ROCKVILLE, Md., Jan. 15 /PRNewswire/ -- FDA has approved Pletal
(cilostazol) a new drug for treating stable intermittent claudication, a
severe pain, aching or cramping in the legs that occurs with walking.
Intermittent claudication results from "peripheral arteriosclerotic vascular
disease" -- a condition more commonly known as atherosclerosis or hardening of
the arteries. Atherosclerosis occurs when deposits of fatty substances build
up, in this case in the legs, leading to an inadequate blood supply to the leg
muscles.
This drug is the first to be approved for this indication in more than 15
years. Pletal has not been evaluated either for safety or effectiveness among
patients with more severe peripheral vascular disease who have claudication
pain at rest, leg ulcer or gangrene.
Intermittent claudication affects several million, predominantly elderly,
Americans. It can greatly impair their ability to walk without considerable
discomfort and can seriously affect their ability to exercise or even engage
in ordinary activities of daily life. Standard effective treatments have
included intensive exercise regimens, and drug treatments, i.e.,
pentoxifylline (Trental), and under certain circumstances, re-vascularization
procedures (operations to open the leg arteries or provide a replacement
artery).
Pletal was studied in eight clinical trials (most of three to six months
duration) that enrolled patients with intermittent claudication whose ability
to walk even short distances was severely compromised. In six of the eight
studies, patients treated with Pletal (at either 50 or 100 mg taken twice
daily) compared to those treated with a placebo, were able to walk further
before claudication began and also before the pain became intolerable and
forced them to stop walking.
Additionally, patients treated with Pletal reported a greater increase in
both walking distance and walking speed during daily routines.
Clinical studies in several thousand patients did not identify serious
toxicity, but there are two important concerns with the use of Pletal that are
identified in physician labeling for the drug and in a patient-directed
brochure.
The first concern is that Pletal is pharmacologically related to a group
of drugs studied for heart failure, the phosphodiestrase III inhibitors,
several which have shown increased deaths rates in patients with severe heart
failure. It is not known what effect these drugs have on people with less
severe heart failure or no heart failure.
Pletal was studied in about 2100 patients with claudication, many of whom
had other conditions such as a history of heart attacks or diabetes, but the
patients did not have severe heart failure. In the patients studied there was
a low mortality rate, 0.8% in patients treated with Pletal, 0.7% in placebo
patients. There was insufficient evidence to determine whether Pletal has an
adverse survival effect in patients without heart failure. The manufacturer
plans to further study the mortality effect in sicker patients with
claudication. Ordinarily Pletal would not be used by severe heart failure
patients because their ability to exercise is limited by heart failure, not
claudication. Labeling will remind both physicians and patients that Pletal
should never be used (is contraindicated) in patients with heart failure. The
labeling will also point out that there is insufficient information to
determine whether Pletal has an adverse survival effect in patients without
heart failure.
The second concern is that Pletal has not been studied in combination with
Clopidogril, a drug recently approved for use in patients with peripheral
vascular disease to reduce the rate of serious events (heart attacks, stroke,
and death). Clopidogril was not available while Pletal was being developed,
but is potentially important for patients with peripheral vascular disease.
Concern arises because both Pletal and clopidogril inhibit platelet function,
and it is possible that combined use could lead to excessive bleeding. Pletal
was, however, used with aspirin, which also inhibits platelet function,
without an apparent adverse interaction (increase in bleeding). Studies of
Pletal and clopidogril will be conducted after marketing of Pletal.
Meanwhile, labeling will remind physicians of the lack of information on this
concomitant use.
The drug will be marketed by Otsuka American Pharmaceutical, Inc. of
Rockville, Md.
SOURCE Food and Drug Administration
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Related links:
http://www.fda.gov
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FDA; Print Media, 301-827-6242, Broadcast
Media, 301-827-3434, or Consumer Inquiries, 888-INFO-FDA
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