What is Duragesic Pain Patch?
Duragesic® is the trade name for a pain-medication patch containing fentanyl, a potent opioid analgesic. Duragesic is a transdermal system—the medicine, fentanyl, is absorbed through the patient’s skin and into the bloodstream, providing pain relief for up to three days (72 hours) from a single patch application.
The Duragesic patch consists of four layers: (1) a backing layer of polyester film; (2) a drug reservoir of fentanyl and an alcohol gel with hydroxyethyl cellulose (to enhance the drug delivery rate); (3) an ethylene-vinyl acetate copylymer membrane that controls the rate of fentanyl delivery to the skin surface; and (4) a fentanyl containing silicone adhesive material.
Once fentanyl is absorbed into the skin, it forms a depot of drug in the upper layers of the skin. It is absorbed by the lungs and fat tissue, and then slowly released in to the systemic circulatory system. Serum concentrations increase gradually following initial Duragesic application, generally leveling off between 12 and 24 hours and remaining relatively constant, with some fluctuation, for the remainder of the 72-hour application period. Absorption also continues up to 12 hours after the removal of a Duragesic patch.
Fentanyl increases the patients’ tolerance to pain and decreases the perception of suffering. This drug is extremely powerful, with an analgesic potency of about 200 times stronger than morphine. Because of its potency, Duragesic is suitable only for the management of severe, chronic pain (such as cancer pain) that requires continuous opioid administration and cannot be managed with less potent medicines such as acetaminophen-opioid combinations and nonsteroidal analgesics.
Fentanyl was found to be a good choice for transdermal application because of its physicochemical properties and high analgesic potency. The drug’s low molecular weight and highly lipohilic nature enables it to be readily absorbed (46-66% of a given dose) through the skin and subsequently distributed throughout the body. The degree of absorption depends on where the patch is applied.
Duragesic Defect – Potential for Fentanyl Overdose
Since Duragesic hit the marketplace in 1991, studies have shown continued high numbers of overdoses involving transdermal delivery of fentanyl. The most serious side effect is respiratory depression, which can be fatal.
One study, published in 1991, examined 112 fentanyl-related deaths in the Eastern United States, mostly in California. Medical Literature 1. Fentanyl deaths appeared to occur rapidly, “probably the result of acute respiratory depression.” While acknowledging the extreme potency of fentanyl, the author suggests that “the incidence of fentanyl-related deaths is probably determined by the general availability of the drug, rather than the relative potency of the analogs.”
In a study published in 2000, the Los Angeles County Department of the Coroner analyzed 25 cases involving fentanyl-related deaths. The author notes that the Los Angeles County Coroner’s Office evaluates nearly one case each month involving fentanyl patch-related death. Another study that same year identified 61 cases of transdermal drug overdoses in a Regional Poison Information System over a five-year period.
Several case reports have described the development of life-threatening overdose caused by a heating pad or rise in body temperature. Frolich et al. reported a narcotic overdose in a patient that was using a warming blanket to relieve pain following surgery. See M.A. Frolich et al., Opioid Overdose in a Patient Using a Fentanyl Patch During Treatment with a Warming Blanket, 93 ANESTH. ANALG. 647-48 (2001) (unable to obtain hard copy). The increase in absorption may account for other heat-related toxicity associated with transdermal fentanyl. G. Newshan, Heat-Related Toxicity with the Fentanyl Transdermal Patch, 16 J. PAIN SYMPTOM MGMT. 277-78 (1998) (unable to obtain hard copy).
One study, in 2003, examined the effect of heat on transdermal fentanyl absorption. The authors concluded that increases in skin temperature may result in increased systemic absorption of fentanyl. Therefore, warming blankets and heating pads should not be either used in conjunction with, or placed over Duragesic patches.
However, as of 2003, the Duragesic label warned that serum fentanyl concentrations may “theoretically” increase by one third in patients with a body temperature of 40 degrees Celsius because of accelerated drug release and increased skin permeability. The current label warns of a “potential for temperature-dependent increases in fentanyl release from the system.”
Duragesic Package Leak – Subsequent Recalls
The design/manufacturing defect most applicable to our case is an improper sealing of one edge of the Duragesic patch, resulting in millions of patches being recalled. During 2004, ALZA (through Janssen) initiated two large Class I recalls of Duragesic for this exact reason. The first was February 17, 2004 at which time Duragesic Control No. 0327192 (75 mcg/hr) was pulled from the market. The cited reason was a potential seal breach on one edge of the patch, which could result in fentanyl leaking from the patch. This recall included about 440,000 patches.
On April 5, 2004, Janssen expanded its recall of Duragesic to include 2.2 million patches (Control Numbers 0327192, 0327193, 0327294, 0327295, and 0330362). Again, the reason cited was the potential for a breach of the seal, which would result in fentanyl leakage. Janssen sent a “Dear Healthcare Professional” letter to inform of the expanded recall.
A leak of fentanyl from a Duragesic patch could cause patients to receive either too much or too little of the drug. If the fentanyl seeps out of the patch before its application to the skin, patients may receive too little medication to adequately treat their pain. In this situation, patients used to a specific does may experience withdrawal effects including sweating, sleeplessness, and abdominal discomfort.
