Annals of Pharmacotherapy最新文献

Background: Direct-acting oral anticoagulants (DOACs) have become the preferred drugs for managing venous thromboembolism (VTE). Despite their advantages over vitamin K antagonists such as warfarin, their use in obese patients remains controversial with many providers reluctant to switch patients managed on warfarin. Outcome research that opts to increase provider confidence when prescribing DOACs for patients with obesity will be invaluable.

Objective: This investigation evaluated whether patients with a body mass index (BMI) 35 kg/m² or greater who were prescribed a DOAC had a higher risk for a recurrent VTE or bleed event relative to warfarin.

Methods: The study was conducted in West Virginia which has the highest rate of obesity in the United States.

Results: Of the total study population (1633), 2.3% (37) had a recurrent thrombotic event, 5.5% (89) had a major bleed event, and 10.7% (174) had some type of bleeding event. No individual patient characteristic was associated with recurrent thrombosis-including BMI. Older age, antiplatelet use, and taking a medication with a theoretical risk of increasing the effect of DOACs were associated with any and major bleeding events. The use of warfarin was associated with major bleeding events more frequently versus a DOAC. Body mass index was not a predictor for recurrent VTE or any bleed or major bleed events.

Conclusions: These findings support the conclusion that DOACs are an appropriate and effective drug class for the management of VTE in patients with obesity.

Objective: Several cases of Fanconi syndrome (FS), a severe form of nephrotoxicity, have been reported in patients with HIV on tenofovir-containing antiretroviral therapy. A systematic review of the published literature on tenofovir-related FS in patients with HIV was conducted.

Data sources: PubMed and Embase were queried to identify articles in English published between January 2005 and June 2023, reporting tenofovir-related FS in adults with HIV. Preclinical studies, conference/poster abstracts, commentaries and responses, and review papers were excluded.

Study selection and data extraction: Of the 256 articles screened, 57 met the inclusion criteria. These comprised 37 case reports, 11 case series, 1 cross-sectional study, 1 case-control study, 4 cohort studies, 1 single-arm open-label clinical trial, 1 sub-analysis of clinical trials, and 1 pooled analysis of clinical trials.

Data synthesis: Among 56 cases on which information was abstracted, median age at FS diagnosis was 50 years, 51.8% were men, and duration of tenofovir use ranged from 6 weeks to 11 years. Ritonavir was co-prescribed in almost half the cases. In observational and interventional studies, incidence of FS was low. Many studies reported resolution of FS symptoms after tenofovir discontinuation. All FS occurrences were identified in those on tenofovir disoproxil fumarate (TDF), except for one patient on tenofovir alafenamide (TAF).

Relevance to patient care and clinical practice: Continuous monitoring of signs and symptoms of renal and bone toxicity is essential for patients with HIV on tenofovir-containing therapy.

Conclusions: Occurrence of FS is low in patients with HIV treated with tenofovir-based regimens. Concomitant use of ritonavir may increase risk of FS. TAF may be a safer alternative than TDF in terms of nephrotoxicity.

Objective: The objective is to review the pharmacology, efficacy, and safety of intranasal zavegepant in the acute treatment of migraine with or without aura.

Data source: PubMed, Embase database, and ClinicalTrials.gov were searched using the following terms: Zavzpret, Zavegepant, BHV-3500, and migraine.

Study selection and data extraction: Articles published in English from January 2013 to September 2023 related to pharmacology, safety, efficacy, and clinical trials were assessed.

Data synthesis: In a phase 2/3 trial, zavegepant 10 and 20 mg were more effective than placebo on primary endpoints of freedom of pain (22.5%, 23.1%, and 15.5%, respectively), and freedom from most bothersome symptoms (MBSs) (41.9%, 47.9%, and 33.7%, respectively) 2 hours after treatment. The incidence of adverse effects for both doses was similar to placebo. In a phase 3 trial, zavegepant 10 mg was compared with placebo. Two hours after treatment, more patients in the zavegepant group achieved pain freedom (24% vs 15%) and relief from MBSs (40% vs 31%) compared with placebo. Common adverse events included dysgeusia (21% zavegepant vs 5% placebo) and nasal discomfort (5% zavegepant vs 1% placebo).

Relevance to patient care and clinical practice in comparison with existing drugs: Zavegepant is indicated for acute treatment of migraine with or without aura in adults. Zavegepant method of administration and prompt relief of migraine symptoms may be an attractive alternative to triptans for those in need of relief.

Conclusion: Zavegepant may be a convenient and useful acute treatment option for migraines with and without aura.

Objective: The objective of this systematic review is to determine the tolerability and safety of psilocybin in a variety of psychiatric and substance-dependence conditions.

Data sources: A systematic review was conducted using Embase, PubMed, Cochrane Central, and Web of Science through September 2023 using the following terminology: "psilocybin" AND "mental-disease" OR "substance-dependence" AND "disease-therapy," in addition to other synonymous key words.

