HEART DRUG PULLED FROM WORLD MARKET

WASHINGTON (AP) -- Roche Laboratories pulled its new heart drug Posicor off
the market Monday because it may cause dangerous, even deadly, interactions
with more than 25 other drugs, from antibiotics to cancer medicines.

About 400,000 people in 38 countries, including almost 200,000 Americans who
take Posicor for high blood pressure or angina, were advised to call their
doctors promptly.

``The main message to them today is, don't stop (taking) their drugs,''
because suddenly stopping is dangerous, said Dr. Murray Lumpkin, the Food
and Drug Administration's drug chief. ``They need to call their physician
and ... get off this drug and on to something else. There are plenty of
other choices.''

Also, until they switch, patients should not begin taking any new drug
without a doctor's specific permission, Roche advised.

Many medicines can interact dangerously with each other; they come with
warning labels so doctors know how to prescribe safely. Indeed, when the FDA
approved Posicor last June, it warned that patients taking certain drugs,
including the antihistamine Hismanal, should not take Posicor.

But the FDA quickly learned that Posicor affected many other drugs. In
December, it warned doctors not to prescribe Posicor to patients taking any
of the popular cholesterol-lowering drugs called ``statins,'' such as Zocor,
after the mix was linked to a rare form of muscle injury in seven patients.

The FDA now has 400 reports of health problems in patients taking Posicor,
including 24 deaths, although Lumpkin stressed that there is no way to prove
how many were actually caused by drug interactions.

The FDA concluded that Posicor affected too many drugs to justify merely
adding further warnings -- especially since there is no evidence that
Posicor offers any advantage over dozens of other blood pressure drugs.

Late Friday, Roche mailed 800,000 health care workers notices that it had
agreed to pull Posicor from the market. It started a hot line Monday for
patients to return unused pills for a refund.

Posicor's chemical construction is different from other blood pressure drugs
in its class, called calcium-channel blockers. Posicor inhibited the liver's
metabolism of medicines, allowing other drugs to accumulate to dangerous
levels in the body, said the FDA's Dr. Robert Temple.

``Lots of drugs do this a little,'' but Posicor ``is an extremely powerful
inhibitor,'' Temple said.

Posicor, known chemically as mibefradil, was controversial from the start.
Calcium-channel blockers are not considered first-choice treatment for high
blood pressure, but studies show they are highly advertised and widely
prescribed over cheaper drugs that heart experts say are much more
effective: diuretics or beta blockers.

Advisers to the FDA argued over whether Posicor should be approved at all,
because testing showed a small number of Posicor users developed strangely
abnormal cardiac waves and low heart rates.

``Given that so many anti-hypertensives have been proven to be safe and
beneficial, I didn't see why the public should take the risk'' of trying
Posicor until those heart findings were better understood, said Dr. Lemuel
Moye of the University of Texas Health Sciences Center.

His advisory panel, however, did vote 5-3 to approve Posicor with warnings,
and the FDA agreed. Ultimately, it wasn't the heart risk but drug
interactions that doomed it.

Still, consumer advocate Dr. Sidney Wolfe of Public Citizen said the FDA is
being pushed by Congress to approve drugs too fast. Roche had more tests
under way that, if the FDA had just waited, would have uncovered the
problems before thousands were put at risk, he said.

``The clarification of a safety concern should precede approval, not follow
it,'' Wolfe said. ``The question is, Why was this drug approved? ... There
were enough elements of danger of this drug and no evidence of benefits over
existing drugs.''

Initially, however, Posicor met all federal standards for approval, Lumpkin
said. ``We knew there was a potential for some drug interactions,'' he said.
``What we did not know early on was the scope.''

Checked-by: Melodi Cornett