The impact of the iPLEDGE program on isotretinoin fetal exposure in an integrated health care system

J Am Acad Dermatol. 2011 Dec;65(6):1117-25. doi: 10.1016/j.jaad.2010.09.017. Epub 2011 May 11.


Background: Preventing fetal exposure to isotretinoin is widely acknowledged as an important safety issue. The iPLEDGE program is the latest in a series of Food and Drug Administration-mandated risk management programs designed to prevent pregnancies in female patients of childbearing potential (FCBP) taking isotretinoin.

Objective: We sought to evaluate the effect of iPLEDGE relative to the prior risk management program (system to manage Accutane-related teratogenicity [SMART]) on the risk of isotretinoin fetal exposure in FCBP in a managed care setting.

Methods: All FCBP at Kaiser Permanente Southern and Northern California who filled at least one prescription for isotretinoin during a 4-year period (March 1, 2004, to February 29, 2008) were included in this retrospective cohort study (n = 8344). Chart review was performed to confirm fetal exposures and outcomes. A Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence intervals.

Results: There were a total of 29 fetal exposures and 9912 isotretinoin treatment courses. After iPLEDGE was implemented, the unadjusted rate of fetal exposure decreased from 3.11 to 2.67 per 1000 treatment courses (P = .69). The hazard ratio = 0.76 (95% confidence interval 0.36-1.61) for fetal exposures to isotretinoin during treatment courses filled after iPLEDGE implementation compared with SMART.

Limitations: Limitations include limited generalizability of results, small sample size (n = 29 total documented fetal exposures), and potential uncontrolled confounders.

Conclusion: Evaluating the impact of iPLEDGE on isotretinoin fetal exposures is important in understanding the full risks and benefits of isotretinoin treatment. We found no evidence that iPLEDGE significantly decreased the risk of fetal exposure in FCBP compared to the SMART program.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cohort Studies
  • Delivery of Health Care, Integrated
  • Dermatologic Agents / adverse effects*
  • Fetal Diseases / chemically induced
  • Fetal Diseases / prevention & control*
  • Humans
  • Isotretinoin / adverse effects*
  • Program Evaluation
  • Retrospective Studies
  • Risk Management
  • Young Adult


  • Dermatologic Agents
  • Isotretinoin