Study selection and data extraction: Literature reporting acute effects and safety data following the use of psilocybin as the pharmacologic intervention in a clinical trial in adult patients with a psychiatric or substance-dependence condition were included. Following the application of inclusion and exclusion criteria, 16 studies were ultimately included in this review.

Data synthesis: The most common treatment-emergent adverse effects reported were transient nausea and headache. Transient anxiety was reported as a frequent psychiatric effect, and 3 participants received a benzodiazepine for refractory anxiety during the psilocybin session. Psilocybin demonstrated modest increases in blood pressure and heart rate, and 1 participant received an antihypertensive for sustained hypertension during the psilocybin session. No cases of psilocybin-induced psychosis or Hallucinogen Persisting Perception Disorder were reported.

Relevance to patient care and clinical practice: Treatment resistance remains a concern for psychiatric patients and novel therapies are needed to help alleviate the burden of morbidity and mortality. Psilocybin demonstrates promising acute and long-term safety that may allow for its use in psychiatric or substance-dependence conditions as an alternative to standards of care or in treatment-resistant patients.

Conclusions: Psilocybin has demonstrated tolerability and safety in recent literature that has investigated its therapeutic potential in a variety of psychiatric or substance-dependence conditions.

Background: Fluoroquinolones (FQs) are associated with increased risk of tendon injury but comparative risk versus other antibiotic options for the same indication has yet to be evaluated.

Objective: Describe the incidence (relative risk) of any tendon injury in patients receiving FQ compared with other (non-FQs) antibiotics for treatment of community-acquired pneumonia (CAP).

Methods: A retrospective propensity score weighted cohort study was performed to evaluate the association between FQ antibiotics and tendon injury risk at 2 time points (within 1 month and within 6 months of use) compared with non-FQ regimens for treatment of CAP. The evaluation was performed using the CCAE (MarketScan Commercial Claims and Encounters) and COB (Medicare Supplemental and Coordination of Benefits) databases from 2014 to 2020. Patients with ICD (International Classification of Diseases) 9/10 coding for outpatient pneumonia who were >18 years and without history of tendon injury were included. Patients with history of tendon injury, who received multiple antibiotic therapies for recurrent pneumonia, or who received both FQ and non-FQ regimens during the study period were excluded. Propensity score weighting was used to adjust for selection bias due to contributing risk factors, including demographics (age, sex), comorbidities (diabetes mellitus, chronic kidney disease), and concurrent medications (corticosteroids).

Results: At 1 month, the odds of tendon injury were estimated to be significantly higher (41.9%) in patients receiving FQs compared with those receiving a non-FQ-based regimen (odds ratio [OR] = 1.419, 95% confidence interval [CI] = [1.188-1.698]). The odds of tendon injury were also estimated to be higher (OR = 1.067, 95% CI = [0.975-1.173]) in the FQ population within 180 days, but this effect was not statistically significant. The most frequent sites of tendon injuries were rotator cuff, shoulder, and patellar tendon.

Conclusions and relevance: Prescribers should recognize the risk of tendon injury within 1 month of FQ use when considering treatment regimens for CAP and use alternative options with lower risk whenever possible.

Objective: This article aims to discuss elacestrant, an oral selective estrogen receptor downregulator approved by the Food and Drug Administration (FDA) in January 2023 for the treatment of hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer.

Data sources: PubMed, Embase, Medline, Clinicaltrials.gov, and the National Comprehensive Cancer Network (NCCN) were searched from inception to August 31, 2023.

Study selection and data extraction: Clinical trials published in English were included and relevant information regarding methodology and results were extracted.

Data synthesis: Phase 1 and 3 trials showed elacestrant was safe and improved progression-free survival in patients with endocrine receptor 1 (ESR1) mutations who failed cyclin-dependent kinase 4/6 inhibitor (CDK 4/6i) plus 1 prior endocrine therapy compared with standard of care (SOC) (fulvestrant, anastrozole, letrozole, or exemestane monotherapy).

Relevance to patient care and clinical practice in comparison to existing drugs: Elacestrant maintains a comparable adverse event profile with other endocrine therapies and offers an alternative to typical sequential therapy which can delay the use of or be used after traditional chemotherapy. Elacestrant is currently being studied in CDK 4/6 inhibitor naïve patients and as a component of combination therapy for first-line use which could lead to future indications.

Conclusions: Elacestrant gained FDA approval in January 2023 and can be considered in patients with HR+ HER2- advanced breast cancer and ESR1 mutations who have progressed despite therapy with either CDK 4/6i plus aromatase inhibitors (AI) or fulvestrant or chemotherapy.

Background: Patiromer and sodium zirconium cyclosilicate (SZC) are 2 oral potassium binders approved for chronic hyperkalemia. It is unknown if one is more effective at reducing serum potassium than the other in acute hyperkalemia.

