Diabetes patients could be risking liver
failure because they are not getting the liver function tests
recommended with their medication.
UC College of Pharmacy researchers
attribute the lack of testing to a failure of some people in "the
system"--physicians, pharmacists and even the patients themselves--to
heed U.S. Food and Drug Administration (FDA) warnings.
The problem came to light when Pamela
Heaton, PhD, assistant professor of pharmacy practice, and Bob Cluxton,
PharmD, associate professor of pharmacy practice and family medicine,
studied 8,700 type 2 diabetes patients using the drug troglitazone
(Rezulin), one of a class of pharmaceuticals called thiazolidinediones.
Their findings are published in the journal Pharmacoepidemiology and Drug Safety.
Because of the risk of liver failure with
troglitazone, the FDA called for routine liver-function monitoring
during therapy. Eventually, following the death of 90 people from liver
failure, the FDA ordered troglitazone withdrawn.
Dr. Heaton and Dr. Cluxton's study showed
that despite repeated FDA warnings, just 26 percent of patients were
tested before they began taking the drug, and only 50 percent received
at least one test while using it.
"These results," says Dr. Heaton, "are
disconcerting in the face of such severe and repeated warnings for
liver failure, a life-threatening, adverse drug event."
Although Rezulin is no longer available,
the FDA has left in place the recommendation for liver enzyme testing
for the two other widely used thiazolidinedione drugs--rosiglitazone
(Avandia) and posiglitazone (Actos).
No deaths have been connected with either
of these Rezulin-type drugs, but FDA recommendations calling for
baseline liver testing, plus bimonthly testing while the drugs are
being taken, apply to them, too.
Both Avandia and Actos were among the top
100 drugs dispensed in the United States in 2003. According to the
Centers for Medicaid and Medicare Services, in 2004 Ohio Medicaid
recipients used 45,409 prescriptions for Avandia, 60,662 for Actos.
Unfortunately, say Drs. Heaton and
Cluxton, despite Rezulin's example of what could go wrong, in the case
of Avandia liver-function testing hasn't improved. Their study showed
that only 19.3 percent of Avandia patients received the baseline test.
Actos was not included in the study because it was not FDA approved
during the study period.
"Because there have been no reported
cases of death due to liver failure during the several years Avandia
has been on the market," says Dr. Heaton, "people are ignoring the FDA
"We don't know exactly why testing isn't
being done," says Dr. Cluxton, "we just know that it isn't, and that
reflects a problem with the system.
"It's probably a mixture of everything
... physicians not ordering the tests, patients not following up and
pharmacists not providing information about appropriate use," he says.
For example, Dr. Cluxton points out,
pharmacists should provide warnings about adverse effects of all drugs
they dispense. They are supposed to remind patients to follow
instructions to assure safe use of whatever drugs they are on--having
liver function monitored regularly while using thiazolidinediones being
one of them.
"We need changes in the system so the
people involved know what needs to be done to ensure safe use of all
drugs," says Dr. Cluxton.
"What is clear from our results is that
the FDA's policy of sending out warning letters to doctors is not an
effective method to improve monitoring for drug safety."
"We don't want to fix blame," says Dr. Cluxton, "we want to fix the problem.