Washington Editor

Recent FDA warnings on the painkiller fentanyl appear to partly relate to misuse of a transdermal formulation of the drug and are not related to Cephalon Inc.'s Actiq, another fentanyl-based product.

The agency's public health advisory followed reports of deaths in patients using the narcotic medication, adverse events that it said could be related to inappropriate use of the patch or factors related to the quality of the product. The FDA, which added that some patients and healthcare providers might not be completely aware of the product's risks, said it is working with fentanyl patch makers to evaluate those risks and to develop a plan to help patients avoid accidental overdose.

"This is still under investigation," Crystal Rice, an agency spokesperson, told BioWorld Today. "The FDA is conducting a review of about 120 fatalities that were possibly due to unintentional overdose reported to the voluntary adverse event reporting system for the fentanyl transdermal patch products."

Manufacturers include Janssen Pharmaceutica Products LP, a Johnson & Johnson division that makes the brand name Duragesic product, and Mylan Technologies Inc., which makes a generic fentanyl patch. Deaths and overdoses have occurred in patients using both Duragesic and the generic product, and Rice noted that information to date "does not demonstrate that there is a difference in risk between the brand-name and generic fentanyl patch products."

Duragesic, which received FDA approval 15 years ago, is indicated for the management of persistent moderate to severe chronic pain. Last year, it generated about $1.3 billion in U.S. sales, and about $2.1 billion worldwide.

"Patient safety is very important to us," Doug Arbesfeld, a Janssen spokesperson, told BioWorld Today. "We always work closely with health authorities to ensure that patients and physicians have the latest and most up-to-date information about safe use of our products."

As an opioid, Duragesic also is subject to abuse, but Arbesfeld said the Titusville, N.J.-based company could not determine whether the agency was blaming deaths on that kind of misuse, product quality issues or both. He acknowledged there was a recall a year ago due to a leaky seal in the product, though that issue has been resolved, and he said Janssen is unaware of any new quality issues.

"But if the universe that they're looking at goes back a year or two," Arbesfeld added, "sure, there may have been some adverse events related to product quality."

There are five approved doses of Duragesic, a product frequently used alongside others to treat patients with a host of conditions. Going forward, he said the company would work to ensure that the public receives proper notices.

"We are in touch with the FDA," Arbesfeld said, "and we're going to work with them on this matter to make sure that people get the information they need."

Officials at St. Albans, Vt.-based Mylan did not return calls seeking comment.

Cephalon's Actiq formulation, which is delivered buccally as a lozenge on a handle, is approved to treat breakthrough pain in opioid-tolerant cancer patients. They typically manage persistent pain with round-the-clock opioid therapy, but about two-thirds experience breakthrough pain, so named because it breaks through the underlying pain treatments. Its onset is quick, within three to five minutes, and is short in duration - episodes usually last about 30 minutes. Enter Actiq, a rapid-onset version of fentanyl.

"The type of issue that was detailed in the public health advisory issued by the FDA is really one that is specific to Duragesic and has nothing to do with Actiq," said Stacy Beckhardt, Cephalon's senior manager of public relations. "They really are fundamentally different with respect to their physical characteristics, as well as their mechanisms of action and their indications for use."

She added that abuse of Actiq is difficult because "the fentanyl cannot be readily extracted to be used in any way other than how the product is intended." Also, the West Chester, Pa.-based company has a risk-management program in place designed in part to minimize the risk of abuse and diversion. But admittedly, that doesn't stop all misuse.

"No opioid is without risk of abuse and diversion," Beckhardt told BioWorld Today. "We take active steps to learn about and try to minimize the risk of any kinds of inappropriate use of our product."

Actiq, which last year generated $345 million in sales, has been commercially available since 1999. Cephalon acquired its rights through a 2000 acquisition of Anesta Corp., of Salt Lake City.

Another version of fentanyl for breakthroug

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