WSJ: Illegal Internet Sales and Accutane

Restrictions Curb Use of Powerful Acne Drug --- Patients Who Want
Isotretinoin,
Despite Risk of Birth Defects, Struggle With Onerous New Rules


Jennifer Corbett Dooren

September 12, 2006

The Wall Street Journal D1

THE GOVERNMENT'S most-aggressive effort yet to curb drug side effects
is having
an impact on a popular and highly effective acne drug -- with some
doctors and
pharmacists saying they have stopped dispensing it and some patients
turning to
illegal Internet sales.
In March, the Food and Drug Administration launched a program known as
iPledge,
which aims to keep pregnant women from taking Accutane or its generic,
isotretinoin. The drug is linked to a very high incidence of birth
defects,
including misshapen heads, missing ears and heart defects. But
patients clamor
for it despite the frightening risks, because it is the only effective
treatment for the most disfiguring form of acne.
There had been a number of previous efforts to educate patients and
require
women to sign statements that they understand the dangers, but still
up to
about 200 women a year were becoming pregnant while using the drug,
according
to FDA estimates. So, under pressure from the FDA, the four
manufacturers of
isotretinoin got together and designed the current program.
Isotretinoin is
sold as Accutane, from Roche Holding AG, and in three generic
versions:
Amnesteem from Mylan Laboratories Inc., Claravis from Barr
Pharmaceuticals Inc.
and Sotret from Ranbaxy Laboratories Ltd.
Now, to obtain the drug, patients must register online for the iPledge
program
with the FDA, see their dermatologist monthly to get a fresh
prescription,
answer monthly online questionnaires and fill their prescription
within a
seven-day window after it is written. Women must also visit a
certified lab for
a blood pregnancy test each month and be on two forms of birth
control. The
testing and office visits are usually covered by insurance. But if the
steps
aren't completed properly, the patient will be denied that month's
prescription
at the pharmacy.
Copyright © Toxic Discovery 1994 - 2006 7
There were many initial glitches with the iPledge system that kept
doctors and
patients on the phone for hours, and prevented many patients from
getting the
drug at first. These have largely been worked out, the FDA says. But
doctors
and patients remain frustrated with the program, saying that people
are
frequently denied access to the drug for even minor missteps,
resulting in
interruption of treatment. Men, too, must participate in parts of the
program,
to monitor other potential serious side effects such as liver damage
and
suicidal thoughts.
Some patients like Tiffany Smith, a college student from Havre de
Grace, Md.,
say that even though they complied with the requirements, they still
couldn't
get isotretinoin. Both Ms. Smith and her dermatologist, David Jaffe,
say she
was listed as "inactive" in the iPledge computer for two months before
she got
her first prescription in July. Ms. Smith also says she had to call
three
pharmacies before finding one that participated in iPledge. "It's been
horrible
trying to get the prescription," says Ms. Smith, who must now drive
home from
school in Pennsylvania for the next few months to complete her
treatment.
"It's just a continuous nightmare," says Lawrence Parish, a
Philadelphia
dermatologist who practices with his daughter, Jennifer Parish. He
says all
five of the patients he has had on the drug have had trouble
registering or
getting their prescriptions each month. Dr. Parish says he recently
had a 40-
year-old male patient denied his monthly supply because he went to the
pharmacy
eight days after the prescription was written, rather than the
required seven.
Sandra Kweder, the FDA's office of new drugs deputy director, concedes
that
isotretinoin is "a pain in the neck to get," but says the restrictions
need to
be tough to be meaningful. "This is a pretty toxic drug," she says.
"It's not
Tylenol."
Indeed, some doctors say that while focusing on preventing pregnancies
is
important, patients on the drug -- including men -- need to be
monitored for
other serious side effects like liver damage, possible links to
suicidal
thoughts in adolescents, brain pressure, vision problems, bone and
muscle
damage, along with blood lipid and cholesterol problems.
Prescriptions and sales of isotretinoin and Accutane are down
dramatically. The
number of Accutane prescriptions fell by 46% and prescriptions for the
leading
generic brand dropped by 16% during the first half of 2006, compared
with the
same time in 2005, according to IMS Health, which tracks prescription
sales.
Roughly one million prescriptions for isotretinoin were written
annually before
this, with about a combined $300 million in sales.
"The intention is good," says David Pariser, who runs a five-clinic
dermatology
practice in the Norfolk, Va., area. "But it's really become a barrier
to care."
Although he still has several patients on the drug, Dr. Pariser says
he will
now use isotretinoin as only a last resort for the most severe cases.
He says
some smaller practices in the area have stopped prescribing it
altogether.
It is too soon to say if iPledge has lowered the pregnancy rate. So
far, no
pregnancies have been reported, according to the FDA. But the program
may turn
into something of a referendum on the agency's ability to manage the
risk and
benefits of powerful drugs. Paul Seligman, the FDA's new director for
drugsafety
policy and communication, says the agency has started a planned review
Copyright © Toxic Discovery 1994 - 2006 8
