Ibrexafungerp in the Treatment of Vulvovaginal Candidiasis.

OBJECTIVE: To review the pharmacology, efficacy, and safety of ibrexafungerp in the management of vulvovaginal candidiasis (VVC). DATA SOURCES: Literature was sought using PubMed (1966-February 2022) and EMBASE (1973-February 2022), and clinicaltrials.gov. Search terms included ibrexafungerp, SCY-078, and VVC. STUDY SELECTION AND DATA EXTRACTION: All studies including humans and published in English with data assessing the efficacy and safety of ibrexafungerp for the treatment of VVC were evaluated. DATA SYNTHESIS: A phase 2 dose-finding study found ibrexafungerp had similar efficacy to fluconazole in the clinical cure of VVC (51.9% vs 58.3%, respectively). Two phase 3 clinical trials demonstrated ibrexafungerp had statistical superiority over placebo for clinical cure in moderate to severe VVC (P < 0.001 and P = 0.023, respectively). The most frequently reported adverse reactions in the clinical trials were gastrointestinal-related symptoms. To date, data comparing efficacy of ibrexafungerp and topical imidazoles in the treatment of VVC are nonexistent. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Topical imidazoles and oral fluconazole are effective for the treatment of uncomplicated VVC. Due to increased resistance, limited fluconazole coverage for non-Candida albicans species, and potential for significant drug interactions associated with fluconazole use, alternative treatments for VVC are needed. Ibrexafungerp is a new oral triterpenoid antifungal agent indicated for the treatment of VVC. Additional clinical trials are needed to evaluate long-term safety data as well as efficacy and safety in specialty populations. CONCLUSION: Ibrexafungerp, a recently approved triterpenoid antifungal agent, is an effective and well-tolerated option for the treatment of VVC.

Adherence rates and outcomes for 17-hydroxyprogesterone caproate use in women with a previous history of preterm birth.

BACKGROUND: Progesterone has been used for preventing preterm birth with mixed results. The American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine recommended the use of 17-hydroxyprogesterone caproate for risk reduction of recurrent spontaneous preterm birth based on the results of a multicenter, randomized trial in the United States. However, recent literature lacks consensus for efficacy in the American population. In addition, partial adherence and outcomes thereof are underreported. Hence, the relationship between practical adherence to 17-hydroxyprogesterone caproate and outcomes were evaluated. OBJECTIVE: The objective of this study was to evaluate the adherence to 17-hydroxyprogesterone caproate, defined as receipt of greater than 80% of intended injections, at an outpatient maternal-fetal medicine center and its effect on maternal and neonatal outcomes. STUDY DESIGN: This retrospective cohort study included women older than 18 years with a singleton gestation, history of spontaneous preterm birth who initiated 17-hydroxyprogesterone caproate weekly injections between 16 and 20 weeks' gestational age and delivered between the years 2014 and 2017. Women receiving 17-hydroxyprogesterone caproate injections outside of the clinic were excluded. The primary outcome of adherence and secondary outcomes of gestational age at delivery, birthweight, and neonatal outcomes were analyzed using descriptive data, independent t-test, Mann-Whitney U test, chi-square test, and Fisher exact test, where appropriate, with a P value <.05 being considered significant. RESULTS: Adherence to 17-hydroxyprogesterone caproate occurred in 38 of 92 (41.3%) women included in the study. At baseline, there was a difference in age between groups of adherent and nonadherent women (adherent: 30.8 years; nonadherent: 27.4 years; P=.002). The rate of spontaneous preterm birth less than 37, 35, and 32 weeks were not significantly different in those who were adherent vs nonadherent to 17-hydroxyprogesterone caproate. There were no differences in gestational age at delivery (adherent: 36.8±2.6 weeks; nonadherent: 36.5±3.8 weeks; P=.66), birthweight (adherent: 2776 g; nonadherent: 2709 g; P=.68), or composite neonatal morbidity (adherent: 18.4%; nonadherent: 20.4%; P=.86) between the adherent and nonadherent groups. Neonatal intensive care unit length of stay was 15.5 days in the adherent group compared with 15 days in the nonadherent group (P=.72). CONCLUSION: Real-world adherence to 17-hydroxyprogesterone caproate is suboptimal with less than half of women adherent to in-clinic administration. Adherence to 17-hydroxyprogesterone caproate was not associated with a difference in gestational age at delivery or birthweight compared with nonadherence. Further studies are needed to assess the outpatient administration and benefit of 17-hydroxyprogesterone caproate therapy.

