CME #112 – September 2002: Pregnancy Prevention
And Risk Management
In the Dermatology Office

Skin & Aging is proud to bring you this latest installment in its CME series. This series consists of regular CME activities that qualify you for two Category One Physician Credit Hours. As a reader of Skin & Aging, you aren’t required to pay a processing fee. For ethical, moral and legal reasons as dermatologists, you should provide practical information about birth control to patients taking any teratogenic products. This month, Eileen Enny Leach, M.P.H., R.N.; Anne Marie Ruszkowski, B.S.N., R.N., D.N.C.; and Robyn Gmyrek, M.D., share tips on how to ensure patients understand and commit themselves to contraception use and how to monitor them for pregnancy risk throughout treatment. At the end of this article you’ll find a 10-question exam. Mark your responses on the postage-paid postcard and return it to HMP Communications. About 1 month after the publication date, we’ll post this course on Skin & Aging’s Web site, which you can access at www.skinandaging.com. I hope this CME contributes to your clinical skills. Cordially, Steven R. Feldman, M.D., Ph.D., CME Editor Principal faculty: Eileen Enny Leach, M.P.H., R.N.; Anne Marie Ruszkowski, B.S.N., R.N., D.N.C., and Robyn Gmyrek, M.D. Method of Participation: Physicians may receive two Category 1 credits by reading the article and successfully answering the questions. A score of 70% is required for passing. Use the postage-paid card provided to submit your answers and evaluation or log on to www.skinandaging.com and respond electronically. Estimated time to complete the educational activity: 2 hours Dates of original release: September 2002 — Expiration Date: September 2003 This activity has been planned and produced in accordance with the ACCME essentials. Accreditation Statement: HMP Communications, LLC is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Designation Statement: HMP Communications, LLC designates this continuing medical education activity for a maximum of 1 credit hour in category 1 credit toward the AMA Physician’s Recognition Award. Each physician should claim only those hours of credit that he/she actually spent in the educational activity. Disclosure Policy: All faculty participating in Continuing Medical Education programs sponsored by HMP Communications are expected to disclose to the meeting audience any real or apparent conflict(s) of interest related to the content of their presentation. Faculty Disclosures: Robyn Gmyrek, M.D., has disclosed that she is a member of the Speakers’ Bureau for Roche. Eileen E. Leach, M.P.H., R.N., has disclosed that she has an employment affiliation as medical director for Roche Laboratories, Inc. Anne Marie Ruszkowski, B.S.N., R.N., has spoken at Roche supported educational activities. Learning Objectives: At the conclusion of this educational activity, the participants should be able to: • identify Category X drugs used in dermatologic practice • evaluate female patients for selection and compliance with birth control methods • identify the contraceptives that are considered primary methods of birth control and those that are considered secondary methods • develop a plan to implement the isotretinoin Pregnancy Prevention and Risk Management Program in the dermatology office setting. Target Audience: Dermatologists, Plastic Surgeons, Internists Commercial support: None A lthough pregnancy prevention may seem far removed from the clinical practice of dermatology, dermatologists prescribe many agents known to be teratogenic. For ethical, moral and legal reasons as dermatologists, you should provide practical information about birth control to your patients taking teratogenic dermatologic products. In addition, ensure patients understand and commit themselves to contraception use and monitor them for pregnancy risk throughout treatment. Here, we’ll provide you with a guide to pregnancy risk management in the office. This guide is based on the isotretinoin (Accutane) Pregnancy Prevention and Risk Management Program (Be Smart, Be Safe, Be Sure Accutane Pregnancy Prevention and Risk Management Program and the System to Manage Accutane Related Teratogenicity (S.M.A.R.T.)1 Even though the examples focus on isotretinoin, the information presented here on pregnancy prevention can also be used for dermatologic patients taking any other teratogenic agents. Teratogens in Dermatology A drug is considered to be teratogenic in humans when at usual pharmacologic doses it disrupts normal development — in other words, when the rate of anomalies associated with exposure is higher than the rate of spontaneous anomalies or when malformed infants have a history of maternal exposure more often than do normal children.2 Investigational and well-supported anecdotal incidents of birth defects are used as evidence of teratogenicity. Animal evidence is also used to determine risk.3 The FDA classifies drugs into five categories — A, B, C, D and X — of gradually increasing potential for birth defects (See FDA Categories of Risk of Birth Defects, page 65).3–5 A surprising number of drugs used in dermatology fall into the classes associated with birth defects — categories C, D and X (See Teratogenic Agents Used in Dermatology Tables, page 66).3–5 Although systemic agents are somewhat more likely than topical to be teratogenic, all three categories contain topical and systemic drugs. An Approach to Risk Management Drug manufacturers and physicians face the issue of pregnancy prevention. Manufacturers have taken a variety of approaches to preventing drug-related birth defects. Package information varies from a straightforward warning to “avoid pregnancy while taking the drug” for fluorouracil to a systematic risk-management program regarding contraindications and warnings for isotretinoin, including pre-, peri- and