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#158 Is less more with isotretinoin and acne?

What is the efficacy and tolerability of low-dose compared to conventional dose isotretinoin in the treatment of acne?

Small randomized controlled trials (RCTs) and observational studies demonstrate low-dose (~20mg/day) isotretinoin improves acne similar to conventional dosing. Low-dose may reduce common side effects (chapped lips, dry skin, epistaxis) by 16-35% but may be associated with increased relapse rates, particularly with severe acne and/or possibly impacted by lower total accumulated dose.

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  • Three RCTs compare conventional to low dosing:
    • 60 moderate acne patients, low (0.25-0.4 mg/kg/day) or “conventional” dosing (0.5-0.7 mg/kg/day) for 24 weeks.1 Low-dose demonstrated:
      • Equivalent efficacy (acne grading and lesion counts).
      • Increased patient satisfaction (76% very satisfied versus 31%).
      • Higher (non-significant) one year relapse rate: 18% versus 13%.
    • 150 severe treatment resistant nodulocystic acne patients, 0.1 mg/kg/day, 0.5 mg/kg/day or 1.0 mg/kg/day for 20 weeks.2
      • Equivalent improvement with all doses.
      • Eighteen month relapse rates, from lowest-highest doses: 42%, 20%, and 10%.
    • Both studies reported 16-35% fewer common side effects (chapped lips, dry skin, and epistaxis) with lower doses.1,2
    • 120 mild-severe acne patients, high (1 mg/kg/day) or low-dose (20 mg/day) alternating days for 16 weeks.3 Low-dose:
      • Decrease in acne load 81% versus 95%.
      • Fewer side effects.
  • Large prospective study (638 moderate acne patients, 20 mg/day for 24 weeks) reported “good results” in ~94% of patients, decreased incidence of side effects and 5% relapse at four years.4
  • Smaller observational studies of ~20mg/day support these findings.5,6,7 Two report improved outcomes with a 120 mg/kg total cumulative dose.5,7
  • FDA approved isotretinoin in 1982 for the treatment of severe acne in patients ≥12 years old. The recommended dosage is 0.5-1 mg/kg divided into two doses daily for 4-5 months.8
  • Many lower-dose studies do not reach a similar total accumulated dose as the higher dose treatment arm(s), which may partly explain higher relapse rates.1-3
  • Recommended laboratory monitoring includes triglycerides, cholesterol, transaminase, and complete blood counts.9,10
  • Although there are reports of mood changes, suicidal ideation and suicide, no causal relationship is proven.9,10
  • Isotretinoin is teratogenic and pregnancy must be prevented one month before, during, and after treatment.9,10

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  • Christina Korownyk MD CCFP
  • Kirti Brar MD CCFP

1. Lee JW, Yoo KH, Park KY. Br J Dermatol. 2011; 164:1369-75.

2. Strauss JS, Rapini RP, Shalita AR, et al. J Am Acad Dermatol. 1984; 10:490-6.

3. Agarwal US, Besarwal RK, Bhola K. Indian J Dermatol Venereol Leprol. 2011; 77:688-94.

4. Amichai B, Shemer A, Grunwald MH. J Am Acad Dermatol. 2006; 54:644-6.

5. Rasi A, Behrangi E, Rohaninasab M, et al. Adv Biomed Res. 2014; 3:103.

6. Merita Grajqevci K. Med Arh. 2015; 69: 28-30.

7. Mandekou-Lefaki I, Delli F, Teknetzis A, et al. Int J Clin Pharmacol Res. 2003; 23:41-6.

8. Roche. Product Monograph. Available from: Last accessed January 25, 2016.

9. Goldsmith LA, Bolognia JL, Callen JP, et al. J Am Acad Dermatol. 2004; 50:900-6.

10. Strauss JS, Krowchuk DP, Leyden JJ. J Am Acad Dermatol. 2007; 56:651-63.

Authors do not have any conflicts to disclose.