Medical patch users discover danger beneath the surface.

"I'm on the patch," say cigarette smokers every January, when the inevitable New Year's resolutions roll around. Wearing a patch that transmits nicotine through the skin to ease a smoker's urge to light up is generally viewed as a benign way to combat a serious health problem.

But medical patches can be dangerous--whether they deliver nicotine or strong medicine such as opiate painkillers, anesthetics, nitroglycerin, birth control, and male and female hormones. Patients and health care providers alike often misunderstand the patches' proper use, meaning users may receive the wrong dose of medication. And defective design caused a recent product recall.

The first transdermal patch, to treat motion sickness, received FDA approval in 1979. It delivered scopolamine over a period of three days. In 1991, the agency approved nitroglycerin patches for treating angina (heart pain), as well as four types of nicotine patches. Total sales of the nicotine patches in their first year on the market reached almost $1 billion.

Patches consist of one or two pieces. Some have a medicated center pouch held tightly against the skin by an adhesive ring (like a round Band-Aid with its sterile-pad center); others use a separate adhesive overlay to hold the patch in place. They deliver doses of drugs over time, usually between one and seven days per patch.

Ideally, a patch is designed to "deliver the drug at an adequate and reasonably constant rate for a sustained period of time, should not irritate the skin or cause allergic reaction, and should deliver most of the drug it contains." (Alza Corp. v. Mylan Labs., Inc., 310 F. Supp. 2d 610, 614 (D. Vt. 2004).)

Patches are a popular choice with physicians because drugs delivered transdermally are absorbed better so smaller doses can be used, maintaining a steady level in the bloodstream, and causing fewer side effects. If side effects do occur, the medicine can quickly be discontinued by removing the patch, and patients' compliance is better because they take a dose every few days rather than every few hours.

Patients like the patch, too: They avoid needles and other invasive delivery methods; they face no food restrictions or timing constraints on doses; and they find patches easy, convenient, and discreet to use.

Only 11 over-the-counter and prescription medications are available in patch form. The number is limited because the drug molecules must be small and preferably hydrophilic (water soluble) to penetrate the skin.

Critics have identified several areas of concern, chiefly connected with the powerful painkiller fentanyl: defective patches that deliver incorrect dosages, patients who overdose through misuse or even correct use, medical personnel who take patient patches for recreational use, and doctors and caregivers who misprescribe or fail to monitor the medication. Problems associated with other patches include user abuse, sales of counterfeit patches, and marketing that makes false and misleading claims.

Just wearing a patch can pose a hazard. The FDA and the American Journal of Nursing have reported that patients have been burned by transdermal patches worn during MRIs. Some patches have an aluminum backing that conducts heat.

The Institute for Sate Medication Practices recommends that health care providers ask all patients getting MRIs whether they use medication patches and tell them to remove them temporarily for the test. But some prescribing doctors caution patients not to remove or change the location of a patch once it's been applied, because doing so may affect the flow of medication or cause the adhesive to loosen so that the patch comes off later.

Duragesic recall

Approved by the FDA in 1990, Duragesic--the brand name for fentanyl--is the most widely prescribed transdermal medication, exceeding $1 billion in sales in 2003. The total number of fentanyl patch prescriptions written in the United States rose from 4.5 million in 2002 to 5.4 million in 2003--a 20 percent increase.

Fentanyl patches were approved for managing severe, chronic pain that cannot be alleviated by less potent analgesics--cancer pain, for example--in patients who require around-the-clock dosing. Black-box warnings on the packaging read, "Not for acute or postoperative use" and "For use in opioid-tolerant patients."

In February 2004, the manufacturer, Johnson & Johnson, recalled about 440,000 patches of Duragesic from a specific lot of the devices that delivered 75 micrograms per hour (mcg/h) over three days.

Although the action was categorized as a Class I recall (risk of serious injury), the company claimed that fewer than 19,000 patches possibly had a seal breach on one edge that might allow the medication to leak. Last April, Johnson & Johnson expanded the recall to include about 2.2 million patches.

