Prescribing Isotretinoin for Transgender Patients: A Call to Action and Recommendations.

Case Scenerio: A 26-year-old patient presents to the dermatology clinic with severe nodulocystic scarring acne. The patient identifies as a transgender male and notes that he has been receiving hormone replacement therapy for the past 4 years with weekly intramuscular testosterone injections.

Measures to prevent the risks associated with exposure to cytostatic drugs in glaucoma filtering surgery. / Medidas para prevenir los riesgos asociados con la exposición a citostáticos en cirugía filtrante de glaucoma.

INTRODUCTION: The use of cytostatic drugs such as Mitomycin C and 5-Fluorouracil is well-known in glaucoma filtering surgery, as well as the management of its complications. However, there is a lack of information regarding the preventive measures to be taken by the professional that handles these types of substances. OBJECTIVE: Raise awareness among professionals of the risks associated with the use of cytostatic drugs without adequate prevention measures. RESULTS: Review of the available literature and legislation on preventive measures in the management of cytostatic drugs in the medical and ophthalmological field. CONCLUSIONS: The prevention and awareness of the risks of the qualified professionals that handle these substances is the most important measure to prevent the possible risks. Coordination is necessary with the Occupational Health teams of the Hospital, as well as the professionals and staff involved in the different phases of the process, from the preparation in Hospital Pharmacy to its elimination.

Optimizing Isotretinoin Treatment of Acne: Update on Current Recommendations for Monitoring, Dosing, Safety, Adverse Effects, Compliance, and Outcomes.

Acne vulgaris is the most common skin disease treated by dermatologists. It can be severe and result in permanent scars. Isotretinoin is the most effective treatment for acne and has the potential for long-term clearance. Prescribing and monitoring protocols can vary widely among prescribers. Recent studies, reports, and consensus statements help shed light on optimizing the use of isotretinoin for acne. A recent literature review is summarized in this article to help the practitioner optimize isotretinoin use for acne. The article outlines the advantages and disadvantages of standard, high-dose, and low-dose isotretinoin regimens; discusses the current status of controversies surrounding isotretinoin (including depression/suicide, pregnancy, and inflammatory bowel disease); reviews monitoring recommendations and treatment for hypertriglyceridemia and elevated transaminase levels; and discusses common adverse effects seen with isotretinoin, along with their treatment and prevention.

Simplifying contraception requirements for iPLEDGE: A decision analysis.

BACKGROUND: For persons of childbearing potential prescribed isotretinoin, the iPLEDGE program requires use of 2 simultaneous methods of contraception or commitment to abstinence. OBJECTIVE: To model the relative effectiveness of a variety of contraception strategies for patients taking isotretinoin, including those that are acceptable according to iPLEDGE. METHODS: We performed a decision analysis modeling the estimated rate of pregnancy with various contraception strategies during a typical 6-month course of isotretinoin. RESULTS: Tier 1 contraception options (eg, subdermal hormonal implant, intrauterine devices) each had effectiveness of >99.5% alone. When combined with a secondary form of contraception, tier 2 contraception options (eg, depot medroxyprogesterone injections, combined oral contraceptives) each had effectiveness >99%. LIMITATIONS: Sensitivity analyses were conducted to evaluate the impact of uncertain parameters on the results. CONCLUSION: There may be opportunities to simplify iPLEDGE by recognizing the high effectiveness of tier 1 contraception options and increasing use of secondary forms of contraception among those using tier 2 contraception options as their primary form of contraception. Future studies are needed to understand the most effective strategies in clinical practice to prevent unintended pregnancy for patients taking isotretinoin to improve outcomes and provide patient-centered care.

High-Risk Medication Prescriptions in Primary Care for Women Without Documented Contraception.

