Diabeta Information
Diabeta () Description
Diaβeta (glyburide) is an oral blood-glucose-lowering drug of the sulfonylurea class. It is a white, crystalline compound, formulated as tablets of 1.25 mg, 2.5 mg, and 5 mg strengths for oral administration. Diaβeta tablets USP contain the active ingredient glyburide and the following inactive ingredients: dibasic calcium phosphate USP, magnesium stearate NF, microcrystalline cellulose NF, sodium alginate NF, talc USP. Diaβeta 1.25 mg tablets USP also contain D&C Yellow #10 Aluminum Lake and FD&C Red #40 Aluminum Lake. Diaβeta 2.5 mg tablets USP also contain FD&C Red #40 Aluminum Lake. Diaβeta 5 mg tablets USP also contain D&C Yellow #10 Aluminum Lake, and FD&C Blue #1. Chemically, Diaβeta is identified as 1-[[p-[2-(5-Chloro-o-anisamido)ethyl]phenyl]sulfonyl]-3-cyclohexylurea.
The CAS Registry Number is 10238-21-8.
The structural formula is:
The molecular weight is 493.99. The aqueous solubility of Diaβeta increases with pH as a result of salt formation.
Diabeta () Clinical Pharmacology
Diaβeta appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which Diaβeta lowers blood glucose during long-term administration has not been clearly established.
With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may play a part in the mechanism of action of oral sulfonylurea hypoglycemic drugs.
In addition to its blood glucose lowering actions, Diaβeta produces a mild diuresis by enhancement of renal free water clearance. Clinical experience to date indicates an extremely low incidence of disulfiram-like reactions in patients while taking Diaβeta.
Diabeta () Indications And Usage
Diaβeta is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Diabeta () Contraindications
Diaβeta is contraindicated in patients:
Diabeta () Precautions
Patients should be informed of the potential risks and advantages of Diaβeta and of alternative modes of therapy. They should also be informed about the importance of adherence to dietary instructions, of a regular exercise program, and of regular testing of blood glucose.
The risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and responsible family members. Primary and secondary failure should also be explained.
Periodic fasting blood glucose measurements should be performed to monitor therapeutic response. A glycosylated hemoglobin determination should also be performed periodically.
The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents, ACE inhibitors, disopyramide, fluoxetine, clarithromycin, and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, monoamine oxidase inhibitors, and beta adrenergic blocking agents. When such drugs are administered to a patient receiving Diaβeta, the patient should be observed closely for hypoglycemia. When such drugs are withdrawn from a patient receiving Diaβeta, the patient should be observed closely for loss of control.
A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the intravenous, topical or vaginal preparations of miconazole is not known.
A possible interaction between glyburide and fluoroquinolone antibiotics has been reported resulting in a potentiation of the hypoglycemic action of glyburide. The mechanism for this interaction is not known.
Possible interactions between glyburide and coumarin derivatives have been reported that may either potentiate or weaken the effects of coumarin derivatives. The mechanism of these interactions is not known.
Rifampin may worsen glucose control of glyburide because rifampin can significantly induce metabolic isozymes of glyburide such as CYP2C9 and 3A4.
Certain drugs tend to produce hyperglycemia and may lead to loss of 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 Diaβeta, the patient should be closely observed for loss of control. When such drugs are withdrawn from a patient receiving Diaβeta, the patient should be observed closely for hypoglycemia.
An increased incidence of elevated liver enzymes was observed in patients receiving glyburide concomitantly with bosentan. Therefore this combination should not be used. (See .)
Diaβeta may increase cyclosporine plasma concentration and potentially lead to its increased toxicity. Monitoring and dosage adjustment of cyclosporine are therefore recommended when both drugs are coadministered.
Diaβeta is non-mutagenic when studied in the Salmonella microsome test (Ames test) and in the DNA damage/alkaline elution assay. Studies in rats at doses up to 300 mg/kg/day for 18 months showed no carcinogenic effects.