An FDA Safety Alert last year stated that skin exposure to medication leaked from fentanyl patches may cause nausea, sedation, drowsiness, or other serious complications. A "Dear Pharmacist" letter from the FDA dated April 7 said, "Exposure to the leaked medication could result in inadvertent ingestion or an increased transdermal absorption of the opiate component fentanyl, leading to potentially life-threatening complications. Conversely, leakage of medication could lead to inadequate dosing, resulting in treatment failure and/or opiate withdrawal."

In 1996, Johnson & Johnson's subsidiary manufacturer Alza Corp. recalled two lots of Duragesic 100 mcg/h patches for "a packaging defect which allows the system reservoir to dry out, which may result in decreased rate of delivery." In 1994, it had recalled several lots of 25 mcg/h and 50 mcg/h patches because "release rate does not meet product specifications."

"Fentanyl is a Class I narcotic," said Scott Webre, a plaintiff attorney in Lafayette, Louisiana, who was involved in the case of a young man who died after being hospitalized to treat chronic pain from advanced sickle cell anemia. Doctors, who believed he was a drug abuser, juggled his pain medications, refusing one and then another until he was abruptly placed on the Duragesic patch. An autopsy revealed fentanyl toxicity as the cause of death.

"Fentanyl is for chronic pain, so as long as you have a base level of pain, you're OK with a time-release narcotic," Webre said. However, it is not for acute pain. "If the pain is going to go away in five hours, but in five hours you're still getting significant amounts of narcotic through a patch, you can get in trouble in a hurry."

He also noted that fentanyl can interact harmfully with other drugs. Patients starting on the patch may need to rake a faster-acting narcotic during the first few days of treatment, while the fentanyl dose is being adjusted, to relieve any "breakthrough" pain. Taking another narcotic with fentanyl can increase the chance of an overdose.

"The irony is, if you're a chronic-pain patient you're seeking relief from pain so you can rest and not suffer sleep deprivation," said John Cushing, a Chicago plaintiff attorney. "So if the patch is working, you can relax. But as you become more relaxed, your respiration decreases, and hypoventilation is a symptom of overdosing. The indication of overdosing is the same as the indication that [the patch is] working."

Cushing represents the family of a woman who died while using the Duragesic patch to treat the pain of reflex sympathetic dystrophy. After her family found out about the 2004 recall, they contacted his office; the box of patches she used carried the recalled lot number.

Cushing knows of lawyers in Alabama, Indiana, Maryland, Ohio, and Pennsylvania who are investigating Duragesic cases, but he's not aware of enough cases to support a class action. "It seems like people using this patch are familiar with heavy drug doses and the uses of drugs for chronic pain. Such educated patients may recognize the symptoms of overdosing and remove the patches before it can happen," he said.

Negligence and misuse

Injuries may also occur when the drug is used to treat children or when it is negligently prescribed by a doctor or misused by a caregiver.

Fentanyl patches were approved for use in children in January 2003, with a label reading, "Duragesic should be administered to children only if they are opioid-tolerant and age 2 years or older." In June 2004, the Pediatric Drug Development division of the FDA's Center for Drug Evaluation and Research reported five pediatric deaths during the mandatory one-year postapproval reporting period and three more after the period ended.

The deaths included a nine-year-old boy who was prescribed a 25 mcg/h patch after a tonsillectomy and adenoidectomy. He died of respiratory arrest two days after surgery. He was also taking acetaminophen with codeine. In another instance, after a woman placed a patch on her four-year-old granddaughter, the child died of cardiac arrest.

The report concluded that many of the pediatric adverse events occurred when doctors prescribed the patches for off-label uses or for uses contraindicated by the manufacturers (for example, to treat acute pain in a patient unaccustomed to taking opioid drugs). The researchers called for additional doctor education in the proper use of fentanyl transdermal systems to minimize off label use, as well as abuse and misuse.

