Valproate: Not All Boxed Warnings Are Created Equal.

OBJECTIVE: Valproate has undergone significant changes in labeling to the boxed warnings associated with it. This review will analyze evidence regarding the valproate-boxed warnings for teratogenicity, hepatotoxicity, and pancreatitis, with a particular emphasis on the fetal risk. DATA SOURCES: A review of Pubmed, Cochrane Central Register, Google Scholar, manufacturer websites, and product labeling was performed from 1963 to February 2022, using the following search terms: valproate, valproic acid, depakote, teratogenicity, birth defects, fetal risk, hepatotoxicity, and pancreatitis. Relevant English-language studies and those conduced in humans were considered. Product labeling was also reviewed. DATA SYNTHESIS: There is a significant fetal risk following in utero valproate exposure (risk of malformation development: 8.6% in 360 women in North America). Current labeling in the United States recommends co-prescribing effective contraception for women of childbearing age. The risk of hepatotoxicity and pancreatitis is much lower in the general population (1/20 000 and 1/40 000 patients, respectively) compared with those patients with certain risk factors who are taking valproate (1/500). CONCLUSIONS: Overstated monitoring recommendations for the potential risk of hepatotoxicity and pancreatitis distracts from a much more common and severe risk of fetal harm. Clinicians must be diligent about discussing this risk with patients and documenting when this discussion occurs. Changes to the current recommendations for monitoring of the boxed warnings associated with valproate therapy should be considered, such as more stringent monitoring requirements for the inherent fetal risk. This could be accomplished through a Risk Evaluation and Mitigation Strategy program or through institution-based policies and procedures. In addition, monitoring recommendations for the risk of hepatotoxicity and pancreatitis should account for contributing risk factors.

Comparison of Hypoglycemia and Safety Outcomes With Long-Acting Insulins Versus Insulin NPH in Pregestational and Gestational Diabetes.

Background: Current guidelines from the American College of Obstetricians and Gynecologists recommend insulin as the standard therapy for treatment of pregestational and gestational diabetes (PGDM and GDM). However, the guidelines do not specify which type(s) of insulin to utilize. Additionally, there are limited published data regarding safety parameters of insulin in this population. Objective: To evaluate if insulin glargine or detemir (long-acting insulin) results in less hypoglycemia, hospitalizations, or delivery complications compared with intermediate-acting insulin neutral protamine Hagedorn (NPH) in PGDM and GDM. Methods: This single-center, retrospective, observational cohort study included pregnant women who were 18 years or older with PGDM or GDM and received insulin therapy during pregnancy at an outpatient obstetric clinic. The primary outcome was the frequency of hypoglycemia (BG < 60 mg/dL). Secondary outcomes included emergency department visits and hospitalizations, delivery complications, and the duration of time at glycemic targets during pregnancy. Results: A total of 63 patients were included for evaluation. There was no significant difference in the frequency of hypoglycemia between the long-acting and NPH groups (4.4 vs 6.2 events per patient, respectively; P = 0.361). Patients receiving long-acting insulin had significantly more encounters with diabetes education (10.6 vs 5.1 visits per patient, P = 0.002) and more consistently provided glucose readings at their appointments (8.3 vs 4.8, P = 0.043). There was no difference in hospitalizations or maternal and neonatal complications. Conclusion and Relevance: Long-acting insulins did not reduce the frequency of hypoglycemia compared with NPH. The results of this study confirm the need for additional investigations with larger populations.

Sarecycline Review.

Objective: Sarecycline is a new oral tetracycline antibiotic recently approved by the US Food and Drug Administration. The aim of this article was to evaluate the data from published clinical trials of sarecycline in the treatment of acne, review the drug's pharmacology, and understand how this new medication may apply to clinical practice. Data Sources: A systematic literature review was performed using the terms sarecycline (Seysara), P005672, and WC-3035 in the MEDLINE and EMBASE databases. ClinicalTrials.gov was searched to identify ongoing or nonpublished studies. Study Selection and Data Extraction: Articles in English between January 2000 and April 2019 relating to clinical trials, pharmacology, safety, and microbiological profile were evaluated. Data Synthesis: In a phase 3 clinical trial (SC1401), absolute change from baseline in facial inflammatory lesion count at week 12 was -15.3 for the sarecycline arm and -10.1 for placebo (P < 0.01). In another phase 3 clinical trial (SC1402), the absolute change in this category was -15.7 for sarecycline and -10.7 for placebo (P < 0.01). Mean percentage change in facial inflammatory lesion count was higher in the sarecycline group than in the placebo group in both studies (P < 0.01). Relevance to Patient Care and Clinical Practice: The 1.5-mg/kg sarecycline dose has efficacy in reducing inflammatory lesions, is well tolerated, and has more targeted antimicrobial activity, which may help reduce the risk of developing antibiotic resistance. Conclusions: This novel, once-daily treatment may represent a useful treatment for patients with moderate to severe acne.

Direct-Acting Antivirals to Prevent Vertical Transmission of Viral Hepatitis C: When Is the Optimal Time to Treat?

