Fentanyl patches recalled over leakage risk

Both brand-name and generic companies selling fentanyl patches have recalled some of their products voluntarily due to the risk of a potentially life-threatening manufacturing defect.

The problems emerged last week when PriCara, a division of Ortho-McNeil-Janssen Pharmaceuticals, said all lots of 25 microgram/hour (mcg/hr) Duragesic (fentanyl transdermal system) CII patches sold by PriCara in the US, as well as all 25 mcg/hr fentanyl patches sold as an authorised generic by Sandoz in the same market, were being recalled voluntarily " as a precaution " from wholesalers and pharmacies.

The action was taken in co-operation with the US Food and Drug Administration (FDA).

The patches involved all had expiry dates of December 2009 or earlier and were all manufactured by Alza, the drug delivery specialist that, like PriCara, is part of the Johnson & Johnson group.

All 25 mcg fentanyl patches manufactured by Alza and sold in Canada - by both Janssen-Ortho as Duragesic and by Ranbaxy as Ran Fentanyl Transdermal System patches, under an October 2006 licensing and supply agreement between Janssen-Ortho and Ranbaxy Pharmaceuticals Canada - were also taken off the market.

The Canadian regulatory authority, Health Canada, issued a public health advisory warning against use of the affected patches.

As PriCara explained, the patches concerned "may have a cut along one side of the drug reservoir" .

That meant there was a possibility the fentanyl gel could be released from the gel reservoir into the pouch in which the patch is packaged, "exposing patients or caregivers to fentanyl gel" .

As the company pointed out, fentanyl is a powerful opioid compound classified under Schedule II of the US Controlled Substances Act.

Exposure to fentanyl gel "may lead to serious adverse events, including respiratory depression and possible overdose, which may be fatal" , it warned.

Nor would patches with a cut edge that had leaked gel provide effective pain relief, PriCara noted.

This is not the first time Johnson & Johnson has run into difficulties with Duragesic.

There have been a number of recalls of the patch since it was originally approved in the US in August 1990, although PriCara spokesman Greg Panico said these involved different manufacturing issues from those behind the current recall.

The manufacturing process for the fentanyl patches involves filling two membranes with the active ingredient, then sealing them together and cutting them.

Panico had no explanation for the history of technical glitches with the patches, commenting only that any manufacturing process is liable to problems.

Nor could he say when production of the 25 mcg/hour patches would be back to normal.

"It's being worked on," he told In-PharmaTechnologist.com.

One of the previous recalls was in April 2004, when Janssen Pharmaceutica Products withdrew four additional lots of Duragesic 75 mcg/hour patches following a single-lot recall in February, when it was found that a "small percentage" of patches in the lot might leak medication along one edge.

Johnson & Johnson is also facing several lawsuits - the last annual disclosure showed a total of 74 filed - holding the company liable for the deaths of people who were using the patch.

In August 2006 a jury in Texas jury awarded $772,500 to the family of a woman who died in 2004 after a leak in her Duragesic patch was said to have flooded her bloodstream with fentanyl.

Panico could not say whether or how many of the pending lawsuits relate to specific manufacturing defects with Duragesic patches.

Only last December, the FDA updated a July 2005 public health advisory warning that the directions for use on fentanyl skin patches " must be followed exactly to prevent death or other serious side-effects from overdosing with fentanyl ".

Despite these efforts, the agency noted, it continued to receive reports of deaths and life-threatening side-effects in patients using the fentanyl patch.

"The reports indicate that doctors have inappropriately prescribed the fentanyl patch to patients for acute pain following surgery, for headaches, occasional or mild pain, and other indications for which a fentanyl patch should not be prescribed," the FDA said in December.

"In addition, the reports indicate that patients are continuing to incorrectly use the fentanyl patch by replacing the patch more frequently than directed in the fentanyl patch instructions, applying more patches than prescribed, or applying a heat source to the patch, all resulting in dangerously high fentanyl levels in the blood."

As the FDA stressed, the fentanyl patch is intended only for treating persistent, moderate to severe pain in patients who are opioid-tolerant, "meaning those patients who take a regular, daily, around-the-clock narcotic pain medicine" .

Despite this fairly specialised indication, Duragesic patches were Johnson & Johnson's eighth biggest product last year, generating sales of $1.16bn worldwide.

According to Panico, the recalled lots make up only a " small percentage " of the total value of Duragesic sales.

Alza also manufactures 12.5, 50, 75 and 100 mcg/hr versions of the fentanyl patch, none of which are affected by the current action.

Another company that has taken precautionary measures over potential defects in fentanyl patches is one of PriCara's generic competitors, Actavis.

The company has voluntarily recalled 14 lots of Fentanyl transdermal system CII patches sold in the US by its subsidiary Actavis South Atlantic LLC.

The lots in question were manufactured for Actavis on contract by Corium International.

The recalled lots " may have a fold-over defect which may cause the patch to leak and expose patients or caregivers directly to the fentanyl gel ", Actavis stated, adding that it was " unaware of any injuries resulting from this issue ".