SULFONYLUREAS

































Kidney disease
Glimepiride (Amaryl®)
  • Clearance is decreased in kidney disease
  • Patients with kidney disease (CrCl ≤ 90ml/min) should be started at 1 mg once daily and titrated slowly to decrease the risk of hypoglycemia
Glipizide (Glucotrol®)
  • Clearance may be decreased in kidney disease
  • Manufacturer makes no specific dosage recommendation
Glyburide (DiaBeta®)
  • Clearance may be decreased in kidney disease
  • Manufacturer makes no specific dosage recommendation

Liver disease
Glimepiride (Amaryl®)
  • Has not been studied in patients with significant liver disease
  • Manufacturer makes no specific dosage recommendation
Glipizide (Glucotrol®)
  • Clearance may be decreased in liver disease
  • Manufacturer states that patients with liver disease may be started on 2.5 mg a day
Glyburide (DiaBeta®)
  • Clearance may be decreased in liver disease
  • Manufacturer makes no specific dosage recommendation

Sulfa allergy
Overview
  • Sulfonylureas contain a sulfonamide group in their structure
  • The sulfonamide group is different from the one that is found in sulfa-based antibiotics
  • Patients with a history of allergy to sulfa-based antibiotics may have a slight increase in risk of an allergic reaction to sulfonylureas
STUDY
Cross-reactivity between sulfa-based antibiotics and sulfonamide nonantibiotics, NEJM (2003) [PubMed abstract]
  • A cohort study in the NEJM looked at the risk of an allergic reaction to nonantibiotic sulfonamides in patients who had a previous reaction to a sulfa-based antibiotic
  • The study found the following:
    • Patients with a history of sulfa-based antibiotic allergy who subsequently took nonantibiotic sulfonamides (including sulfonylureas) had a 10% risk of having a reaction to the nonantibiotic sulfonamide
    • In patients without a history of allergic reaction to a sulfa-based antibiotic, 1.6% had a reaction to a nonantibiotic sulfonamide
    • In addition, patients with a history of sulfa-based antibiotic allergy had a 14% chance of having a reaction to a penicillin antibiotic. This finding led researchers to conclude that a history of allergic reactions in general may be more predictive of a reaction than reactions to any specific medication [15]
Summary
  • Sulfonylureas may be prescribed to patients with a history of sulfa-based antibiotic allergy
  • Patients should be aware that a cross-sensitivity reaction may occur with a risk of around 10%
  • Patients with a history of severe reactions to sulfa-based antibiotics should avoid nonantibiotic sulfonamides if they can. If not, then the initial dosing should be done under medical supervision.

G6PD deficiency



All sulfonylureas

  • Aspirin - Aspirin may potentiate the effects of sulfonylureas. The significance of this effect with low-dose aspirin is unclear.
  • Beta blockers (ex. propranolol, metoprolol, etc.) - Beta blockers may potentiate the effect of sulfonylureas. The significance of this effect is unclear.
  • Clarithromycin (Biaxin®) - Clarithromycin may potentiate the effect of sulfonylureas. The significance of this effect is unclear.
  • Colesevelam (Welchol™) - colesevelam decreases the absorption of sulfonylureas. Take sulfonylureas at least 4 hours prior to colesevelam.
  • CYP2C9 inhibitors and inducers - may affect blood levels of sulfonylureas
  • NSAIDs (ibuprofen, naprosyn, Motrin®, etc.) - NSAIDs may potentiate the effect of sulfonylureas. The significance of this effect is unclear.
  • Quinolone antibiotics (Levaquin®, Cipro®, gatifloxacin, etc.) - Quinolone antibiotics may potentiate the effects of glyburide and glipizide. Monitor for hypoglycemia.
  • Sulfamethoxazole (Bactrim®) - Sulfamethoxazole may potentiate the effect of sulfonylureas. The significance of this effect is unclear.
  • Topiramate (Topamax®) - Topiramate may decrease glyburide levels
  • Warfarin (Coumadin®) - In an observational study, the combined use of warfarin with glimepiride or glipizide was associated with a higher risk of hypoglycemia in patients ≥ 65 years old. The mechanism behind this possible interaction is unclear. [22]

Glyburide (Diabeta®)

  • Bosentan (Tracleer®) - glyburide should not be given with bosentan. Liver enzyme elevations have occurred.

Metabolism and clearance
Glimepiride (Amaryl®)
Glipizide (Glucotrol®)
Glyburide (DiaBeta®)