinued if cholestatic jaundice appears.

These symptoms usually disappear after discontinuation of treatment.

As with any glucose-lowering medication, transient visual disturbances may occur on initiation of treatment due to changes in blood glucose levels.

See also:
What are the possible side effects of Metformin (Glizid MV)?

During treatment initiation, the most common adverse reactions are nausea, vomiting, diarrhoea, abdominal pain and loss of appetite which resolve spontaneously in most cases.

In a US double-blind clinical study of Metformin (Glizid MV) in patients with type 2 diabetes, a total of 141 patients received Metformin (Glizid MV) therapy (up to 2550 mg/day) and 145 patients received placebo. Adverse reactions reported in >5% of the Metformin (Glizid MV) patients, and that was more common in Metformin (Glizid MV) than placebo-treated patients, are listed in Table 2.

Diarrhea led to discontinuation of study medication in 6% of patients treated with Metformin (Glizid MV). Additionally, the following adverse reactions were reported in >1% to <5% of Metformin (Glizid MV) patients and were more commonly reported with Metformin (Glizid MV) than placebo: Abnormal stools, hypoglycemia, myalgia, lightheaded, dyspnea, nail disorder, rash, increased sweating, taste disorder, chest discomfort, chills, flu syndrome, flushing, palpitation.

In worldwide clinical trials, over 900 patients with type 2 diabetes have been treated with Metformin (Glizid MV) extended-release tablet in placebo- and active-controlled studies. In placebo-controlled trials, 781 patients were administered Metformin (Glizid MV) extended-release tablet and 195 patients received placebo. Adverse reactions reported in >5% of the Metformin (Glizid MV) extended-release tablet patients and that were more common in Metformin (Glizid MV) extended-release tablet than placebo treated patients, are listed in Table 3.

Diarrhea led to discontinuation of study medication in 0.6% of patients treated with Metformin (Glizid MV) extended-release tablet. Additionally, the following adverse reactions were reported in >1% to <5% of Metformin (Glizid MV) extended-release tablet patients and were more commonly reported with Metformin (Glizid MV) extended-release tablet than placebo: Abdominal pain, constipation, abdomen distention, dyspepsia/heartburn, flatulence, dizziness, headache, upper respiratory infection, taste disturbance.

In clinical trials with Metformin (Glizid MV) in pediatric patients with type 2 diabetes, the profile of adverse reactions was similar to that observed in adults.

Other reported adverse events with use of Metformin (Glizid MV) are: Skin reactions eg, erythema, pruritus and urticaria; isolated reports of liver function tests abnormalities or hepatitis resolving upon Metformin (Glizid MV) discontinuation; lactic acidosis; decrease of vitamin B12 absorption with decrease of serum levels during long-term use of Metformin (Glizid MV), consideration of such etiology is recommended if a patient presents with megaloplastic anaemia.

Gastrointestinal disorders eg, diarrhea, loose stools, abdominal pain, constipation, anorexia, nausea, vomiting, abdominal pain and loss of appetite may occur with the combination of Voglibose (Glizid MV). These adverse reactions occur most frequently during initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that Voglibose (Glizid MV) hydrochloride be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.

Skin and Subcutaneous Tissue Disorders: Very rarely skin reactions eg, erythema, pruritus, and urticaria have been seen. In such a case, Voglibose (Glizid MV) tablets should be discontinued. Increased AST or ALT may also occur. When Voglibose (Glizid MV) is used in combination with other antidiabetic drugs, hypoglycemia may occur (0.1% to <5%).