Contents

Search

troglitazone (Rezulin)

Tradename: Rezulin. FDA HAS WITHDRAWN TROGLITAZONE FROM THE US MARKET (3/2000). Indications: 1) treatment of diabetes mellitus type 2 with poor control despite 30 or more units of insulin/day 2) treatment of diabetes mellitus type 2 in conjunction with a sulfonylurea 3) initial monotherapy as an adjunct to diet & exercise to lower blood glucose in patients with type 2 diabetes The 1st of a new class of thiazolidinedione derivatives for treatment of non-insulin dependent diabetes & in patients taking more than 30 units of insulin/day with Hgb A1c > 8.5%. Contraindications: 1) class III or class IV heart failure 2) pregnancy 3) hepatic dysfunction Dosage: 1) start 200 mg PO QD 2) increase dose in 4 weeks if response is inadequate 3) usual dose is 400 mg QD 4) maximum: 600 mg PO QD 5) take with food Tabs: 200 & 400 mg. Pharmacokinetics: 1) extensively metabolized in the liver 2) inhibits cyt P450 1A1, 1A2, 2A6, 2B6, 2D6, 2E1 & 3A4 3) bioavailability: absolute 4) elimination 1/2life 16-34 hours 5) time to peak plasma levels is 2-3 hours 6) elimination: 85% in feces, 3% in urine 7) maximum effect is seen after 12 weeks of therapy 8) discontinue patients not responding on 600 mg/day after 12 weeks 9) 20-50% of patients will not respond to therapy with troglitazone Monitor: 1) liver function tests at start & monthly for 1st 6 months, every other month for the following 6 months & periodically thereafter 2) blood glucose daily during dose titration Adverse effects: 1) common (> 10%) - headache, apin, infection 2) less common (1-10%) - peripheral edema, dizziness, nausea, diarrhea, pharyngitis, urinary tract infection, neck pain, weakness, rhinitis, hepatoxicity* 3) other - mild reversible increases in serum aminotransferases *Note: approved on a fast track by the FDA. - In one year, 33 deaths occurred from hepatotoxixity of troglitazone - jaundice - 6-8% increase in plasma volume - cardiac hypertrophy in laboratory animals Drug interactions: 1) cholestyramine decreases absorbtion of troglitazone. They should be taken at different times of the day 2) Troglitazone lowers serum concentrations of oral contraceptives & Terfenadine (Seldane), which are also metabolized by CYP3A4 3) coadministration of troglitazone with glyburide may result in hypoglycemia Mechanism of action: 1) troglitazone decreases insulin resistance through binding to nuclear peroxisome proliferator receptors involved in transcription of insulin-responsive genes. 2) in the presence of insulin, troglitazone has the following properties: a) decreases gluconeogenesis & triglyceride synthesis in liver b) increases glucose uptake & utilization in skeletal muscle c) increases glucose uptake & decrease fatty output in adipose tissue 3) has no known effect on insulin secretion

Interactions

drug interactions drug adverse effects (more general classes) monitor with thiazolidinediones (glitazones)

Related

peroxisome proliferator-activated receptor gamma; PPAR-gamma; nuclear receptor subfamily 1 group C member 3 (PPARG, NR1C3)

General

peroxisome proliferator; PPAR agonist; PPAR gamma agonist thiazolidinedione; glitazone; TZD

Properties

MISC-INFO: elimination route LIVER 1/2life 16-34 HOURS pregnancy-category B safety in lactation -

Database Correlations

PUBCHEM cid=5591

References

  1. The Medical Letter vol. 39 (10001) May 23, 1997
  2. *The Fresno Bee, Dec 6, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998 (withdrawn 3/2000)