Dosing and uses of Glucovance (glyburide-metformin)
Adult dosage forms and strengths
glyburide/metformin
tablet
- 1.25mg/250mg
- 2.5mg/500mg
- 5mg/500mg
Type 2 Diabetes Mellitus
1.25/250 mg glyburide/metformin PO qDay or q12hr
May titrate up at 2 week intervals; maximum 20/2000 mg/day
Dosage modifications
Hepatic impairment: Avoid use; cases of lactic acidosis reported
Renal impairment
- Obtain eGFR before starting metformin
- eGFR <30 mL/min/1.73 m²: Contraindicated
- eGFR 30-45 mL/min/1.73 m²: Not recommended to initiate treatment
- Monitor eGFR at least annually or more often for those at risk for renal impairment (eg, elderly)
- If eGFR falls below 45mL/min/1.73 m² while taking metformin, risks and benefits of continuing therapy should be evaluated
- If eGFR falls below 30 mL/min/1.73 m²: while taking metformin, discontinue the drug
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
1.25/250 mg glyburide/metformin PO qDay or q12hr
Adjust conservatively in patients with advanced age; do not use in patients >80 years unless renal function is assessed (do not titrate to maximum dose)
Glucovance (glyburide-metformin) adverse (side) effects
Frequency not defined
Dermatologic reactions
Heartburn
Hypoglycemia
Nausea/vomiting
Postmarketing Reports
Cholestatic jaundice and hepatitis may occur rarely which may progress to liver failure; discontinue drug
Warnings
Black box warnings
Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30-60 mL/minute/1.73 m²; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinate contrast
Lactic acidosis
- Characterized by elevated blood lactate levels (>5 mmol/L)
- Rare but serious complication that can occur because of metformin accumulation; increased risk with sepsis, dehydration, excess alcohol intake, hepatic insufficiency, renal impairment, and acute congestive heart failure
- Subtle onset with nonspecific symptoms (eg, malaise, myalgias, respiratory distress, somnolence, nonspecific abdominal distress)
- Monitor lab for decreased serum pH, increased anion gap, and elevated blood lactate If suspected, discontinue drug and hospitalize patient immediately
- Metformin is highly dialyzable (clearance up to 170 mL/min under good hemodynamic conditions); prompt hemodialysis is recommended to correct the acidosis and to remove accumulated metformin
Contraindications
Hypersensitivity to glyburide or metformin
Congestive heart failure, metabolic acidosis
Diabetic ketoacidosis, with or without coma (treat with insulin)
Coadministration with bosentan; increased risk of hepatotoxicity
Severe renal disease: eGFR <30 ml/min/1.73 m²
Cautions
Use with caution in patients with risk of severe hypoglycemia: elderly, debilitated, or malnourished, adrenal or pituitary insufficiency
Use with caution in patients with stress due to infection, fever, trauma, or surgery
Pregnancy/lactation
Use with caution in patients with dehydration, heavy use of alcohol, hypoxic states, impaired hepatic or renal function
Hemolytic anemia may occur with glucose 6-phosphate dehydrogenase (G6PD) deficiency when treated with sulfonylurea agents
Iodinated contrast imaging procedures
- Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30-60 mL/minute/1.73 m²; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinate contrast
- Reevaluate eGFR 48 hr after the imaging procedure; restart metformin if renal function is stable
Pregnancy and lactation
Pregnancy category: B
Lactation: Excretion in milk unknown; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Glucovance (glyburide-metformin)
Mechanism of action
Initial effect is to increase beta-cell insulin secretion
May also decrease rate of hepatic glucose production, increase insulin receptor sensitivity, and increase number of insulin receptors
Pharmacokinetics
Onset: 2-3 hr
Metabolites: 4-trans-hydroxyglyburide, 3-cis-hydroxyglyburide (active)
Half-Life
- Glyburide: Approx. 10 hr
- Metformin: Approx. 6 hr
Duration
- Glyburide: 24 hr
- Metformin: No data
Protein Bound
- Glyburide: 99%
- Metformin: Minimal
Vd
- Glyburide: No studies
- Metformin: 650 L
Metabolism
- Glyburide: Extensively, in liver to less active metabolites
- Metformin: Not metabolized
Excretion
- Glyburide: Urine 50%, bile 50%
- Metformin: Urine 90%
Dialyzable
- Glyburide: No data
- Metformin: Hemodialysis
