Dermatology Times editorial advisor, Dr. Elaine Siegfried continues the discussion on isotretinoin with James Leyden, M.D., emeritus professor of dermatology at the University of Pennsylvania. Here, the two discuss isotretinoin dosing and side effects.
Dr. Siegfried: One of the things that I think really complicates treatment with regard to dosing is the prescribing information (1 mg/kg for five months), because the insurance companies really adhere to those recommendations. I have had to take patients who I’ve started on low dose off of the drug at five months, because their insurance won't pay for it anymore. Then, they have to wait for a couple of months before restarting it. How do you get around that?
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Dr. Leyden: That sounds like a hassle and that may be more local geographic issues in that regard. Name a drug of significance that 30 years later is still being officially advised exactly the way it was when it first came out. The only one I know of is Accutane. I really think there is a need to reassess dosing of isotretinoin. Part of the problem is, right now there’s nobody really interested enough to try to modify dosing because it’s a hassle. The FDA isn’t going to just do things the way it used to, and I wouldn’t either if I were in their shoes.
It costs a lot of money to modify a drug label; then you have to ask the question: Will we get it back? Back when they approved this drug, the FDA went out on the limb, because it was clear that this molecule in several species of animals was a teratogen. The question was: Will it be a teratogen in humans? We found out within a year and a half that it was. There were potential bone effects, elevated lipids, etc.The FDA fairly courageously agreed that there were a lot of people with very severe disease for which the treatments were pretty pitiful, and so they approved it specifically for that group of patients. Obviously, as the specialty has become more comfortable with the drug, we have extended the boundaries of whom we will treat with this molecule.
I am really now of the strong opinion that if you have a 12- or 13-year-old with really bad acne, and he has older brothers and sisters who had bad acne, that they should be treated with isotretinoin sooner than later. Many have the clinical impression that pre-teens and young teenagers relapse at a much higher rate than older patients, and that is being confirmed by the I-Pledge data. An important aspect of the dose ranging studies done in the late 1970s was the failure to find a non-effective dose in very severe inflammatory acne (0.1 mg/kg was as effective as 1 mg/kg). The relapse rate one year post treatment showed a dose effect. That follow-up period was for safety purposes. Noone ever dreamed that any of them would stay clear. From that point, the focus of many has been to determine the best way to give a single course, and the trend has been to push the dose higher. I raised the question that since all of these patients were 18 and older and in the time frame of when acne resolves on its own, that younger patient could be different, and we now know that is a reality. I am of the opinion that at least males should be treated with a dose that is free of side effects and, once clear for two or three months, titrate the dose down and restart if needed. In young girls, my approach is the same and as they clear I transfer them to spironolactone to avoid prolonged isotretinoin exposure.