Benzodiazepines in Pregnancy.

Benzodiazepine use and dependence are on the rise as well as the number of deaths attributable to the combination of opioids and benzodiazepines. Anxiety, the most frequent condition for which benzodiazepines are prescribed, occurs commonly, and is increasingly noted to coincide with pregnancy. Use of both benzodiazepine anxiolytics and anxiety in pregnancy is associated with preterm delivery and low birth weight. Short-term neonatal effects of hypotonia, depression, and withdrawal are described but long-term sequelae, if any, are poorly understood. Benzodiazepines are associated with physical dependence and withdrawal symptoms which can be serious. To avoid withdrawal, tapering off these medications is recommended. What is known about the pharmacology and pharmacokinetics, pregnancy implications, tapering schedules, and alternative strategies for anxiety are discussed.

Smoking Cessation Following Text Message Intervention in Pregnant Women.

BACKGROUND: Smoking during pregnancy has detrimental effects on mother and fetus. Text messaging has been utilized to improve patient care. OBJECTIVE: To evaluate the impact of text messaging on smoking cessation rates among pregnant women in addition to standard of care (SOC) smoking cessation services. Our SOC includes pharmacist-driven education with or without nicotine patch or bupropion. METHODS: This randomized, open-label, prospective trial was conducted at a maternal fetal care center from May 2014 to January 2016. Pregnant patients in the preparation stage of change were randomized to text messaging or SOC. The primary outcome was smoking cessation verified with exhaled carbon monoxide levels (eCO) 2 weeks from quit date. All received clinical pharmacist weekly calls for 3 weeks and biweekly visits until pharmacotherapy completion. The text messaging group also received predetermined motivational messages. RESULTS: Of 49 randomized patients, 13 withdrew, and 6 were lost to follow-up. The remaining included 14 texting and 16 SOC patients. eCO-verified cessation was achieved by 57.1% in the texting group versus 31.3% in the control ( P = 0.153). Overall, 64.3% of the texting group achieved an eCO below 8 ppm at ≥1 visit versus 37.5% in the control group ( P = 0.143). No difference was found in birth outcomes. The study was underpowered because of slow enrollment and high drop-out rates. CONCLUSIONS AND RELEVANCE: Text messaging had minimal impact on improving smoking cessation rates in the obstetric population. However, further research is warranted because of the underpowered nature of this trial. Given the detrimental effects of smoking in pregnancy, more comprehensive cessation strategies are warranted.

Guide for Drug Selection During Pregnancy and Lactation: What Pharmacists Need to Know for Current Practice.

OBJECTIVE: To provide guidance for clinicians on risk assessment of medication use during pregnancy and lactation. DATA SOURCES: Authors completed PubMed searches to identify articles focused on the use of medications in pregnancy, including fetal development, drug transfer across the placenta, trimester exposure, chronic conditions in pregnancy, medications in lactation, and lactation and chronic disease. STUDY SELECTION AND DATA EXTRACTION: Articles were reviewed to provide overall guidance to medication selection during pregnancy. The following information was reviewed: medication use in pregnancy, including fetal development, drug transfer across the placenta, trimester exposure, chronic conditions in pregnancy, medications in lactation, and lactation and chronic disease. DATA SYNTHESIS: This article will provide an overview of medication safety considerations during pregnancy and lactation. Information was interpreted to help clinicians predict the potential risk and benefit in each patient to make an evidence-based decision. The article concludes with guidance on risk assessment and how pharmacists may support fellow health care providers and their patients when considering medication use. CONCLUSIONS: Information about the effects of medication use during reproductive periods is limited. With the removal of the Food and Drug Administration pregnancy categories, clinicians will be relying on pharmacists to aid in the appropriate selection of therapies for patients. It is critical that pharmacists keep abreast of resources available and be able to assess data to help prescribers and their patients.

