What information do you give a patient who has never heard of isotretinoin?

Joseph Bikowski, MD: First, it is the safest most effective medication for the treatment of acne. Second, it is a normal constituent of the human body; you have it in your body right now. We all need vitamin A. Vitamin A becomes isotretinoin in our bodies. When we give you this pill we increase the levels of isotretinoin in your body just enough to produce the biggest problem associated with this medication, a bad baby. If you get pregnant while taking this medication, there is a good chance you will have a deformed baby. Nine-point-eight days after you take your last pill, isotretinoin is eliminated from you body and if you would conceive a child from that point on you would have no problems. The government says wait 30 days.

This drug does not cause depression. We have six studies in the last five to six years that show that it does not cause depression. You may hear on the Internet that this drug causes Ulcerative Colitis. That is not true; there is no evidence. There are many adverse events that can occur with this drug but the majority of those are minor and can all be managed.

What do you tell patients to expect from isotretinoin treatment?

Dr. Bikowski: I tell them that I have treated about four to five thousand patients with this medication over the last 30 years, and I have never seen a patient who did not respond to it and who did not clear on the drug. It is the only medication that I can say this about—that it works essentially 100 percent of the time. If you take the medication for the full course you will clear. This is the only time I say something that definitive in medicine. The worse you are, the better your chances are of being cured and never having acne return.

But there are a lot of patients who just don’t do well on a conventional course of isotretinoin. You put them on isotretinoin they clear and you take them off and they flare back up. That happens at times. For the males I will put them on low-dose long-term isotretinoin and I have had some patients on it for four to five years until everything burns out. For females I have them take additional conventional courses.

What are the main points you cover when talking to someone about isotretinoin for the first time?

Joshua Zeichner, MD, FAAD: The majority of patients I put on isotretinoin are known patients who have tried other medications with me. I explain that this is a heavy-duty medication that comes with side effects. But these can safely be managed with continued monitoring during therapy. After one course, some patients will be clear forever. Others may have a recurrence, but the acne will never be as bad as it was before isotretinoin. A minority of patients do need a second or even a third course.

Do you have tips for introducing isotretinoin?

Julie C. Harper, MD: It’s not a quick visit, because there is a lot of ground to cover. Even if the patient hasn’t been on other medications, if they have severe acne with scarring I will introduce isotretinoin as a treatment option. I explain that this is the only product that is potentially a cure for acne and that we need to be aggressive, since there is already evidence of scarring. I talk about the risks of the medication versus the risk of scarring and when you compare them, you have, in my opinion, a clear advantage to taking isotretinoin.

When I talk about the risks I still mention depression. I say that there is evidence when people start out depressed they actually become less depressed, but it is still a small risk and if they have any symptoms of depression (which I describe) they should stop the medication and call me. I talk about inflammatory bowel disease and I lean heavily on the literature, telling patients that the most current studies do not show an increased risk, but if they have severe abdominal pain, blood in the stool, etc. to stop the medication. I quickly talk about the mucocutaneous side effects.

The other group for which I discuss isotretinoin are patients who have been on topical medications and antibiotics but who still have moderate acne; Nothing is clearing them up, and they will have to be on antibiotics much longer than I am comfortable with. I even consider isotretinoin for non-responsive patients with more mild acne, if they ask about isotretinoin, they understand the risks, and can stick with the monthly monitoring.

For patients where isotretinoin is the treatment of choice but other options may yield results, how do you explain the difference between treatments?

Dr. Bikowski: You have one of two choices. I can put you on conventional therapies, medications that we have used for the last 30 years or so. These are systemic antibiotics and topical medications. Over a period of time—three to six months—they may well be effective to a certain extent. You will have to be on them for an average of two to four years, and you are putting a foreign chemical into your body every time you take the antibiotic. I explain that the real reason we use the antibiotic is for the anti-inflammatory activity. If you go on isotretinoin you are putting something in your body that is already there and probably after six months of therapy you may never need anything else again. It is your one chance for a cure.

When do you bring up isotretinoin for patients with more moderate acne?

Dr. Harper: I almost never talk about isotretinoin with this group on the first visit. I use combinations of different therapies and talk about the pathophysiology of acne and why combination therapy is needed. When the patient is, for example, four months into treatment and only 50 percent better or less or there is an issue with compliance or side effects, I start talking about isotretinoin or changing their combination therapy. I explain that isotretinoin carries increased risk, but you are on it for a predetermined amount of time and you have a relative cure for acne. If patients need to be on antiobiotics long-term, I think it is really worth having the discussion about the risks and benefits of isotretinoin.

If a person who clearly would benefit from isotretinion does not want to consider it and wants to be on long-term antibiotic instead, I will keep them on long-term antibiotics. Hopefully I don’t have to this very often, because I think in global terms of antibiotic resistance, it is not the right thing to do. However in the individual person I can’t find any data showing long-term antibiotics do harm to that person.

Isotretinoin Dosing: QD or BID?

Dr. Harper: I am probably in the minority here but I favor once daily dosing. The adherence is much better and the day I stop seeing results with QD dosing I will change to BID dosing. I see people getting results with all brands and I see their lips and skin get dry and their hair is not greasy and their acne clears, so I have objective evidence that patients are absorbing this drug and it is working. It would be really interesting to see a head-to-head study of QD vs. BID dosing and see if there is any difference in clinical outcomes.

Dr. Bikowski: I think most people don’t realize you have to get a certain amount through the intestinal tract into the blood stream, through the skin, and into the pilosebaceous unit. Peaks and troughs on a 24-hour dinural basis makes no difference in the overall ability of the drug to absorb. Once you get it in to your body, the studies say it works. So I think once a day is fine and you get better compliance. Even at doses beyond 1mg/kg/day, I still use once daily dosing.

Dr. Zeichner: I prefer twice daily dosing whenever possible. Studies have shown in the steady state, average drug trough levels with twice daily dosing are actually higher than peak levels of once daily dosing. Moreover, you are getting smaller drug level fluctuations at twice daily dosing compared with once daily dosing. Some patients just are not compliant with twice daily dosing, so in those cases I prescribe once daily dosing. Finally, the drug should ideally be taken with a fatty meal to enhance absorption, as less than half is absorbed in the absence of food. Isotretinoin with lidose technology has the advantage of being better absorbed on an empty stomach than the generics, especially important when patients do not take the pill with a cheeseburger.

Do you have tips on interaction with iPLEDGE?

Dr. Zeichner: iPLEDGE can seem overwhelming initially, but once you take the time to understand the process it is not difficult to navigate, at least from the provider perspective. You need to take time to educate patients on the system so they are compliant. In my practice I have a “three strikes you’re out” policy, and if patients can’t stay on track with iPLEDGE we don’t continue to invest our time with that patient.

Do you direct patients to a particular pharmacy?

Dr. Zeichner: I like as much as possible for my patients to consistently take the same drug throughout the course of therapy. There is variation among the generics, even though they are all AB rated. Moreover, when they getting drugs with different names it leads to patient confusion. For these reasons, I am a fan of specialty pharmacies that can provide the same drug throughout the course of therapy or sticking to a single branded drug. 

Steven Leon, MS, PA-C is on staff at Dermatology and Laser Centre in greater Los Angeles. He is cofounder of FixWarts.com.