Duragesic

Duragesic and Durogesic ( /ˌdɜrəˈdʒiːzɪk/) are trade names of fentanyl transdermal therapeutic systems, and are used for relief of moderate to severe pain. Since Duragesic/Durogesic release Fentanyl, a potent opioid, slowly through the skin, one patch may provide 72 hours of pain relief. Its initial onset after a patch has been applied is roughly 8–12 hours under normal conditions, thus Duragesic patches are often prescribed with another opioid (such as morphine sulfate) to handle breakthrough pain.

Approval and usage

Duragesic was first approved by the College ter Beoordeling van Geneesmiddelen, the Medicines Evaluation Board^{[disambiguation needed ]} in the Netherlands, on 17 July 1995 as 25, 50, 75 and 100 µg/hr formulations after a set of successful clinical trials, and on October 27 2004 the 12 µg/hr formulation was approved as well. On Jan 28, 2005, the U.S. Food and Drug Administration approved first-time generic formulations of 25, 50, 75, and 100 µg/hr fentanyl transdermal systems (made by Mylan Technologies, Inc.; brand name Duragesic, made by Alza Corp.) through an FTC consent agreement derailing the possibility of a monopoly in the treatment of Breakthrough Chronic Pain by Alza Corp. In some cases, physicians instruct patients to apply more than one patch at a time, giving a much wider range of possible dosages. For example, a patient may be prescribed a 37.5 µg dosage by applying one 12 µg patch and one 25 µg patch simultaneously, or contingent on the large size of the (largest) 100μg/hr patch, multiple patches are commonly prescribed for doses exceeding 100μg/h, such as two 75μg/hr patches worn to afford a 150μg/hr dosage regimen. Although the commonly referred to dosage rates are 12/25/50/75/100 µg/hr, the "12µg" patch actually releases 12.5 µg/hr.^[1] It is designed to release half the dose of the 25 µg/hr dose patch.

Duragesic is manufactured by ALZA Corporation and marketed by Janssen Pharmaceutica (both subsidiaries of Johnson & Johnson). During the period of June 2002 through June 2003, Duragesic sales totaled over one billion.

Pain clinic physicians who prescribe Duragesic may also recommend dextromethorphan, a non-prescription cough syrup, as it helps opioids work better and help with withdrawal symptoms felt during patch change over time.

As of July 2009, construction of the Duragesic patch had been changed from the problematic gel pouch and membrane design to "a drug-in-adhesive matrix designed formulation", as described in the prescribing information.^[2] This construction eliminates the possibility of leakage and leakage-related accidental overdosing, and makes illicit use of the fentanyl more difficult. Generic substitutes still utilize the gel pouch design and there have been some anecdotal reports questioning the efficacy of these generics (specifically, consistency of delivery and inflammation beneath the adhesive border).

Warnings

Since Duragesic and Durogesic are highly potent, there are many black box warnings in Duragesic's and Durogesic's prescribing information (PDF file). Additionally, due to the risk of serious adverse drug reactions, it is highly important that the patches be applied correctly and as prescribed. Also, care must be taken to guard against the application of external heat sources (such as direct sunlight, heating pads, etc.) which in certain circumstances can trigger the release of too much medication and cause life-threatening complications.

In July 2005, the FDA issued a Public Health Advisory, which advised that "deaths and overdoses have occurred in patients using both the brand name product Duragesic and the generic product." In December 2007, as part of this continuing investigation, the FDA issued a second Public Health Advisory stating, "The FDA has continued to receive reports of deaths and life-threatening side effects in patients who use the fentanyl patch. The reports indicate that doctors have inappropriately prescribed the fentanyl patch... In addition, the reports indicate that patients are continuing to incorrectly use the fentanyl patch..."

Fentanyl patches are designed to be used by patients with a higher opiate tolerance. They should not be used for mild or moderate acute pain and should not be used for short-term treatment of pain. Full benefits of pain relief from patches may take 4 to 10 days, although "relief" can be felt within hours.

Recalls

In February 2004, a leading fentanyl supplier, Janssen Pharmaceutica Products, L.P. recalled one lot of fentanyl (brand name: Duragesic) patches because of seal breaches which may allow the drug to leak from the patch. The recall notice warned that "exposure to the Duragesic hydrogel contents could result in an increased absorption of the opioid component, fentanyl, leading to increased drug effect, including nausea, sedation, drowsiness, or potentially life threatening complications." Janssen also later recalled additional lots; a series of Class II Recalls were then initiated in March 2004 due to a potentially life-threatening manufacturing defect. At least one fatality, possibly due to the defect, has been reported to the American FDA.

The 25 mcg/hr Duragesic patches manufactured by ALZA Corporation were also recalled in February 2008 due to a concern that small cuts in the gel reservoir could result in accidental exposure of patients or health care providers to the fentanyl gel. Overexposure in patients, or even slight exposure in non opioid tolerant people, could possibly result in a fatal overdose. ^[3]

In February 2011, the manufacturer suspended production of all Duragesic patches due to quality control issues involving unspecified "microscopic crystallization" detected during the manufacturing process of the 100 µg/hr strength. According to the Ortho-McNeil-Janssen Pharmaceuticals Scientific Affairs Public Information Center (800-526-7736) the issues were resolved and existing stocks were released for shipment beginning mid-April for the 25 & 50 µg/hr strengths. The remaining strengths are scheduled to resume distribution in late April. Widespread rumors circulating about the manufacturer discontinuing this product line are completely false. 100mg patches have also returned to the market, along with many other doses/preparations of Fentanyl, however it is not known whether the aforementioned 100mg patches are actually Duragesic products, or simply a generic alternative.

Legal action

On June 19, 2007, a $5.5 million jury verdict was awarded in a case against Johnson & Johnson subsidiaries, Alza Corporation and Janssen Pharmaceutica Products, the manufacturers of the Duragesic fentanyl transdermal pain patch. This case, the first Federal trial involving the Duragesic fentanyl patch, was tried in the Federal District Court for the Southern District of Florida, West Palm Beach Division.

J&J has filed an opposition [1] to the trademark application Dermogesic filed by Minnesota High Tech Resources, LLC for their iontophoretic transdermal patch. The litigation has been ongoing since 2002. The trial has been completed. The parties are now drafting and filing their final briefs. J&J's main argument is that the Dermogesic mark dilutes their Durogesic brand and adds confusion in the marketplace. Obviously, Minnesota High Tech Resources, LLC disagrees with this position. Minnesota High Tech Resources, LLC is a very small biomedical research company owned by two individuals in Red Wing, MN.

The website DangerousDrugs.US has posted numerous documents revealed during discovery in Duragesic lawsuits, including FDA inspection reports, depositions of ALZA executives, and expert witness reports.

References

1. ^ http://www.duragesic.com/duragesic/shared/pi/duragesic.pdf Official Duragesic Full Prescribing Information
2. ^ http://www.duragesic.com/duragesic/shared/pi/duragesic.pdf
3. ^ PRICARA RECALLS 25 mcg/hr DURAGESIC (fentanyl transdermal system) CII PAIN PATCHES, FDA, 2008-02-12, http://www.fda.gov/oc/po/firmrecalls/pricara02_08.html 

External links

• [2] - Manufacturers's productlist for Europe, including Durogesic
• FDA recall notice
• FDA petition - classification of different transdermal systems
• Duragesic.com - Manufacturer's Duragesic website
• Duragesic.com - Prescribing Information in the United States