Conversely, fentanyl leaks that occur while the patch is on the skin expose patients to a potentially life-threatening overdose of fentanyl. Duragesic is designed to deliver only a controlled amount of fentanyl into the patient’s skin. Patients wearing a defective patch that leaks fentanyl directly onto the skin will receive too much of the medication. If this occurs, patients could experience minor complications such as sedation, drowsiness, and nausea. Fentanyl overdose may result in more serious complications, including fatal hypoventilation (respiratory depression) or cardiac arrest.
When Jansen placed Duragesic on the market in 1991, reports of toxicity due to fentanyl overdosing were fairly common. In fact, one study in California of 112 deaths associated with fentanyl concluded that the general availability of the drug may be responsible for the high incidence of overdoses.
Potential for Duragesic Misuse Leading to Overdose
Largely because of its potency, fentanyl has been misused since it was first introduced. A number of studies have noted the high potential for abuse of fentanyl as a substitute for heroin or other illegal drugs. Recreational abuse of fentanyl is extremely dangerous due to the low concentrations necessary to induce respiratory depression. Several overdose deaths of health professionals and non-health professionals have been reported involving ingestion, injection, or smoking of fentanyl transdermal patches.
In one study involving the overdose death of a woman who applied multiple Duragesic patches at a time in order to experience enhanced pain relief, the author noted: “No doubt the out-patient prescribing of transdermal patches will increase in the future. To prevent fentanyl toxicity, both patient and care giver must be properly instructed on the use and hazards of fentanyl patches.”
Government Recalls of Duragesic
In 2004, the FDA influenced Janssen and ALZA to issue two Class I Recalls of Duragesic, “due to improper sealing of one of their edges,” which could result in a life-threatening overdose of fentanyl. Govt Regulation 7. Yet, this was not the first time the FDA encountered problems with the companies’ handling of Duragesic. In fact, prior to the recalls in 2004, the FDA has required Duragesic labeling revisions 13 times. And, as recently as July 2005, the FDA issued a Public Health Advisory concerning the use of Duragesic Patches in response to reports of deaths in patients using the patch.
Beginning in 1994, the FDA sent ALZA a “warning letter” identifying certain violations and deviations from Good Manufacturing Practices (GMP) regulations under the Food and Drug Act. This prompted the company to issue a letter to all health care professionals warning of Duragesic misuse.
In the late 1990s, the Department of Health and Human Services warned Janssen that its promotional materials to expand the use of Duragesic were in direct violation of the Federal Food, Drug, and Cosmetic Act and contained misrepresentations as to the safety and efficacy of the product. The agency determined that the promotional pieces were “false or misleading because they contain misrepresentations of safety information, broaden Duragesic’s indication, contain unsubstantiated claims, and lack fair balance.”
Following Janssen’s “voluntary” recall of Duragesic in 2004, the FDA issued a “Safety Alert” warning that the recall was “due to a potential leak in the product seal,” which could result in skin exposure to fentanyl. Govt Regulation 6. The warning adds that “skin exposure to any leaked medication from a DURAGESIC patch may cause nausea, sedation, drowsiness, or potentially life-threatening complications.” Janssen also wrote a letter to “Healthcare Professional[s]” informing them of the expanded recall in April 2004.
Furthermore, on September 2, 2004 the FDA issued Janssen another “warning letter.” This letter states that the latest Duragesic promotional pieces make “false or misleading claims about the abuse potential and other risks of the drug, including unsubstantiated effectiveness claims for Duragesic.” The letter states, “By suggesting that Duragesic has a lower potential for abuse compared to other opioid products, the file card could encourage the unsafe use of the drug, potentially resulting in serious or life-threatening hypoventilation.”
The Duragesic product label was again updated in June 2005 to add new safety information in several areas of labeling, and Janssen issued another “Dear Healthcare Professional” letter about these changes. Under a section entitled “Hypoventilation (Respiratory Depression),” the letter warns that “Serious or life-threatening hypoventilation may occur at any time during the use of DURAGESIC® especially during the initial 24-72 hours following initiation of therapy and following increases in dose.” Janssen also warns of a “potential for temperature-dependant increases in fentanyl released from the system resulting in possible overdose and death.” Therefore, the letter instructs all patients to avoid exposing Duragesic to “direct external heat sources, such as heating pads or electric blankets, heat lamps, saunas, hot tubs, and heated water beds, etc., while wearing the system.”
Finally, on July 15, 2005 the FDA issued a “Public Health Advisory” concerning the use of Duragesic Patches in response to reports of deaths in patients using the patch. The FDA stated it is conducting an investigation into the deaths related to fentanyl overdose in patients using Duragesic. According to the FDA, “Some patients and health care providers may not be fully aware of the dangers of this very strong narcotic painkiller. Therefore, FDA is issuing this public health advisory to alert patients and their caregivers and health care professionals by highlighting the following important safety information.”
Contact a Duragesic/Fentanyl Overdose Lawyer
To contact a Top Chicago Personal Injury Lawyer with the knowledge and experience to help you with a potential lawsuit related to a Duragesic or Fentanyl-related overdose, call Passen & Powell at (312) 527-4500 or fill out a Free Case Evaluation.