INTRODUCTION: During pregnancy, women may be exposed to teratogenic medications resulting in a risk of complications and poor maternal-fetal outcomes. The objective of this study was to evaluate the prescription of teratogenic medications in women of childbearing age and the associated prescription of contraception in the primary care setting. METHODS: The use of high-risk, potentially teratogenic, medications was retrospectively evaluated in women of childbearing age (13 to 45 years old) at 2 family medicine practices. Charts were reviewed for medication use and whether patients received a form of birth control (medication, sterilization, or postmenopausal) with the teratogenic medications. A multivariable logistic regression model was used to estimate the age-adjusted association between receiving a teratogenic medication and contraception. A subgroup analysis excluding ondansetron was also performed. RESULTS: A total of 3,956 nonpregnant women were included with 988 (25%) prescribed at least 1 high-risk medication. The most commonly prescribed high-risk medications were ondansetron (n = 724, 73%) and lisinopril (n = 195, 20%). More than half (55%) of the women prescribed a high-risk medication were without a form of birth control. When ondansetron was excluded, 10% of the population was prescribed at least 1 high-risk medication with 62% also without a form of birth control. Women less than 25 years of age had decreased odds of receiving contraception when prescribed a teratogenic medication (adjusted odds ratio, 0.47; 95% confidence interval, 0.34-0.66). CONCLUSION: In a family medicine setting, 25% of women of childbearing age were prescribed a high-risk medication with over half not having evidence of contraception management. Interestingly, younger age women had lower odds of receiving contraceptive management when prescribed high-risk medications. Prescribers should be aware of and counsel on the risks of teratogenic medications and regularly evaluate reproductive plans for patients.

Improving the Safety of Teratogen Prescribing Practices in a Pediatric Rheumatology Clinic.

OBJECTIVES: Although teratogenic medications are commonly used to treat rheumatic disease, no standard model currently exists for educating adolescent patients about teratogenic risk or performing routine pregnancy screening. We performed a quality improvement project to increase education and pregnancy screening in girls and women of childbearing age prescribed teratogenic medications in our pediatric rheumatology clinic. METHODS: Eligible participants included female patients age 10 and older prescribed teratogenic medications in a single-center tertiary care pediatric rheumatology clinic. Seven plan-do-study-act cycles were completed to test the following interventions: visible project reminders, physician and nurse education, progress updates, previsit planning, and development of an electronic health record education template. Chart reviews were performed, and control charts were created for each aim to analyze improvement over time. RESULTS: At baseline, 57 of 231 (24.7%) clinic encounters of female patients age 10 years and older taking teratogenic medications had education documented within the last 12 months, and 47 of 231 (20.3%) had pregnancy screening performed at the visit. Implementation of our interventions resulted in improvement in documentation of annual teratogen education (904 of 1135; 79.6%) and routine pregnancy screening (940 of 1135; 82.8%), both of which were statistically significant (P < .0001). Control charts revealed special cause with sustained improvement over >1 year. CONCLUSIONS: The interventions made through this quality improvement project increased the frequency of both teratogen education and urine pregnancy screening in patients taking teratogenic medications. Development of a standardized education template in the electronic health record played a key role in sustaining these improvements over time.

Knowledge, attitudes, and practice regarding medication use in pregnant women in Southern Italy.

The study assessed knowledge, attitudes, and medication use of a random sample of pregnant women attending outpatient Gynecology and Obstetrics clinics at randomly selected public General and Teaching hospitals in Naples, Italy. A total of 503 women participated. Those more likely to know that a pregnant woman with chronic condition must discuss whether or not to take a medication with the physician were Italian, aged 31-40 years, employed, with no history of abortion, having had a medical problem within the previous year, with a better self-perceived health status, who knew how to use medications during pregnancy, and who needed information on medications. The knowledge of the potential risk of using non-prescribed medications during pregnancy was significantly higher in employed women, who received information from physicians, who knew how to use medications during pregnancy, and who knew the possible damages related to medications use. More than half had used at least one medication. Those aged 26-35 years, Italian, non-graduated, in the third trimester, having had a medical problem within the previous year, with a risky pregnancy, and with a knowledge that women with chronic condition must discuss whether or not to take a medication with the physician were more likely to use medication. Less than half had used medication without a physician's advice. Those who were more likely to self-medicate were older, Italian, multiparous, with no history of abortion, who knew that women with chronic condition must discuss whether or not to take a medication with the physician, who did not know the potential risk of using non-prescribed medication during pregnancy, who had used prescribed medication during pregnancy, and who needed information about medications. Educational programs for women about medication use are important to increase their knowledge of the potential risks to the pregnant women and the unborn child in order to reduce self-medication.

A comparative review of the isotretinoin pregnancy risk management programs across four continents.

