On August 9, 2001, the voluntary withdrawal of Baycol by Bayer
was announced, due to 31 deaths in the United States post-marketing. Of these
31 deaths, 12 occurred in patients also taking the cholesterol-lowering drug
gemfibrozil. The deaths were attributed to the condition rhabdomyolysis. Baycol
did account for 3.5% of the market share of anti-hypercholesterolemia drugs
in the U.S.
Baycol (cerivastatin) is one of the 'statin' class of drugs, which includes
Lipitor, Mevacor, Zocor, Pravachol, and Lescol. AstraZeneca has a statin,
Crestor, which was close to approval but now is likely to undergo more rigorous
evaluation by FDA, which may delay the approval of this 'super-statin'. Statins
work by limiting the liver's production of cholesterol, by inhibiting the
enzyme HMG-CoA reductase (full name: 3- hydroxy-3-methylglutaryl-coenzyme
A reductase). This enzyme catalyzes the conversion of HMG-CoA to mevalonate,
an early and rate-limiting step in cholesterol biosynthesis. Such cholesterol
limiting drugs are one of the fast-growing segments of the drug industry with
sales expected to hit $20-25 billion by 2005 from $14 billion in 2000. Non-statin,
second generation cholesterol lowering drugs, which decrease intestinal absorption
of cholesterol, are expected to be approved as soon as 2002.
Rhabdomyolysis is the breakdown of muscle cell membranes and release of the
contents of muscle cells into the bloodstream. Symptoms: Signs of rhabdomyolysis
include muscle pain, weakness, tenderness, malaise, fever, dark urine, nausea
and vomiting. In severe case, patients develop potentially fatal kidney failure.
Diagnosis: The definitive proof of rhabdomyolysis is myoglobinemia (presence
of myoglobin in blood) and myogloburinuria (presence of myoglobin in urine).
Myoglobin is the oxygen-carrying protein normally found only inside muscle
cells, so that its presence outside muscle cells indicates lysis or the rupture
of muscle cell membranes. Differential etiology: If a patient presents with
rhabdomyolysis, other common causes to be excluded are: Intrinsic muscle dysfunction
(caused by direct injury to muscles or excessive physical activity), metabolic
disorders (including diabetes, blood electrolyte imbalances, genetic disorders,
etc.), hypoxia (e.g., suffocation), other drug toxins (large amounts of alcohol,
heroin, cocaine, aspirin, etc.), major infections, hypo- or hyperthermia,
and unknown causes. Even if the other contributing causes listed above are
present, the use of Baycol in addition to these is likely to have a stronger
causal effect. Other than death, the long-term harm caused by Baycol-induced
rhabdomyolysis is likely to be similar to other forms of kidney damage.
There are reported to be 6 million users of Baycol worldwide,
and 700,000 inside the U.S. Outside the U.S., the trade name for the drug
is Lipobay. As many as 20 million patients in the U.S. use cholesterol-lowering
drugs of some kind in the U.S., but not all of these will necessarily are
statins.
Gemfibrozil is a non-statin anti-hypercholesterolinemic drug which has been
used together with statins. The use of gemfibrozil together with Mevacor is
noted in pharmacology texts to be associated with rhabdomyolysis. Itraconazole
inhibits the metabolism of Mevacor and this combination has also been associated
with rhabdomyolysis. The association of Mevacor with these dangers does not
imply that other statins are necessarily safe in this regard.
Conclusions: Patients may die from rhabdomyolysis as a result of rhabdomyolysis-induced
kidney failure after taking any statin. Since the withdrawal of Baycol physicians
have heightened expectations:
Vigilance for rhabdomyolysis in patients treated with any cholesterol-lowering
drug
Avoiding the combination of any cholesterol-reducing statins with
gemfibrozil
Caution concerning the combination with statins of any drugs that
might interfere with metabolism of the statin
Warning patients to report immediately any of the preliminary symptoms
of rhabdomyolysis: muscle pain, weakness, tenderness, malaise, fever, dark
urine, nausea and vomiting
Update 22 July 2002: Statins have become recognized as linked
and probably causal of peripheral neuropathies. "Neuropathy" means that nerves
degenerate, usually in a progressive and graded fashion. Sensory nerves (those
sensing heat or pain, for instance) are typically most sensitive, but motor
nerves (which control muscles) and nerves involved in coordination of movement
are also involved.
Update 14 Feb 2003: Death toll due to Baycol seems to have
stabilized somewhere above 100, but lawsuits continue to climb. See Bayer
Statin.
The excessively high doses and inadequate safety warnings about rhabdomyolysis
by Baycol resulted in 39 deaths that FDA could document via MedWatch reports
so that in August 2001 FDA asked Bayer to take the drug off the market. The
worldwide body count topped 100, according to Bayer, surprisingly low based
on the generally accepted view that 1% to 10% of Adverse Events are reported
via MedWatch. The number of complaints filed against Bayer has gone off the
charts by comparison - 7800 complaints, according to Annette Josten speaking
for Bayer in Leverkusen, Germany. Chicago class action attorney Ken Moll was
said to have pegged the total possible number of cases at 15,000, and the
Out-of-Court Settlement for individual Deaths as high as $1.5 million each.
There has been talk of recruiting cases from outside the United States to
increase the number of plaintiffs. So far Bayer has settled 420 cases.
See also Table of Statins:
Trade Name (Brand Name), Generic Name, and Manufacturer