A Novel Patient Support Program to Address Isotretinoin Adherence: Proof-of-Concept Analysis

April 2015 | Volume 14 | Issue 4 | Original Article | 375 | Copyright © April 2015

Lawrence F. Eichenfield MD and Andrew C. Krakowski MD

Division of Pediatric and Adolescent Dermatology, Rady Children's Hospital, and Departments of Pediatrics and Medicine (Dermatology), UC San Diego School of Medicine, San Diego, CA

The iPLEDGE protocol for isotretinoin treatment requires multiple steps to be completed within strict timing windows, resulting in many interruptions or discontinuations of treatment. The US Food and Drug Administration has indicated that approximately 40% of isotretinoin prescriptions written over the course of one year of the iPLEDGE program were denied due to failure to comply with iPLEDGE. Insurance restrictions add to the likelihood of prescriptions not being filled. Here, we describe a novel program implemented specifically to assist patients and providers with improving isotretinoin therapy adherence. This innovative isotretinoin support program provides assistance with insurance questions and hurdles, an uninterrupted treatment supply, educational support, reminder communications, and an indigent patient assistance program. Proof-of-concept analysis shows that 17 months after implementation of the program, 93% of prescriptions received have been filled. Utilization of the program appears to improve adherence to an isotretinoin treatment regimen, with fewer interruptions due directly to unfilled prescriptions.

J Drugs Dermatol. 2015;14(4):375-379.


Acne is a condition that affects approximately 40 to 50 million people in the United States.1 Isotretinoin, first introduced in 1982, is used to treat severe nodular acne that is unresponsive to conventional therapy, including systemic antibiotics. However, isotretinoin is associated with an increased risk of birth defects, spontaneous abortion, and premature births. Given its teratogenic potential, isotretinoin should be prescribed for female patients of childbearing potential only if sufficient precautions have been taken to prevent pregnancy during the treatment period.2

Isotretinoin and the iPLEDGE

Due to its teratogenicity, isotretinoin is marketed under a special restricted distribution program called iPLEDGE. Isotretinoin can only be prescribed and dispensed by providers and pharmacies registered with the iPLEDGE program, and can only be dispensed to patients registered and compliant with iPLEDGE.3 The iPLEDGE program was introduced in 2006 with the goal of preventing pregnancy and minimizing potential fetal exposure to the drug in females undergoing treatment with isotretinoin.4 However, the iPLEDGE protocol requires several restrictions for both patients and providers that may be burdensome.5 Restrictions for female patients include a 1-month waiting period before treatment can commence, monthly pregnancy tests, the need to access the iPLEDGE system each month to answer questions about pregnancy and contraception, and a requirement to fill each monthly prescription within a 7-day window. Healthcare providers must spend time counseling patients on their isotretinoin medication as well as on the importance of contraception. Providers are also responsible for obtaining and entering pregnancy test results into the iPLEDGE system. To add to the complexity of the process, the provider’s office must enter the patient’s pregnancy test results before the patient can complete the iPLEDGE questionnaire or the pharmacy can fill the prescription.4 If a patient misses the 7-day window to fill her prescription, she must restart the entire process of pregnancy screening before isotretinoin treatment can be administered again.
These appointment timing and prescription filling restrictions have had a negative impact on the overall use of isotretinoin, frequently causing treatment to be interrupted or discontinued entirely.4 An IMS longitudinal study (2004- 2008) of new isotretinoin prescriptions for female patients 13 to 45 years of age revealed that the number of isotretinoin prescriptions significantly decreased with the introduction of iPLEDGE.6 A report by the US Food and Drug Administration (FDA) evaluating the operational aspects of the iPLEDGE program indicated that over a 3-year period (March 1, 2008 to February 28, 2011), more than 1 million prescriptions for isotretinoin were written each year, but an average of 423,052 were denied each year due to failure to comply with iPLEDGE guidelines.3 The majority of these denials were to females of childbearing potential (59%). The primary reason for prescription denials was that patients did not complete the monthly questionnaire during the 7-day prescription window. Of note, 39% of prescription denials were to males, primarily due to the prescriber not confirming counseling