E-DRUG: U.S. FDA issues warning for new heart drug
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T97-65 Susan M. Cruzan: 301-827-6242
Dec. 18, 1997 Broadcast Media: 301-827-3434
Consumer Inquiries: 800-532-4440
WARNING LABELING CHANGES FOR NEW HEART DRUG POSICOR
FDA is advising doctors about new warnings in the labeling of the
drug Posicor (mibefradil), a treatment for hypertension and chronic
angina. The new warnings provide additional information about two
risks associated with the drug: extremely low heart rates, and, when
Posicor is taken with certain cholesterol lowering drugs, a risk of
muscle injury that can be life-threatening. The following may be used
to respond to questions.
The new warning regarding low heart rates advises physicians against
prescribing Posicor to patients at high risk of developing dangerously
low heart rates. Such patients, especially older people, include those
whose heart rates are already relatively low and those taking another
drug that slows heart rate.
Posicor's risk of inducing excessively slow heart rates is similar to
that of several other commonly used drugs, and was described in the
labeling when the drug was first approved in June l997. The new,
strengthened warning was developed after FDA and the manufacturer,
Roche Laboratories, of Nutley, NJ, received reports of dangerously
lowered heart rates in about 20 patients who had taken Posicor. Many
of the patients described in the reports had relatively low heart
rates before starting Posicor, or had certain types of pre-existing
heart disease that put them at high risk of such low rates. More than
half of them were also taking another heart-rate-lowering drug,
usually a beta-blocker. No deaths have been reported, but many
patients became weak and lightheaded.
The second new warning states that Posicor should not be given to
patients who are also receiving lovastatin or simvastatin. These drugs
used to lower cholesterol are known as statins. In addition, pending
availability of further information, coadministration of Posicor with
atorvastin or cerivastatin is strongly discouraged.
The new label also warns against the simultaneous use of Posicor with
any statin or with the immunosuppressants tacrolimus or cyclosporine.
This new warning was added after the agency received 7 reports of
drug-associated muscle injury among patients who had taken Posicor
and simvastatin. Drug-induced muscle injury is a known rare side
effect of all of the statin cholesterol-lowering drugs including
atorvastatin, cervistatin, lovastatin, pravastatin, and simvastatin,
and it seems to increase in frequency with increasing dose. Patients
with drug-induced muscle injury usually experience nonspecific
muscular symptoms (weakness, tenderness, and pain), but the most
important consequence of injury are not muscular. The breakdown
products of muscle can cause temporary or permanent damage to kidneys;
and in severe cases, the heart can also be affected. Either of these
complications can lead to death.
Although Posicor does not itself cause muscle injury, administration
of Posicor interferes with the body's metabolism of lovastatin and
simvastatin and may interfere with the metabolism of atorvastatin and
cerivastatin. The observed incidence of muscle injury with
coadministration of Posicor and simvastatin appears to be much higher
than the incidence seen during treatment with simvastatin alone. The
immunosuppressants tacrolimus and cyclosporine interfere with the
elimination of all of the statins, and Posicor increases blood levels
of cyclosporine and tacrolimus, so the three-way combination of
Posicor, a "statin", tacrolimus, and cyclosporine should also be
avoided. Health care providers should report any adverse events
related to Posicor to Roche Laboratories (800-526-6367) or to FDA.
Reports may be submitted to FDA by telephone (800-332-1088), by fax
(800-332-0178), or by mail using a postage paid MedWatch form from
the back of the Physicians Desk Reference Medwatch report should be
mailed to:
MedWatch (HF-2)
Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857
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