Mefoglip Tablet 2.5 mg+250 mg

Mefoglip Tablet 2.5 mg+250 mg Uses, Dosage, Side Effects, Food Interaction and all others data.

Glipizide lowers blood glucose by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells. The extrapancreatic effects of Glipizide are increase in insulin sensitivity and decrease in hepatic glucose production.

Glipizide is a blood glucose-lowering agent. The initial onset of blood glucose-lowering effect occurs around 30 minutes post-administration with the duration of action lasting for about 12 to 24 hours. While the chronic use of glipizide does not result in elevations in the fasting insulin levels over time, the postprandial insulin response, or insulin response to a meal, is observed to be enhanced, even after 6 months of treatment. The main therapeutic actions of glipizide primarily occur at the pancreas where the insulin release is stimulated, but glipizide also mediates some extrapancreatic effects, such as the promotion of insulin signaling effects on the muscles, fat, or liver cells. Due to its action on the endogenous cells, sulfonylureas including glipizide is associated with a risk for developing hypoglycemia and weight gain in patients receiving the drug. Chronic administration of glipizide may result in down-regulation of the sulfonylurea receptors on pancreatic beta cells, which are molecular targets of the drug, leading to a reduced effect on insulin secretion.

Like other sulfonylureas, glipizide may work on pancreatic delta (δ) cells and alpha (α) cells to stimulate the secretion of somatostatin and suppress the secretion of glucagon, which are peptide hormones that regulate neuroendocrine and metabolic pathways. Other than its primary action on the pancreas, glipizide also exerts other biological actions outside of the pancreas, or "extrapancreatic effects", which is similar to other members of the sulfonylurea drug class. Glipizide may enhance the glucose uptake into the skeletal muscles and potentiate the action of insulin in the liver. Other effects include inhibited lipolysis in the liver and adipose tissue, inhibited hepatic glucose output, and increased uptake and oxidation of glucose. It has also been demonstrated by several studies that the chronic therapeutic use of sulfonylureas may result in an increase in insulin receptors expressed on monocytes, adipocytes, and erythrocytes.

Mefoglip Tablet 2.5 mg+250 mg
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Mefoglip Tablet 2.5 mg+250 mg
Generic	Glipizide + Metformin Hydrochloride
Weight	2.5 mg+250 mg
Type	Tablet
Therapeutic Class
Manufacturer	Incepta Pharmaceuticals Ltd.
Available Country	Bangladesh
Last Updated:	October 19, 2023 at 6:27 am

Uses

Glipizide is used for an adjunct to diet for the control of hyperglycaemia and its associated symptomatology in the treatment of non-insulin-dependent diabetes mellitus (NIDDM type II) when diet modification has not been proved effective on its own. In certain patients who are receiving insulin, the concurrent use of Glipizide would allow a reduction in the daily dose of insulin.

Use of Glipizide must be viewed by both the physician and patient as a treatment in addition to diet and not as a substitute for diet or as a convenient mechanism for avoiding dietary restraint. Furthermore, short term administration may be required if diet control alone results in transient control of blood glucose level.

During maintenance, if satisfactory lowering of blood glucose is no longer achieved, use of Glipizide should be discontinued.

Mefoglip Tablet 2.5 mg+250 mg is also used to associated treatment for these conditions: Type 2 Diabetes Mellitus

How Mefoglip Tablet 2.5 mg+250 mg works

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder with increasing prevalence worldwide. Characterized by higher-than-normal levels of blood glucose, T2DM is a complex disorder that arises from the interaction between genetic, environmental and behavioral risk factors. Insulin is a peptide hormone that plays a critical role in regulating blood glucose levels. In response to high blood glucose levels, insulin promotes the uptake of glucose into the liver, muscle cells, and fat cells for storage. Although there are multiple events occurring that lead to the pathophysiology of T2DM, the disorder mainly involves insulin insensitivity as a result of insulin resistance, declining insulin production, and eventual failure of beta cells of pancreatic islets that normally produce insulin. Early management with lifestyle intervention, such as controlled diet and exercise, is critical in reducing the risk of long-term secondary complications, such as cardiovascular mortality.