post-therapy pregnancy testing, informed consent, monthly contraceptive counseling and a survey of women taking isotretinoin.5 The revised isotretinoin pregnancy prevention program was developed because despite extensive warnings, pregnant women continued to receive isotretinoin prescriptions. Of women who report pregnancy while taking isotretinoin, just under one-third (26%) of them are pregnant when they receive or fill their first prescription for the drug,6 and about two-thirds become pregnant during therapy.6 Prescribers must ensure that no women are pregnant when they start isotretinoin or other teratogenic therapies (See Identifying Patients at Risk: Pregnancy Testing, page 67) and to monitor them for pregnancy during and for 1 month after therapy. A recent analysis of data describing reported pregnancies in women taking isotretinoin revealed that certain patients are at particularly high risk.7 The data show that most of the pregnancies that occur during therapy can be attributed to one or a combination of the following factors: 1. inability to maintain a commitment to abstinence 2. use of less effective methods of contraception because of a lack of education about efficacy 3. inconsistent use of contraception because of lack of information 4. unexpected sexual intercourse 5. failure of contraceptive method. To prevent pregnancy, prescribers should assess and deal with each of these five factors (See Identifying Patients at Risk: Contraception, page 68). Some patients may be poor risks for pregnancy prevention, and prescribers must use their judgment to determine whether a potential teratogenic therapy recipient will be reliable enough to avoid factors one and four. You can use patient education materials to try to help prevent pregnancies caused by factors two and three. Since all contraception methods have some risk of failure associated even with perfect use, you should address factor five by requiring a second reliable method of contraception. The revised isotretinoin program meets the published standards of the FDA8 for augmented risk management by introducing enhancements to educating the public and prescribers, and by providing a process for certifying prescribers understand and will implement it. The model begins with the identification of a risk issue and the creation of a context. Risk and benefit are then assessed, and various options are identified and analyzed. The evaluation of options leads to the selection of a strategy. Alternatives for implementing the strategy are weighed, and a program is adopted. The results are periodically evaluated to determine the success of the program and challenges to it. The program is continually being reviewed and refined.8 Be Smart The S.M.A.R.T. program takes into account factors known to influence the efficacy of contraception, including the demonstrated efficacy of a contraceptive method based on its correct and consistent application and the user’s knowledge of her contraceptive method(s) and the ability of the prescriber to assess pregnancy risk and educate patients.9 Much of the Be Smart, Be Safe, Be Sure brochure is similar to the previous isotretinoin pregnancy prevention program, which had been in place since 1988. New to the program are a review of all approved contraception methods; the percentage of pregnancies occurring with the typical and perfect uses of contraception; and methodologies for evaluating the pregnancy risk profile of patients who will receive prescriptions for isotretinoin. Prescribing requirements are now more categorical and involve the pharmacist’s support. The main changes are: • Prescribers must qualify female patients using the following criteria: -verifying negative pregnancy test results -confirming the patient’s selection and commitment to use two forms of effective contraception - obtaining informed consent relative to pregnancy risk - encouraging the patient to join the Accutane Survey. • Prescribers must attach to each prescription an Accutane Qualification Sticker that includes the qualification date. • Pharmacists may not dispense an isotretinoin prescription without a qualification sticker. • Isotretinoin prescriptions can no longer be filled by telephone, by mail or electronically. The S.M.A.R.T. Prescriber S.M.A.R.T. provides the following main components for clinicians: • The S.M.A.R.T. Guide to Best Practices discusses the teratogenic potential of isotretinoin, presents information on pregnancy testing and gives specific information about effective contraception. • The S.M.A.R.T. Letter of Understanding for prescribers attests that prescribers know isotretinoin to be a teratogen, have read the Guide to Best Practices and understand their responsibilities to minimize risk of fetal exposure to isotretinoin, and understand how to qualify female patients for isotretinoin. Contained in the Letter of Understanding is the prescriber checklist, a self-certification form that each potential isotretinoin prescriber must sign, verifying that the prescriber: - understands the risk and severity of fetal injury/birth defects caused by isotretinoin - knows how to diagnose and treat various presentations of acne -knows risk factors for unplanned pregnancy and effective measures for avoiding it - understands it’s the informed patient’s responsibility to avoid pregnancy during isotretinoin therapy and for 1 month after stopping isotretinoin. To ensure that patients will have the knowledge and tools needed to do so, the prescriber agrees that before treating female patients with isotretinoin he will refer them for expert, detailed pregnancy-prevention counseling and prescribing reimbursable by the manufacturer, or if he has the expertise to perform this function, he will himself do it. - understands and will properly use throughout the isotretinoin treatment course the S.M.A.R.T. procedures, including