(GLYE byoor ide)
Type 2 diabetes mellitus: Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (noninsulin dependent, NIDDM)
Hypersensitivity to glyburide or any component of the formulation; type 1 diabetes mellitus or diabetic ketoacidosis, with or without coma; concomitant use with bosentan.
Canadian labeling: Additional contraindications (not in U.S. labeling): Diabetic precoma or coma, stress conditions (eg, severe infections, trauma, surgery); liver disease or frank jaundice; renal impairment; pregnancy; breast-feeding.
Documentation of allergenic cross-reactivity for sulfonylureas is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Micronized glyburide tablets are not bioequivalent to conventional glyburide tablets; retitration should occur if patients are being transferred to a different glyburide formulation (eg, micronized-to-conventional or vice versa) or from other hypoglycemic agents. When converting to glyburide from other oral hypoglycemic agents with a long half-life (eg, chlorpropamide), observe patient carefully for 2 weeks due to overlapping hypoglycemic effects.
Type 2 diabetes: Oral:
Conventional tablets (Dia ˇ ²eta):
Initial: 2.5-5 mg daily, administered with breakfast or the first main meal of the day. In patients who are more sensitive to hypoglycemic drugs, start at 1.25 mg daily.
Adjustment: Increase in increments of no more than 2.5 mg daily at weekly intervals based on the patients blood glucose response
Maintenance: 1.25-20 mg daily given as single or divided doses. Some patients (especially those receiving >10 mg daily) may have a more satisfactory response with twice-daily dosing. Maximum: 20 mg daily
Micronized tablets (Glynase PresTab):
Initial: 1.5-3 mg daily, administered with breakfast or the first main meal of the day. In patients who are more sensitive to hypoglycemic drugs, start at 0.75 mg daily. Increase in increments of no more than 1.5 mg daily in weekly intervals based on the patient's blood glucose response.
Maintenance: 0.75-12 mg daily given as a single dose or in divided doses. Some patients (especially those receiving >6 mg daily) may have a more satisfactory response with twice-daily dosing. Maximum: 12 mg daily
Management of noninsulin-dependent diabetes mellitus in patients previously maintained on insulin: Oral: Initial dosage dependent upon current insulin dosage, see table.
Dose Conversion: Insulin to GlyburideCurrent Daily Insulin Dosage
(units daily)
Initial Glyburide Dosage
Conventional Formulation
(mg daily)
Initial Glyburide Dosage
Micronized Formulation
(mg daily)
Insulin Dosage Change
(after glyburide started)
<20
2.5-5
1.5-3
Discontinue
20-40
5
3
Discontinue
>40
5
(increase in increments of 1.25-2.5 mg every 2-10 days)
3
(increase in increments of 0.75-1.5 mg every 2-10 days)
Reduce insulin dosage by 50% (gradually taper off insulin as glyburide dosage increased)
Table has been converted to the following text.
Dose Conversion: Insulin to Glyburide
Current insulin dose: <20 units daily
- Initial daily glyburide dose: 2.5-5 mg (conventional formulation) OR 1.5-3 mg (micronized formulation)
- Discontinue insulin after glyburide is started.
Current insulin dose: 20-40 units daily
- Initial daily glyburide dose: 5 mg (conventional formulation) OR 3 mg (micronized formulation).
- Discontinue insulin after glyburide is started.
Current insulin dose: >40 units daily
- Initial daily glyburide dose: 5 mg (conventional formulation) and increase in increments of 1.25-2.5 mg every 2-10 days OR 3 mg (micronized formulation) and increase in increments of 0.75-1.5 mg every 2-10 days.
- Reduce insulin dosage by 50%; gradually taper off insulin as glyburide dosage is increased.
Conventional tablets (Dia ˇ ²eta): Oral: Initial: 1.25 mg daily. Conservative initial and maintenance doses are recommended to avoid hypoglycemic reactions.
Micronized tablets (Glynase PresTab): Initial: 0.75 mg daily. Conservative initial and maintenance doses are recommended to avoid hypoglycemic reactions.
There are no specific dosage adjustments provided in the manufacturers labeling; however, use in patients with eGFR <60 mL/minute is not recommended (Alsahli 2015).
There are no dosage adjustments provided in the manufacturers labeling; however, use conservative initial and maintenance doses.
Administer with meals at the same time each day (twice-daily dosing may be beneficial if conventional glyburide doses are >10 mg or micronized glyburide doses are >6 mg). Patients that are NPO or require decreased caloric intake may need doses held to avoid hypoglycemia.
Should be taken with meals at the same time each day (twice-daily dosing may be beneficial if conventional glyburide doses are >10 mg or micronized glyburide doses are >6 mg). Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.
Conventional tablets (Dia ˇ ²eta): Store at 25 ‚ °C (77 ‚ °F); excursions are permitted between 15 ‚ °C and 30 ‚ °C (59 ‚ °F and 86 ‚ °F).