Administration Rates of the Tdap Vaccine in Obstetric Patients.

BACKGROUND: Infants younger than 6 months of age are at high risk for contracting pertussis because of not being fully vaccinated. The Advisory Committee on Immunization Practices (ACIP) recommends vaccinating all pregnant women with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) between 27 and 36 weeks to offer passive immunity to the infant to help protect them until they are able to receive the full pertussis series. OBJECTIVE: To assess and compare compliance with the 2013 ACIP recommendation of vaccinating pregnant women with Tdap at 27 to 36 weeks' gestation in 2 obstetric clinics. METHODS: This cross-sectional, retrospective chart review evaluated Tdap vaccine compliance in a random sample of obstetric patients from October 2013 to September 2014. The primary outcome evaluated the proportion of patients who received Tdap between 27 and 36 weeks' gestation. Secondary outcomes included the proportion of patients who received Tdap at any point in pregnancy and within 30 days postpartum. RESULTS: The charts of 573 patients were reviewed, and 237 met inclusion criteria. For the primary outcome, 142 patients (59.9%) received the Tdap vaccine. Overall, 156 patients (65.8%) received Tdap at some point during the pregnancy. Factors associated with receiving the Tdap vaccination were insurance status, prenatal care risk level and site of prenatal care, receipt of the influenza vaccine, and preterm labor in the current pregnancy. CONCLUSION: The Tdap vaccine rate was 65.8%, with 59.9% of patients receiving the vaccine within the recommended ACIP timeframe. Further education, improvements in documentation, and chart reminders are needed to enhance administration.

Buprenorphine Versus Methadone for Opioid Dependence in Pregnancy.

OBJECTIVE: To evaluate maternal and neonatal safety outcomes for methadone and buprenorphine in the obstetric population. DATA SOURCES: A literature search of PubMed (1966 to March 2016) and EMBASE (1973 to March 2016) was completed using the search terms buprenorphine, methadone, pregnancy, opioid, and neonatal abstinence syndrome Priority was given to randomized controlled trials and trials directly comparing buprenorphine and methadone during pregnancy. The bibliographies were reviewed for other relevant articles. STUDY SELECTION AND DATA EXTRACTION: All human studies published in English, that compared methadone and buprenorphine use in pregnancy were evaluated. Because of the limited number of obstetric studies, only 5 critical studies were found. DATA SYNTHESIS: Buprenorphine significantly improved or had similar outcomes to methadone for development of neonatal abstinence syndrome (NAS), percentage of infants requiring treatment for NAS (20%-47% vs 45.5%-57%, respectively), total amount of morphine used to treat NAS (0.472-3.4 vs 1.862-10.4 mg, respectively), duration of NAS (4.1-5.6 vs 5.3-9.9 days, respectively), peak NAS (3.9-11 vs 4.9-12.8 score, respectively), infant hospital stay (6.8-10.6 vs 8.1-17.5 days, respectively), and gestational age at delivery (38.8-39.7 vs 37.9-38.8 weeks, respectively). No difference was found with other neonatal or maternal outcomes. CONCLUSIONS: Both methadone and buprenorphine are effective agents, with improved safety compared with continued nonmedical opioid use during pregnancy. There is evidence to suggest that buprenorphine should be considered as an equivalent option to methadone for use in pregnancy; however, larger studies are still needed to fully evaluate buprenorphine safety and advantages over methadone in the obstetric population.

Should pregnant women be included in phase IV clinical drug trials?

Relatively few drugs, especially those recently approved by the US Food and Drug Administration, have published human pregnancy experience. Although all drugs contain animal reproduction data, these are usually not predictive of human risk. Clinical trials in pregnant women are rarely conducted because of ethical and legal concerns, and it may be many years before sufficient observational data are collected to guide clinical treatment decisions. Because many of these drugs will be used in pregnancy, human data are needed shortly after the drugs come to the market. Lack of human data leads to uncertainty over whether a drug can be safely prescribed for a pregnant patient. Unless there are compelling scientific and ethical reasons to exclude them, pregnant women should be included in phase IV clinical trials (postmarketing studies to obtain additional information, including the risks, benefits, and optimal use of a drug). This paper examines how physicians currently counsel pregnant women when there are no human data and proposes an alternative method in which knowledge regarding risks associated with the use of drugs during pregnancy can be enhanced in a clinical trial setting.

