Glyburide (Glibenclamide) is a second-generation sulfonylurea that is indicated for the treatment of diabetes mellitus type 2 patients. Compared to other sulfonylureas, it may be preferred in pregnant female patients with gestational diabetes mellitus. Apart from metformin, it is the only oral medication that may be used to treat GDM (gestational diabetes mellitus).

Uses of Glyburide (Glibenclamide):

• Type 2 Diabetes mellitus:

  • It can be used in addition to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Glyburide (Glibenclamide) Dose in Adults

• Glyburide pills that have been micronized are not bioequivalent to regular glyburide tablets..
• If a patient is switching from another hypoglycemic medication to a different glyburide formulation (such as from micronized to conventional or vice versa), they should get the appropriate education.
• As the hypoglycemic effects of glyburide and other oral hypoglycemic medications with lengthy half lives (such chlorpropamide) can overlap for two weeks, the patient should be watched closely.

Glyburide (Glibenclamide) Dose in the treatment of type 2 Diabetes mellitus: Oral:

It is noteworthy that sulfonylureas may be used in conjunction with or as an alternative to metformin monotherapy for people whose responses are subpar.  However, due to their mode of action, sulfonylureas are known to have a considerably higher risk of resulting in hypoglycemia than other non-insulin antidiabetic drugs.  Glyburide is not suggested if a sulfonylurea is administered.

• (Diaβeta) Conventional tablets :

  • Initial dosage ranges from 2.5 to 5 mg per day, taken with breakfast or the first substantial meal of the day.
  • Start with 1.25 mg per day in people who are particularly sensitive to hypoglycemic medications.
  • Dosage adjustment:
    • Depending on the patient's response to their blood sugar level, doses may be increased at weekly intervals by no more than 2.5 mg/day.
  • Maintenance:
    • It can be administered as single or divided dosages of 25 to 20 mg/day.
    • Some individuals, particularly those receiving more than 10 mg per day, might respond better to twice-daily dosage.
    • The daily dose cap is set at 20 mg.

• Micronized tablets (Glynase PresTab):

  • At beginning, it can be provided as 1.5 to 3 mg/day with breakfast or the first substantial meal of the day.  Start at 0.75 mg per day in people who are more sensitive to hypoglycemic medications.

  • Adjustment of dose:
    • Depending on how the patient's blood sugar responds, the dose may be increased by no more than 1.5 mg/day every other week.
  • Maintenance:
    • Given as a single dose of 5 to 12 mg/day or in divided doses.
    • Some patients, particularly those receiving more than 6 mg/day, can respond better to a twice-daily dose.
    • The daily dose cap is set at 12 mg.

Treatment of previously insulin-dependent patients with non-insulin-dependent diabetic mellitus:

Dose Conversion: Insulin to Glyburide

Use in Children:

Not indicated.

Glyburide (Glibenclamide) Pregnancy Category: C

• Glyburide has been known to pass through the placenta.
• Pregnancy can alter the pharmacokinetic properties.
• Infants born to mothers who received a sulfonylurea during delivery can experience severe hypoglycemia lasting from 4 to 10 days.
• In some trials, additional adverse maternal or fetal events were also noted.
• This could be due to maternal glycemic control, as well as differences in study design.
• Congenital malformations and maternal hyperglycemia are associated with adverse pregnancy outcomes.
• By keeping maternal blood glucose levels and HbA1c close to their objective targets but without inducing severe hypoglycemia, it is feasible to prevent negative consequences from happening before conception and during pregnancy.
• Pregnant women with diabetes should not be treated with glyburide alone.
• According to the manufacturer, pregnant women should not use glyburide during pregnancy. Glyburide should be withheld for at least 14 days prior to the delivery date.