OBJECTIVE: To describe the most current evidence for the use of direct-acting antivirals (DAAs) to treat hepatitis C along the pregnancy-pediatric continuum in the United States. DATA SOURCES: The MEDLINE/PubMed databases were searched (January 1995 to February 2018) for articles in English using the terms: hepatitis C, vertical transmission, pregnancy, pediatrics, ribavirin, interferon, direct acting antivirals, daclatasvir, dasabuvir, elbasvir, glecaprevir, grazoprevir, ledipasvir, ombitasvir, paritaprevir, pibrentasvir, simeprevir, sofosbuvir, and velpatasvir. STUDY SELECTION AND DATA EXTRACTION: All relevant studies, meta-analyses, systematic reviews, guidelines, and review articles were evaluated for inclusion. References from pertinent articles were assessed for additional content that was not found during the initial search. DATA SYNTHESIS: The primary route of transmission for hepatitis C virus (HCV) in pediatric patients is vertical transmission (VT), with the rate estimated to be 5.8%. Screening for HCV during pregnancy is not routinely part of clinical care, and the data for the use of DAAs in pregnancy is limited. A significant number of infected infants will clear the HCV infection spontaneously, and ledipasvir/sofosbuvir and sofosbuvir have recently been Food and Drug Administration approved for use in pediatric patients older than 12 years. CONCLUSIONS: Data to determine the best treatment point along the pregnancy-pediatric continuum are limited; however, given the lack of human data for use of DAAs during pregnancy, low rate of VT, high rate of spontaneous pediatric clearance, and recent approval of DAAs for pediatric patients, treatment of chronically infected children seems to be the optimal strategy currently.

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.

Fatores associados ao uso nocivo do tabaco durante a gestação / Factors associated with harmful use of tobacco during pregnancy

Resumo Objetivo Calcular a prevalência e analisar os fatores associados ao uso de tabaco uma vez na vida e verificar o seu uso nocivo entre gestantes. Métodos Estudo transversal em 330 gestantes atendidas em centro especializado no atendimento à saúde das mulheres na atenção básica (Brasil Central). Os dados dos antecedentes pessoais/familiares e o rastreamento de uso de tabaco foram obtidos por meio de questionário sociodemográfico (Alcohol, Smokeand Substance Involvement Screening Test) e analisados usando regressão logística. Resultados O uso de tabaco uma vez na vida mostrou estar associado à renda, antecedentes familiares de consumo de álcool e pessoais de transtorno mental. O uso nocivo de tabaco durante a gestação foi associado a antecedentes familiares de tabagismo e consumo de álcool. Conclusão A prevalência de uso de tabaco uma “vez na vida” na amostra estudada foi de 37,1% (124) e “uso nocivo” de tabaco na gestação foi de 9,6% (32).

Abstract Objective To calculate the prevalence and analyze factors associated with tobacco use once in a lifetime and check their harmful use among pregnant women. Methods Cross-sectional study conducted with 330 pregnant women assisted in specialized center for women primary health care (Central Brazil). The data of personal/family history and tracing of tobacco use were obtained through a sociodemographic questionnaire (Alcohol, Smoke and Substance Involvement Screening Test) and analyzed using logistic regression. Results The use of tobacco once in a lifetime was associated with income, family history of alcohol and personal mental disorder. The harmful use of tobacco during pregnancy was associated with a family history of smoking and alcohol consumption. Conclusion The prevalence of tobacco use as “once in a lifetime” in the sample was 37.1% (124) and “harmful use” of tobacco during pregnancy was 9.6% (32).

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.

Predictors of Pregnancy in Female Veterans Receiving a Hormonal Contraceptive Pill, Patch, or Ring.

BACKGROUND: Pregnancy rates in veterans are an understudied phenomenon. OBJECTIVE: The objective of this study was to identify predictors of pregnancy within 1 year of starting hormonal contraception among female veterans. METHODS: This was a retrospective, cohort study of female veterans from Veterans Affairs facilities within Southern California and Nevada, who newly started hormonal contraception (pill, patch, or ring only) between October 2008 and September 2012. Pregnancy was defined as any event corresponding to a pregnant state using ICD-9 codes. Patients were followed for 1 year post-initiation. Multivariate logistic regression analysis was performed. RESULTS: The final analysis included a total of 2166 patients. Approximately 5.9% (n = 127) of patients became pregnant during follow-up. Increased odds of pregnancy were associated with the following: mental health disease (odds ratio [OR] 1.69, 95% confidence interval [CI] 1.15-2.58), lowest socioeconomic quintile (OR 1.50, 95% CI 1.05-2.09), and Christian faith (OR 1.69, 95% CI 1.31-2.41). Age groups 25 to 34 years (OR 0.55, 95% CI 0.38-0.92] and 35 to 44 years (OR 0.32, 95% CI 0.06-0.64) were both associated with decreased odds of pregnancy versus age group 18 to 24 years. CONCLUSION: This study successfully identified several predictors of pregnancy in female veterans starting a pill, patch, or ring form of hormonal contraception. Female veterans in the lowest socioeconomic quintile, aged 18 to 24 years, diagnosed with a mental health disorder, and of Christian faith were found to be at significantly higher odds of a pregnancy. Identification of these at-risk populations may help clinicians and policy makers choose strategies to identify which patients could benefit the most from more effective long-acting reversible contraception therapy.