Roles of the pharmacist in the use of safe and highly effective long-acting reversible contraception: an opinion of the women's health practice and research network of the American College of Clinical Pharmacy.

The U.S. population continues to experience an alarmingly high rate of unintended pregnancies that have an impact on individual families and society alike. Lack of effective contraception accounts for most unintended pregnancies, along with incorrect use of contraceptives. The most common reversible contraceptive method used in the United States is the oral contraceptive pill, which has significant failure and discontinuation rates. Use of long-acting reversible contraceptive (LARC) methods has been increasing in recent years after efforts to educate providers and patients. Women are more likely to use LARC methods when barriers such as access and cost are removed. An uptake in the use of LARC methods would allow for markedly reduced contraception failure rates and higher user satisfaction and thus higher continuation rates than those seen with current contraception use. Promoting the use of LARC methods is an important strategy in improving both individual and public health outcomes by reducing unintended pregnancies. The pharmacist's role in family planning is expanding and can contribute to these efforts. Although knowledge regarding LARC has not been studied among pharmacists, a knowledge deficit exists among health care professionals in general. Thus pharmacist education and training should include LARC methods along with other contraceptives. The American College of Clinical Pharmacy Women's Health Practice and Research Network advocates for the pharmacist's role in the use of safe and highly effective LARC methods. These roles include educating patients, informing providers, facilitating access by providing referrals, and modifying institutional procedures to encourage provision of LARC methods.

Ospemifene in the treatment of vulvovaginal atrophy.

OBJECTIVE: To review the pharmacology, efficacy, and safety of ospemifene in the management of dyspareunia. DATA SOURCES: Literature was sought using PubMed (1966-January 2014) and EMBASE (1973-January 2014). Search terms included ospemifene, FC-1271a, dyspareunia, vulvovaginal atrophy, and vaginal atrophy. STUDY SELECTION AND DATA EXTRACTION: All studies, including studies on humans, published in English with data assessing the efficacy and safety of ospemifene in the management of dyspareunia were evaluated. DATA SYNTHESIS: Ospemifene is a new oral estrogen receptor agonist/antagonist indicated for moderate to severe dyspareunia. Clinical trials evaluating efficacy have shown a significant improvement in superficial cells, parabasal cells, vaginal pH, vaginal dryness, and dyspareunia. The most frequently reported adverse drug reactions in the clinical trials included hot flashes, vaginal discharge, muscle spasms, and hyperhidrosis. Similar to systemic estrogen, boxed warnings with ospemifene include risk for thromboembolism and cerebrovascular disease. Additionally, patients with a uterus still need to use a progestogen with ospemifene to reduce the risk of hyperplasia. CONCLUSIONS: Ospemifene has been effective in improving symptoms of vulvovaginal atrophy when compared with placebo; however, no studies comparing ospemifene with estrogen products exist. Additional clinical trials are needed to evaluate the efficacy and safety in specialty populations, and long-term safety data are needed to assess the potential for serious adverse events. With the risks being similar to that for systemic estrogen therapy, ospemifene appears to be an alternative agent to estrogen therapy but does not have any advantages over estrogen.

The use of galactogogues in the breastfeeding mother.

OBJECTIVE: To review data regarding the efficacy of galactogogues available in the US to increase breast milk production in postpartum mothers. DATA SOURCES: Literature was sought using PubMed (1966-June 2012) and EMBASE (1973-June 2012). Search terms included breastfeeding, breast milk, lactation, galactogogue, metoclopramide, oxytocin, fenugreek, milk thistle, silymarin, growth hormone, thyroid releasing hormone, medroxyprogesterone, domperidone, goat's rue, beer, Asparagus racemosus, shatavari, Medicago sativa, alfalfa, Onicus benedictus, blessed thistle, Galega officinalis, brewer's yeast, and herbals. STUDY SELECTION AND DATA EXTRACTION: All studies including humans and published in English with data assessing the efficacy of galactogogues for increasing breast milk production were evaluated. DATA SYNTHESIS: Breast milk is considered the optimal food source for newborns through 1 year of age. Many factors influence overall maternal production, including maternal pain, illness, balance of time when returning to work, anxiety, or emotional stress. Although a variety of herbal and pharmaceutical options have anecdotal evidence of their ability to improve breast milk production, peer-reviewed studies proving their efficacy are lacking. Metoclopramide, oxytocin, fenugreek, and milk thistle have shown mixed results in improving milk production; however, the trials were small and had a variety of limitations. CONCLUSIONS: Nonpharmacologic recommendations should be exhausted before adding therapy. Although anecdotal evidence encourages the use of metoclopramide, fenugreek, asparagus, and milk thistle for their galactogogue properties, efficacy and safety data in the literature are lacking. Oxytocin and domperidone are potentially available for compounding purposes, but safety data are limited. More studies are needed to evaluate the effects of available galactogogues on breast milk production.