of all of its restricted-distribution programs to see "what is working
and what
is not."
The FDA has been under increasing pressure since Merck & Co.'s Vioxx
was taken
off the market two years ago to do more to protect consumers from
being hurt by
prescription drugs. A recent drug-safety bill introduced last month by
Sen.
Michael Enzi (R., Wyo.) and Sen. Edward Kennedy (D., Mass.) would
require drug
makers to submit post-marketing risk-management plans as part of the
drugapproval
process. The bill is unlikely to pass this year, but legislators need
to approve a funding bill for the FDA next year, which could provide a
vehicle
for drug-safety provisions.
Isotretinoin is one of roughly two dozen drugs subject to some type of
restricted-access plan intended to curb misuse or unnecessary side
effects.
Most of the FDA's risk-management programs are reserved for drugs that
are
administered in hospitals or doctors' offices, such as the multiple
sclerosis
drug Tysabri, or certain cancer drugs. But some -- like Accutane, or
the
antipsychotic clozapine, which can lead to a condition that harms the
immune
system -- are filled at pharmacies. Because these drugs are
self-administered,
regulators are especially concerned about ensuring proper use. FDA
officials
say that Accutane faces more hurdles for patients and doctors than any
of the
other restricted drugs.
While a treatment interruption is inconvenient, many dermatologists
say it
doesn't derail acne treatment because isotretinoin appears to work
cumulatively
even with breaks in treatment. The drug is approved to treat severe
nodular
acne that can lead to disfiguring scars and doesn't respond well to
other
existing treatments, such as Retin-A or antibiotics. However, many
dermatologists also use isotretinoin to treat milder cases of acne
that have
failed to respond to treatment. Most cases of all types clear up
permanently
with a one-time four- or five-month treatment course with
isotretinoin.
Ms. Smith, the college student in Pennsylvania, says she is aware of
the
dangers of isotretinoin. But after living since her early teens with
severe
acne that she struggled to hide, and spending "thousands and thousands
of
dollars" on treatments, this is the first thing that is starting to
work. "I
can look in the mirror and I'm totally satisfied," she says. "There
are a lot
of risks but it's worth it."
A few dermatologists try to give patients additional medicine so there
is no
break in the treatment, says Dr. Parish. The iPledge program is
designed to
dispense only a 30-day supply of medicine at one time. But Dr. Parish
explains
that because it is dosed by weight, a prescription can be written
based on a
heavier weight, giving patients additional medicine.
Sandra Read, a Washington, D.C., dermatologist, says she sees a few
patients
who have turned to the Internet to buy isotretinoin illegally. But
when she
tells them she won't treat them under those terms and urges them to go
through
iPledge, "they don't come back," she says.
FDA officials don't want patients to turn to the Internet and say they
will
discuss with the four drug manufacturers during the next six months
ways to
make some changes to iPledge -- including more flexibility in the
monthly
scheduling of office visits. They may also ease the seven-day rule for
picking
Copyright © Toxic Discovery 1994 - 2006 9
up a prescription, or allow pharmacists and doctors to override
denials in some
cases.
The agency is also working on a consumer-education Web site designed
to pop up
whenever someone might type in "buy isotretinoin" into a search engine
to help
them think twice about buying over the Internet by warning them about
the risks
associated with the drug.
Toeing the Line for an Acne Drug
Some features of the iPledge program that restricts access to
isotretinoin
(brand name Accutane), which carries a high risk of birth defects if
taken
while pregnant. Patients typically take a four-or five-month course of
the
acne medication.
-- All patients, physicians, pharmacists and drug distributors
involved
with isotretinoin must register with iPledge, via a password-protected
Web
site ( www.ipledgeprogram.com ).
-- Women of child-bearing age must take an initial pregnancy test and
then
be on two forms of birth control for 30 days. They then must obtain a
second, blood test for pregnancy within five days of their periods to
receive their prescription.
-- Each month, women must visit their dermatologists, visit a lab for
another pregnancy test, and use the online iPledge system to answer
questions about pregnancy prevention and attest to using two forms of
birth
control. Doctors also must enter the patient's birth-control
information
each month.
-- Answers from doctors and patients about the birth control being
used
must match, or the system will deny the monthly prescription at the
pharmacy. If women don't log on to iPledge every month, they also
would be
denied a prescription at the pharmacy.
-- Men also must visit their doctors each month to receive a new
30-day
prescription. A doctor cannot call or fax in a prescription without
first
seeing the patient.
-- Patients have seven days -- including weekends and holidays --
after a
prescription is written to get it filled, otherwise they will be
denied that
month's prescription. Women must obtain a negative pregnancy test
during
that same time frame.
-- If a pregnancy test were to be positive, a woman wouldn't be able
to
receive isotretinoin. As of March 31, the most recent time frame for
which
figures are available, there were no reports of pregnancies.
Source: The Food and Drug Administration


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