Glipizide, like other sulfonylurea drugs, is an insulin secretagogue, which works by stimulating the insulin release from the pancreatic beta cells thereby increasing the plasma concentrations of insulin. Thus, the main therapeutic action of the drug depends on the functional beta cells in the pancreatic islets. Sulfonylureas bind to the sulfonylurea receptor expressed on the pancreatic beta-cell plasma membrane, leading to the closure of the ATP-sensitive potassium channel and reduced potassium conductance. This results in depolarization of the pancreatic beta cell and opening of the voltage-sensitive calcium channels, promoting calcium ion influx. Increased intracellular concentrations of calcium ions in beta cells stimulates the secretion, or exocytosis, of insulin granules from the cells. Apart from this main mechanism of action, the blood-glucose-lowering effect of glipizide involves increased peripheral glucose utilization via stimulating hepatic gluconeogenesis and by increasing the number and sensitivity of insulin receptors.

Dosage

Mefoglip Tablet 2.5 mg+250 mg dosage

Like any other oral hypoglycaemic agent, dosage of Glipizide is not fixed and may be adjusted through periodic monitoring of blood glucose level. Short term administration of Glipizide may be sufficient during periods of transient loss of control of blood glucose in patients, usually controlled well on diet.

In general, Glipizide should be given approximately 30 minutes before a meal to achieve the maximum reduction in postprandial hyperglycaemia.

Initial dose: The recommended starting dose is 5 mg, given before breakfast. Geriatric patients or those with liver disease may be started on 2.5 mg.
Dosage adjustments: Dosage adjustment may be done at intervals of several days by an increment of 2.5-5 mg, as determined by blood glucose response. If response to a single dose is not satisfactory, dividing that dose might prove effective. The maximum recommended once daily dose is 15 mg. Doses above 15 mg should ordinarily be divided and given before meals of adequate calorie content. The maximum recommended total daily dose is 40 mg.
Maintenance: Some patients may be effectively controlled on a once daily regimen, while others show better response with divided dosing. Total daily dose above 30 mg have been safely given on bid basis to long term patients. Patients can usually be stabilized on a dosage ranging from 2.5 to 30 mg daily.

In elderly, debilitated or malnourished patients, and patients with impaired renal or hepatic function:

The initial and maintenance dosing should be conservative to avoid hypoglycaemic reactions.

Patients receiving insulin: Many stable non-insulin-dependent diabetic patients receiving Insulin may be safely placed on Glipizide if the physician decides to do so.

Patients receiving other oral hypoglycaemic agents: As with other sulphonylurea, no transition period is necessary while transferring patients to Glipizide. Patients should be observed carefully for any possible hypoglycaemic effect due to overlapping of drug effects.

Side Effects

The most potential adverse reaction is hypoglycemia (1% to 3.4%). Other side effects reported were asthenia, headache, dizziness, nervousness, tremor, diarrhea, flatulence.

Toxicity

In rats, the oral LD₅₀ is reported to be greater than 4000 mg/kg and the intraperitoneal LD₅₀ is 1200 mg/kg. The lowest published toxic dose (TDLo) via oral route in child was 379 μg/kg.

Symptoms of overdose in sulfonylureas, including glipizide, may be related to severe hypoglycemia and may include coma, seizure, or other neurological impairment. These are symptoms of severe hypoglycemia and require immediate treatment with glucagon or intravenous glucose and close monitoring for a minimum of 24 to 48 hours since hypoglycemia may recur after apparent clinical recovery. Mild hypoglycemic symptoms without loss of consciousness or neurologic findings should be treated with oral glucose.

Precaution

Hypoglycaemia: All sulphonylurea drugs are capable of producing severe hypoglycaemia. Proper patient selection, dosage and instructions are important to avoid hypoglycaemic episodes. Renal or hepatic insufficiency may cause elevated blood levels of Glipizide and the latter may also diminis gluconeogenic capacity, both of which increase the risk of serious hypoglycaemic reactions. Elderly, debilitated or malnourished patients and those with adrenal or pituitary insufficiency are particularly susceptible to the hypoglycaemic actions of glucose lowering drugs. Patients should be instructed to take their meals regularly and not to exercise excessively without additional calorie intake.