Obstetrical opportunities: will pharmacy ever realize them?

Based on a survey of the American College of Clinical Pharmacy Women's Health Practice and Research Network and our own experience, the pharmacy profession has limited involvement in obstetric pharmacotherapy. We believe that such involvement in pregnancies with complicated conditions can result in significant improvement of pregnancy outcomes. Moreover, we believe this involvement would be welcomed by the physicians caring for these patients. This commentary documents current obstetrical pharmacy practices and proposes changes for the profession of pharmacy to consider.

Bevacizumab for the treatment of neovascular age-related macular degeneration.

OBJECTIVE: To review data regarding the efficacy and safety of bevacizumab for the treatment of neovascular age-related macular degeneration (nARMD). DATA SOURCES: Literature was searched using MEDLINE (1976-September 2011) and EMBASE (1973-September 2011). Search terms included bevacizumab, Avastin, neovascular macular degeneration, age-related macular degeneration, vascular endothelial growth factor, intravitreal, and safety. Reference citations were reviewed for relevant information. STUDY SELECTION AND DATA EXTRACTION: All randomized clinical trials published in English with data assessing the safety and efficacy of bevacizumab for nARMD were evaluated. DATA SYNTHESIS: The only Food and Drug Administration-approved treatments for nARMD are photodynamic therapy (PDT) with verteporfin, intravitreal pegaptanib, and ranibizumab. However, bevacizumab has gained attention as a potential agent in treating nARMD and is now widely used in practice. PDT with verteporfin and pegaptanib has shown only stabilization of visual acuity (VA). When the efficacy of bevacizumab was compared to these therapies, bevacizumab clinically and statistically improved VA outcomes. When compared to ranibizumab, which has also been shown to improve VA, bevacizumab showed no significant difference in VA outcomes and was associated with a decrease in average annual cost of $22,805. CONCLUSIONS: Bevacizumab administered intravitreally is appropriate for prevention of vision loss and recovery of VA in patients with nARMD. Although further analysis of long-term effects of bevacizumab on VA and safety is needed, it is potentially a more cost-effective option than ranibizumab for the treatment of nARMD.

Changing oral contraceptives from prescription to over-the-counter status: an opinion statement of the Women's Health Practice and Research Network of the American College of Clinical Pharmacy.

Addressing the issue of unintended pregnancy is a national priority. One proposed strategy to reduce unintended pregnancy is to improve access to oral contraceptives by changing them to over-the-counter (OTC) status. Existing data indicate that oral contraceptives meet safety criteria required of OTC products. Available literature demonstrates that women can self-screen for contraindications to oral contraceptives and can do this as well as clinicians, and experience with OTC emergency contraception suggests that OTC oral contraceptives would not increase sexual risk-taking behavior. Women support OTC access to oral contraceptives, but express an interest in accessing pharmacist counseling. On the basis of these data, the Women's Health Practice and Research Network of the American College of Clinical Pharmacy supports changing oral contraceptives to OTC status under two conditions: that they are sold where a pharmacist is on duty and that there are mechanisms in place to cover OTC contraceptives through Medicaid. Future research should address the issues of out-of-pocket costs to individuals, label-comprehension studies, and models for pharmacist reimbursement for time spent counseling on contraception.

Safety of the HPV Bivalent and Quadrivalent Vaccines During Pregnancy.

