Mage V

Mage V Uses, Dosage, Side Effects, Food Interaction and all others data.

Repaglinide stimulates release of insulin from pancreatic β-cells by inhibiting K efflux via closure of ATP regulated K channels. This results in depolarization of the cell and opening of voltage-dependent Ca channels, which increases influx of Ca into the beta cells and causes release of insulin.

Insulin secretion by pancreatic β cells is partly controlled by cellular membrane potential. Membrane potential is regulated through an inverse relationship between the activity of cell membrane ATP-sensitive potassium channels (ABCC8) and extracellular glucose concentrations. Extracellular glucose enters the cell via GLUT2 (SLC2A2) transporters. Once inside the cell, glucose is metabolized to produce ATP. High concentrations of ATP inhibit ATP-sensitive potassium channels causing membrane depolarization. When extracellular glucose concentrations are low, ATP-sensitive potassium channels open causing membrane repolarization. High glucose concentrations cause ATP-sensitive potassium channels to close resulting in membrane depolarization and opening of L-type calcium channels. The influx of calcium ions stimulates calcium-dependent exocytosis of insulin granules. Repaglinide increases insulin release by inhibiting ATP-sensitive potassium channels in a glucose-dependent manner.

Alpha-glucosidase inhibitors are saccharides that act as competitive inhibitors of enzymes needed to digest carbohydrates: specifically alpha-glucosidase enzymes in the brush border of the small intestines. The membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the small intestine. Acarbose also blocks pancreatic alpha-amylase in addition to inhibiting membrane-bound alpha-glucosidases. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine. Inhibition of these enzyme systems reduces the rate of digestion of complex carbohydrates. Less glucose is absorbed because the carbohydrates are not broken down into glucose molecules. In diabetic patients, the short-term effect of these drugs therapies is to decrease current blood glucose levels: the long term effect is a small reduction in hemoglobin-A1c level.

Voglibose, an alpha-glucosidase inhibitor, is a synthetic compound with potent and enduring therapeutic efficacies against disorders of sensory, motor and autonomic nerve systems due to diabetes mellitus. The drug was approved in Japan in 1994 for the treatment of diabetes, and it is under further investigation by Takeda for the treatment of impaired glucose tolerance. Alpha-glucosidase inhibitors are oral anti-diabetic drugs used for diabetes mellitus type 2 that work by preventing the digestion of complex carbohydrates (such as starch). Complex carbohydrates are normally converted into simple sugars (monosaccharides) which can be absorbed through the intestine. Hence, alpha-glucosidase inhibitors reduce the impact of complex carbohydrates on blood sugar.

Trade Name Mage V
Generic Voglibose + Repaglinide
Weight 0.3mg
Type Tablet
Therapeutic Class
Manufacturer Eris Life Sciences Pvt Ltd
Available Country India
Last Updated: September 19, 2023 at 7:00 am
Mage V
Mage V

Uses

Repaglinide is used for an adjunct to diet and exercise to lower the blood glucose level in patients with type 2 diabetes mellitus (NIDDM) whose hyperglycaemia cannot be controlled satisfactorily by diet and exercise alone. It is also used for use in combination with Metformin to lower blood glucose in patients whose hyperglycaemia cannot be controlled by exercise, diet, and either Repaglinide or Metformin alone. Repaglinide binds to specific receptors in the cell membrane leading to the closure of ATP dependent K+ channels and the depolarisation of cell membrane. This in turn, leads to Ca++ influx, increased intracellular Ca++ and the stimulation of insulin secretion.

Voglibose is used in diabetes mellitus (DM) for reduction in Post-Prandial Hyperglycaemia (PPHG), only when diet and/or exercise with lifestyle modification or Oral Hypoglycaemic Agents (OHAs) or insulin preparations, in addition to diet and/or exercise, do not result in an adequate glycaemic control.Thus, Voglibose is used for:

  • In non-insulin-dependent diabetes mellitus (NIDDM) patients as immunotherapy
  • In combination with other OHAs
  • In addition to insulin in diabetes mellitus patients
  • In prevention of onset of type 2 diabetes mellitus in impaired glucose tolerance (only for Voglibose 0.2 mg Tablets) (However, Voglibose Tablets should be used only when impaired glucose tolerance has not been improved in patients already undergoing appropriate dietary treatment and/or exercise therapy.)
  • In elderly patients and in those with hepatic dysfunction or mild to moderate renal impairments in whom other OHAs are contraused or they need to be used with caution, Voglibose will be helpful.
  • In glycogen storage disease: Voglibose is helpful in prevention of hypoglycaemia in patients with type lb glycogen storage disease, it being an amylase (a glucosidase) inhibitor.
  • In non-diabetic Hyperinsulinemia, Voglibose is helpful in preventing hypoglycaemic attacks.
  • In steroid induced diabetes mellitus also, Voglibose is helpful. However, clinical data in this setting are limited.

Voligbose has general properties similar to acarbose and selectively inhibits α-glucosidase in the enteric canal, delaying the digestion and absorption of carbohydrate, thereby suppressing sharp increase in post-prandial plasma glucose.

