LAS VEGAS — Even though acitretin is labeled as a pregnancy category X drug, Dr. Craig L. Leonardi claimed he sees at least one patient of childbearing potential per month who is referred to him on the agent.
“I think that's a terrifically bad practice,” said Dr. Leonardi at a dermatology seminar sponsored by Skin Disease Education Foundation. “You need to think this one through.”
The chief risk posed by use of the drug in women of childbearing potential is retinoid embryopathy, which occurs in 33% of preterm infants exposed to the drug in utero. “As a consequence this drug should not be used in females of childbearing potential, which takes the drug off the list for half the population of our younger psoriasis patients,” said Dr. Leonardi, clinical professor of dermatology at St. Louis University. “Since there is no teratogenic threshold established for any of the oral synthetic retinoids, this drug just shouldn't be used in females of childbearing potential.”
The recommended acitretin pregnancy avoidance period is 3 years in the United States and 2 years in Europe.
Another downside of the drug is that it converts to detectable levels of etretinate in the presence of alcohol ingestion (based on consumption of 8 ounces by a patient weighing at least 75 kg).
A second-generation retinoid, acitretin (Soriatane, Stiefel Laboratories) is available in 10-g and 25-g gel caps. Common doses in psoriasis treatment are 25 mg twice daily, 25 mg twice daily for 1 month followed by 25 mg once daily, or starting off at 25 mg once daily.
Dr. Leonardi said he rarely prescribes acitretin as monotherapy for psoriasis because it has a modest effect on the disease, compared with cyclosporin and methotrexate, resulting in about a 50% reduction of body surface area over a period of 8-24 weeks. In addition, acitretin was approved for psoriasis based on trials involving only 275 patients, and “interpretation of the trial data is difficult,” he said. “If this were a biologic drug it would be shelved.”
Adverse events that occur in more than 20% of patients taking 50 mg/day over 8 weeks include chelitis, skin peeling, pruritus, rhinitis, dry skin, and alopecia. “It's a little bit less of an issue if you use the smaller dose, but nonetheless, these are significant numbers,” Dr. Leonardi said. “There are some significant, common adverse events while on this therapy.”
Despite its modest effect as monotherapy, acitretin “has a very unique mechanism of action,” he noted. “It decreases hyperproliferation of keratinocytes, it decreases inflammation directly, and it helps to normalize differentiation of the skin.”
He went on to point out that acitretin is most effective when combined with other treatments, particularly psoralen and ultraviolet light radiation (PUVA). One study of this combination demonstrated 89% clearance of psoriatic lesions at 8 weeks and 94% clearance at 12 weeks (Dertmatologica 1988;177:218-24).
A more recent trial evaluated the impact of 25 mg/day acitretin plus narrow band ultraviolet B light three times a week in 40 difficult-to-treat psoriasis patients (J. Dermatolog. Treat. 2003;14[suppl 2]:17-20). It found that 88% of patients had at least a moderate improvement of psoriasis and 73% had an improvement of at least 75%.
Dr. Leonardi disclosed he is a consultant, investigator, and member of the speakers bureau for several pharmaceutical companies. SDEF and this news organization are owned by Elsevier.
An interview with Dr. Leonardi can be viewed by visiting www.youtube.com/user/FamilyPracticeNews#p/u/8/XA5NCq4fihQ
'There is no teratogenic threshold established for any of the oral synthetic retinoids.'
Source DR. LEONARDI