OBJECTIVE: To evaluate the safety of the human papillomavirus (HPV) bivalent and quadrivalent vaccines in pregnancy. DATA SOURCE: PubMed (1966-August 2010) was searched using the terms human papillomavirus, human papillomavirus vaccine, and pregnancy. References were reviewed for relevant information. STUDY SELECTION AND DATA EXTRACTION: All studies including humans that were published in English with data describing HPV vaccine administration in pregnancy were evaluated. DATA SYNTHESIS: Two combined analyses of 7 Phase 3 efficacy trials have retrospectively evaluated the safety of unintentional administration of either the bivalent (n = 1786) or quadrivalent (n = 2085) HPV vaccine during pregnancy. In addition, postmarketing pregnancy registry surveillance data (prospective, n = 787; retrospective, n = 76) for the quadrivalent HPV vaccine have been published. However, only 279 pregnancies from the studies and 90 pregnancies from the registry occurred within 30 days of receiving the vaccination. Overall, the vaccine does not appear to be associated with an increased risk of spontaneous abortion, fetal malformations, or adverse pregnancy outcomes beyond that found in the general population. Although the data are limited, neither HPV vaccine appears to be associated with an increased risk of adverse pregnancy outcomes. However, limitations of the data include small patient populations, minimal to no adjustments for factors known to influence pregnancy outcomes or malformations, and the majority of the available pregnancy data are from retrospective analysis of Phase 3 efficacy trials. CONCLUSIONS: Neither HPV vaccine should be routinely administered during pregnancy. If a pregnancy occurs midseries, the remaining vaccines should be given after pregnancy completion. Further studies are required to determine actual risk.

Impact of online lecture-capture on student outcomes in a therapeutics course.

OBJECTIVES: To examine the correlation between students accessing recorded lecture files (audio and slides) online and course grades and class attendance. METHODS: Second professional year (of 6-year program) students in a therapeutics course had access to recorded online lectures for 72 hours following live lectures. The number and duration of lecture accessions were compared to final course grades and class attendance. Course grades were compared to those of a historical control group. At the end of the semester, students completed a brief survey instrument regarding their use and perceptions of online lectures. RESULTS: No correlation was found between final course grades and the number of lecture accessions (r = 0.0014) or total number of minutes lectures were viewed (r = 0.033), nor between class attendance and minutes viewed (r = 0.2158). Students with access to recorded lectures outperformed the historical control group on the final examination (p < 0.002). Seventy-two percent of students reported no influence of online files on class attendance. CONCLUSIONS: Posting lectures online did not affect student outcomes, but students did score higher on the final examination.

Nicotine replacement therapy effect on pregnancy outcomes.

OBJECTIVE: To review data assessing the effects of nicotine replacement therapy (NRT) during pregnancy on fetal, neonatal, and maternal outcomes. DATA SOURCES: A literature search of PubMed (1966-July 2010) was performed using the terms smoking, smoking cessation, pregnancy, and nicotine replacement therapy. Bibliographies and the Cochrane Database were reviewed to identify additional relevant articles. STUDY SELECTION AND DATA EXTRACTION: All studies including humans and published in English with data describing NRT effects on pregnancy outcomes or malformations as a primary or secondary outcome were evaluated. DATA SYNTHESIS: Currently, behavior modification therapy is recommended for smoking cessation in pregnancy as first-line treatment, but NRT should be offered to patients who are not successful. NRT is currently a pregnancy category D medication. Pregnancy outcomes and malformation rates for NRT in pregnancy were evaluated as either primary or secondary outcomes in several trials. Four studies examined pregnancy outcomes after a full course of nicotine gum or patch therapy. NRT use significantly decreased the risk of preterm delivery and low birth weight compared to that of smokers. Only 1 study evaluated the risk of malformations after exposure to the NRT patch during the first trimester. In a retrospective analysis, NRT users had an increased risk for any fetal malformation but not for major or musculoskeletal ones. However, no adjustments were made for many known factors associated with malformations. CONCLUSIONS: Behavior modification therapy should always be the first method tried for smoking cessation in the pregnant population. If behavior modification therapy is attempted without success, NRT should be offered because of decreased risk for low birth weight and preterm delivery compared to continued smoking. Additionally, NRT does not appear to increase the risk for malformations.

