FDA
TALK PAPER

T97-61                        Marian Segal:       301-827-6242
December 1, 1997              
                              Consumer Hotline:   800-532-4440

      PATIENT TESTING AND LABELING STRENGTHENED FOR REZULIN

     The U.S. Food and Drug Administration today announced that
patients taking the diabetes drug Rezulin (troglitazone) should
be monitored more frequently for signs of injury to the liver. 
In addition, warning information about potential liver toxicity
will be more prominently featured in the drug's labeling. 
     These actions, taken with the full cooperation of the drug's
manufacturer, re-emphasize for health care providers and patients
the importance of monitoring patients taking Rezulin to ensure
that it is used in the safest manner.   
     Rezulin is used in combination with insulin or sulfonylurea
in patients with type II diabetes (adult-onset diabetes mellitus)
whose blood glucose levels are not adequately controlled by these
other therapies alone.  
     On November 3, FDA and the drug's manufacturer announced
changes in the prescribing information for Rezulin, including a
new warning and recommendations for monitoring liver function. 
In making these changes, FDA was aware of approximately 35
post-marketing reports of liver injury among U.S. and Japanese
patients taking Rezulin, including liver failure leading to one
liver transplant and one death.  
     At that time, FDA asked for reports on additional adverse
events associated with the use of Rezulin, and the agency has now
received a total of approximately 150 adverse event reports,
including three deaths from liver failure linked to the use of
Rezulin in Japan.  Approximately 600,000 patients in the U.S. and
200,000 in Japan have been treated with this drug.  The deaths in
Japan occurred in patients treated before the stronger label
warning and recommendation for liver enzyme testing took effect
there.    
     FDA has concluded that liver enzyme levels should be
measured in patients taking Rezulin at the start of therapy,
every month for the first six months of treatment, every other
month for the next six months, and periodically thereafter.  In
addition, liver function tests should be performed on any patient
on Rezulin who develops symptoms of liver dysfunction, such as
nausea, vomiting, fatigue, loss of appetite, or dark urine and
jaundice.  The product's current labeling advises that 
patients with significant elevation of these liver enzymes stop
taking the drug.  Previously, liver enzyme testing was
recommended during the first two months of therapy and then every
three months. 
     The increased monitoring of patients taking Rezulin is
designed to detect those few patients in whom use of the drug can
lead to serious liver damage.  Warner-Lambert, the manufacturer
of the drug, will send a letter within the next week to U.S.  
health care professionals to inform them of these changes.  
     While Rezulin was being studied in patients before FDA
approval, approximately two percent of all patients were found to
develop elevation of liver enzymes in the blood.  These
elevations, which serve as markers of potential liver injury,
were mostly mild, unassociated with symptoms, and usually
resolved when the drug was discontinued.   
     Although FDA will carefully monitor and evaluate reports of
liver problems associated with Rezulin, at present the agency
continues to find the benefits outweigh the risks for treating
appropriately selected and monitored type-2 diabetes patients
with Rezulin.  
     Type 2 diabetes is a serious, life-threatening disease that
affects 18 million Americans.  It is a leading cause of coronary
heart disease, blindness, kidney failure, and limb amputation. 
Adequate control of blood sugar appears to be the most important
means of preventing these complications.  
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