Fentanyl patches are regularly misused by caregivers in patients' homes, doctors' offices, day care facilities, emergency rooms, and other settings, according to FDA Patient Safety News. In situations involving several caregivers. information about when a patch was applied and when the next one is due may not be passed along. Also, caregivers and patients may be confused about dosage: Different patches use different measures of dosage strength (for example, mg/h, mg/day, mg/day/week). They are also administered at different frequencies, and they come in varied sizes, shapes, and colors.

Sometimes even prescribing doctors confuse different patch formulations" dosing intervals, strength, and instructions for use. Or they might prescribe a medication to be taken by mouth that duplicates the one being delivered by patch, resulting in an overdose.

"I think when the patch contains a chemical that can easily kill and there is any [patient] compliance question at all, there can be a case against the doctor for improperly prescribing and instructing the patient," said Lori Bencoe of Albuquerque. She represents the family of a patient who was prescribed 50 mcg/h fentanyl, patches by a family doctor, even though the doctor knew the patient had a history of closed head injury, depression, and drug dependence.

It was "like giving a known suicidal person a loaded gun," said Bencoe. The patient put on two patches at once. which killed him.

Duragesic's marketing has also come under fire. In September 2004, the FDA sent Johnson & Johnson research-and-development subsidiary Janssen Pharmaceutica, Inc., a letter warning that some of its promotional materials for the patch were false and misleading. It said that a pamphlet the company sent to health cave professionals contained "unsubstantiated" claims about the drug's effectiveness. The letter said that the pamphlet made other questionable claims about the drug's safety, suggesting that Duragesic has a lower potential for abuse than other drugs based on data from a national health-surveillance database. The FDA said it was not aware of such evidence or of clinical experience to support that claim.

The government has questioned the authenticity and marketing of other types of patches as well. The FDA approved transdermal contraceptive patches in November 2001. In February 2004, the agency issued a joint warning with manufacturer Johnson & Johnson, cautioning that offshore Internet sites--including a site maintained by American Style Products in New Delhi, India--were selling counterfeit patches containing no active ingredients. The FDA is investigating these and other fake versions of Johnson & Johnson's Ortho Evra transdermal patches, which contain the hormones estrogen and progestin.

The Federal Trade Commission (FTC) is also going after dubious patch marketing. In FTC v. Advanced Patch Technologies, Inc., the manufacturer and marketers of the "Peel Away the Pounds" patch--a seaweed-based product--settled charges that they made false and unsubstantiated weight-loss claims, paying consumers more than $1 million in refunds. In December 2003, the agency filed a complaint lodging similar charges against manufacturers and marketers of two other seaweed-based transdermal patches.

Intentional misuse of nicotine patches--and manufacturers' awareness of it--may also generate liability questions. Reports in medical journals of such misuse date back a decade. The September/October 1994 issue of the Journal of the American Board of Family Practice reported that nicotine patches contain reservoirs of enough drug to be potentially toxic if used incorrectly In one apparent suicide attempt, the patient applied several nicotine patches, leading to a serious overdose.

The December 1996 issue of the Journal of Toxicology--Clinical Toxicology described nine incidents of "self-poisoning" with nicotine patches reported by U.S. poison centers, categorizing them as either intentional misuse or suicide attempts. Eight people were hospitalized and all recovered, but the report concluded that "simultaneous application of several transdermal nicotine patches can be implicated in adult suicide attempts," and that as accessability to patches increases, so will their misuse.

Only a few lawsuits over pain patches have been filed to date. Attorneys say causation is a difficult issue and damages may be low. "Transdermal pain medicine patches aren't given to many outpatients who are expected to live long," said Bencoe. "Usually they are given [in hospitals] to patients with terrible pain, or on an outpatient basis to end-stage cancer victims."

But with so much that can go wrong, as the use of transdermal patches increases, so should awareness of their dangers.