The prophylactic role for the human papillomavirus quadrivalent vaccine in males.

OBJECTIVE: To determine the role of human papillomavirus (HPV) quadrivalent vaccine in males. DATA SOURCE: PubMed (1966-March 2010) was searched using the terms human papillomavirus, human papillomavirus vaccine, quadrivalent, males, cancer, and genital warts. Reference citations were reviewed for relevant information. STUDY SELECTION AND DATA EXTRACTION: All studies including humans and published in English with data describing HPV quadrivalent vaccine administration in males were evaluated. DATA SYNTHESIS: The HPV quadrivalent vaccine is currently recommended in females, but its role in males is still being defined. Three clinical trials evaluated the immunogenicity and tolerability of the vaccine in more than 1100 males 9-26 years of age. Greater than 99.5% of males seroconverted for HPV 6, 11, 16, and 18 at 1 month post-completion and titers were found to be numerically higher than those in females 16-26 years old. One study found that immune response persisted in >92.5% of males at 1 year. The results show high efficacy against detection of new anogenital lesions in males 29 months after receiving the quadrivalent HPV vaccine. In addition, the quadrivalent HPV vaccine appears to be well tolerated, with the most common adverse effects being syncope, fever, local site reactions, dizziness, nausea, and headache. CONCLUSIONS: The HPV quadrivalent vaccine appears to be safe and induces an effective immune response in males. It may also decrease the incidence of anogenital and penile cancer, although current data are limited in number and duration of follow-up. Further analysis of the long-term immunogenicity and effects on HPV-associated complications is needed.

Levetiracetam use in pregnancy.

OBJECTIVE: To review data evaluating levetiracetam management of epilepsy during pregnancy. DATA SOURCES: A literature search of PubMed (1966-June 2009) was performed using the terms pregnancy, epilepsy, levetiracetam, and anticonvulsants. Bibliographies of all articles retrieved were reviewed to identify additional relevant articles. STUDY SELECTION AND DATA EXTRACTION: All studies including humans and published in English with data describing levetiracetam management during pregnancy were included. DATA SYNTHESIS: The pharmacokinetic studies included in this review demonstrate that the clearance of levetiracetam increases during pregnancy, particularly during the third trimester, which subsequently leads to decreased serum levetiracetam concentrations. The increase in clearance is most likely due to an increase in renal blood flow. The teratogenic studies included in this review included a total of 147 patients. Of these patients, 2% experienced a major congenital malformation (MCM) and 4.8% experienced a minor anomaly. All of the patients who had either an MCM or a minor anomaly were receiving antiepileptic drug (AED) polytherapy. It was unknown whether 10.9% of the 147 patients discussed were receiving levetiracetam monotherapy or AED polytherapy. None of the published literature assessed adherence to AED therapy. Folic acid supplementation was addressed in only one of the case series presented. CONCLUSIONS: If levetiracetam is used during pregnancy, women should receive adequate amounts of folic acid (0.4-5 mg/day) and serum concentrations of levetiracetam should be determined before conception if possible and during each trimester, especially during the middle of the third trimester, to assess therapeutic concentrations. The dose may need to be increased during the third trimester to provide concentrations consistent with those before conception. Patients should be informed that there appears to be a small chance of malformations with levetiracetam, but that the data are limited.

New hormonal contraceptives: a comprehensive review of the literature.

Over 16 million women in the United States take oral hormonal contraceptives, yet approximately 5% experience an unintended pregnancy during the first year of use. Compliance with the regimen is important in maintaining cycle control and preventing pregnancy. New hormonal contraceptive agents, norelgestromin-ethinyl estradiol patch, etonogestrel-ethinyl estradiol vaginal ring, and medroxyprogesterone-estradiol cypionate injection, were designed to increase compliance and decrease adverse effects while maintaining efficacy. Each one has potential advantages for women seeking alternatives to traditional oral contraceptives or for those who have trouble remembering to take a daily pill. Each agent also may have its own disadvantages, including application site reactions, need for monthly injections, and device-related events; however, all have similar efficacy and adverse-effect profiles compared with current oral hormonal contraceptives.