monthly pregnancy avoidance counseling, pregnancy testing and the use of the qualification stickers. Qualification stickers must be affixed to all prescriptions for isotretinoin. Prescriptions for men need a qualification sticker with the word male checked and the qualification date left blank. Prescribers can obtain stickers only after reading the S.M.A.R.T. Guide to Best Practices and signing and returning the Letter of Understanding. The S.M.A.R.T. Pharmacist Elements of S.M.A.R.T. intended for pharmacists include: • the Accutane Dispensing Guide, which describes S.M.A.R.T. and the use of the qualification stickers to confirm a patient’s suitability to receive isotretinoin • an Accutane Medication Guide describing S.M.A.R.T., which, by regulation, pharmacists must include with all prescriptions they dispense. The new Guide is printed on yellow paper to distinguish it from the earlier Guide dated January 2001  telephone verification of authorization to use qualification stickers. This non-mandatory option allows pharmacists to check to see if a prescriber has agreed and signed the Letter of Understanding. The Patient’s Role Separate male and female versions of the materials are provided. For Women The booklet Be Smart, Be Safe, Be Sure Accutane Pregnancy Prevention and Risk Management Program for Women contains all the essential elements of the isotretinoin pregnancy prevention program. There’s an education section, which contains information about contraindications, precautions and warnings. Also contained in this section is a referral form for contraception counseling by a reproductive specialist. It includes instructions to the specialist concerning the requirements for isotretinoin therapy. This form is provided in triplicate, providing the specialist with the convenience of a copy which, filled out with his recommendations, he can send back to the isotretinoin prescriber. A consent section contains several forms for the patient or her parent or guardian to read and sign. In this context, informed consent may be seen as part of the educational process, as the patient’s initials after each statement and the signature at the bottom of the forms confirm and document that she has read and understood the contents. The booklet includes duplicates of the forms that may be filed in the prescriber’s records. There’s also an informed consent/patient agreement form on adverse events, which is intended to document that the patient or her parent or guardian understands and accepts the risks and benefits of isotretinoin treatment. Next comes a patient information/consent form, which concerns compliance with pregnancy testing and contraception requirements. This third form, like the second form, is also to be signed by the patient or her parent or guardian. Completing both forms is mandatory for female patients. There’s also a patient qualification form, which documents that the patient understands that she is agreeing to avoid pregnancy. There’s also a section on education reinforcement, which provides detailed information on available contraceptive methods; the selection and use of appropriate, effective contraception; and the rates of possible contraceptive failure. A subsection lists contraception myths and explains the facts. It’s important that prospective patients read this subsection, as many women obtain information about sexual activity from sources other than health professionals. The myths were derived from statements made by women who have had unwanted or mistimed pregnancies. Also in the section is an instruction sheet for the urine pregnancy test kits. The kits may be used in the prescriber’s office or, when appropriate, by the patient at home. Finally, the section gives information on how to access other resources, including a toll-free line that provides information on isotretinoin in 13 languages, a toll-free contraception counseling line and a video about the most common reasons for unplanned pregnancies. >For Men The booklet for male patients includes the same three sections as does the booklet for women. • The education section gives information on isotretinoin therapy, information about male reproduction and a warning not to share isotretinoin with others or to donate blood during isotretinoin therapy and for 1 month following the discontinuation of isotretinoin. Because isotretinoin does not significantly affect sperm, male patients have no other restrictions. • The consent section has only the informed consent/patient agreement form, which male patients must sign before receiving isotretinoin prescriptions. • The educational reinforcement section tells patients how to access the toll-free Accutane InfoLine. Implementing a Program in the Office Crucial to implementing any pregnancy-risk–management program is the development of an office protocol for evaluating and managing patients. Choose a patient coordinator from among your staff members to manage paperwork, get in touch with patients for monthly follow-up and be the primary contact with the manufacturer and dermatology sales specialists to keep educational materials in good supply and up to date. Reading matter on the drug and the associated pregnancy prevention program should be left in various office locations. It can be labeled with the coordinator’s name and telephone extension. Because other staff members should be able to carry out all or some of the program components, another duty of the coordinator could be cross-training some of the staff. Staff-to-staff instruction, team meetings and sharing case studies or frequently encountered situations will not only develop individual skills but also help the staff work together more effectively in implementing the program. The following scenario provides an approach to ensuring the best possible outcome for a female patient who has been assessed and determined to be