Mage V is also used to associated treatment for these conditions: Type 2 Diabetes MellitusPost Prandial Hyperglycemia, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Glycemic Control

How Mage V works

Repaglinide activity is dependent on the presence functioning β cells and glucose. In contrast to sulfonylurea insulin secretatogogues, repaglinide has no effect on insulin release in the absence of glucose. Rather, it potentiates the effect of extracellular glucose on ATP-sensitive potassium channel and has little effect on insulin levels between meals and overnight. As such, repaglinide is more effective at reducing postprandial blood glucose levels than fasting blood glucose levels and requires a longer duration of therapy (approximately one month) before decreases in fasting blood glucose are observed. The insulinotropic effects of repaglinide are highest at intermediate glucose levels (3 to 10 mmol/L) and it does not increase insulin release already stimulated by high glucose concentrations (greater than 15 mmol/L). Repaglinide appears to be selective for pancreatic β cells and does not appear to affect skeletal or cardiac muscle or thyroid tissue.

Alpha-glucosidase inhibitors are saccharides that act as competitive inhibitors of enzymes needed to digest carbohydrates: specifically alpha-glucosidase enzymes in the brush border of the small intestines. The membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the small intestine. Acarbose also blocks pancreatic alpha-amylase in addition to inhibiting membrane-bound alpha-glucosidases. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine. Inhibition of these enzyme systems reduces the rate of digestion of complex carbohydrates. Less glucose is absorbed because the carbohydrates are not broken down into glucose molecules. In diabetic patients, the short-term effect of these drugs therapies is to decrease current blood glucose levels: the long term effect is a small reduction in hemoglobin-A1c level. (From Drug Therapy in Nursing, 2nd ed)

Dosage

Mage V dosage

Repaglinide has to be taken just before or up to 30 minutes before the meal. Repaglinide can be taken two, three or four times a day, depending on how many meals are taken. If a meal is missed, Repaglinide should also be avoided. If an extra meal is taken, an extra dose of Repaglinide should be taken with that meal. If a dose of Repaglinide is missed, it should not be taken between meals.

Rather the usual dose should be taken before the next meal. The dose ranges from 0.5 to 4 mg before each meal. The starting dose of Repaglinide in patients with HbA1c <8% is 0.5 mg before each meal. In patients with HbA1c >8% the starting dose is 1 or 2 mg before each meal. The dose may be increased gradually up to 4 mg before each meal.

Normal Adult Dose: Usually, Voglibose 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.

Pediatrics: The safety and effectiveness of Voglibose in children has not been established.

Geriatrics: Since elderly patients generally have a physiological hypofunction, it is desirable that such caution be taken as starting the administration at a lower dose (eg, 0.1 mg at a time). Furthermore, this drug 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.

Side Effects

Hypoglycaemia is possible with all blood glucose lowering drugs. If there are symptoms of low blood glucose (for example, headache, dizziness, tiredness, nervousness or shakiness, rapid heartbeat, or nausea), blood glucose should be tested right away. If it is low (less than 70 mg/dl on a home glucose meter), a simple carbohydrate food (for example, orange juice, quick dissolving sugar, candies, or glucose tablets) should be taken. If the symptoms do not go away, doctor should be informed. Some of the other common symptoms reported by patients taking Repaglinide include cold and flu-like symptoms, diarrhoea, joint ache, and back pain. There is some evidence that oral anti-diabetic drugs may increase the risk of heart problems. But experts are not sure what the real risk is, if any, from taking oral anti-diabetic drugs.

Diarrhoea, loose stools, abdominal pain, constipation, loss of appetite, urge to vomit (nausea), vomiting, heartburn, increased gas, and intestinal obstruction like symptoms due to increased intestinal gas. OHAs plus voglibose may cause hypoglycaemia (0.1% to <5%), delay in digestion and absorption of disaccharides, fulminant hepatitis, serious liver dysfunction with increased liver enzymes, jaundice, anaemia, numbness, edema, blurred vision, hot flushes, malaise, weakness, hyperkalemia, increased pancreatic enzyme (serum amylase).

Toxicity

LD50 >1 g/kg (rat) (W. Grell)

Precaution

Repaglinide should also be used with caution in renal and hepatic insufficiency.