Micronized tablets (Glynase PresTab): Store at 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Diabeta: 1.25 mg [DSC], 2.5 mg [DSC], 5 mg [DSC] [scored]
Glynase: 1.5 mg, 3 mg, 6 mg [scored]
Generic: 1.25 mg, 1.5 mg, 2.5 mg, 3 mg, 5 mg, 6 mg
Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Monitor therapy
Alcohol (Ethyl): Sulfonylureas may enhance the adverse/toxic effect of Alcohol (Ethyl). A flushing reaction may occur. Monitor therapy
Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Aminolevulinic Acid: Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid. Monitor therapy
Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination
Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy
Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Antidiabetic Agents (Thiazolidinedione): May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose adjustments in patients taking thiazolidinediones and monitor for hypoglycemia. Consider therapy modification
Beta-Blockers: May enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Exceptions: Levobunolol; Metipranolol. Monitor therapy
Bosentan: GlyBURIDE may enhance the hepatotoxic effect of Bosentan. GlyBURIDE may increase the metabolism of Bosentan. Bosentan may increase the metabolism of GlyBURIDE. Avoid combination
Carbocisteine: Sulfonylureas may enhance the adverse/toxic effect of Carbocisteine. Specifically, sulfonylureas may enhance adverse effects of alcohol that is present in liquid formulations of carbocisteine-containing products. Monitor therapy
Ceritinib: May increase the serum concentration of CYP2C9 Substrates. Management: Concurrent use of ceritinib with a CYP2C9 substrate that has a narrow therapeutic index (e.g., warfarin, phenytoin) should be avoided when possible. Monitor therapy
Chloramphenicol: May decrease the metabolism of Sulfonylureas. Monitor therapy
Cimetidine: May increase the serum concentration of Sulfonylureas. Monitor therapy
Clarithromycin: May increase the serum concentration of GlyBURIDE. Monitor therapy
Colesevelam: May decrease the serum concentration of GlyBURIDE. Management: Administer glyburide at least 4 hours prior to colesevelam. Consider therapy modification
Cyclic Antidepressants: May enhance the hypoglycemic effect of Sulfonylureas. Monitor therapy
CycloSPORINE (Systemic): May diminish the therapeutic effect of GlyBURIDE. GlyBURIDE may increase the serum concentration of CycloSPORINE (Systemic). Monitor therapy
CYP2C9 Inducers (Strong): May increase the metabolism of CYP2C9 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates. Monitor therapy
CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP2C9 Substrates. Management: Seek alternatives to the CYP2C9 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dexketoprofen: May enhance the adverse/toxic effect of Sulfonamides. Monitor therapy
DPP-IV Inhibitors: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Enzalutamide: May decrease the serum concentration of CYP2C9 Substrates. Management: Concurrent use of enzalutamide with CYP2C9 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C9 substrate should be performed with caution and close monitoring. Consider therapy modification
Fibric Acid Derivatives: May enhance the hypoglycemic effect of Sulfonylureas. Monitor therapy
Fluconazole: May increase the serum concentration of Sulfonylureas. Management: Seek alternatives when possible. If used together, monitor closely for increased effects of sulfonylureas if fluconazole is initiated/dose increased, or decreased effects if fluconazole is discontinued/dose decreased. Consider therapy modification
GLP-1 Agonists: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Avoid the use of lixisenatide in patients receiving both basal insulin and a sulfonylurea. Consider therapy modification
Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy
Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Lumacaftor: May decrease the serum concentration of CYP2C9 Substrates. Lumacaftor may increase the serum concentration of CYP2C9 Substrates. Monitor therapy
MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Mecamylamine: Sulfonamides may enhance the adverse/toxic effect of Mecamylamine. Avoid combination
Metreleptin: May enhance the hypoglycemic effect of Sulfonylureas. Management: Sulfonylurea dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely. Consider therapy modification
Miconazole (Oral): May enhance the hypoglycemic effect of Sulfonylureas. Miconazole (Oral) may increase the serum concentration of Sulfonylureas. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP2C9 Substrates. Management: Use CYP2C9 substrates at the lowest recommended dose, and monitor closely for adverse effects, during and in the 2 weeks following mifepristone treatment. Consider therapy modification
Mitiglinide: May enhance the adverse/toxic effect of Sulfonylureas. Avoid combination
Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy
Probenecid: May decrease the protein binding of Sulfonylureas. Probenecid may increase the serum concentration of Sulfonylureas. Monitor therapy
Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy
RaNITIdine: May increase the serum concentration of Sulfonylureas. Monitor therapy
RifAMPin: May decrease the serum concentration of Sulfonylureas. Management: Seek alternatives to these combinations when possible. Monitor closely for diminished therapeutic effects of sulfonylureas if rifampin is initiated/dose increased, or enhanced effects if rifampin is discontinued/dose decreased. Consider therapy modification
Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
SGLT2 Inhibitors: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Sulfonamide Derivatives: May enhance the hypoglycemic effect of Sulfonylureas. Monitor therapy
Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy
Vitamin K Antagonists (eg, warfarin): Sulfonylureas may enhance the anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may enhance the hypoglycemic effect of Sulfonylureas. Monitor therapy
Voriconazole: May increase the serum concentration of Sulfonylureas. Monitor therapy
Signs and symptoms of hypoglycemia, urine glucose test, fasting blood glucose, hemoglobin A1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2016a])
Frequency not defined.