a candidate for isotretinoin therapy: Initial visit. While the patient is waiting for her appointment, have the receptionist or nurse give her educational materials describing the drug she will be taking and any requirements for receiving it. If the patient is new to the office, you or a designated staff member should spend some time getting to know her, as well as perform an examination and draw blood for initial tests. Make sure the patient understands the teratogenic effects of the medication and the necessity of effective birth control. For example, for isotretinoin patients, be sure they know they must use two forms of effective birth control simultaneously before, during and for at least 1 month after therapy, as well as the need for monitoring for pregnancy. Stress the need for two negative pregnancy tests prior to the initiation of therapy and monthly tests throughout therapy. The initial interview. Assess the patient’s childbearing potential, pregnancy status and current contraceptive use, and ascertain the time of last unprotected sex. With the program for isotretinoin, progress/continuation notes, available from the manufacturer, include the facts you must obtain initially and at every visit. Don’t allow a patient to dismiss questions; make sure she fully understands them. Also, be aware that some patients respond to questions according to what they think their sexual activity should be or what they think you want to hear. Pay particular attention to nonverbal clues that may prompt you to question the response. Based on the information you receive, determine if a referral to a specialist in family planning services for contraceptive counseling is warranted or if you or a staff member will provide counseling to help the patient decide what contraceptive methods will best fit her lifestyle. The goal of counseling is to give patients what they need to know to help them make wise contraceptive choices. During counseling, address the patient’s misconceptions about contraception and compare risks of contraception with risks of pregnancy. Describe the acceptable methods of birth control, including efficacy, major side effects and contraindications. Discuss emergency contraception in case she forgets to use effective birth control or has a method failure. Teach patients signs of early pregnancy. Make sure each patient understands that if she thinks she may be pregnant, she should stop taking the teratogenic prescription and get in touch with you. Include the patient’s sex partner in your discussion. Encourage the patient to discuss with him the contraceptive measures required for drug use. Assure her that you’ll be happy to speak with her partner and answer any of his questions. Once the patient understands the material you have presented, have her complete a patient information/consent form. Have the patient take a first pregnancy test at this time, if possible. If the test is negative, schedule a second pregnancy test or provide her with a kit with which to perform the test herself at home within the first 5 days of her next normal menstrual period that immediately precedes the planned initiation of therapy. Second visit. The patient may return to receive a prescription if the result of the second test is also negative, she has chosen two birth control methods and has been using them for at least 1 month. Monthly visits. At each visit during treatment and for 1 month after the patient has discontinued treatment, reassess the patient’s reproductive history, knowledge of contraception, and recent and current use of contraception methods. For example, if on reassessment for isotretinoin, the patient remains qualified according to S.M.A.R.T. criteria, she may receive another 30-day prescription with a dated qualification sticker. Choosing Effective Contraception Patients on isotretinoin are required to use two effective forms of birth control simultaneously for 1 month before, during and for 1 month after treatment. At least one of the methods must be a primary method. Primary methods of birth control are those that are most effective.10 They include the combination birth control pill, injectable hormones, implantable hormones, insertable hormones (vaginal contraceptive ring), transdermal hormones (the patch), IUDs and sterilization (tubal ligation, partner’s vasectomy). Secondary methods are considered to be moderately effective10 and must be used simultaneously with a primary method. Among secondary methods are the diaphragm with spermicide, the cervical cap with spermicide and male latex condoms with spermicide. Common methods of birth control that aren’t acceptable for patients on isotretinoin include the progestin-only minipill, the female condom, withdrawal and natural family planning (rhythm method). Outcome Measurements Several independent outcome approaches are being used to measure the success of S.M.A.R.T. One is the Accutane Survey, in which Roche has committed to increasing the enrollment of female patients to 60% from the current 25% to 40%. The company is asking prescribers to remind and encourage patients to join the Accutane Survey. A second objective measure is a review of prescriptions by an independent corporation to determine the use of Accutane Qualification Stickers. It’s expected that the stickers will be used on at least 90% of the isotretinoin prescriptions by the end of the first year. Taking a proactive approach, the aim of a pregnancy prevention and risk management program should be to try to prevent fetal exposure to known teratogenic drugs. Any program should provide patient education, informed consent for pregnancy prevention, reinforcement of educational messages and tools for contraception compliance. The S.M.A.R.T. program is an example of a pregnancy prevention program that’s also applicable to other teratogenic drugs used in the dermatology office.