Use of glyburide during breastfeeding

• It can also be found in milk, according to studies.
• Based on the highest breastmilk concentration, the relative infant dose (RID), of glyburide was 0.08%.
• This is in comparison to a maternal weight-adjusted dose of 90 mg/day.
• When the RID of the medication is less that 10%, breastfeeding is generally acceptable.
• A daily baby dose via breastfeeding of 0.001 mg/kg/day was computed using the RID of glyburide and a milk content of 7.3ng/mL.
• This milk content was attained with the administration of very high doses of glyburide to the mother (up to 90 mg/day) to cure the KCNJ11-mutated persistent newborn diabetes mellitus (PNDM) (Kir6.2).
• The serum of babies whose mothers took glyburide while breastfeeding can also contain this drug, even if it has been stopped for 6 days.
• Short-term maternal treatment with standard doses of Glyburide did not result in the detection of Glyburide in breast milk. But, it was not possible to study the long-term effects of therapy.
• All women, even those with diabetes, are advised to breastfeed, according to current recommendations.
• Women with pre-gestational diabetics may find it helpful to eat a small snack before they breastfeed.
• The clinician must assess whether the benefits of the drug should be continued or if breastfeeding is possible.
• Other sources indicate that glyburide can be used by breastfeeding mothers.
• Glyburide is compatible with breastfeeding, if the infant's condition is controlled.

Dose in Kidney disease:

• Chronic renal disease should not be treated with glyburide.
• There are no dosage adjustments. If necessary, you can choose other drugs from the sulfonylurea category.

Dose in Liver disease:

Use of low dose regimes is recommended in liver disease however, no specific dose adjustments are indicated.

Side Effects of Glyburide (Glibenclamide):

• Gastrointestinal:

  • Heartburn
  • Nausea
  • Epigastric Fullness

• Hypersensitivity:

  • Hypersensitivity Reaction

• Central Nervous System:

  • Disulfiram-Like Reaction

• Endocrine & Metabolic:

  • Hypoglycemia
  • Weight Gain
  • Hyponatremia

• Genitourinary:

  • Diuresis (Minor)

• Hematologic & Oncologic:

  • Hemolytic Anemia

• Hepatic:

  • Cholestatic Jaundice
  • Hepatitis
  • Hepatic Failure

Contraindications to Glyburide (Glibenclamide):

• Contraindications include hypersensitivity to glyburide or any ingredient in the formulation.
• Diabetic ketoacidosis with or without coma and type 1 diabetes.
• Bosentan use concurrently

Canadian labeling: Additional contraindications not included in US labeling

• Intolerance to any sulfonylurea or sulfonamide.
• Diabetic coma or precoma.
• Severe infections, trauma, and surgery are examples of stress-related conditions.
• Jaundice that is overt or renal impairment.
• Breastfeeding and pregnancy.
• There is not much evidence of cross-reactivity between sulfonylureas and allergens. Cross-sensitivity is possible due to similarities in chemical structure or pharmacologic effects.

Warnings and precautions

• Cardiovascular mortality

  • These oral hypoglycemic drugs are associated with higher morbidity and deaths than insulin or insulin plus diet.
  • However, large trials were not conducted to support the hypothesis.
  • Patients suffering from advanced atherosclerotic diseases should be prescribed other agents.

• Hypoglycemia

  • All sulfonylurea medications can cause severe hypoglycemia.
  • Hypoglycemia can be exacerbated by inadequate caloric intake or concomitant use of oral hypoglycemic drugs. It can also be worsened by alcohol ingestion.
  • It is important to exercise caution when prescribing this drug for frail and elderly diabetics.

• Allergy to sulfonamide ("sulfa")

  • Wide-ranging contraindications for patients who have previously experienced an adverse reaction to sulfonamides are listed on FDA approved product labels for drugs that contain sulfonamide chemical groups.
  • Crossreactivity is possible. Crossreactivity concerns have been raised before for all compounds with the sulfonamide structural.
  • Recent investigations have demonstrated a decreased cross-reactivity between antibiotic and non-antibiotic sulfonamides.
  • Recent trials with non-antibiotic sulfonamide have shown that anaphylaxis is not uncommon.
  • Less research has been done on type IV reactions, which are T-cell-mediated and include skin rashes including maculopapular rash.  Based on the most recent results from several investigations, it is impossible to rule out this possibility.
  • Some clinicians will avoid treating patients with severe Stevens-Johnson syndrome (or TEN) if there are any prior cases.

