EDITORIALS
TEMAFLOXACIN VOLUNTARY WITHDRAWAL: CONCERNS ABOUT MULTICENTER TESTING AND POSTMARKETING SURVEILLANCE Robert P. Rapp
OVER THE WEEKEND OF JUNE 6-7, 1992, many
newspapers in the US published stories about the Food and Drug Administration (FDA) asking Abbott Laboratories to voluntarily remove their recently marketed antibiotic temafloxacin (Omniflox) from the market. The FDA said that distribution of the drug had been halted due to severe adverse reactions including three deaths. As a result, several issues regarding drug trials, the marketing of drugs in the US, and the importance of so-called Phase IV, postmarketing surveillance studies, need to be addressed. Obviously, the importance of reporting adverse drug reactions to the FDA again comes into prominence. The US is one of the few countries where such reporting, although voluntary, is stressed by many pharmacists and physicians, and has even become an important feature of hospital accreditation by the Joint Commission on Accreditation of Healthcare Organizations. Temafloxacin has already been marketed in a number of western European and South American countries, and although there might have been some concern regarding adverse reactions in these countries, there is presently no public knowledge of this in the US. Again, the importance of adverse drug reaction reporting programs needs to be emphasized as a result of this additional unfortunate incident. Additionally, pharmaceutical manufacturers are under enormous pressure to obtain approval for new drugs in the fastest, most efficient, and most cost-effective way possible. This has resulted in a change in the way drug trials ROBERT P. RAPP, Pharm.D., is a Professor, and the Director, Division of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, KY 40536. Reprints: Robert P. Rapp, Pharm.D.
have been conducted in the US over the past five years or so. In order to accumulate a sufficient number of patients in clinical trials to satisfy FDA criteria, most trials are now conducted in a multicenter fashion. Many of these studies also use patients enrolled in trials outside the US. This means that individual investigators do not recruit enough patients from a single center to result in a meaningful article in a peer-reviewed journal and that such articles must await the compilation of data by the sponsors from the overall multicenter trial. Thus, in spite of the fact that temafloxacin had already been approved for marketing by the FDA, few publications of clinical trials have appeared in peer-reviewed journals to date. In addition, few principal investigators, both pharmacists and physicians, have gained experience with a drug such as temafloxacin that has been studied in this fashion. Even now, the primary reports of clinical trials with temafloxacin appear mainly in abstract form in the proceedings of national and international meetings some three or four months after the drug was marketed. Perhaps these experienced investigators, who are primarily at university centers, playa very important role in determining the clinical efficacy and safety of new antibiotics. Certainly we do not know if that is the case with temafloxacin, but the issue is worthy of further study. Finally, all pharmacists and physicians will be interested in knowing the details of the adverse reactions that have been reported and why a fluoroquinolone antibiotic would be associated with reactions including hypoglycemia, severe life-threatening breathing difficulties, hemolytic anemia, liver dysfunction, and kidney dysfunction severe enough to require hemodialysis.
The Annals ofPharmacotherapy •
1992 July/August, Volume 26 •
995
TEMAFLOXACIN VOLUNTARY WITHDRAWAL: CONCERNS ABOUT MULTICENTER TESTING AND POSTMARKETING SURVEILLANCE Robert P. Rapp
OVER THE WEEKEND OF JUNE 6-7, 1992, many
newspapers in the US published stories about the Food and Drug Administration (FDA) asking Abbott Laboratories to voluntarily remove their recently marketed antibiotic temafloxacin (Omniflox) from the market. The FDA said that distribution of the drug had been halted due to severe adverse reactions including three deaths. As a result, several issues regarding drug trials, the marketing of drugs in the US, and the importance of so-called Phase IV, postmarketing surveillance studies, need to be addressed. Obviously, the importance of reporting adverse drug reactions to the FDA again comes into prominence. The US is one of the few countries where such reporting, although voluntary, is stressed by many pharmacists and physicians, and has even become an important feature of hospital accreditation by the Joint Commission on Accreditation of Healthcare Organizations. Temafloxacin has already been marketed in a number of western European and South American countries, and although there might have been some concern regarding adverse reactions in these countries, there is presently no public knowledge of this in the US. Again, the importance of adverse drug reaction reporting programs needs to be emphasized as a result of this additional unfortunate incident. Additionally, pharmaceutical manufacturers are under enormous pressure to obtain approval for new drugs in the fastest, most efficient, and most cost-effective way possible. This has resulted in a change in the way drug trials ROBERT P. RAPP, Pharm.D., is a Professor, and the Director, Division of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, KY 40536. Reprints: Robert P. Rapp, Pharm.D.
have been conducted in the US over the past five years or so. In order to accumulate a sufficient number of patients in clinical trials to satisfy FDA criteria, most trials are now conducted in a multicenter fashion. Many of these studies also use patients enrolled in trials outside the US. This means that individual investigators do not recruit enough patients from a single center to result in a meaningful article in a peer-reviewed journal and that such articles must await the compilation of data by the sponsors from the overall multicenter trial. Thus, in spite of the fact that temafloxacin had already been approved for marketing by the FDA, few publications of clinical trials have appeared in peer-reviewed journals to date. In addition, few principal investigators, both pharmacists and physicians, have gained experience with a drug such as temafloxacin that has been studied in this fashion. Even now, the primary reports of clinical trials with temafloxacin appear mainly in abstract form in the proceedings of national and international meetings some three or four months after the drug was marketed. Perhaps these experienced investigators, who are primarily at university centers, playa very important role in determining the clinical efficacy and safety of new antibiotics. Certainly we do not know if that is the case with temafloxacin, but the issue is worthy of further study. Finally, all pharmacists and physicians will be interested in knowing the details of the adverse reactions that have been reported and why a fluoroquinolone antibiotic would be associated with reactions including hypoglycemia, severe life-threatening breathing difficulties, hemolytic anemia, liver dysfunction, and kidney dysfunction severe enough to require hemodialysis.
The Annals ofPharmacotherapy •
1992 July/August, Volume 26 •
995
