Pharmacovigilance of Drug-Drug Interactions with Nirmatrelvir/Ritonavir.

Introduction: Nirmatrelvir/ritonavir (NMV/r) is approved in the United States (US) and more than 70 other countries for the treatment of mild to moderate COVID-19 in nonhospitalized adults at high risk for severe disease. Because ritonavir inhibits several drug metabolizing enzymes, potential drug-drug interactions (DDIs) between ritonavir and concomitant medications are an important consideration for prescribers. Here, we conducted a real-world analysis of data from Pfizer's global safety database regarding adverse events (AEs) reported during use of NMV/r concomitantly with potentially interacting drugs.

Oral Nirmatrelvir-Ritonavir as Postexposure Prophylaxis for Covid-19.

Background: Clinical trials of treatments for coronavirus disease 2019 (Covid-19) have not shown a significant benefit of postexposure prophylaxis.

Methods: We conducted a phase 2-3 double-blind trial to assess the efficacy and safety of nirmatrelvir-ritonavir in asymptomatic, rapid antigen test-negative adults who had been exposed to a household contact with Covid-19 within 96 hours before randomization. The participants were randomly assigned in a 1:1:1 ratio to receive nirmatrelvir-ritonavir (300 mg of nirmatrelvir and 100 mg of ritonavir) every 12 hours for 5 days or for 10 days or matching placebo for 5 or 10 days.

Nirmatrelvir for Vaccinated or Unvaccinated Adult Outpatients with Covid-19.

Background: Nirmatrelvir in combination with ritonavir is an antiviral treatment for mild-to-moderate coronavirus disease 2019 (Covid-19). The efficacy of this treatment in patients who are at standard risk for severe Covid-19 or who are fully vaccinated and have at least one risk factor for severe Covid-19 has not been established.

Methods: In this phase 2-3 trial, we randomly assigned adults who had confirmed Covid-19 with symptom onset within the past 5 days in a 1:1 ratio to receive nirmatrelvir-ritonavir or placebo every 12 hours for 5 days.

Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19.

Background: Nirmatrelvir is an orally administered severe acute respiratory syndrome coronavirus 2 main protease (M) inhibitor with potent pan-human-coronavirus activity in vitro.

Methods: We conducted a phase 2-3 double-blind, randomized, controlled trial in which symptomatic, unvaccinated, nonhospitalized adults at high risk for progression to severe coronavirus disease 2019 (Covid-19) were assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir (a pharmacokinetic enhancer) or placebo every 12 hours for 5 days. Covid-19-related hospitalization or death from any cause through day 28, viral load, and safety were evaluated.

The use of extrapolation based on modeling and simulation to support high-dose regimens of ceftaroline fosamil in pediatric patients with complicated skin and soft-tissue infections.

A model-informed drug development approach was used to select ceftaroline fosamil high-dose regimens for pediatric patients with complicated skin and soft-tissue infections caused by Staphylococcus aureus with a ceftaroline minimum inhibitory concentration (MIC) of 2 or 4 mg/L. Steady-state ceftaroline concentrations were simulated using a population pharmacokinetics (PK) model for ceftaroline fosamil and ceftaroline including data from 304 pediatric subjects and 944 adults. Probability of target attainment (PTA) for various simulated pediatric high-dose regimens and renal function categories were calculated based on patients achieving 35% fT>MIC (S.

Phase 2 Study of the Safety, Pharmacokinetics and Efficacy of Ceftaroline Fosamil in Neonates and Very Young Infants With Late-onset Sepsis.

Background: With increasing antimicrobial resistance, antibiotic treatment options for neonatal late-onset sepsis (LOS) are becoming limited. Primary objective of this study was assessment of the safety of ceftaroline fosamil in LOS.

Methods: Eligible neonates and very young infants 7 to <60 days of age with LOS were enrolled in this phase 2, open-label, multicenter study (NCT02424734) and received ceftaroline fosamil 4 or 6 mg/kg every 8 hours by 1-hour intravenous infusion plus intravenous ampicillin and optional aminoglycoside for 48 hours-14 days.

Bupropion Use During Pregnancy: A Systematic Review.

Objective: To evaluate data on birth outcomes following bupropion use during pregnancy.

