Glibesifar

Uses

Glibenclamide is used in the treatment of non insulin dependent diabetes melitus (NIDDM). It is ineffective in completely pancreatectomized patients and in juvenile-onset type of diabetes, in which the pancreas has lost all or nearly all of its capacity to secrete insulin. Such patients require insulin and attempts to control them with oral therapy are dangerous and doomed to failure.

Glibesifar is also used to associated treatment for these conditions: Gestational Diabetes Mellitus (GDM), Glycemic Control, Type 2 Diabetes Mellitus

How Glibesifar works

Glibesifar belongs to a class of drugs known as sulfonylureas. These drugs act by closing ATP-sensitive potassium channels on pancreatic beta cells. The ATP-sensitive potassium channels on beta cells are known as sulfonylurea receptor 1 (SUR1).

Under low glucose concentrations, SUR1 remains open, allowing for potassium ion efflux to create a -70mV membrane potential.

Normally SUR1 closes in response to high glucose concentrations, the membrane potential of the cells becomes less negative, the cell depolarizes, voltage gated calcium channels open, calcium ions enter the cell, and the increased intracellular calcium concentration stimulates the release of insulin containing granules.

Glibesifar bypasses this process by forcing SUR1 closed and stimulating increased insulin secretion.

Dosage

Glibesifar dosage

Initially stabilization dosage: Glibenclamide half tablet (2.5 mg) should be taken initially during or immediately after breakfast. 3-5 days after initiation of the drug, the blood sugar level and urine sugar level should be checked. Daily dose of ½ tablet (2.5 mg) may be continued as maintenance therapy if good control has been achieved. If the result is not good, increment of daily dose in steps of ½ tablet (2.5 mg) is necessary at intervals of 3-5 days up to a maximum of 3 tablets. Daily doses in excess of 10 mg may be taken in 2 divided doses. Patients should be given ½ to 1 tablet of Glibenclamide in changing over from other oral anti-diabetics with a similar action.

Change over from insulin to Glibenclamide:The mildly diabetic patient whose insulin requirement is fewer than 20 units daily, can be started on the initial dosage of Glibenclamide with immediate discontinuation of insulin. If the insulin requirement is moderate or high, the changeover should be made gradually by giving insulin and Glibenclamide simultaneously and slowly cutting down the dose of insulin.

When insulin requirements are increased as in fever, surgical interventions or trauma, the Glibenclamide alone is inadequate and the patient must be given insulin to carry him or her through such critical situation.

This changeover from insulin to Glibenclamide is strictly for NIDDM of fairly recent onset which is being controlled on small doses of insulin. This should preferably be done in hospital or with daily medical supervision.

Side Effects

Glibenclamide is well tolerated. Few side effects that may arise include nausea, vomiting, epigastric pain, dizziness, weakness, paraesthesia and headache. Allergic skin reactions and haemopoietic reactions (leukopenia, thrombocytopenia, etc.) are occasionally observed.

Toxicity

The oral LD₅₀ in rats is >3200mg/kg, in mice is >1500mg/kg, in rabbits is >10,000mg/kg, and in guinea pigs is >1500mg/kg.

Patients experiencing an overdose may present with hypoglycemia. Mild hypoglycemia should be treated with oral glucose and adjustments to drug doses or meal schedules. Severe hypoglycemia may present with coma, seizure, and neurological impairment. This should be treated immediately in hospital with intravenous glucose and monitoring for 24-48 hours.

Precaution

Weight reduction is of the greatest importance in the treatment of diabetes. A vigorous effort must be made by the patient and the physician to reduce the patient's weight as an integral part of diabetic treatment, irrespective of the drug chosen.

Interaction

Alcohol, cyclophosphamide, dicoumarol, monoamino oxidase inhibitors, phenylbutazone, propranolol and other beta-adrenergic blocking agents and certain long-acting sulphonamides may enhance the hypoglycemic effect of Glibenclamide

Food Interaction

• Avoid alcohol. Alcohol increases the risk of hypoglycemia.
• Take before a meal. Take 30-60 minutes before breakfast.

[Moderate] GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes.

Hypoglycemia most frequently occurs during acute consumption of alcohol.

Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise.

The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia.

Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion.

By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia.

Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes.

A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis.

Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan.

Alcohol should not be consumed on an empty stomach or following exercise.

Glibesifar Drug Interaction

Moderate: aspirin, aspirin, sitagliptin, sitagliptin, insulin glargine, insulin glargine, furosemide, furosemideUnknown: rosuvastatin, rosuvastatin, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, atorvastatin, atorvastatin, clopidogrel, clopidogrel, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol

Glibesifar Disease Interaction

Major: cardiovascular risk, DKA, renal/liver diseaseModerate: hypoglycemia, G6PD deficiency, hyponatremia

Volume of Distribution

Elderly patients have a volume of distribution of 19.3-52.6L, while younger patients have a volume of distribution of 21.5-49.3L.

Elimination Route

Elderly patients taking glyburide reached a C_max of 211-315ng/mL with a T_max of 0.9-1.0h, while younger patients reached a C_max of 144-302ng/mL with a T_max of 1.3-3.0h. Patients taking glyburide have and AUC of 348ng*h/mL.

Half Life

Elderly patients have a terminal elimination half life of 4.0-13.4h, while younger patients have a terminal elimination half life of 4.0-13.9h.

Clearance

Elderly patients have a clearance of 2.70-3.55L/h, while younger patients have a clearance of 2.47-4.11L/h.

Elimination Route

Unlike other sulfonylureas, glyburide is 50% excreted in the urine and 50% in the feces. Glibesifar is mainly excreted as the metabolite 4-trans-hydroxyglyburide.

Pregnancy & Breastfeeding use

There is no information on the use of Glibenclamide in human pregnancy but it has been in wide, general use for many years without apparent ill consequence. Animal studies have shown no hazard. It has not yet been established whether Glibenclamide is transferred to human milk. However, other sulphonylureas have been found in milk and there is no evidence to suggest that Glibenclamide differs from the group in this respect.

Contraindication

Severe metabolic de-compensation with acidosis, pre-comatose states and diabetic coma, severe renal or hepatic dysfunction or serious impairment of typhoid or adrenal function; pregnancy, diabetes mellitus complicated by fever, trauma or gangrene.

Acute Overdose

Symptoms: Hypoglycaemia.

Management: Mild hypoglycaemic symptoms without loss of consciousness or neurologic findings may be treated with oral glucose and adjust drug dosage and/or meal patterns.

Storage Condition

Should be stored in a dry place below 30˚ C.

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