Questions and Answers on Trovafloxacin Public Health Advisory

1. What action is FDA announcing today?

FDA is issuing a Public Health Advisory to inform physicians and the public regarding new safety information about Trovan (trovafloxacin/alatrofloxacin), an antibiotic used to treat many different types of infections. Trovafloxacin was approved for marketing in December, 1997, and became available on the market in February, 1998. Its approved indications include many (14) types of infections that constitute a wide range of degrees of seriousness. Based on new safety data related to serious liver injury, FDA is advising physicians that trovafloxacin should be reserved for treatment ONLY in patients who meet ALL of the following criteria:

• Who have at least one of five types of serious and life or limb-threatening infections listed below that is judged by the treating physician to be serious and life or limb-threatening;

• Nosocomial pneumonia (pneumonia acquired in the hospital):
• Community acquired pneumonia
• Complicated intra-abdominal infections, including post-surgical infections
• Gynecololgical and pelvic infections
• Complicated skin and skin structure infections, including diabetic foot infections

• Who begin their therapy in inpatient health care facilities (i.e., hospitals and long term nursing care facilities).
• The treating physician believes that, given the new safety information, the benefit of the product for the patient still outweighs the potential risk.

2. What are the problems occurring with the use of Trovan?

Following the marketing of Trovan in the United States in February 1998, FDA began receiving reports of patients who experienced serious liver reactions in association with use of the product. In July of 1998, FDA worked with the manufacturer to add further information about this toxicity of the drug to Trovan’s label, or package insert, in order to inform practitioners . Since that time, FDA has received over 100 reports of cases of patients who were ill with symptoms of liver toxicity, in addition to others in which patients were without symptoms. Some of these patients developed serious liver injury leading to liver transplant and/or death. At present, FDA is aware of 14 cases in patients whose livers actually failed to function that are strongly associated with Trovan exposure.

• Four patients required liver transplantation (one of whom subsequently died).
• Five additional patients died of liver-related disease.
• Three patients recovered from their acute liver failure without requiring a liver transplant.
• The final outcome of two other patients is pending.

Trovan-associated liver failure appears to be unpredictable. It has been reported with treatment duration as short as two days and also in longer term exposure. It has been reported to occur in individuals over a wide range of ages, in men and in women, and in patients who were being treated for a wide variety of types of infection, many of which would not be considered serious or life-threatening. Also, when use exceeds two weeks there appears to be a substantial increase in risk of this toxicity. Liver failure has also been reported following Trovan re-exposure after some period of being off the drug.

These uncommon, but very serious adverse reactions, are typical of drug toxicities which, because of their rarity, may not be detected in clinical trials of drugs before marketing. However, they may become apparent after marketing when wider use of products occur among significantly more people. In the studies of Trovan approximately 7,000 patients were exposed to the drug. No cases of acute liver failure were reported in these pre-market clinical trials.

3. What does "limit distribution" mean?

In this case, the manufacturer of Trovan has agreed to direct distribution of the product only to pharmacies in inpatient health care facilities (i.e., hospitals and long-term nursing care facilities). This, in combination with labeling changes, educational programs and other risk communication strategies, will better ensure that Trovan is only used in clinical situations in which its demonstrated benefits can be expected to outweigh its presently known risks. In this manner, FDA believes that the product can continue to be made available to those patients who need it to treat serious life or limb-threatening infections, while minimizing other patients’ risk of exposure to the product.

 4. When will the labeling changes take effect?

FDA is working with the manufacturer of Trovan to make appropriate changes to the product’s label expeditiously. While the details of that change are being worked out, we are putting forward a Public Health Advisory to inform physicians and patients of this new information.

5. What should patients do if they are currently using Trovan?

Patients should contact their physician. Patients should NOT stop taking Trovan until their physician has recommended that they do so.

6. What are alternative therapies?

Alternative therapies are different depending on what infection the patient is currently being treated for. That is why it is extremely important that patients direct questions about alternative therapy to their physician, who can then make an appropriate recommendation tailored to their needs.

7. How many people are currently using Trovan?

It is estimated that approximately 300,000 prescriptions are written for Trovan per month in the United States.

FDA/Center for Drug Evaluation and Research
Last Updated: January 21, 200006 Jan 2006 15:40:46 -0500
Originator: CDER/OTCOM/DCM and CDER/ORM
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