• Glucose-6phosphate dehydrogenase deficiencies:

  • Patients with G6PD deficits may be more susceptible to hemolytic anaemia brought on by sulfonylureas. Patients without a G6PD deficiency have also had cases, according to post-marketing surveillance.

  • Patients who lack G6PD should take precautions

• Renal impairment

  • In renal impairment, glyburide metabolism and excretion may be sluggish. Active metabolites may build up as a result of advanced renal failure.
  • Hypoglycemia can last for a long time
  • Glyburide is not recommended for CKD.

• Stress-related disorders:

  • When under stress, in a coma, or with any other acute illness such as shock, fever, or sepsis, oral hypoglycemic must be switched to insulin.

Glyburide (glibenclamide): Drug Interaction

Monitoring parameters:

• You should be aware of symptoms like extreme appetite, perspiration, and exhaustion.
• Blood sugar and HbA1c should be measured at least twice a year in patients who have achieved glycemic control stability and treatment goals.
• Reporting blood glucose and HbA1c on a quarterly basis is advised for patients who are not achieving their treatment objectives or who have undergone therapeutic adjustments.
• Tests of renal function.

How to administer Glyburide (Glibenclamide)?

• Oral: Take the medication with meals.

• For patients who take conventional glyburide doses larger than 10 mg or micronized doses greater than 6 mg, dosing twice daily may be advantageous. Lower doses may be required for patients who are NPOs or who consume less calories in order to prevent hypoglycemia.

Mechanism of action of Glyburide (Glibenclamide):

• The pancreatic beta cells produce more insulin, and the liver produces less glucose. Additionally, it can improve the sensitivity of peripheral target areas to insulin.

The beginning of action:

• After a single dose, insulin levels start to rise within 15-60 minutes.

Duration:

• ≤24 hours

Absorption:

• Significant within 1 hour

Protein binding, plasma:

• Extensive, primarily to albumin

Metabolism:

• Hepatic; forms metabolites (weakly active)

Bioavailability:

• Variable among oral dosage forms

Half-life elimination:

• Diaβeta: 10 hours.
• Glynase PresTab: ~4 hours;
• may be prolonged with renal or hepatic impairment

Time to peak, serum:

• Adults: 2-4 hours

Excretion:

• Feces (50%) and urine (50%) as metabolites

International Brand Names of Glyburide (Glibenclamide):

• Diabeta
• Glynase
• APO-GlyBURIDE
• Diabeta
• DOM-GlyBURIDE
• Euglucon
• MYLAN-Glybe
• NTP-GlyBURIDE
• PMS-GlyBURIDE
• PRO-Glyburide
• RIVA-GlyBURIDE
• SANDOZ GlyBURIDE
• TEVA-GlyBURIDE
• TRIA-GlyBURIDE
• Allase
• Apo-Glibenclamide
• Benclamin
• Benil
• Betanase
• Betanese 5
• Bevoren
• Brucen
• Calabren
• Clamiben
• Clamide
• Daonil
• Daosin
• Diaben
• Diabenol
• Diabesulf
• Diabetin
• Dibelet
• Dynor
• Euclamin
• Euglucan
• Euglucon
• Gilemal
• Glamide
• Glarin
• Gliban
• Glibedal
• Gliben
• Gliben-CP
• Glibenclamid
• Glibenclamid Pharmavit
• Glibenclamid-ratiopharm
• Glibenhexal
• Glibesyn
• Glibet
• Glibetics
• Glibil
• Glibil-5
• Gliboral
• Glidiabet
• Glihexal
• Glimel
• Glipiz
• Glisulin
• Glitisol
• Gluben
• Glucobene
• Glucolon
• Glucomid
• Gluconic
• Gluconil
• Glucoven
• Gluzo
• Glycomin
• Glynase
• Hemi-Daonil
• Hipexal
• Lodulce
• Maninil
• Manoglucon
• Melix
• Miglucan
• Orabetic
• Padonil
• Pira
• Renabetic
• Semi-Daonil
• Semi-Euglucon
• Sentionyl
• Sugril
• Variglyben

Glyburide (Glibenclamide) Brand Names in Pakistan: