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U.S. Department of Health and Human Services
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T99-26                   Print Media:          301-827-6242
June 9, 1999         
                  Consumer Inquiries:          888-INFO-FDA

FDA ISSUES PUBLIC HEALTH ADVISORY ON LIVER TOXICITY
ASSOCIATED WITH THE ANTIBIOTIC TROVAN

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:

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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