Careful Administration (should be administered with care in following patients):

  • Patients who are receiving other antidiabetic drugs as hypoglycaemia may occur
  • Patients with a history of laparotomy or ileus (intestinal obstruction-like symptoms are liable to develop due to an increase in intestinal gas, etc.)
  • Patients with chronic intestinal disease accompanied by a disturbance in digestion and absorption (the action of this drug may aggravate the pathologic conditions)
  • Patients with Roemheld’s Syndrome, severe hernia, Stenosis or ulceration of the large intestine, etc. (Symptoms may worsen due to an increase in the intestinal gas, etc.)
  • Patients with serious hepatic dysfunction (Because of possible changes in metabolic condition, the status of plasma glucose control may greatly vary. In patients with severe liver cirrhosis, hyperammonemia may worsen, followed by disturbance of consciousness.)
  • Patients with serious renal dysfunction (Because of possible changes in metabolic conditions, the status of plasma glucose control may greatly vary.)
  • Elderly patients

Interaction

The dose of Repaglinide may need to be adjusted, if taken with other medications. The possible interactions of Repaglinide with other drugs are:

  • Inhibitors of the cytochrome P450 enzyme system (azole antifungals and macrolides) may lead to lower Repaglinide clearance and longer half life.
  • Inducers of the cytochrome P450 enzyme system (Rifampin, Phenobarbital, Carbamazepine, Troglitazone, etc.) may accelerate Repaglinide metabolism and shorten its effect.
  • Cimetidine has no significant effect on Repaglinide absorption or clearance.
  • Repaglinide has no significant effect on Digoxin, Theophyllin, or Warfarin.
  • Highly protein bound drugs (e.g., NSAIDs) may increase the plasma level of unbound Repaglinide and potentiate its glucose lowering effect. Thus, co-administration of these drugs with Repaglinide may increase the risk of hypoglycaemia.
  • The risk of hypoglycaemia may also be increased when hypoglycaemic agents are co-administered with certain drugs such as salicylates, sulphonamides, Chloramphenicol, coumarins, Probenecid, monoamine oxidase (MAO) inhibitors, and adrenergic blockers.

Voglibose should be administered with care when co-administered with the following drugs:

Antidiabetic drugs: Derivative(s) of sulfonylamide and sulfonylurea, biguanide derivatives, insulin preparations and improving agents for insulin resistance.

For the concomitant use of antldlabetlc drugs and the drugs which enhance or diminish the hypoglycaemic action of antldlabetlc drugs:

  • Drugs enhancing the hypoglycaemic action of antidiabetic drugs: β-blockers, salicylic acid preparations, monoamine oxidase inhibitors, fibrate derivatives for the treatment of hyperlipemia, warfarin, etc.
  • Drugs diminishing the hypoglycemic actton of antidiabetic drugs: Adrenaline, adrenocortical hormone, thyroid hormone, etc.

Volume of Distribution

31 L following IV administration in healthy individuals

Elimination Route

Rapidly and completely absorbed following oral administration. Peak plasma concentrations are observed within 1 hour (range 0.5-1.4 hours). The absolute bioavailability is approximately 56%. Maximal biological effect is observed within 3-3.5 hours and plasma insulin levels remain elevated for 4-6 hours. When a single 2 mg dose of repaglinide is given to healthy subjects, the area under the curve (AUC) is 18.0 - 18.7 (ng/mL/h)^3.

Slowly and poorly absorbed. The reported pharmacokinetic parameters of voglibose with metformin are Cmax corresponds to 1.38 mcg/ml while AUC is 8.17 mcg.h/ml and tmax is of 2.5 hours.

Half Life

1 hour

The half-life of voglibose is very similar to the one found for metformin and it is reported to be of 4.08 hours.

Clearance

33-38 L/hour following IV administration

Elimination Route

90% eliminated in feces (<2% as unchanged drug), 8% in urine (0.1% as unchanged drug)

Pregnancy & Breastfeeding use

In pregnancy, safety of Repaglinide has not been established. Hence, Repaglinide should be used during pregnancy only if it is clearly needed. It is not known whether Repaglinide is excreted in human milk. Because many drugs are excreted in human milk and because of potential for serious adverse reactions in nursing infants from Repaglinide, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.

Pregnancy: The safety of Voglibose in pregnancy has not been established. However, no adequate and well controlled studies have been done on pregnant women.

Lactation and Nursing Mothers: Although the levels of Voglibose reached in human milk are exceedingly low, it is recommended that Voglibose may not be administered to such women.

Contraindication

Repaglinide is contraindicated in patients with diabetic ketoacidosis, with or without coma, in patients with type I diabetes and in patients with known hypersensitivity to any of the components of the product.

Contraindicated in patients with Hypersensitivity to Voglibose or to any of the excipients; Diabetic ketoacidosis, diabetic pre-coma; Severe infection, before and after operation or with serious trauma; Gastrointestinal obstruction or predisposed to it.

Special Warning

Dosage in Renal Failure: Voglibose 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.

Acute Overdose

Patients receiving up to 80 mg of Repaglinide developed few adverse effects other than lowering of blood glucose. Hypoglycemia did not occur when meals were given with these high doses. Severe hypoglycemic reactions with coma, seizure or other neurological impairment occur infrequently.

Unlike sulfonylureas or insulin, an overdose of Voglibose tablets will not result in hypoglycaemia. An overdose may result is transient increase in flatulence, diarrhoea and abdominal discomfort. Because of lack of extra-intestinal effects soon with Voglibose, no serious systemic reactions are expected in the event of an overdose.

Storage Condition

Store below 25° C. Protect from moisture.

Keep in a cool and dry place. Keep out of the reach of children. Protect from light.

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