Accutane's broader use, side effects lead to costly, time-consuming U.S. restrictions
Don't dawdle on the way to your local pharmacy with that Accutane prescription.
That's the hard lesson Lynette Yarnick of Indiana, Pa., learned in May when she tried to obtain the potent anti-acne drug for her 17-year-old son Joey at a local CVS drugstore, only to be told it was out of stock.
When she returned a week later, "they said the prescription had expired and I'd have to make an appointment with Joey's dermatologist to start the process all over again," Mrs. Yarnick said.
The Yarnicks are farmers and don't have insurance, so the new doctor's appointment cost them an extra $300 -- and disrupted her son's treatment.
"It was such a shame," she added, "because Accutane has just been a miracle drug for Joey."
That hoop that Mrs. Yarnick and her son had to jump through is just one of many erected since March to strictly control isotretinoin, the generic name for Accutane, which has become the gold standard for people suffering from acne since its approval by the U.S. Food and Drug Administration 23 years ago.
Accutane was originally formulated for severe acne that is resistant to over-the-counter and prescription-only remedies: benzoyl peroxide, salicyclic acid, Retin-A and antibiotics.
Increasingly, though, dermatologists have been prescribing Accutane for milder forms of acne, which afflicts nearly 85 percent of people 18 to 24 years old.
Because Accutane has severe side effects, including a risk of birth defects, there always have been restrictions on its use. Monthly blood tests monitoring liver function, cholesterol and other conditions have been required for both men and women, as well as pregnancy tests for women of childbearing potential.
Accutane can cause miscarriages, stillborn babies and severe birth defects, including heart and central nervous system abnormalities, deformed limbs and heads, asymmetrical facial features and mental retardation. Some researchers suspect it may lead to depression or suicide, although others say the data is inconclusive.
But under the new, federally mandated "iPledge" program, patients must undergo lengthy counseling about the drug and enroll in an online registry to answer questions about its use and risks, while medical staffers must spend increased time online recording lab results and on the phone with iPledge representatives and pharmacists.
Sometimes, though, staffers have been put on hold for hours, and if they don't meet certain deadlines, the patient's case is eliminated from the iPledge system and they must start the process again.
In fact, dermatologists say iPledge has proved to be so cumbersome and complicated that a number of them -- both nationally and in Pittsburgh -- no longer prescribe the drug.
Before iPledge went into effect March 1, dermatologists wrote 170,000 prescriptions a month. In the 41/2 months since, according to iPledge, 150,000 Accutane users have been entered into the program.
"The iPledge program is killing us," said Monroeville dermatologist Lisa Pawelski. "I have stopped prescribing it for women of childbearing potential until the mess is fixed, but I do not see much happening toward a fix."
In recent years, some drug safety advocates and a Michigan congressman whose son committed suicide while taking Accutane have sought to ban or severely restrict the drug, complaining that it is overprescribed.
The FDA has declined to ban it, but in March, at the agency's urging, four manufacturers hired Covance Inc., a global biotech company, to create iPledge to control its distribution and thoroughly educate patients about possible side effects.
The result seems to have satisfied no one.
While FDA officials have said they hope iPledge will reduce pregnancies among Accutane users to zero, early indications aren't encouraging.
Since March, "we've received calls from women on Accutane who have become pregnant and who were in the iPledge system," said Dr. Christina Chambers, president of the Organization of Teratology Information Specialists, a birth defects prevention group.
Meanwhile, the American Academy of Dermatology, which strenuously lobbied to delay iPledge until flaws in its computer-based program were worked out, says that startup problems have created numerous delays in treatment.
Dr. Pawelski's medical assistant was put on hold for four hours before she could reach an iPledge official to clear up a problem with one prescription. Since then, iPledge phone waiting times have gone down to 20 minutes, "but that's still unacceptable," Dr. Pawelski said.
Also, because iPledge requires that 30 days elapse between doctors' visits, a patient who can't fill an Accutane prescription within seven days of receiving it at a doctor's office is "locked out" of iPledge's computer system, and must wait 23 more days before seeing a doctor for a new prescription.
"It's infuriating to me that, after 14 years of post-secondary training and 14 additional years of experience in medical practice, not to mention a zero percent pregnancy rate, I have to now comply with this poorly written, time-wasting, confusing, mockery of a program," Dr. Pawelski said. "It's also thoroughly unjust to the women whom I cannot now treat."
