Tag Archives: isotretinoin

Is Abstinence Contraception?

For many women, abstinence is a reliable way to prevent unwanted pregnancy. But is it a valid form of contraception for young women who are taking the powerful teratogenic drug isotretinoin?

Courtesy Wikimedia Commons user Diacritica

Advisers to the Food and Drug Administration danced around that topic at a meeting examining whether the risk management program for isotretinoin — called iPLEDGE — was effectively reducing the number of pregnancies in women of child-bearing age who take the drug.

Isotretinoin is indicated for a severe, scarring form of acne, but is used off-label for other types of acne, as well.

iPLEDGE began in 2006. As part of the program, young women who are capable of getting pregnant are required to have monthly pregnancy tests during their course of treatment, and to use two methods of birth control. But it’s left up to the women to decide what they will use. According to data submitted to the FDA by isotretinoin maker Mylan Pharmaceuticals, after birth control pills, abstinence was the top choice for all women as a primary method of birth control.

About 13% of women who became pregnant on the program were using abstinence as their primary method, with no back-up contraception. Twenty-five percent of women in the program who were not pregnant used abstinence and no back-up, and another 10% used abstinence as their primary method, with oral contraceptives as the secondary method.

Among isotretinoin-using pre-teen and teenaged girls, abstinence was listed as the primary method. It was the second most popular contraceptive technique for 20- to 29-year-olds.

Mylan reported that there have been 836 pregnancies in the 5 years since iPLEDGE began. Four hundred women chose to end their pregnancies, possibly because of the risk of birth defects. The company does not know the outcomes in 282 of the pregnancies. There were 45 live births; of those there were 8 children born with congenital anomalies.

Pregnancies are declining, though, as reported in our news coverage of the meeting. But even Mylan said in its background materials that, “the most common reason for iPLEDGE pregnancy as reported by the prescriber and the patient, was failure to comply with the iPLEDGE contraceptive requirements (e.g., did not use two forms of birth control, did not use contraception on the date of conception, unsuccessful at abstinence).”

How many pregnancies could be avoided with more specific education for prescribers and for young women about which birth control methods are the most effective?

The FDA advisers heard from Dr. Eleanor B. Schwarz, a University of Pittsburgh ob.gyn., who pleaded for the iPLEDGE program to make a strong recommendation for young women to use IUDs or contraceptive implants.

Some members of the advisory committees agreed that perhaps it was time to provide a more comprehensive guide to the effectiveness of various contraceptive techniques.

FDA officials were largely silent on that matter. And it’s hard to imagine them — or the isotretinoin makers — weighing in on such a dicey topic as which birth control method young women should be using.

What do you think? Should the iPLEDGE program be giving young women more evidence-based information about contraceptives?

—Alicia Ault (@aliciaault on Twitter)

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Filed under Dermatology, Drug And Device Safety, Family Medicine, IMNG, Internal Medicine, Obstetrics and Gynecology, Pediatrics, Primary care

New Isotretinoin Drug May Address Safety Concerns

Isotretinoin has taken a beating over the last several years. From IBD to suicide, the acne drug has been at the forefront of lawsuits and clinical debate.

Could a new isotretinoin drug be the answer to quelling the drug’s saftey concerns?

Dr. Hilary E. Baldwin

According to Dr. Hilary E. Baldwin, vice chair of the Department of Dermatology at SUNY-Downstate in Brooklyn, N.Y., the answer could be yes, and a new isotretinoin drug may be just around the corner.

She reported the news at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

She said that a phase III trial of CIP-isotretinoin (Cipher Pharmaceuticals) is wrapping up and results will soon be submitted to the FDA for review. 

The double-blind, randomized trial compared CIP-isotretinoin to commercially available isotretinoin in more than 900 patients with severe recalcitrant nodular acne. The drug utilizes Lidose technology, which helps enhance absorption of the active ingredient of the therapy.

According to Dr. Baldwin, the drug addresses safety concerns, such as IBD and depression. The gelatin capsules of CIP-istoretinoin help reduce GI irratation and the drug is less food dependent.

But it won’t solve all isotretinoin’s problems.

Dr. Baldwin said a question she always gets is whether iPLEDGE is going to get easier. “No. Moving onto the next question,” she responded, to a room full of laughter.

Phase III CIP-isotretinoin results should be released in the near future. We’ll keep you posted!

– Amy Pfeiffer

Disclosure: SDEF and my employer, International Medical News Group, are both owned by Elsevier.

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Isotretinoin – Caught Between Help and Hype

The James Marshall Accutane trial has been highly anticipated – at least by some, including:

  • Rabid fans of the actor who at one time was dubbed “The next James Dean.”
  • Lawyers hungry to cast more chum upon the churning Accutane waters.
  • And dermatologists, who must balance yet another risk/benefit ratio: the risk of being named in a multimillion dollar lawsuit vs. the benefit of isotretinoin to young people with disfiguring acne.

Marshall – who goes by his legal name James Greenblatt in the case filed in New Jersey Superior Court – was the free-wheeling biker in “Twin Peaks,” and Pfc. Louden Downey in the Academy Award-winning film “A Few Good Men.” He used isotretinoin and developed an inflammatory bowel disease that required a colectomy. Mr. Greenblatt claimed this resulted in incontinence, derailing his acting career. The suit, scheduled to go to trial today, had an all-star cast of witnesses: Brian Denehy, Martin Sheen, and Rob Reiner.


