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Low-Dose Isotretinoin for Acne Vulgaris
Adverse effects are dose-related, so lower-dose isotretinoin is an exciting prospect.
Isotretinoin is indicated for nodular acne or severe acne that is unresponsive to conventional therapies. The usual dose is 0.5 to 1.0 mg/kg/day for 20 weeks, or a cumulative dose of 120 mg/kg. As side effects are dose-related, the idea of low-dose isotretinoin therapy for less severe forms of acne is attractive, but little data exist on the safety and efficacy of this strategy.
Investigators in Israel conducted a prospective, observational, open-label study of isotretinoin in 638 patients with moderate acne. Patients were divided into two groups. Group 1 contained 495 patients aged 12 to 20 years with a 2:1 female:male ratio. Group 2 contained 122 patients aged 21 to 35 years with a 3.5:1 female:male ratio. All patients received 20 mg/day of isotretinoin for 6 months. Patients were evaluated every 2 months through unblinded clinical examinations and laboratory tests. Pregnancy tests were done at baseline for women with childbearing potential. Follow-up was not explicitly reported but took place over a period of up to 4 years.
A total of 617 patients completed the study. In group 1, 95% of patients achieved considerable improvement or complete remission of their acne; 26 patients (5%) did not respond and either their isotretinoin dose was increased to 30–40 mg/day, oral erythromycin was added, or the low-dose isotretinoin was continued for 8 months until remission occurred. The mean cumulative dose in group 1 was 70 mg/kg. In the follow-up period, 20 patients (4%) relapsed. Polycystic ovary syndrome was subsequently diagnosed in 7 of the patients who relapsed.
In group 2, 93% achieved significant improvement or remission, and 7% did not respond. In these nonresponders, the isotretinoin dose was either increased or continued at the low-dose level for 9 months until remission was achieved. The mean total dose was 67 mg/kg. Seven patients (6%) relapsed; of these, polycystic ovary syndrome was diagnosed in two.
The most common side effects were mild cheilitis (91%) and mild xerosis (43%). Epistaxis was reported in 2.5%. There were no pregnancies and no reported depression or other psychological side effects. A slight and transient elevation of liver enzymes (5%) and serum lipids (4%) was seen. One patient discontinued the medication due to a marked increase in triglycerides.
Comment: Low-dose isotretinoin is an attractive proposition for the treatment of moderate acne, and one that seems supported by this large, independently funded study. However, the following conclusions can be made:
1. Low-dose isotretinoin should be studied in randomized, blinded, placebo-controlled trials with long follow-up periods to determine safety and efficacy.
2. Polycystic ovary syndrome should be considered in females with recalcitrant acne.
3. Serial laboratory and pregnancy tests are still requirements for low-dose therapy.
4. Conventional dosing remains better for severe and nodular acne.
5. The low-dose regimens require longer duration of isotretinoin exposure, which may lead to increased risk for exposure during pregnancy.
6. Alternative dosing and schedules may prove difficult in the U.S. under the new federal monitoring program.
— Mary Wu Chang, MD
Published in Journal Watch Dermatology April 25, 2006
Citation(s):
Amichai B et al. Low-dose isotretinoin in the treatment of acne vulgaris. J Am Acad Dermatol 2006 Apr; 54:644-6.
- Medline abstract (Free)