Even those who still prescribe Accutane are unhappy with iPledge. Dr. Douglas Kress, a pediatric dermatologist with Children's Hospital of Pittsburgh who also has a private practice,, said his academic position gives him access to enough staff to maneuver through iPledge's requirements, which he nonetheless calls "ridiculous."
The company running iPledge only had "maybe two operators on staff at the beginning for who knows how many calls. "It's almost as though the system is being designed to fail so the FDA will ban it," he said.
Not so, said Dr. Peter A. Gross, who chaired the FDA drug safety panel that mandated iPledge.
"Our job was to do what's best for the patient. If that meant a little bit more time with the patient to ensure appropriate and safe delivery of the drug, so be it," said Dr. Gross, who chairs the department of internal medicine at Hackensack University Medical Center in New Jersey.
If anything, Dr. Gross said, he would have liked to see the FDA re-examine the risks versus the benefits of Accutane and a host of other popular drugs that were approved years ago, because it's possible that many of the side effects were not known then. That proposal to FDA officials "didn't go anywhere."
"The FDA is often accused of letting drugs out there that cause all sorts of serious side effects, but then when they do something, they're criticized on the other side. They're in a no-win situation," he said.
For example, the book that patients are required to read -- about an hour's worth of material -- before receiving a prescription is "huge, daunting," said Dr. Melanie Costa, who has a dermatology practice in Friendship.
"There are amazing things in that book," he said. "There's talk about possible association with diabetes and all kinds of bizarre things. They really pile on the overly frightening rhetoric."
Sharon Mohale, a certified physician's assistant in Dr. Kress' office, questions the age-inappropriateness of some of iPledge's requirements. Some Accutane patients are as young as 12, she said, "and they have to go online and answer questions like which form of birth control they should use and what they should do if a condom breaks."
Another sticking point is making boys and women who can't get pregnant subject to iPledge's rules. Jackie Funt, who manages her husband's Mt. Lebanon dermatology practice, said she doesn't understand why teenage boys are required to read an hours' worth of material about pregnancy risks before being allowed to receive the drug.
"It doesn't make any sense," she said.
On June 12, after being deluged by complaints from dermatologists, eight U.S. senators of both parties wrote Dr. Andrew C. von Eschenbach, the acting head of the FDA, expressing concern about iPledge and urging him to "address the procedural barriers plaguing the operation."
An FDA spokeswoman declined to comment on the letter or Dr. von Eschenbach's response.
Officials at Covance did not respond to requests for an interview, instead issuing a statement acknowledging "some confusion and delays" in March and April, when large numbers of prescribers and patients registered with iPledge.
Staffing has since been increased.
Covance will be required to track how many women registered in the iPledge system become pregnant while on Accutane, and make that information public, although no data has been released yet.
It's not clear, in fact, how many women have actually gotten pregnant over the years while taking the drug before iPledge was instituted; such reporting has been voluntary.
One study by Roche, one of the drug's manufacturers, found that nearly 2,000 women became pregnant while on the drug since its approval nearly 24 years ago, and 383 gave birth. Almost half of those babies had birth defects.
Rep. Bart Stupak, a Democrat from Michigan whose teenage son committed suicide while on Accutane, remains skeptical that iPledge will lower those numbers. Mr. Stupak, who held a much-publicized hearing in 2002 on Accutane's dangers, suspects the pregnancy rate among Accutane users is much higher than that, as well as the suicide rate.
Already, he claims, there have been reports of pregnancies involving women in the iPledge system. As long as Accutane continues to be prescribed in such high volume, he said, he doubts these kinds of serious side effects can be avoided.
"For people who face severe disfigurement from acne, fine. Let those families weigh the options of whether they want to do it. But dermatologists are handing it out like it is candy," he said.
It's true that Accutane has become the most widely prescribed acne medication in the country. But Dr. Diane Thiboutot, professor of dermatology at Penn State Milton S. Hershey Medical Center, argued that the FDA is limiting how dermatologists practice medicine.
And it's unfair to penalize hundreds of thousands of patients -- men as well as women -- who have benefited from Accutane because a small percentage of women will ignore the warnings and become pregnant anyway, added Dr. Kress.
"You can't legislate against people's poor judgment."