We might be able to handle the truth about isotretinoin -- if we could only decide just what it is. Photo by Flickr Creative Commons user rot ist die farbe der hoffnung

When I called the court this morning to confirm the case, court administrator Rob Helsabeck told me it had been indefinitely adjourned. “No continuance date has been set,” he said. “I don’t know the details, but I heard that there is ongoing discussion between Roche and Mr. Greenblatt’s attorneys.”

Will Roche settle, sacrificing a few million to keep a high-profile case low-profile?

Or, perhaps science will prevail?

And that leads us to the science…

Flckr Creative Commons user cemre - before and after isotretinoin

Accutane was practically birthed with a bad reputation. In 1982, it went to market with fewer than 100 cases under its clinical belt, Dr. Hilary Baldwin said at the summer meeting of the American Academy of Dermatology.

Its teratogenic dangers were already well-established, and the prescribing information made it abundantly clear that it could cause thalidomide-like birth defects. But it wasn’t long before — like an eighth-grade girl caught kissing in the bathroom —  Accutane began to acquire a long list of horror stories.

Alopecia. Aggression. Violence. Depression. Suicide.

And, beginning in 1986, ulcerative colitis and Crohn’s disease. Subsequent reports led to a 1988 modification of the package insert, warning of a possible association with inflammatory bowel disorders, and urging patients to be on the lookout for GI pain, rectal bleeding, and diarrhea.

“In 2007, the lawyers got hold of this by the neck,” said Dr. Baldwin, a dermatologist in Brooklyn, N.Y. “Since then, more than 5,000 suits have been filed.

Seven of those have gone to trial, and Roche lost every one of them, with a total settlement amount of $45 million. Three, however, have been overturned on appeal – one just last week, with  Roche recovering more than $10 million.

It’s a victory for the company to be sure, but 45 more cases are lined up in the New Jersey Superior Court case docket. One of Roche’s biggest legal handicaps, Dr. Baldwin said, is that it has been unable to fully tell its side of the story.  “You certainly don’t want to make light of the poor young person who has developed this terrible disorder, and yes, it’s sad that someone would get IBD after treating their acne. But the jury only hears the numerator – they were never able to hear the denominator, that 18 million people have taken isotretinoin” and only a tiny minority developed IBD.

“The picture gets even cloudier when you consider that a time of peak onset for IBDs is 15-30 years – also the prime time for isotretinoin treatment.”

Two clinical reviews, one conducted in 2006 and one in 2009, found no statistically significant association between the drug and either ulcerative colitis or inflammatory bowel disease. The 2006 case-control study found 85 cases of IBD concurrent with isotretinoin use – a rate of 14 per year. “Interestingly, the expected results from this age population would have been about 59 new cases per year, so you could look at it that isotretinoin was actually protective of developing IBD,” Dr. Baldwin said.

According to a probability scale used in the study, four cases (5%) scored in the “highly probable” range for isotretinoin as the cause of IBD, 58 cases (68%) were “probable,” 23 cases (27%) were “possible,” and no cases were “doubtful,” – a conclusion that would leave most doctors unconvinced of a direct causality.

Lawyers have a different interpretation. “Study confirms 100% of IBD cases may have been caused by Accutane,”
trumpets the website of The Orlando firm, P.C., of Athens, Ga.

So who’s right?

The answer is still fuzzy, Dr. Baldwin said. Things looked pretty good for isotretinin through 2009, when a Canadian study looked at 12 years of data on 1 million Manitoba residents. There were no significant associations between the drug and the disease in the case-control analysis.

But earlier this year, an American team came up with a slightly different conclusion. Looking at about 15 million people in 12 health care claims databases, the authors concluded that 24 cases and 36 controls had been exposed to isotretinoin. Cases were 4.5 times more likely than controls to develop ulcerative colitis, but there was no link between the drug and Crohn’s disease.

“With our two most vigorous studies showing conflicting data, we are left not knowing what to do,” Dr. Baldwin said.

In the meantime, she said, the best physicians can do is strongly warn patients (and their parents) to be on the lookout for GI symptoms, and to report them immediately. The warning must be repeated at every follow-up visit and the medication discontinued if anything untoward develops.

The reality? As Oscar Wilde said,  “The truth is rarely pure – and never simple.”

— Michele Sullivan (@MGSullivan on Twitter)

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Filed under Dermatology, Family Medicine, Gastroenterology, IMNG, Internal Medicine, Pediatrics, Primary care, Psychiatry, The Mole

Quelling Fears About Teens and Isotretinoin

From depression to suicide, the controversy surrounding the use of isotretinoin in teenage patients is well known. While there is not much you can do to put out the fire surrounding isotretinoin, you may be able to quell parental fears by being thorough. Dr. Lawrence Eichenfield introduced the Symptom Survey Tool at today’s meeting at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation, a division of Elsevier.

Image via Flickr user jo-h by Creative Commons Attribution License

Dr. Eichenfield created the Symptom Survey Tool and uses it in his office to monitor his isotretinoin patients. He said the benefits of the survey tool include improved clinical assessment, efficiency, and billing and documentation. The survey asks patients whether or not they experience a list of adverse events. Some of the items included on the survey are dry lips, nose bleeds, headache, dry skin, depression, mood swings, and suicidal thoughts…

To read more of this post, please visit our sister blog The Mole, which is located at SkinandAllergyNews.com.

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Filed under Dermatology, Drug And Device Safety, Family Medicine, IMNG, Practice Trends