tolazamide (Tolinase)

Introduction

Tradename: Tolinase. 1st generation sulfonylurea.

Indications

• treatment on non-insulin-dependent diabetes mellitus

Dosage

• start with 100-250 mg PO QD
• max: 1000 mg QD or divided BID
• best given QAM with morning meal
• conservative dosing in patients with hepatic failure

Tabs: 100, 250, 500 mg.

Pharmacokinetics

• onset of action is within 4-6 hours
• duration of action is 10-24 hours
• > 98% protein binding
• extensively metabolized by the liver
• excreted in the urine

elimination via liver

elimination via kidney

1/2life = 7 hours

protein binding = >98 %

Adverse effects

• common (> 10%)
  • headache, constipation, diarrhea, heartburn, anorexia, epigastric fullness, dizziness
• less common (1-10%)
  • rash, urticaria, photosensitivity
• uncommon (< 1%)
  • aplastic anemia, hemolytic anemia,
  • bone marrow suppression
  • cholestatic jaundice
  • thrombocytopenia, agranulocytosis
  • hypoglycemia
• other
  • nausea/vomiting

• drug adverse effects of sulfonylureas
• drug adverse effects of hypoglycemic agents

Drug interactions

• drugs that may enhance hypoglycemic effect of tolazamide:
  • anticoagulants, fluconazole, gemfibrozil
  • H2 receptor antagonists, MAO inhibitors
  • probenecid, salicylates, sulfonamides
  • tricyclic antidepressants (TCA)
  • alcohol (may cause disulfiram-type reaction when used in combination)
• drugs that may diminish hypoglycemic effect of tolazamide:
  • beta blockers, diazoxide, cholestyramine, hydantoins (phenytoin, dantrolene etc), rifampin, thiazide diuretics

• drug interaction(s) of sulfonylureas with warfarin
• drug interaction(s) of beta-adrenergic receptor antagonists with sulfonylureas
• drug interaction(s) of fluroquinolones with sulfonylureas
• drug interaction(s) of macrolides with sulfonylureas
• drug interaction(s) of salicylates with sulfonylureas
• drug interaction(s) of gliptins with sulfonylureas
• drug interaction(s) of fluoroquinolones with hypoglycemic agents

Laboratory

• tolazamide in specimen
  • tolazamide in serum/plasma
  • tolazamide in urine

Mechanism of action

stimulates insulin release from the pancreas

More general terms

• sulfonylurea

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5503