toxicologist did note in internal discussions that .4mg was the highest daily dose that should be developed for clinical use because the dose
response curve of cerivastatin was steeper than that of other statins. Nonetheless, the risk of rhabdomyolysis was one of many listed in the warnings section in the insert that accompanied the U.S. prescribing information for all statins.
Clinical trials, however, are poor instruments for detecting rare adverse effects because the relatively small numbers involved make it
difficult to observe rare events rhabdomyolysis was detected more
(Farmer, 2001). frequently after 8
As a result, the statins had
approved and used more widely from doctors and hospitals submitting reports of adverse events to the FDA (“spontaneous reports”).
The situation was complicated by the common co-prescription and
concurrent use of fibrates and statins. drugs used to control high cholesterol.
Fibrates are another class of But prescribing statins at the
same time as fibrates substantially increases the risk of
the risk of rhabdomyolysis was thought control by monitoring of CK levels and
to be rare and suitable for muscle pain (Lau, 2001).
the .2 and .3
the trade name
over the next
Cerivastatin was released in the United States in February 1998 at
occurred, usually when the patient was also taking the fibrate
7 Letter by Professor Dr. Schuluter, Professor Kühlmann and Dr. Ziegler, Bayer AG Geschhäftsbereich Pharma, Forschung und Entwicklung Medizin und Entwicklung, Wuppertal, Germany to Dr. MacCarthy MILES INC, Pharmaceutical Division, West Haven, Conn. 2/8/91. Halton v. Bayer Corp. 699 L Plaintiffs’ Exhibits.
8 Some have concluded that the post-release monitoring of adverse events and spontaneous reports by federal regulatory agencies needs to be increased (Farmer, 2001).