Isotretinoin has revolutionized the treatment of severe acne vulgaris, a condition which if left untreated may result in significant socio-psychological implications for those affected. Timely access to isotretinoin therapy is important to avoid the risks of potential physical and emotional scarring. However, due to its high risks of teratogenicity, isotretinoin must be used with care in females of childbearing potential. Since isotretinoin's introduction, numerous risk management programs have been implemented across the world in an attempt to prevent isotretinoin use in pregnancy. This paper aims to provide an evidence-based review of the risk management programs for isotretinoin in Australia, Europe, Singapore, New Zealand, and the United States of America. The effectiveness of these programs and the factors leading to isotretinoin exposure in pregnancy are critically analyzed in an effort to inform the future direction with respect to designing the ideal regulatory program. Stringent risk management programs, such as the iPLEDGE in the US and Pregnancy Prevention Program (PPP) in Europe, may not be effective in reducing the risks of fetal exposure to isotretinoin when used alone. There is evidence that such strenuous regulation results in increased fear of teratogenic risks but does not translate into a reduced rate of pregnancies exposed to isotretinoin. A successful program must prioritize education about effective contraception, while minimizing any extraneous requirements, to ensure that women are not inadvertently undertreated for acne.

Effects of posted point-of-sale warnings on alcohol consumption during pregnancy and on birth outcomes.

In 23 states and Washington D.C., alcohol retailers are required by law to post alcohol warning signs (AWS) that warn against the risks of drinking during pregnancy. Using the variation in the adoption of these laws across states and within states over time, I find a statistically significant reduction in prenatal alcohol use associated with AWS. I then use this plausibly exogenous change in drinking behavior to establish a causal link between prenatal alcohol exposure and birth outcomes. I find that AWS laws are associated with decreases in the odds of very low birth weight and very pre-term birth.

[Monitoring of pregnancies exposed to drugs in France: the experience of the registries of congenital malformations]. / Surveillance des grossesses exposées aux médicaments en France : les registres de malformations congénitales.

Registries of congenital malformations were implemented in many industrialized countries following the drama of thalidomide. In 2013, four French registries of congenital malformations in France provide the systematic epidemiological surveillance of birth defects. All are part of international networks of registries, especially European surveillance of congenital anomalies (EUROCAT). If the development of prevention actions including prenatal diagnosis has gradually led the registries to play a key role of assessment on the impact of public health policies, one of the major roles of registries of congenital malformations remains early detection of clusters of malformations secondary to teratogenic effects.

Community drinking water quality monitoring data: utility for public health research and practice.

CONTEXT: Environmental Public Health Tracking (EPHT) tracks the occurrence and magnitude of environmental hazards and associated adverse health effects over time. The EPHT program has formally expanded its scope to include finished drinking water quality. OBJECTIVES: Our objective was to describe the features, strengths, and limitations of using finished drinking water quality data from community water systems (CWSs) for EPHT applications, focusing on atrazine and nitrogen compounds in 8 Midwestern states. METHODS: Water quality data were acquired after meeting with state partners and reviewed and merged for analysis. RESULTS: Data and the coding of variables, particularly with respect to censored results (nondetects), were not standardized between states. Monitoring frequency varied between CWSs and between atrazine and nitrates, but this was in line with regulatory requirements. Cumulative distributions of all contaminants were not the same in all states (Peto-Prentice test P < .001). Atrazine results were highly censored in all states (76.0%-99.3%); higher concentrations were associated with increased measurement frequency and surface water as the CWS source water type. Nitrate results showed substantial state-to-state variability in censoring (20.5%-100%) and in associations between concentrations and the CWS source water type. CONCLUSIONS: Statistical analyses of these data are challenging due to high rates of censoring and uncertainty about the appropriateness of parametric assumptions for time-series data. Although monitoring frequency was consistent with regulations, the magnitude of time gaps coupled with uncertainty about CWS service areas may limit linkage with health outcome data.

Concomitant use of isotretinoin and contraceptives before and after iPledge in the United States.

