Isotretinoin still the best drug for acne

As part of its updated guidelines for the treatment of acne published early last year, the American Academy of Dermatology included new recommendations for the use of oral isotretinoin.

“The indication for using isotretinoin is extended beyond severe nodular cystic acne,” says Joshua Zeichner, M.D., an assistant professor of dermatology at Mount Sinai Hospital in New York City. “It should be considered in patients who have failed traditional therapies and those who have scarring -- both physical scarring in the skin and emotional or psychosocial scarring.”

Dr. Zeichner embraces the expanded guidelines. “I think that dermatologists often wait longer than they should to prescribe isotretinoin,” he says. “Perhaps dermatologists will now be open to prescribing the drug slightly earlier than before. Ultimately, this means better care for our patients, with fewer permanent scars.” 

In an interview with Dermatology Times, following his presentation on isotretinoin at the American Academy of Dermatology (AAD) Acne Boot Camp in March, Dr. Zeichner says the lipophilic drug is best absorbed along with a fatty meal.

Patients also need to be educated on how to use the drug, rather than merely being written a prescription.  “It is important to tell patients to take the medicine not only with food, but with a high-fat meal,” Dr. Zeichner notes. “Otherwise, in the absence of food, less than half the concentration of the drug is absorbed. Therefore, our prescribed dose may be very different than the effective dose that is reaching the patient.”

Patients should be evaluated in follow-up visits to the office. “If they are not experiencing any dryness of the skin or of the lips, then perhaps they are not absorbing the drug,” Dr. Zeichner says.

The one brand name version of the medication (Absorica, Ranbaxy/Sun Pharma) employs technology that includes fats in the actual tablet. “In the absence of a fatty meal, a higher concentration of the drug is absorbed compared to the generic medications,” Dr. Zeichner says. “However, if the drug is taken the way it should be, then there is little difference in the absorption rates between the generic and brand medications.”

Traditionally, isotretinoin has been dosed to reach a target cumulative dose of 120 to 150 mg/kg, which was determined based on the studies of Accutane (isotretinoin), which was subsequently removed from the U.S. market in 2003.

“There are now several generic medications that are all substitutable for each other,” Dr. Zeichner says. And according to the FDA, all these drugs are bioequivalent. “This means that the drugs must be absorbed between 80% and 125% of each other,” Dr. Zeichner points out.

Moreover, regardless of which version of the drug is selected, treatment needs to continue until the patient “is 100% clear,” Dr. Zeichner says. But studies have shown that twice-daily dosing of the medication “more effectively delivers higher drug levels to the body as compared to once-daily dosing.”

Patients with severe acne who take isotretinoin may experience flaring of the disease. “This is the direct result of the effect of the drug during the first few weeks of treatment,” Dr. Zeichner says. “Unfortunately, significant flaring itself may cause permanent scars; so initial dosing should be at very low levels in your most severe patients.”

In addition, severe patients can start on oral prednisone to lessen the likelihood of flaring.

Studies in the United States and Canada have shown questionable associations between isotretinoin use and development of ulcerative colitis. However, dermatologists who are concerned about this connection should take comfort in a 2014 French nationwide study published in the American Journal of Gastroenterology.  “Investigators evaluated nearly 40,000 patients and found no causal association between oral isotretinoin and ulcerative colitis,” Dr. Zeichner reports. “In fact, the drug appeared to lower the risk of developing Crohn’s disease.”

The other major side effect of isotretinoin is its questionable link to depression and suicide. “We know that retinoids may affect the central nervous system (CNS) and may inhibit serotonin signaling,” Dr. Zeichner says

One study, published in 2010 in BMJ (formerly the British Medical Journal), concluded that the suicide risk among acne patients taking isotretinoin was actually less than those not treated with the drug.

Despite lingering doubts over side effects, “oral isotretinoin is the closest option that we have in finding a cure for acne,” Dr. Zeichner concludes. “It is the only drug that addresses all of the main pathogenic factors in acne. It is also safe to prescribe when patients are closely monitored.”

Disclosure: Dr. Zeichner has served as a consultant to Promius Pharmaceuticals and Ranbaxy/Sun Pharma.