Pharmacotherapy最新文献

Introduction: Intravenous regular insulin is often used for the management of hyperkalemia due to its rapid onset of action and predictable potassium-lowering effects. Various studies have been conducted to determine optimal insulin dosing strategies that reduce serum potassium levels without increasing hypoglycemia risk. As data shifts towards lower or fixed insulin doses, validating the appropriateness of these dosing regimens for the management of hyperkalemia in overweight patients is warranted. The purpose of this study was to evaluate the serum potassium-lowering effects of 5 units versus 10 units of intravenous regular insulin in hyperkalemic patients with a body mass index (BMI) ≥ 25 kg/m².

Methods: A multicenter, retrospective study was performed in adult patients with BMI ≥ 25 kg/m² who received 5 or 10 units of intravenous regular insulin for the treatment of hyperkalemia. The primary outcome was the potassium-lowering effects of 5 units versus 10 units of intravenous regular insulin. Secondary outcomes include the incidence of hypoglycemic episodes within 6 h of insulin administration, hospital length of stay (LOS), and treatment failure.

Results: Of 699 patients screened, 81 patients received 5 units and 81 patients received 10 units. There was no difference in the serum potassium-lowering effects of 5 units versus 10 units of intravenous regular insulin (0.5 (0.1-1.1) mmol/L vs. 0.5 (0.2-1) mmol/L; p = 0.65). No significant differences were observed for any secondary outcomes. Subgroup analyses revealed no significant differences for BMI; the number of concomitant acute potassium-lowering therapies received; or the degree of renal impairment, aside from a significantly larger potassium-lowering effect with 10 units of intravenous regular insulin observed in the subgroup receiving no concomitant acute potassium-lowering therapies as well as the subgroup with a creatinine clearance of 30-60 mL/min.

Conclusion: In this small, retrospective cohort study, treatment with 5 units of intravenous regular insulin did not compromise the serum potassium-lowering effect when compared to 10 units in overweight patients with hyperkalemia. Further controlled studies are warranted to confirm these findings.

Introduction: Levetiracetam (LEV) is indicated for benzodiazepine (BZD) refractory status epilepticus (SE) and is traditionally administered as an intravenous piggyback (IVPB) infused over 15 min, although rapid intravenous push (IVP) administration over 2 to 5 min has gained popularity. Current literature surrounding IVP LEV administration supports increased efficiency and equal safety of IVP compared with IVPB, though efficacy comparisons, such as seizure duration, are limited. The objective of this study was to assess the impact of IVP LEV on seizure duration and BZD requirements.

Methods: This retrospective cohort study assessed adult patients who received IVP or IVPB LEV following a BZD for an acute or suspected seizure. The primary outcome was the number of patients who required additional BZD doses between LEV order and administration. Secondary outcomes included additional BZD requirement within 6 h after LEV administration, time from LEV order to administration, need for intubation, and intensive care unit (ICU) admission. Safety outcomes assessed included bradycardia, hypotension, and infusion site reactions.

Results: A total of 299 patients were included, 144 in the IVP group and 155 in the IVPB group. Fewer patients required additional BZD doses between LEV order and administration in the IVP group than the IVPB group (8 patients [5.6%] vs. 27 patients [17.4%]; p = 0.002). Additionally, the median time from LEV order to administration was shorter in the IVP group than in the IVPB group (14.5 min vs. 29.0 min; p < 0.001). Bradycardia occurred more frequently in the IVPB group compared with the IVP group (8.8% vs. 2.3%; p = 0.03).

Conclusion: IVP LEV was associated with less frequent requirement of additional BZD doses for treatment of acute or suspected seizures compared with IVPB, as well as a faster time to medication administration and potentially a lower risk of bradycardia.

Introduction: Opioids are commonly used to manage chronic pain in older adults, despite their well-documented adverse events (AEs) and the potential for additional less well-known risks. Post-marketing surveillance methods applied in real-world settings are essential to monitor AEs. Prescription Sequence Symmetry Analysis (PSSA) is a method that compares medication initiation patterns within individuals and can detect signals of prescribing cascades and drug AEs. This study applied PSSA to Medicare claims data to explore potential AEs following the initiation of long-term opioid therapy (LOT).

Methods: We used Texas-Medicare data to identify adults who initiated LOT (≥ 90 consecutive days) in 2016-2019. Prescription sequence symmetry analysis (PSSA) was performed to explore associations between opioids and related adverse events treated by marker drugs. The observation period for sequences of incident marker drug prescriptions was limited to 12 months before and after opioid initiation. Marker drugs were categorized based on the Anatomical Therapeutic Chemical (ATC) Classification System. Adjusted sequence symmetry ratios (aSSR) and 95% confidence intervals were calculated to account for prescribing trend changes.