Data Sources: A systematic literature review of PubMed and PsycINFO was performed through June 2017 for clinical studies published in English. The following keywords were used: bupropion, pregnancy, depression, smoking cessation, birth outcomes, miscarriage, and spontaneous abortion.

Minimizing weight gain for patients taking antipsychotic medications: The potential role for early use of metformin.

Background: Patients taking antipsychotic medications are at high risk for weight gain, which in turn leads to poor health outcomes, nonadherence with treatment, and low self-esteem.

Methods: We reviewed published studies of pharmacologic interventions aimed at minimizing antipsychotic-induced weight gain. Treatments initiated prior to onset of weight gain were compared with those that started once weight gain already had occurred.

Antidepressant use during pregnancy and childhood autism spectrum disorders.

Context: The prevalence of autism spectrum disorders (ASDs) has increased over recent years. Use of antidepressant medications during pregnancy also shows a secular increase in recent decades, prompting concerns that prenatal exposure may contribute to increased risk of ASD.

Objective: To systematically evaluate whether prenatal exposure to antidepressant medications is associated with increased risk of ASD.

Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment.

Context: Pregnancy has historically been described as a time of emotional well-being, providing "protection" against psychiatric disorder. However, systematic delineation of risk of relapse in women who maintain or discontinue pharmacological treatment during pregnancy is necessary.

Objective: To describe risk of relapse in pregnant women who discontinued antidepressant medication proximate to conception compared with those who maintained treatment with these medications.

An Update on Mood and Anxiety Disorders During Pregnancy and the Postpartum Period.

Because women in the childbearing years are vulnerable to mood and anxiety disorders, physicians in all patient care specialties need to be familiar with the prevalence and course of these disorders, particularly during pregnancy and the postpartum period. Systematic prospective data are limited on the onset of mood and anxiety disorders during pregnancy and the postpartum period as well as on the risk of relapse during these time periods in women with prior histories of the disorders. The literature on mood and anxiety disorders during pregnancy is frequently complicated by the use of various methodologies, procedures, and study populations, and inconsistencies in the postpartum time frame (up to 6 months after delivery) make the literature on epidemiology of postpartum disorders difficult to interpret.

Placental passage of antidepressant medications.

Objective: This study determined the placental transfer of antidepressants and their metabolites.

Method: A total of 38 pregnant women taking citalopram, fluoxetine, paroxetine, or sertraline participated. Maternal and umbilical cord blood samples were obtained to determine antidepressant and metabolite concentrations.

Weight gain in breastfed infants of mothers taking antidepressant medications.

Background: Little is known about the physical development of infants who are exposed to antidepressant medications through breast milk.

Method: Seventy-eight breastfeeding women taking antidepressant medications were included in the study. Maternal mood was prospectively evaluated at 6, 12, and 18 months postpartum.

Birth outcomes after prenatal exposure to antidepressant medication.

Objective: The purpose of this study was to examine prospectively the incidence of congenital anomalies and neonatal complications after prenatal exposure to antidepressant medication.

Study Design: Birth outcomes were obtained from a review of obstetric and neonatal records of 138 women who were treated with selective serotonin reuptake inhibitor antidepressant medications (SSRIs) during pregnancy.

Results: The incidence of congenital anomalies in this study was 1.

Etiology and treatment of postpartum depression.

This article reviews the risk factors, pathogenesis, treatment, and prevention of postpartum depression. Postpartum depression is common and occurs in up to 18% of newly delivered mothers. Though the hormonal changes occurring after childbirth are believed to play a role in postpartum depression, no hormonal etiology has been identified.

Estimates of nursing infant daily dose of fluoxetine through breast milk.

Background: This study compared three methods of estimating the daily dose of fluoxetine to nursing infants and the relationship between these estimates and infant serum concentrations.

Methods: Breast milk and infant serum concentrations of fluoxetine and norfluoxetine were obtained from 10 nursing mother-infant pairs. Quantification of daily infant dose was determined by three methods: 1) collection of the total volume of breast milk over 24 hours and determination of the average breast milk concentration (Baby's Total Daily Dose); 2) determination of the maximum and minimum breast milk concentrations during 24 hours and an estimated milk consumption of 150 mL/kg/day (Atkinson Model); and 3) determination of the gradient of excretion of medication into breast milk at a specified time after the maternal dose, applying this gradient to each nursing collection and summing the values for 24 hours (Mathematical Model).