PURPOSE: The major concern associated with isotretinoin treatment is its high teratogenic potential. Therefore, ensuring use of contraception while on therapy is an important strategy for at-risk patients and has been emphasized in all risk management programs. iPledge, the latest and most rigorous isotretinoin program, requires, among other stipulations, monthly assessments of contraceptive use for patients undergoing isotretinoin treatment. The purpose of this study is to evaluate isotretinoin usage patterns and assess concomitant use of isotretinoin and contraceptives before and after iPledge. METHODS: Female patients aged 13-45 years with a new prescription for isotretinoin products during 2004-2008 were identified in the IMS Health longitudinal prescription claims database. Monthly concomitant use of isotretinoin and contraceptives was estimated. Segmented regression analysis of interrupted time series data was used to assess changes in monthly proportion of concomitant use in the 24 months preceding versus following iPledge implementation. RESULTS: The number of isotretinoin prescriptions decreased after iPledge implementation. A small but significant increase in monthly proportion of patients concomitantly using isotretinoin and contraceptive therapies was observed immediately after iPledge implementation (1.3%, p-value = 0.02), particularly among younger patients (2.5%, p-value < 0.01). No changes in the proportion of concomitancy over time (i.e. slope) between the periods before and after iPledge implementation were observed. CONCLUSION: The findings of this pharmacy prescription claims-based study suggest a small increase in concomitant use of isotretinoin and contraceptives coincident with the time of implementation of iPledge, particularly among younger women. Published 2013. This article is a U. S. Government work and is in the public domain in the USA.

Healthcare professional surveys to investigate the implementation of the isotretinoin Pregnancy Prevention Programme: a descriptive study.

OBJECTIVE: Three online surveys explored compliance with the PPP by pharmacists and dermatologists, in the Netherlands. In 2007 and 2011, two pharmacist surveys were conducted to assess improvement over time. METHODS: In 2007, survey was sent to members of the Utrecht Pharmacy Panel for Education & Research (UPPER) network (n = 1000) and in 2011, to the research group of the Dutch Association of Pharmacists (KNMP) (n = 556). In 2010, a survey was sent to 564 dermatologists of the Dutch Association of Dermatology and Venereology (NVDV). RESULTS: Both pharmacists' questionnaires had response rates of 20% and the dermatologist questionnaire of 28%. Pharmacists' checks on 30-day dispensing remained 82%, but a check whether the prescription is out-of-date decreased (61 to 53%). Pharmacists asked the patient for a negative pregnancy test in 15%, but use of contraception was checked by 44 - 49%. One hundred and five dermatologists (64%) always prescribe contraception; 35 (22%) occasionally. Ninety-three percent of the dermatologists were of the opinion that they performed the PPP. Analysis of different elements of the PPP showed that 41 (25%) were compliant. CONCLUSIONS: The observed non-adherence to the isotretinoin PPP calls for careful evaluation of risk minimisation plans and participation of all stakeholders in the development of these plans.

Drug safety in pregnancy: utopia or achievable prospect? Risk information, risk research and advocacy in Teratology Information Services.

Even though from preclinical testing to drug risk labeling, the situation with drugs in pregnancy has improved substantially since the thalidomide scandal, there is still an increasing need to provide healthcare professionals and patients with updated individualized risk information for clinical decision making. For the majority of drugs, clinical experience is still insufficient with respect to their safety in pregnancy. There is often uncertainty in how to interpret the available scientific data. Based on 20 years of experience with Teratology Information Services (TIS) cooperating in the European Network of Teratology Information Services (ENTIS) methods of risk interpretation, follow-up of exposed pregnancies through the consultation process and their evaluation is discussed. Vitamin K antagonists, isotretinoin and angiotensin (AT) II-receptor-antagonists are presented as examples of misinterpretation of drug risks and subjects of research based on observational clinical data recorded in TIS. As many TIS are poorly funded, advocacy is necessary by establishing contacts with decision makers in health politics and administration, informing them of the high return in terms of health outcomes and cost savings provided by TIS as reference institutions in clinical teratology.

Managing the teratogenic risk of thalidomide and lenalidomide: an industry perspective.

Celgene has developed and operated pregnancy prevention programs since 1998 with the first approval of thalidomide in the US. With the development and marketing of lenalidomide, an analog of thalidomide, the company further advanced its risk management activities, which now cover several territories across the globe. To date, the program is a success in as much as it has minimized the risk of fetal exposure and subsequent development of fetal malformations. Nonetheless, the company understands the need to provide a mechanism for intervention and remediation when at-risk behaviors are identified, and this forms an integral part of the risk management processes. The implementation of the thalidomide and lenalidomide pregnancy prevention program partners patients, healthcare professionals, regulators and the company in a spirit of shared responsibility. This paper also presents the authors' experience and perspective on the challenges of managing a pregnancy prevention program, which at its core aims at ensuring that the product's benefits outweigh the risk of fetal exposure.