Results: Among 11,233 incident opioid users, we identified incident marker drugs belonging to 145 distinct ATC classes, 36 of which had statistically significant aSSRs. We found signals of increased post-opioid prescriptions related to known opioid AEs (e.g., propulsives, antiemetics, laxatives, naltrexone) and less well-documented associations (antimicrobials, hormones, antiarrhythmics, and antipsychotics).

Conclusions: PSSA applied to administrative claims data effectively identified both expected and potentially underrecognized adverse effects of long-term opioid use. This approach can enhance post-marketing surveillance by uncovering real-world prescribing cascades in older adults.

V. Shah, D. Cordwin, S. L. Hummel, M. P. Dorsch, "Chloride Dipstick to Rapidly Estimate Urine Sodium During Diuresis in Acute Heart Failure." Pharmacotherapy. 45, (2025): 352-355. https://doi.org/10.1002/phar.70026. The author's name, V Shah, was corrected to Vacha Shah in the online version. We apologize for this error.

Background: Peroxisome proliferator-activated receptor α (PPARα) has been reported to exert protective roles in immune-mediated intestinal diseases through inhibition of interleukin-6 (IL-6)-induced signal transducer and activator of transcription factor 3 (STAT3) activation.

Aim: To investigate the potential anti-inflammatory effect of fenofibrate, as an add-on therapy to mesalamine, on IL-6/STAT3 and nitric oxide (NO) in patients with ulcerative colitis (UC).

Methods: This pilot, double-blind, randomized, controlled trial included 60 patients diagnosed with mild-to-moderate UC. Patients were randomly allocated into two groups. The placebo group (n = 30) received placebo plus mesalamine 1 g three times daily, and the fenofibrate group (n = 30) received mesalamine 1 g three times daily and fenofibrate 160 mg once daily. The study duration was 6 months. The severity of UC was evaluated using the Disease Activity Index (DAI), and quality of life (QoL) was assessed using the Short Form-36 questionnaire (SF-36). Serum levels of IL-6, NO, C-reactive protein (CRP), and STAT3 were measured for all patients.

Results: After treatment, both groups showed a significant reduction in DAI, IL-6, STAT3, NO, and CRP, along with an increase in SF-36 scores. Furthermore, the fenofibrate group demonstrated a significantly greater decrease in DAI (p = 0.0002), IL-6 (p = 0.04), STAT3 (p = 0.004), NO (p = 0.013), and CRP (p = 0.034), as well as a greater increase in SF-36 (p = 0.04) compared with the placebo group.

Conclusion: Fenofibrate may represent a promising add-on therapy in patients with mild-to-moderate UC by modulating inflammation and improving QoL.

Trial registration: NCT05753267.

Background: Abrupt cessation of alcohol consumption after prolonged periods of use leaves patients at risk for experiencing withdrawal symptoms. Alcohol is a central nervous system depressant that increases the activity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and suppresses the activity of the excitatory neurotransmitter glutamate. Stopping consumption of alcohol reduces this inhibitory response and leads to a net excitatory state and symptoms of withdrawal, including anxiety, tremors, and even seizures. Benzodiazepines have traditionally been the treatment of choice for patients with alcohol withdrawal. Gabapentin has recently been studied as an adjunctive agent for the treatment and prevention of alcohol withdrawal, given its structural similarity to GABA and lower risk for dependence compared with benzodiazepines.

Objective: The primary objective of this study was to determine if a gabapentin-based regimen is benzodiazepine-sparing in patients experiencing alcohol withdrawal.

Methods: This was a retrospective, single center, pre- and post-implementation analysis of a gabapentin taper-based alcohol withdrawal protocol in place of a traditional benzodiazepine-based protocol used in patients admitted to a large, urban academic medical center in the Midwest for alcohol withdrawal between January 1, 2017, and January 1, 2023. The primary outcome was a comparison of cumulative benzodiazepine dose (in lorazepam equivalents) received throughout admission between groups.

Results: This study included 200 patients with 100 patients in each of the pre- and post-implementation groups. Baseline characteristics were similar between groups except for baseline serum alcohol level, which was higher in the pre-implementation group. Patients in the post-implementation group on average were exposed to 9.7-mg lorazepam equivalents during admission compared with 22.8-mg lorazepam equivalents in the pre-implementation group (p = 0.001). Patients between groups had similar symptom progression as characterized by average daily alcohol withdrawal assessment scale (AWAS) scores and length of stay.

Conclusion: Utilization of a gabapentin taper resulted in significantly lower cumulative exposure to benzodiazepines and similar clinical outcomes in patients admitted for acute alcohol withdrawal.

Objective: Angiotensin-II Receptor Blockers (ARBs) are commonly prescribed; however, their adverse events may prompt new drug prescriptions, known as prescribing cascade (PC). We aimed to identify potential ARB-induced PCs using high-throughput sequence symmetry analysis.

