washington -- Army Master Sgt. Harold Kinamon entered a military hospital in Ohio for routine respiratory surgery to help him sleep better. The operation, in October 2005, progressed smoothly. He went home with nothing more than a raw throat and a painkiller contained in an adhesive patch on his skin.
That night, Kinamon, 41, died in his sleep -- killed by an overdose of the drug delivered through the patch.
What made his death even more tragic was that the dangers of using skin patches to administer the particular painkiller he received, an opiumlike drug called fentanyl, were clearly understood at the time. Only three months earlier, the Food and Drug Administration -- responding to a number of similar deaths -- had issued a strong warning: Though beneficial under appropriate conditions, fentanyl patches should be used with great caution, and not for postoperative pain relief.
Kinamon’s death reflects more than an individual misfortune. Healthcare providers nationwide are still not getting the message as fentanyl patches continue to be implicated in scores of deaths.
Failure to solve the problem is all the more serious because the use of patches is spreading to other drugs, including other painkillers, contraceptives and medications for children with attention deficit disorder. Moreover, a new generation of high-tech patches is expected to make many more drugs available in patch form.
The benefits of patches have been accompanied by problems, replicating a pattern common to many medical advances: Breakthroughs often come with risks and downsides that may not be fully recognized until later.
Drug safety experts are urging the FDA to reexamine the issue of medicinal patches. One primary problem seems to be how to get the right dose of a drug through a patch for different patients under differing conditions.
Patches are “a neat way of delivering drugs,” but they are not an unalloyed blessing, said Dr. Curt D. Furberg of the Wake Forest University medical school.
The appeal of the patches is clear: They solve a host of problems with more traditional methods of administering medications. Unlike injections, they don’t hurt. Unlike pills, they don’t have to be swallowed. They resolve the common problem of patients not taking drugs in the right amount at the prescribed intervals. And their medicine enters the bloodstream directly, rather than via the stomach.
Those advantages are real, medical experts say, but they are not the whole story.
Sales of Ortho Evra, the first birth-control patch, plunged last year after the FDA cautioned that it exposed women to higher levels of a hormone linked to dangerous blood clots than do oral contraceptives.
With pills, the drug level spikes after consumption, dropping as the time for the next dose approaches. Patches maintain a steadier level, but, over time, this can lead to higher total exposure to the drug. That can cause problems, and the trade-offs are not well understood, experts say.
“What is the corresponding patch level that would be equivalent to oral drugs?” Furberg asked. “People use different formulas and there is disagreement.”
The Daytrana patch for attention deficit disorder recently ran into problems. Opening the patch and getting it to stick was difficult. (The maker says the adhesion problem has been fixed.) And the medication can irritate the skin, causing welts. The FDA is investigating.
The effect of any patch can vary considerably from patient to patient. “Some people may not get enough of the drug, which defeats the purpose of taking it. And some may get too much . . . which is going to hurt some people,” Furberg said.
For instance, heat affects the rate at which the skin absorbs a drug. Sunbathing, a hot shower or exercise can trigger an overdose.
Also, some people have thicker skin, which is more resistant to absorbing a drug. Speed of absorption can vary by a factor of about three, which can complicate finding the right dosage.
Another problem is psychological: Patients and medical professionals have a tendency to see patches as benign devices akin to a bandage. It’s easy to forget the powerful, potentially dangerous drug within.
“Patches are not innocuous,” said Kenneth Sloan, a medicinal chemist at the University of Florida whose research has shown wide variations in how quickly individuals absorb drugs through the skin. “One patch does not fit all.”
That’s why the FDA said in July 2005 that in the case of fentanyl, patches should be prescribed at the lowest practicable dose, should not be used to treat short-term pain or pain after an operation, and should only be used by patients already established on opioid drugs.
Patients and caregivers must be fully informed about safety, the FDA said.
According to Kinamon’s sister Deana, that did not happen in his case. His patch provided the second-highest available dose of fentanyl. And she said she did not recall receiving special instructions about the patch when she picked her older brother up at the hospital. “They didn’t even tell me it was a narcotic,” she said. “They just said, ‘Change it in three days.’ ”
He went in on his day off for surgery to correct his sleep apnea, said his sister. “There’s honor in dying for your country on the battlefield, but there is really no kind of honor associated with that.”
Harold Kinamon’s case is an example of “totally inappropriate prescribing,” according to Larry D. Sasich, pharmacist and professor at the Lake Erie College of Osteopathic Medicine in Pennsylvania.
Kinamon’s hospital, Wright-Patterson Medical Center, declined to comment on his case, citing privacy laws. His doctor also declined an interview. The hospital says it has established safeguards for fentanyl patches since the Defense Department Patient Safety Program issued recommendations last year. (A hospital spokesman said federal law prevented him from discussing what the precautions entailed.)
In Los Angeles County and Florida, similar deaths continue to occur, statistics show. The L.A. County coroner’s office investigated 32 accidental deaths related to fentanyl in 2006, the same number as in 2005, the year the FDA issued its warning. Florida authorities reported 126 accidental deaths related to fentanyl in 2006, a rate one expert in the state described as “steady.”
Ortho-McNeil, which manufactures Duragesic, the brand-name form of the fentanyl patch, says stronger safety measures are needed. “Philosophically, we would support any new efforts that would strengthen safety and ensure this product is used appropriately,” said spokesman Greg Panico.
Whereas the opioid patch was intended for cancer patients and others with unrelenting pain, Ortho Evra, the birth-control patch, was designed for active younger women.
Kristen Britt, 28, a veterinary nurse from Stockton, said she thought the patch would fit her lifestyle. “I was looking to find something easy and safe,” she said. “To put one on and not have to change it for a week, I liked that a lot.”
Seven months after she started using the patch in 2005, she felt a pain in her right leg. At first, she said, she thought it was muscle strain, but the pain grew worse.
“One day, I couldn’t walk anymore,” she said. “I was literally screaming in pain.” Doctors found a blood clot. For months she had to take blood-thinning medications, which have risks of their own.
Soon after Britt’s experience, the FDA issued a new warning for Ortho Evra, saying the patch exposed women to about 60% more estrogen than did a typical birth-control pill. Estrogen is known to increase the risk of blood clots, which can cause strokes and other complications.
The maker of Ortho Evra says the patch has not been conclusively linked to a higher blood-clot risk.
Now Britt is at higher risk of blood clots, especially if she becomes pregnant. She is suing the company. Her attorney, Lori E. Andrus of San Francisco, says about 1,900 plaintiffs have filed federal suits and hundreds more cases are in state courts.
The president of the Institute for Safe Medication Practices, Michael R. Cohen, said: “Patches are convenient, and patients do like them, but there are reasons to examine the whole patch issue.”
So far, the FDA is sticking with the status quo. “FDA reviews patch products, like any other products, on a case-by-case basis for safety and effectiveness,” said Susan M. Cruzan, a spokeswoman.
But critics say that in the case of fentanyl, the FDA has been ineffective. Fentanyl patch sales grew 10% the year after the warning, with more than 4.7 million prescriptions written, according to Verispan, a market analysis firm.
Said Furberg: “The purpose of the [warning] was to cut back on prescriptions, so it’s a failure.”