In the end, we are dependent on creatures we have made.
Goethe 

Isotretinoin and iPledge  on the Global Stage
by Ava Atri, B.A. and David J. Elpern, M.D.

Keywords: isotretinoin, regulation, iPledge program, teratogen

Introduction
Isotretinoin has revolutionized the treatment of acne since it was approved by the U.S. Federal Drug Administration in 1982. Because it is teratogenic, some countries rigorously regulate its prescriptions.  In the United States, prescribers and patients must comply with the iPledge Program in order to write or fill isotretinoin prescriptions.¹  A chance discussion with a colleague from Iran, where isotretinoin can now be purchased without a prescription, led us to survey a number of other countries to see what impediments there are to prescribing isotretinoin around the world.

Methods
We devised a questionnaire on Survey Monkey and sent it to dermatologists from how many? countries. Our survey document solicited responses to these questions:

1. Is the prescription of isotretinoin regulated in your country?
2. Is there a national database for patients on isotretinoin similar to iPledge (the database used in the United States)?
3. Do men need to be registered as well as women?
4. Do female patients need to have a pregnancy test done each month and the results recorded before a prescription is written?
5. Do female patients need to verify that they understand the pregnancy risks of isotretinoin on a monthly basis?
6. Is isotretinoin covered by insurance?
7. Can isotretinoin be prescribed in your country for more than one month without an office visit?

Results. (We need to work on this)
Of the 46 requests, we received 17 usable surveys (Appendix). The United States is the only country with a national program that controls the prescription of isotretinoin.  The regulations controlling isotretinoin vary considerably between countries. (Table) In the U.S. all prescribers must be registered while in India the drug can be purchased by anyone, without a prescription, from beauty parlors! Men who take isotretinoin must be registered in iPledge even though it has no adverse effect on a partner’s pregnancy. No other country has such a requirement.  We have summarized the data in a simplified table:
Summary Table

Discussion
The face of acne in many countries around the world has changed since the introduction of isotretinoin in the United States in 1982.  The medication has one common serious side-effect: significant teratogenicity in women who take isotretinoin during pregnancy.  This has led to robust regulations in some, but not all, countries.  In the U.S., the country with the most restrictive policy, some practitioners are unwilling to prescribe the medication because of the pregnancy risk and onerous paper work; and some patients are fearful about taking it because of what they read on the internet.

In spite of stringent pregnancy prevention programs in the U.S. and Canada, it does not appear that the pregnancy rate in women of childbearing potential has been appreciably lowered.^2,3 Since the iPledge Program was inaugurated in 2006, there has been little research done on its effectiveness in preventing pregnancies in women who take it. . The only report on the efficacy of iPledge we could locate was in 2011.² It is curious that this vast bureaucracy does not make its results available to practitioners. Burdensome regulatory programs may well prove to be ineffective. iPledge is difficult to use and prescribers can easily cut corners to get around the stipulations. Prescriber fear of the punitive actions of the iPledge program may actually discourage physicians from reporting pregnancies in their patients.

Our data document wide variation in isotretinoin regulations around the world. The U.S. has the strictest program; yet there are no studies that attest to iPledge’s success since it’s introduction in 2006. Physicians have been kept in the dark about whether this program is effective over a decade.

Dealing with iPledge in the United States can be a time-consuming hassle.  No other country has such strict regulations. The close monthly scrutiny of all females of childbearing potential (FCP) appears to be overkill for many patients. iPledge, while allowing for abstinence strongly encourages all women of childbearing potential to use two methods of birth control.  This applies to abstinent women (such as nuns), lesbians and transgendered men are mandated to have monthly pregnancy tests.⁴

Limitations of study: We only have one response per country so the data may not be completely accurate and we received responses from only 17 of XX questionnaires sent out. Still, the data indicate no conformity with regards to isotretinoin regulation around the world.

References

1, iPledge program: https://www.ipledgeprogram.com/

2. Maloney ME, Stone SP. Isotretinoin and iPledge: a view of results. J Am Acad Dermatol. 2011 Aug;65(2):418-9. J Am Acad Dermatol. 2011 Aug;65(2):418-9

3. Henry D, et. al. Occurrence of pregnancy and pregnancy outcomes during isotretinoin therapy. CMAJ. 2016 Jul 12;188(10):723-30.

4. Yeung H, et. al. Prescribing isotretinoin in the United States for transgender individuals: Ethical considerations. J Am Acad Dermatol. 2016 Sep;75(3):648-651.

Appendix:

Data from Study