INTRODUCTION
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