No drug related effects were noted in any of the criteria evaluated in the two year oncogenicity study of glyburide in mice.
In US clinical studies of glyburide, 1406 of 2897 patients were ≥60 years and 515 patients were ≥70 years. Differences in safety and efficacy were not determined between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Elderly patients are particularly susceptible to hypoglycemic action of glucose-lowering drugs. Hypoglycemia may be difficult to recognize in the elderly (see ). The initial and maintenance dosing should be conservative to avoid hypoglycemic reactions.
In three published studies of 20 to 51 subjects each, mixed results were seen in comparing the pharmacokinetics of glyburide in elderly versus younger subjects. However, observed pharmacodynamic differences indicate the necessity for dosage titration to a specified therapeutic response.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
In elderly, debilitated, or malnourished patients, or in patients with renal or hepatic insufficiency, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions. Hypoglycemia may be difficult to recognize in the elderly and in people who are taking beta-adrenergic blocking drugs or other sympatholytic agents. (See ; and .)
Diabeta () Adverse Reactions
Porphyria cutanea tarda and photosensitivity reactions have been reported with sulfonylureas.
In addition to dermatologic reactions, allergic reactions such as angioedema, arthralgia, myalgia and vasculitis have been reported.
Diabeta () Overdosage
Overdosage of sulfonylureas, including Diaβeta, can produce hypoglycemia. Mild hypoglycemic symptoms without loss of consciousness or neurologic findings should be treated aggressively with oral glucose and adjustments in drug dosage and/or meal patterns. Close monitoring should continue until the physician is assured that the patient is out of danger. Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalization. If hypoglycemic coma is diagnosed or suspected, the patient should be given a rapid intravenous injection of concentrated (50%) glucose solution. This should be followed by a continuous infusion of a more dilute (10%) glucose solution at a rate that will maintain the blood glucose at a level above 100 mg/dL. Patients should be closely monitored for a minimum of 24 to 48 hours, since hypoglycemia may recur after apparent clinical recovery.
Diabeta () Dosage And Administration
There is no fixed dosage regimen for the management of diabetes mellitus with Diaβeta or any other hypoglycemic agent. The patient's fasting blood glucose must be measured periodically to determine the minimum effective dose for the patient; to detect primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication; and to detect secondary failure, i.e., loss of adequate blood glucose lowering response after an initial period of effectiveness. Periodic glycosylated hemoglobin determinations should be performed.
Short-term administration of Diaβeta may be sufficient during periods of transient loss of control in patients usually controlled well on diet.
In elderly patients, debilitated or malnourished patients, and patients with impaired renal or hepatic function, the initial and maintenance dosing should be conservative to avoid hypoglycemic reactions. (See Section.)
Diabeta () How Supplied
Diaβeta (glyburide) tablets USP are available in the following strengths and package sizes:
1.25 mg (peach, capsule-shaped, flat faced, beveled edge tablet debossed "Dia β" with a score line between the "Dia" and the "β" on one side and plain on the other side).
Bottles of 50 (NDC 0039-0053-05)
2.5 mg (pink, capsule-shaped, flat faced, beveled edge tablet debossed "Dia β" with a score line between the "Dia" and "β" on one side and plain on the other side).
Bottles of 100 (NDC 0039-0051-10)
Bottles of 500 (NDC 0039-0051-50)
5 mg (green, capsule-shaped, flat faced, beveled edge tablet debossed "Dia β" with a score line between the "Dia" and "β" on one side and plain on the other side).
Bottles of 100 (NDC 0039-0052-10)
Bottles of 500 (NDC 0039-0052-50)
Bottles of 1000 (NDC 0039-0052-70)
Diabeta ()
Diabeta () Principal Display Panel - . Mg Tablets Label
Diabeta () Principal Display Panel - . Mg Tablets Label
Diabeta () Principal Display Panel - Mg Tablets Label