Renal and hepatic disease: The metabolism and excretion of Glipizide may be slowed in patients with impaired renal and/or hepatic function. These patients may suffer from prolonged hypoglycaemia and appropriate measures should be instituted.

Loss of control on blood glucose: When a patient stabilized on any antidiabetic regimen is exposed to stress such as fever, trauma, infection or surgery, a loss of control on blood glucose may occur. At that time it may be necessary to discontinue Glipizide and administer Insulin.

The effectiveness of any oral hypoglycaemic drug including Glipizide, in lowering blood glucose to a desired level, decreases in many patients over a period of time, which may be due to secondary failure, i.e., progression of the severity of the diabetes or diminished responsiveness to the drug.

Interaction

The hypoglycaemic action of sulphonylurea may be potentiated by certain drugs including non-steroidal anti inflammatory agents and other drugs that are highly protein bound e.g., Salicylates, Sulphonamides, Chloramphenicol, Probenecid, Coumarins, Monoamine Oxidase Inhibitors, and β adrenergic blocking agents. When such drugs are administered to a patient receiving Glipizide, the patients should be observed closely for hypoglycaemia. When such drugs are withdrawn from a patient receiving Glipizide, the patient should be observed closely for loss of control on blood glucose.

Certain drugs tend to produce hyperglycaemia and may lead to loss of control on blood glucose. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, oestrogens, oral contraceptives, Phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs and Isoniazid. When such drugs are administered to or withdrawn from a patient receiving Glipizide, the patient should be closely observed for loss of control on blood glucose. Diabetic control may be altered also in patients treated with cyclophosphamide.

Volume of Distribution

The mean volume of distribution was approximately 10 L following administration of single intravenous doses in patients with type 2 diabetes mellitus. In mice and rat studies, the presence of the drug and its metabolites was none to minimal in the fetus of pregnant female animals. Other sulfonylurea drugs were shown to cross the placenta and enter breast milk thus the potential risk of glipizide in fetus or infants cannot be excluded.

Elimination Route

Gastrointestinal absorption of glipizide is uniform, rapid, and essentially complete. The absolute bioavailability of glipizide in patients with type 2 diabetes receiving a single oral dose was 100%. The maximum plasma concentrations are expected to be reached within 6 to 12 hours following initial dosing. The steady-state plasma concentrations of glipizide from extended-release oral formulations are maintained over the 24-hour dosing interval. In healthy volunteers, the absorption of glipizide was delayed by the presence of food but the total absorption was unaffected.

Half Life

The mean terminal elimination half-life of glipizide ranged from 2 to 5 hours after single or multiple doses in patients with type 2 diabetes mellitus.

Clearance

The mean total body clearance of glipizide was approximately 3 L/hr following administration of single intravenous doses in patients with type 2 diabetes mellitus.

Elimination Route

Glipizide is mainly eliminated by hepatic biotransformation, where less than 10% of the initial dose of the drug can be detected in the urine and feces as unchanged glipizide. About 80% of the metabolites of glipizide is excreted in the urine while 10% is excreted in the feces.

Pregnancy & Breastfeeding use

Pregnancy: Glipizide should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. Prolonged severe hypoglycaemia (4-10 days) has been reported in neonates born to mothers who were receiving sulphonylurea (e.g., Glipizide) at the time of delivery. So, if Glipizide is used during pregnancy, it should be discontinued at least one month before the expected delivery date.

Lactation: Although it is not known whether Glipizide is excreted in human milk, some sulphonylurea drugs are known to be so. Breast feeding is not therefore recommended while taking this medication.

Contraindication

Glipizide is contraindicated in the following conditions :

Patients who are hypersensitive to Glipizide or any component of the product
Juvenile onset diabetes
Severe or unstable ‘brittle’ diabetes
Diabetes complicated by ketosis and acidosis, major surgery, severe sepsis or severe trauma
Severe renal, hepatic or thyroid impairment, co-existent renal and hepatic disease