Cardiovascular: Vasculitis
Central nervous system: Disulfiram-like reaction, dizziness, headache, paresthesia
Dermatologic: Erythema, maculopapular rash, morbilliform rash, pruritus, skin photosensitivity, skin rash, urticaria
Endocrine & metabolic: Hypoglycemia, hyponatremia (SIADH reported with other sulfonylureas), porphyria cutanea tarda
Gastrointestinal: Anorexia, constipation, diarrhea, epigastric fullness, heartburn, nausea
Genitourinary: Diuresis (minor), nocturia
Hematologic & oncologic: Agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, pancytopenia, purpura, thrombocytopenia
Hepatic: Cholestatic jaundice, hepatic failure, hepatitis, increased serum transaminases
Hypersensitivity: Angioedema, hypersensitivity reaction
Neuromuscular & skeletal: Arthralgia, myalgia
Ophthalmic: Blurred vision
Concerns related to adverse reactions:
- Cardiovascular mortality: Product labeling states oral hypoglycemic drugs may be associated with an increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. Data to support this association are limited, and several studies, including a large prospective trial (UKPDS) have not supported an association.
- Hypoglycemia: All sulfonylurea drugs are capable of producing severe hypoglycemia. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when ethanol is ingested, or when more than one glucose-lowering drug is used. It is also more likely in elderly patients, malnourished or debilitated patients, and in patients with severe renal and hepatic impairment, adrenal and/or pituitary insufficiency; use with caution.
- Sulfonamide ( "sulfa " ¯) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.
Disease-related concerns:
- Glucose-6-phosphate dehydrogenase deficiency: Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency may be at an increased risk of sulfonylurea-induced hemolytic anemia; however, cases have also been described in patients without G6PD deficiency during postmarketing surveillance. Use with caution and consider a nonsulfonylurea alternative in patients with G6PD deficiency.
- Renal impairment: Use caution in advanced renal insufficiency due to accumulation of active metabolites (Snyder 2004).
- Stress-related states: It may be necessary to discontinue therapy and administer insulin if the patient is exposed to stress (fever, trauma, infection, surgery).
Special populations:
- Elderly: If therapy is initiated, dosing should be conservative; monitor closely for hypoglycemia.
Dosage form specific issues:
- Glyburide tablet formulations: Micronized glyburide tablets are not bioequivalent to conventional glyburide tablets; retitration should occur if patients are being transferred to a different glyburide formulation (eg, micronized-to-conventional or vice versa) or from other hypoglycemic agents.
Other warnings/precautions:
- Secondary failure: Loss of efficacy may be observed following prolonged use as a result of the progression of type 2 diabetes mellitus which results in continued beta cell destruction. In patients who were previously responding to sulfonylurea therapy, consider additional factors which may be contributing to decreased efficacy (eg, inappropriate dose, nonadherence to diet and exercise regimen). If no contributing factors can be identified, consider discontinuing use of the sulfonylurea due to secondary failure of treatment. Additional antidiabetic therapy (eg, insulin) will be required.
B/C (manufacturer dependent)
Outcomes of animal reproduction studies differ by manufacturer labeling. Glyburide crosses the placenta. Some pharmacokinetic properties of glyburide may change during pregnancy (Hebert 2009).
Severe hypoglycemia lasting 4 to 10 days has been noted in infants born to mothers taking a sulfonylurea at the time of delivery. Additional adverse maternal and fetal events have been noted in some studies and may be influenced by maternal glycemic control and/or differences in study design (Bertini 2005; Ekpebegh 2007; Joy 2012; Langer 2000; Langer 2005).
In women with diabetes, maternal hyperglycemia can be associated with congenital malformations as well as adverse effects in the fetus, neonate, and the mother (ACOG 2005; ADA 2015; Kitzmiller 2008; Metzger 2007). To prevent adverse outcomes, prior to conception and throughout pregnancy maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ACOG 2013; ADA 2015; Blumer 2013; Kitzmiller 2008). Prior to pregnancy, effective contraception should be used until glycemic control is achieved (Kitzmiller 2008).
Glyburide may be used to treat GDM when nonpharmacologic therapy is not effective in maintaining glucose control (ACOG 2013; ADA 2015; Blumer 2013). Women with type 2 diabetes are usually treated with insulin prior to and during pregnancy (Blumer 2013). According to the manufacturer, if glyburide is used during pregnancy, it should be discontinued at least 2 weeks before the expected delivery date.
Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites
Significant within 1 hour
Hepatic; forms metabolites (weakly active)
Feces (50%) and urine (50%) as metabolites
Serum insulin levels begin to increase 15-60 minutes after a single dose
Serum: Adults: 2-4 hours
≤24 hours
Dia ˇ ²eta: 10 hours; Glynase PresTab: ~4 hours; may be prolonged with renal or hepatic impairment
Plasma: Extensive, primarily to albumin
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience nausea, heartburn, or bloating. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), arrhythmia, severe dizziness, passing out, vision changes, bruising, or bleeding (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.