Acetaminophen is the most commonly used analgesic and antipyretic during pregnancy. Evidence of neuro-disruptive properties is accumulating. Therefore, we sought to evaluate the risk for attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD) in the offspring of women exposed to acetaminophen during pregnancy. We searched MEDLINE, EMBASE, and Cochrane up to January 2017. Data were independently extracted and assessed by two researchers. Seven eligible retrospective cohorts included 132,738 mother and child pairs and with a follow-up period of 3-11 years. Pooled risk ratio (RR) for ADHD was (RR=1.32, 95% CI 1.18,1.45, I2=61%), for ASD (RR=1.23, 95% CI1.13,1.32, I2=17%), and for hyperactivity symptoms (RR=1.23, 95% CI 1.01,1.49, I2=94%). In meta-regression analysis, the association between exposure and ADHD increased with childs' age upon follow-up and with the mean duration of exposure (β=0.0354, 95% CI 0.001,0.07), (β=0.006, 95% CI 0.009,0.01). The available data is of observational nature only. Studies differed gravely in exposure and outcome assessment. Acetaminophen use during pregnancy is associated with an increased risk for ADHD, ASD and hyperactivity symptoms. These findings are concerning, however, results should be interpreted with caution as the available evidence consists of observational studies and susceptible to several potential sources of bias.

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Exposure to SSRIs or SNRIs during pregnancy is associated with an increased risk for PPHN. According to our findings, sertraline ranked as most likely to have the lowest risk for PPHN compared to other SSRIs, suggesting it may have the best safety profile for use in pregnancy in this regard. Further studies are needed to fully establish these results.

Studies reporting an increased risk for cardiac toxicities with macrolide antibiotics have raised concern regarding their cardiovascular safety. We sought to assess the cardiac safety of macrolide antibiotics as a class and of the individual agents by conducting a systematic review and network meta-analysis. Medline, Embase, and the Cochrane Library were searched up to February 2018 for studies reporting on cardiovascular outcomes with macrolides. We followed the PRISMA 2009 guidelines for data selection and extraction. Outcomes were pooled using random-effects models and odds ratios (OR), and 95% confidence intervals (CI) were calculated for arrhythmia, cardiovascular death, and myocardial infarction (MI). A total of 33 studies and data on 22,601,032 subjects were retrieved and included in the current meta-analyses. Macrolide use was not associated with the risk of arrhythmia or cardiovascular mortality. In the primary analysis, macrolide use was associated with a small but statistically significant 15% increase in risk for MI (OR = 1.15 [95% CI, 1.01 to 1.30]). In indirect network meta-analysis, erythromycin and clarithromycin were ranked considerably more likely to be associated with a higher risk for MI and significantly associated with increased risk of MI compared to azithromycin (OR = 1.58 [95% CI, 1.18 to 2.11] and OR = 1.41 [95% CI, 1.11 to 1.81], respectively). Our findings indicate that macrolide antibiotics as a group are associated with a significant risk for MI but not for arrhythmia and cardiovascular mortality. Among the macrolides, erythromycin and clarithromycin were associated with a greater risk of MI. However, it is possible that the association between macrolide use and risk of MI is the result of residual confounding.

BackgroundDue to the limited safety data available at the time that a new medication is first marketed, it is essential to continue the collection and monitoring of safety data about adverse drug reactions (ADRs) during the medication’s life cycle. This activity, known as pharmacovigilance (PV), is performed worldwide by the pharmaceutical industry as well as by regulatory agencies. In 2012, the Israeli Ministry of Health (MOH) established a Pharmacovigilance and Drug Information Department. The Department is tasked with identifying, monitoring, and initiating activities aimed at minimizing risks associated with medication utilization. To enable this, the MOH has devised procedures for PV and promoted extensive legislation in this area that require marketing authorization holders (MAHs) and medical institutions in Israel to report ADRs and new safety information to the MOH. A computerized database was created to support the reporting process. The objective of this article is to characterize the PV tools and activities implemented in Israel.MethodsSince September 2014, The Israeli Pharmacovigilance and Drug Information Department receives ICSRs at a central computerized database developed for this purpose. The data were analyzed by Department personnel and ICSRs were characterized according to their seriousness, source, categories of drugs involved, and the reporting format. Additionally, the Department reviewed signals detected from ADR reports and from other sources and assessed the resulting regulatory actions.ResultsAn analysis of the Individual Case Safety Reports (ICSRs) submitted to the MOH’s ADRs central database reveals that during the review period, a total of 16,409 ICSRs were received by the Department and 850 signals were identified, resulting in the following PV activities: inquiry and enhanced follow-up (430, 50.6%), prescriber’s and patient’s leaflets updates (204, 24%), recall of products/batches (6, 0.7%), alerts for health care professionals (63, 7.4%). Eighty five (10%) of the signals required a comprehensive investigation involving external specialist and 1 (0.1%) resulted in initiation of epidemiologic study. Additionally, in 2015 the Department incorporated comprehensive framework for risk minimization of marketed medicinal products, also known as risk management plans (RMPs).ConclusionsAs practiced by other health authorities, the Israeli MOH effectively implemented various PV tools to ensure the safety of the Israeli health consumer.

Benzathine Penicillin G (BPG) is commonly used for treatment of penicillin-susceptible infections and secondary prevention of rheumatic fever. Death following administration of BPG is extremely rare—only a handful of cases have been described in the literature since the 1950's. In this case series from Israel and Switzerland, we describe nine cases of serious adverse reactions—six fatal reactions and three near-fatalities—occurring within minutes of receiving intramuscular BPG. Allergic reactions or faulty administration were not implicated in any of the cases; however, all patients had cardiac risk factors. This case series describes a relatively rare risk that should be borne in mind when prescribing BPG.

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