Methods: Using claims data from a national sample of Medicare beneficiaries (2011-2020), we identified new ARB users aged ≥ 66 years with continuous enrollment ≥ 360 days before and ≥ 180 days after ARB initiation. We screened for initiation of 446 other (non-antihypertensive) "marker" drug classes within ±90 days of ARB initiation. Sequence ratios (SRs) with 95% confidence intervals (CIs) were calculated as the ratio of the number of ARB users initiating the marker class after versus before ARB initiation. Adjusted SRs (aSRs) accounted for prescribing trends over time, and for significant aSRs, we calculated the naturalistic number needed to harm (NNTH); significant signals were reviewed by clinical experts for plausibility.

Results: We identified 320,663 ARB initiators, age (mean ± standard deviation) 76.0 ± 7.2 years; 62.5% female; and 91.5% with hypertension. Of the 446 marker classes evaluated, 17 signals were significant, and three (18%) were classified as potential PCs after clinical review. The strongest signals ranked by the lowest NNTH included benzodiazepine derivatives (NNTH 2130, 95% CI 1437-4525), adrenergics in combination with anticholinergics, including triple combinations with corticosteroids (NNTH 2656, 95% CI 1585-10,074), and other antianemic preparations (NNTH 9416, 95% CI 6606-23,784). The strongest signals ranked by highest aSR included other antianemic preparations (aSR 1.7, 95% CI 1.19-2.41), benzodiazepine derivatives (aSR 1.18, 95% CI 1.08-1.3), and adrenergics in combination with anticholinergics, including triple combinations with corticosteroids (aSR 1.12, 95% CI 1.03-1.22).

Conclusion: The identified PC signals reflected known and possibly under-recognized ARB adverse events in this Medicare cohort. These hypothesis-generating findings require further investigation to determine the extent and impact of these PCs on patient outcomes.

Introduction: Patients with burns are at an increased risk of multidrug-resistant pathogens including Pseudomonas aeruginosa and may need specialized dosing regimens due to alterations in physiology due to their injuries.

Methods: Therefore, we conducted a single-dose, open-label, pharmacokinetic study of ceftolozane (2 g)/tazobactam (1 g) infused over 60 min in six patients with partial- or full-thickness burns and central line access. Serial blood samples were obtained at the following time points: 0 (predose) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 h following the start of infusion for determination of plasma drug concentrations.

Results: Similar estimates of clearance (CL) were observed between the groups, and as a consequence the half-life (T1/2) was longer in the six patients with burns in the current study compared to previous studies of healthy volunteers on average. Although these mean comparisons suggest similarity in exposure based on area under the curve (AUC) and maximum concentration (Cmax), it is important to recognize that the interindividual variability is approximately 2- to 5-fold higher in patients with burns compared to healthy volunteers.

Conclusions: We did not find sufficient deviations in the concentrations of ceftolozane/tazobactam to recommend an empiric dose adjustment for patients with burns. However, this finding is limited by our small sample size and lack of clinical outcome data. Therefore, we also provide a conditional recommendation to conduct therapeutic drug monitoring to adjust ceftolozane/tazobactam dosing or to switch to a continuous infusion approach in cases of a suboptimal clinical response.

Background: Osteomyelitis (OM) is a complex inflammatory bone infection typically requiring prolonged antibiotic therapy. Oritavancin (ORI), a long-acting lipoglycopeptide with activity against biofilm-embedded pathogens, has emerged as a potential treatment option despite previous US Food and Drug Administration (FDA) warnings against its use in OM.

Methods: We conducted a systematic review and meta-analysis of observational studies in seven databases through August 8, 2024 (PROSPERO registration: CRD42025635473) to evaluate the available evidence on ORI's efficacy and safety in OM. Clinical success was defined as the improvement or resolution of infection without requiring additional gram-positive antibiotics, surgical debridement, or amputation. Study quality was assessed using the Newcastle-Ottawa Scale.

Results: Our systematic review included nine observational studies comprising 316 patients with OM treated with ORI. Quality assessment using the Newcastle-Ottawa Scale revealed scores ranging from 5/9 to 8/9, with most studies demonstrating adequate outcome assessment but limitations in cohort selection and comparability. Meta-analysis demonstrated a pooled clinical success rate of 81% (95% CI: 76%-85%). Comparative analysis of two studies yielded an odds ratio of 2.99 (95% CI: 0.86-10.36) favoring ORI over comparators (daptomycin and dalbavancin), though with substantial heterogeneity (I² = 80.2%, p = 0.0247).

Conclusions: Despite previous warnings, we found no evidence of ineffectiveness with ORI for OM. ORI's infrequent dosing schedule may provide convenience over daily parenteral therapy, particularly for difficult-to-treat pathogens like MRSA and VRE. Further research is needed to optimize dosing strategies based on pathogen susceptibility and establish appropriate therapeutic drug monitoring protocols.