Trending Topics in Health-System Pharmacy
APhA Staff
Which SSRIs are best for panic disorder?
Panic attacks are treated with several types of medications, including tricyclic antidepressants, benzodiazepines, SSRIs, monoamine oxidase inhibitors, and SNRIs. SSRIs are generally recommended as the primary treatment for panic disorder, but questions remain as to which SSRI is most effective. Anothaisintawee and colleagues from Mahidol University (Bangkok, Thailand) conducted a systematic review and network metaanalysis to determine which SSRIs are most effective and pose the lowest risk of adverse events.
The study, published on January 19, 2022, in the BMJ, included randomized controlled trials that included adults aged 18 years or older with a diagnosis of panic disorder, compared drugs used to treat the panic disorder, and measured the outcomes of interest, including remissions, dropouts, and adverse events.
Benzodiazepines, tricyclic antidepressants, and SSRIs were identified as the top three best treatments for remission but were also significantly associated with increased risk of adverse events compared with placebo.
When considering both remission and adverse events, SSRIs were associated with high remission and low risk of adverse events.
Among individual SSRIs, sertraline and escitalopram provided high remission with an acceptable risk of adverse events.
Fosfomycin could be superior to I.V. antibiotics for treating complicated UTIs
Rising rates of community-acquired resistance to fluoroquinolone antibiotics have resulted in difficulty in treating complicated UTIs with oral antibiotics. Because oral options for treating infections caused by fluoroquinolone- and trimethoprim–sulfamethoxazole–resistant pathogens are limited, patients with these infections typically receive I.V. antibiotics even if they are clinically stable and can tolerate oral medications. A group of researchers at the Los Angeles County–University of Southern California Medical Center and the Keck School of Medicine led by Noah Wald-Dickler, MD, investigated the comparative efficacy of fosfomycin and ertapenem for outpatient treatment of complicated UTIs.
The multicenter, retrospective cohort study was published in the January 2022 issue of Open Forum Infectious Diseases and involved patients with complicated UTI treated with oral fosfomycin or intravenous ertapenem at 3 public hospitals in Los Angeles County between January 2018 and September 2020. The primary outcome was resolution of clinical symptoms 30 days after diagnosis. Most infections were due to extended-spectrum b-lactamase–producing E. coli and Klebsiella pneumoniae, 80% to 90% of which were resistant to other oral options.
Results of the analysis showed that patients treated with fosfomycin had significant reductions in length of both hospital stay and antimicrobial therapy and had fewer adverse events. Fosfomycin outcomes were similar irrespective of duration of lead-in I.V. therapy or fosfomycin dosing interval. The authors suggest that these results support a randomized controlled trial to verify efficacy and that fosfomycin may be a reasonable stepdown from I.V. antibiotics for treatment of complicated UTIs.
Researchers examine CVD, cancer risk with tofacitinib
Treatment of rheumatoid arthritis with tofacitinib has shown to cause increased lipid levels and cancers, prompting a study comparing major adverse cardiovascular events and cancers in patients with rheumatoid arthritis receiving tofacitinib or a tumor necrosis factor (TNF) inhibitor.
A worldwide group of researchers (the ORAL Surveillance Investigators) led by Steven R. Ytterberg, MD, at the Mayo Clinic conducted a randomized, open-label, noninferiority, postauthorization, safety end-point trial involving patients with active rheumatoid arthritis despite methotrexate treatment who were 50 years or older and had at least one additional cardiovascular risk factor. Patients received oral tofacitinib at a dose of either 5 mg or 10 mg twice daily or a subcutaneous TNF inhibitor (30 mg adalimumab every two weeks or 50 mg etanercept once weekly).
Results of the study, published in the New England Journal of Medicine on January 27, 2022, showed that during a median 4-year follow-up, the incidences of major adverse cardiovascular events and cancer were higher for patients who received tofacitinib doses (3.4% and 4.2%, respectively) than for those who received a TNF inhibitor (2.5% and 2.9%). In addition, the incidence of adjudicated opportunistic infections (including herpes zoster and tuberculosis) and adjudicated nonmelanoma skin cancer were higher with tofacitinib than with a TNF inhibitor. Efficacy was similar in all three groups.
Treating advanced endometrial cancer
Although the incidence of endometrial cancer is increasing worldwide, preferred treatment for advanced or recurrent endometrial cancer after the failure of platinum-based chemotherapy is unclear.
A global group of researchers (the Study 309–KEYNOTE-775 investigators) led by Vicky Makker, MD, of the Memorial Sloan Kettering Cancer Center (New York) conducted a phase 3 trial to compare the efficacy of lenvatinib (20 mg, administered orally once daily) plus pembrolizumab (200 mg, administered intravenously every three weeks) or chemotherapy of the treating physician’s choice (doxorubicin at 60 mg/m2 of body-surface area administered intravenously every three weeks or paclitaxel at 80 mg/m2 administered intravenously with a cycle of three weeks on and one week off) in patients with advanced endometrial cancer who had previously received at least one platinum-based chemotherapy regimen. The two primary endpoints were progression-free survival and overall survival.
A total of 827 patients were randomly assigned to receive lenvatinib plus pembrolizumab (411 patients) or chemotherapy (416 patients). The median progression-free survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (7.2 vs. 3.8 months) and the median overall survival was also longer with lenvatinib plus pembrolizumab than with chemotherapy (18.3 vs. 11.4 months). Adverse events occurred in 88.9% of the patients who received lenvatinib plus pembrolizumab and in 72.7% of those who received chemotherapy. The study was published in the February 3, 2022, issue of the New England Journal of Medicine.
Determining patient risk factors for opioid-related adverse drug events
The incidence of opioid-related adverse drug events has increased significantly with the recent increase in opioid use. Research has shown that such adverse drug events are strongly associated with adverse clinical outcomes in hospitalized patients, suggesting that caution is needed when prescribing opioids in patients with risk factors for adverse events. In a recent study published online on February 1, 2022, in Pharmacotherapy, Penm and colleagues at the University of Sydney used 5 databases (Medline, Embase, Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts, and Scopus) to summarize common patient risk factors for opioid-related adverse drug effects in hospitalized patients.
Seven of the identified studies focused on severe adverse drug effects, including over-sedation and respiratory depression, with comorbidities (e.g., sleep apnea, renal diseases), concurrent use of sedatives, and prior opioid exposure identified as risk factors. Nine studies focused on a combination of general opioid-related adverse drug effects and identified advanced age, male gender, comorbidities (e.g., chronic obstructive pulmonary disease, neurologic disorders), concurrent use of sedating medications, and prior opioid exposure as common risk factors.
The authors suggest successful identification of patient risk factors for opioid-related adverse drug effects could benefit clinicians when deciding on the appropriateness of opioid therapy in hospitalized patients and that future studies could focus on developing a validated risk assessment tool based on these risk factors.