Objective: The objective of this study was to determine if there was a difference between patiromer and SZC in the reduction of serum potassium in patients with acute hyperkalemia.

Methods: This was a single-center, retrospective, observational study. Patients with a nonhemolyzed serum potassium level of 5.5 mEq/L or greater and received at least one dose of patiromer or SZC were included. The primary outcome was to determine the difference in effectiveness between patiromer and SZC in lowering of serum potassium 6 to 24 hours after administration. Secondary outcomes included description of total dosage received in 24 hours and incidence of electrolyte changes.

Results: A total of 200 patients were included in this study, with 100 patients in each group. Serum potassium was significantly reduced by both patiromer (-1.2 mEq/L, 95% confidence interval [CI]: -2.3 to -0.2) and SZC (-0.8 mEq/L, 95% CI: -1.0 to -0.7), but there was no difference between the 2 medications in the amount of potassium reduction (P = 0.464). No clinically significant differences in electrolyte changes were seen.

Conclusions and relevance: This study represents the first head-to-head comparison of patiromer and SZC in the setting of acute hyperkalemia. No difference in effectiveness between patiromer and SZC in reducing serum potassium was seen. Both agents can be considered in acute hyperkalemia management.

Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are first-line treatment for type 2 diabetes. Evidence has shown a 3- to 5-fold increase in the risk of genitourinary infections with their use due to inhibition of renal glucose reabsorption, resulting in glucosuria. Increased glucosuria is thought to increase the risk of genitourinary infections at a greater degree in patients with a significantly elevated HbA1c (≥10%), and initiation of SGLT2i is often delayed in these patients. While a limited body of evidence exists indicating that A1c level is not an independent risk factor for SGLT2i-induced genitourinary infection, pragmatically this concern remains a barrier to SGLT2i utilization.

Objective: Evaluate the real-world genitourinary (GU) infection rate in patients receiving SGLT2i with a baseline HbA1c ≥10% compared to patients with a baseline HbA1c <10%.

Methods: This retrospective cohort study evaluated data from 5542 adult patients treated between January 2013 and January 2023, who were prescribed an SGLT2i. Data collected included sex, age, race/ethnicity, renal function, date of SGLT2i start, number of SGLT2i orders, name and dose of SGLT2i, HbA1c, and a predetermined set of diagnosis codes related to bacterial and fungal genitourinary infections. The primary outcome was the overall GU infection rate after SGLT2i initiation within groups of baseline HbA1c of ≥10% and <10%, and the secondary outcome was total GU infections within these same groups.

Results: The primary outcome was equivalent between those with HbA1c <10% and HbA1c ≥10% (0.0064 ± 0.0565 vs 0.0030 ± 0.0303 infection per month [mean ± standard deviation]; P < 0.0001 for both lower and upper bounds). There was no statistically significant difference in total GU infections between the same groups (0.027 ± 0.21 vs 0.015 ± 0.14, P = 0.11). Female gender and prior recurrent infection were associated with increased GU infection after SGLT2i.

Conclusion and relevance: A baseline HbA1c ≥ 10% was not significantly associated with an increased risk of GU infection following the initiation of SGLT2i compared to those with a baseline HbA1c of <10%.

Objective: Summarize the studies evaluating the use of subcutaneous (SQ) insulin in the management of diabetic ketoacidosis (DKA) in adults and pediatrics.

Data sources: A PubMed literature search was conducted for articles published between 2000 and the end of May 2024 which contained the following terms in their title: (1) subcutaneous, glargine, or basal and (2) ketoa*.

Study selection and data extraction: Review articles, guidelines, meta-analysis, commentaries, studies not related to the acute management of DKA, studies evaluating continuous SQ insulin, animal studies, if the time to DKA resolution was not clearly defined, and studies where basal insulin was administered greater than 6 hours after the insulin infusion was started were excluded.

Data synthesis: The electronic search identified 58 articles. Following the initial screening 38 articles were excluded and 3 were added after bibliography review. Of the 23 articles assessed for eligibility, 7 were excluded. Sixteen articles were included. Five studies compared SQ rapid/short-acting insulin and intravenous (IV) insulin infusions in adults, 4 compared SQ rapid/short-acting insulin and IV insulin infusions in pediatrics, 4 evaluated IV insulin infusions with or without SQ basal insulin in adults, and 3 evaluated IV insulin infusions with or without SQ basal insulin in pediatrics.

Relevance to patient care and clinical practice: In comparison with IV insulin infusions, rapid/short-acting SQ insulin regimens were associated with reduced ICU admission rates, hospital length of stay, and hospitalization costs. IV insulin infusion regimens that included a single SQ basal insulin dose upon therapy initiation were associated with reduced concurrent IV insulin infusion durations.

Conclusion: Studies reviewed suggest that SQ insulin regimens may be as effective and safe as IV insulin infusions in the management of DKA and are associated with the conservation of resources. Providers may refer to this review when establishing or modifying their DKA management protocols.