Isotretinoin (Accutane®) and Pregnancy

    Isotretinoin (Accutane®) is given orally in the treatment of cystic acne and other dermatological diseases.  Isotretinoin cream is used topically to treat photo-damaged and wrinkled skin.  Very little systemic absorption occurs after topical application.  
    A very uncommon but strikingly similar pattern of congenital anomalies has been observed in more than 80 children whose mothers were treated orally with isotretinoin in therapeutic doses during early pregnancy.  Characteristic features of this isotretinoin embryopathy include central nervous system (CNS) malformations, microtia/anotia, micrognathia, cleft palate, cardiac and great vessel defects, thymic abnormalities, and eye anomalies.  Among 115 pregnant women treated with isotretinoin that were voluntarily reported to the manufacturer before the outcome was known, 18% ended in spontaneous abortion.  Of the 94 live born infants, almost all of whose mothers had been treated during the first trimester, 28% had at least one major malformation.  Typical malformations occurred in children born to women who took various dosages of isotretinoin (0.2-1.5 mg/kg), even within the usual therapeutic range and in women who were treated for less than one week in the first trimester of pregnancy.  In a follow-up study of 31 five-year-old children born to women who had been treated with isotretinoin during the first 60 days after conception, 47% performed in the subnormal range on standard intelligence tests.  Of 12 children who had major malformation, 6 (including 4 with major CNS anomalies) had an IQ < 70, 4 (including one with major CNS anomalies) had an IQ 70-85, and 2 had an IQ > 85.  Six of 19 children with no major malformations had an IQ = 70-85, and the others had an IQ > 85.          
    Based on the half life of isotretinoin, it is thought that most of its metabolites would be removed from the body within ten days of the last dose.  Thus the current recommendation is to discontinue isotretinoin at least one month prior to conception and it is also highly recommended that while taking isotretinoin, women should be on 2 forms of birth control.  There has been some question regarding the possibility that isotretinoin may be stored or persist in certain cells in the body.  The concern raised was if isotretinoin were kept in reserve would it be able to effect the development of a fetus.  This issue has yet to be resolved.  There is a published report from the manufacturer that reported 101 pregnancies in women who discontinued isotretinoin from days to weeks prior to conception.  No increased incidence in miscarriage or birth defects was reported.  An additional prospective study followed 88 pregnancies with exposure to isotretinoin 2-60 days prior to conception.  Again, no cases of isotretinoin embryopathy were reported.  
    In conclusion, isotretinoin is a potent human teratogen.  A high percentage of the recipients of this drug are women in their child-bearing age, with 38% of isotretinoin users being women of age 13-19 years.
   

North American Isotretinoin Information & Survey Line

   Isotretinoin (Accutane®) is the most potent human teratogen (a teratogen interferes with the development of a fetus and causes birth defects).  Women who become pregnant while using isotretinoin have a high risk for pregnancy loss or for having babies with severe birth defects.  These defects usually affect the development of the fetus' brain, face, ears, thymus, and heart.

   If you, your patient, or someone you know is pregnant and has used isotretinoin during the pregnancy, PLEASE CALL (TOLL FREE) 1-800-645-6164.

   The caller/patient will receive:

            - Telephone counseling regarding the birth defects associated with the use of isotretinoin.

            - The patient will be asked to participate in a research project to understand why pregnancies
               are continuing to occur even though a pregnancy prevention program is in place.  There is no
               cost to you for helping with this study and you are under no obligation to participate.

            - Until it is better understood why pregnancies continue to happen during the exposure to this
               agent, preventing them will NOT be possible.  The study will go a long way towards helping to
               develop strategies to better prevent this tragedy.  Therefore, your help with the project is
               extremely important.

We look forward to receiving your referrals and thank you in advance for your help!

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