E-DRUG: U.S. FDA on Trovafloxacin
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[Editorial note: The U.S. FDA just released the following Talk Paper on
trovafloxacin. For additional info including questions and answers,
please visit the FDA website: www.fda.gov. Syed Rizwanuddin Ahmad]
FDA ISSUES PUBLIC HEALTH ADVISORY ON LIVER TOXICITY
ASSOCIATED WITH THE ANTIBIOTIC TROVAN
June 09, 1999
The Food and Drug Administration today issued a public health advisory
to physicians concerning the risks of liver toxicity associated with the
use of Trovan (trovafloxacin, an oral antibiotic) and Trovan-IV
(alatrofloxacin, the intravenous formulation of the drug). This action
follows postmarketing reports of rare but severe liver injuries leading
to transplants and deaths.
In issuing this advisory, FDA is informing physicians that Trovan should
be reserved for use only in patients who meet all of the following
criteria:
.Patients who have at least one of several specified infections such as
nosocomial (hospital-acquired) pneumonia or complicated intra-abdominal
infections that, in the judgment of the treating physician, is serious
and life- or limb-threatening; �Patients who begin their therapy in
in-patient health care facilities (hospitals or longterm nursing care
facilities); �And patients for whom the treating physician believes that
even given the new safety information, the benefit of the product
outweighs the potential risks.
FDA is further informing physicians that, in general, therapy with
Trovan should not continue for longer than 14 days. Therapy should be
discontinued sooner if the patient experiences any clinical signs of
liver dysfunction, including fatigue, loss of appetite, yellowing of the
skin and eyes, severe stomach pain with nausea and vomiting, or dark
urine.
FDA is also advising physicians that for most patients who meet the
treatment criteria, therapy would most likely begin with intravenous
Trovan. After clinical stabilization patients may be switched to the
oral dosage form. Although oral therapy might be appropriate in some
cases as an initial therapy, the agency emphasizes that the oral form of
Trovan is not warranted for infections other than those specified.
In addition, the manufacturer has agreed to limit distribution of the
product to hospitals and long-term nursing care facilities. The
manufacturer will be communicating in the near future with other
appropriate pharmacies to provide directions concerning possible return
of their present inventories of Trovan.
FDA is taking this action to reduce the potential risk from Trovan,
while at the same time preserving for physicians and patients alike the
clinical option of an effective broad-spectrum antibiotic for serious
and life- threatening infections. The agency considers this advisory an
interim measure until revised labeling for the product can be approved.
It is estimated that 2.5 million prescriptions have been written for
Trovan, a quinolone antibiotic, since its February 1998 market launch in
oral and intravenous formulations. Trovan was initially approved for
treating a broad range of infections, from minor skin infections to
severe infections in hospitalized patients.
No reports of liver failure, liver transplant, or death due to liver
problems were reported in the 7,000 patients studied in premarketing
clinical trials for Trovan. In July 1998, FDA worked with the
manufacturer to strengthen the product's labeling concerning liver
problems after receiving reports of elevated liver enzymes and
symptomatic hepatitis in patients after short- and long-term therapy.
Since then, FDA has continued to receive reports of liver toxicity,
including reports of a more serious nature.
FDA is now aware of 14 cases of acute liver failure that it has
concluded are strongly associated with the drug. Six of these patients
died: five due to liver failure and one of four additional patients who
received liver transplants. Three patients recovered without requiring
liver transplants, and for the remaining two patients the final outcome
is still pending.
More information about Trovan, including FDA's public health advisory,
is available on the World Wide Web at
www.fda.gov/cder/news/trovan/default.htm and from Pfizer, the
manufacturer of the drug, at 1-800-438-1985.
The FDA asks that any adverse events associated with Trovan be reported
to the agency through MedWatch, FDA's adverse event reporting system.
Reports may be submitted to FDA by telephone (800-332-1088), by fax
(800-332-0178) or by mail to MedWatch, HF-2, FDA, 5600 Fishers Lane,
Rockville, Md. 20857. Reports can also be filed via the internet at
www.fda.gov/medwatch. Reports may also be filed directly to the
manufacturer.
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