Since its introduction in the United States in 1982, oral isotretinoin has come to be regarded as something of a miracle drug for acne. One recent study, for example, reported complete clearing in 96.4% of patients and a 7.9% relapse rate during the 5-year follow-up period.1
Although isotretinoin is the most effective agent available in the treatment of acne, it can also exert severe teratogenic effects. Prenatal exposure has been linked with an estimated 20% to 35% risk for birth defects, such as cardiovascular, craniofacial, thymic, and central nervous system malformations.2 In addition, neurocognitive impairment has been observed in 30% to 60% of children with a history of in utero exposure.
Considering these risks, pregnancy should be avoided during isotretinoin treatment. With the aim of preventing fetal exposure to the drug, the US Food and Drug Administration (FDA) created a risk evaluation and mitigation strategy called iPLEDGE.3 The program requires providers to educate patients about the fetal risks of isotretinoin, and women of childbearing capacity must commit to using 2 forms of contraception while taking it, and during the month before and after treatment. These patients must also have 2 negative pregnancy tests before initiating treatment and must show a negative result on a monthly pregnancy test to continue receiving the drug.
The contraception use is also required in patients taking methotrexate. Researchers in a paper published in January 2018 in the British Journal of Dermatology noted that methotrexate is increasingly used to treat difficult-to-control eczema, psoriasis, and localized scleroderma in children.4 However, they found that clinicians were substantially less likely to discuss contraception with adolescent patients taking methotrexate compared with patients taking isotretinoin.
As a result of the contraception requirements associated with these agents, dermatologists may have to navigate confidentiality issues with their adolescent patients, who may not want to involve their parents in discussions of their sexuality and contraceptive use. “This is a complex issue with a lot of relevant legal, regulatory, and practical considerations, in addition to the ethical issues,” according to Benjamin K. Stoff, MD, MA, an assistant professor of dermatology at the Emory University School of Medicine, and senior faculty fellow at the Emory Center for Ethics in Atlanta, Georgia.
To learn more about these potential challenges, Dermatology Advisor spoke with Dr Stoff and Temitayo A. Ogunleye, MD, an assistant professor of dermatology in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.
Dermatology Advisor: What are the ethical challenges that dermatologists may face when prescribing drugs such as methotrexate or isotretinoin to a minor, considering the contraception requirement and the likelihood that many adolescents have not informed their parent or guardian that they are sexually active or may already be taking contraceptives?
Dr Stoff: Isotretinoin is the drug most commonly prescribed by dermatologists for which there are regulatory requirements for contraceptive counseling for all patients of childbearing potential, including adolescents. Other drugs, like methotrexate and some oral antibiotics, are also prescribed by dermatologists for adolescents, and counseling for these drugs should also include some discussion of contraception. However, isotretinoin is by far the most regulated of these drugs. The iPLEDGE program, which controls dispensation of isotretinoin, requires that patients of childbearing potential receive contraceptive counseling and, in many cases, contraception.
There are several ethical issues surrounding contraceptive counseling in adolescents considering teratogenic drugs like isotretinoin. To what degree should healthcare providers respect the developing autonomy of adolescent patients in being informed and making medical decisions about contraception? Under what circumstances might the influence of a parent or guardian hinder important discussions with adolescents about sexual activity and access to contraception?
There are also relevant legal and regulatory considerations. In most states, for example, adolescent minors (children between age 12 and 18) can seek and provide legal consent for contraceptive services without a parent or guardian.5 However, the iPLEDGE program requires the consent of parents or guardians for patients under age 18 to be enrolled in the program and receive the drug. Also, there are rare circumstances in which an adolescent may not require the consent of a parent or guardian for any medical interventions, as with marriage, pregnancy, or parenthood.
Finally, there are practical medical considerations relevant to scenarios like this. In many cases of severe acne in adolescents of childbearing potential, oral contraceptive pills benefit acne as well. So, there is a medical rationale for adding contraceptives to the therapeutic regimen independent of contraception. This is not necessarily the case with other skin diseases that may require consideration of teratogenic drugs, however.
Dr Ogunleye: The main ethical challenge that dermatologists face when prescribing these drugs is placing minor patients in a position in which they have to reveal information about their sexual activity that they may not want to reveal. It can also be a potentially awkward situation for the dermatologist, as most dermatologist visits do not require questions about a minor’s sexual practice or health.
Dermatology Advisor: How should these issues be handled in clinical practice?
Dr Stoff: There is a not one single course of action that applies in all scenarios. In general, an open discussion of contraception that respects an adolescent’s growing autonomy — while also including input from parents or guardians — is ideal. However, in circumstances in which a dermatologist suspects that an adolescent patient may benefit from a private discussion about sexual activity and contraception, it is reasonable to request that the parent(s) leave the exam room for that part of the encounter.
Dr Ogunleye: There are several approaches to address this issue.
The easiest way it is to make it standard practice for all women with reproductive capacity to be started on oral contraceptives, except in situations in which there is a a medical reason for exclusion from this practice — such as a personal or family history of deep vein thrombosis — by their gynecologist, family practitioner, or dermatologist, regardless of prior sexual activity. This practice should also be encouraged because oral contraceptives can sometimes be helpful in the treatment of acne, which can remove the stigma that some parents may have regarding their child using oral contraceptives.
Dermatologists can also make it standard practice to ask parents or guardians to leave the room while discussing sexual history and sexual health with minor patients, although this can admittedly be awkward.
In situations in which minor patients choose abstinence as their form of birth control, candor regarding the serious adverse events that can result if pregnancy were to occur while on these medications — including events that would lead to recommendation for termination of pregnancy — is also helpful so that the patient and parents are fully informed. Sometimes hearing the breadth of effects is a good motivator for both parents and minors to consider the use of a hormonal contraceptive, or at the very least to always use a secondary barrier to pregnancy such as condoms if sexual activity occurs.
- Rasi A, Behrangi E, Rohaninasab M, Nahad ZM. Efficacy of fixed daily 20 mg of isotretinoin in moderate to severe scar prone acne. Adv Biomed Res. 2014;3:103.
- Choi JS, Koren G, Nulman I. Pregnancy and isotretinoin therapy. CMAJ. 2013;185(5):411-413.
- Risk evaluation and mitigation strategy (REMS). The iPLEDGE program. Single shared system for isotretinoin. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM234639.pdf. Accessed February 13, 2018.
- Griffin L, Ryan S, Hackett C, Ramsay B. The use of methotrexate in adolescents: contraception, confidentiality and consent [published online January 17, 2018].Br J Dermatol. doi:10.1111/bjd.16356
- Guttmacher Institute. An overview of minors’ consent law, as of February 2018. www.guttmacher.org/state-policy/explore/overview-minors-consent-law. Accessed February 13, 2018.