Glyburide

FDA label

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Titration Increase in increments of no more than 2.5 mg at weekly intervals based on blood glucose response.

Renal Conservative initial and maintenance dosing — renal insufficiency elevates glyburide levels and increases risk of serious hypoglycemia.

Hepatic Conservative initial and maintenance dosing — hepatic insufficiency elevates glyburide levels, may diminish gluconeogenic capacity, and increases risk of serious hypoglycemia.

Instructions

• Take with breakfast or the first main meal.
• Administer at least 4 hours before colesevelam (colesevelam reduces glyburide exposure).
• Transfer from other oral agents needs no transition period, EXCEPT chlorpropamide: exercise care for 2 weeks (prolonged retention, overlapping effect may provoke hypoglycemia).
• Insulin conversion: insulin <20 units/day → substitute 2.5–5 mg QD; 20–40 units/day → 5 mg QD directly; >40 units/day → cut insulin 50%, start 5 mg QD, then withdraw insulin progressively while raising glyburide 1.25–2.5 mg every 2–10 days.
• Not recommended in pregnancy or in pediatric patients; if used in pregnancy, discontinue at least 2 weeks before the expected delivery date.

Available strengths

• tab 1.25, 2.5, 5 mg
• tab 1.5, 3, 6 mg (micronized)

Contraindications

• Diabetic ketoacidosis, with or without coma (treat with insulin)
• Type 1 diabetes mellitus
• Concomitant administration of bosentan

Cautions

• Special warning: oral hypoglycemics associated with increased cardiovascular mortality vs diet alone or diet plus insulin (UGDP study).
• Hypoglycemia — all sulfonylureas can produce severe hypoglycemia; risk ↑ with renal or hepatic insufficiency, elderly/debilitated/malnourished patients, adrenal or pituitary insufficiency, deficient caloric intake, severe or prolonged exercise, alcohol, or >1 glucose-lowering drug; beta-blockers may mask symptoms.
• Loss of glycemic control under stress (fever, trauma, infection, surgery) — may need to stop glyburide and give insulin temporarily.
• Secondary failure (loss of response over time) may occur.
• Hemolytic anemia with sulfonylureas in G6PD deficiency — consider a non-sulfonylurea alternative; also reported without known G6PD deficiency.

Adverse reactions

• Hypoglycemia.
• GI disturbances — nausea, epigastric fullness, heartburn (1.8%; dose-related).
• Cholestatic jaundice and hepatitis (rare), may progress to liver failure — discontinue; liver function abnormalities incl. isolated transaminase elevations.
• Allergic skin reactions (1.5%): pruritus, erythema, urticaria, morbilliform/maculopapular eruptions; porphyria cutanea tarda and photosensitivity reported with sulfonylureas.
• Hematologic (sulfonylureas): leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia, pancytopenia.
• Hyponatremia and SIADH; disulfiram-like reactions (very rare).
• Changes in accommodation/blurred vision (glucose fluctuation); angioedema, arthralgia, myalgia, vasculitis.

Pregnancy Not recommended — many experts recommend insulin to keep glucose near normal in pregnancy. Animal studies (500× human dose) show no teratogenicity; no adequate human studies. Prolonged severe neonatal hypoglycemia reported with sulfonylureas at delivery — discontinue ≥2 weeks before expected delivery date.

Lactation Unknown if glyburide is excreted in human milk (some sulfonylureas are). Potential hypoglycemia in nursing infants — decide whether to discontinue nursing or the drug; if discontinued and diet alone is inadequate, consider insulin.