Drug Interaction Between Febuxostat and Thiopurine Antimetabolites: A Review of the FDA Adverse Event Reporting System and Medical Literature.

BACKGROUND: There is a known drug interaction (DI) between xanthine oxidase (XO) inhibitors and the thiopurine immunosuppressants, azathioprine (AZA) and mercaptopurine (6-MP). Xanthine oxidase inhibition increases concentrations of AZA and 6-MP active metabolites, possibly resulting in myelosuppression. When allopurinol is used with AZA or 6-MP, dose reduction of AZA or 6-MP is recommended. Febuxostat is a newer XO inhibitor approved for the treatment of gout. OBJECTIVE: To determine the clinical impact of the febuxostat-thiopurine DI. DESIGN AND SETTING: Case series derived from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and published medical literature. PATIENTS: Nineteen patients who received concomitant febuxostat and either AZA or 6-MP. MEASUREMENTS: Laboratory and clinical data. RESULTS: Nineteen cases reporting myelosuppressive events were identified in patients receiving febuxostat with AZA or 6-MP. Eighteen cases were treated with the combination of AZA and febuxostat. A median of 1.6 months elapsed from initiation of the drug combination until discovery of the event. Sixteen cases required hospitalization; 15 reported administration of blood products. Thirteen cases reported resolution of the event with discontinuation of both drugs, two reported discontinuation of the thiopurine only, and one reported discontinuation of febuxostat only. LIMITATIONS: Thiopurine monotherapy may cause myelosuppression. Complications of immunosuppression that may contribute to the real-world morbidity and mortality associated with the febuxostat-thiopurine DI were not examined. Finally, FAERS data are limited by the voluntary nature of reporting. CONCLUSION: Current febuxostat labeling contraindicates concomitant administration of febuxostat with either AZA or 6-MP. This case series demonstrates that the DI can result in clinically significant adverse events and is supportive of current febuxostat labeling.

Role of topical tranexamic acid in the management of idiopathic anterior epistaxis in adult patients in the emergency department.

PURPOSE: The role of topical tranexamic acid in the management of anterior epistaxis in adult patients in the emergency department (ED) is examined. SUMMARY: The use of alternative agents for the treatment of epistaxis before the use of nasal packing may be reasonable due to patient discomfort, potential complications, and the need for follow-up with a healthcare provider for packing removal. One such agent is tranexamic acid. Two published studies evaluated the off-label use of topical tranexamic acid for the treatment of epistaxis. The first trial compared the efficacy of a topical gel containing 10% tranexamic acid with a placebo gel containing glycerin for the treatment of epistaxis. The percentage of patients whose bleeding ceased within 30 minutes of the intervention did not significantly differ between the tranexamic acid and placebo groups (p = 0.16). The second trial compared the efficacy of cotton pledgets soaked in the i.v. formulation of tranexamic acid inserted into the bleeding naris with standard nasal packing therapy. Bleeding cessation occurred within 10 minutes in 71% of the tranexamic acid group versus 31.2% of the standard treatment group (odds ratio, 2.28; 95% confidence interval, 1.68-3.09; p < 0.001). Additional information is necessary to fully evaluate the role of topical tranexamic acid in treatment algorithms; however, the use of topical tranexamic acid may be beneficial in select populations. CONCLUSION: Topical tranexamic acid may have a role in the treatment of anterior epistaxis in select ED patients, though additional studies are needed to confirm its role in treatment algorithms.

Evidence-based diagnosis and thrombolytic treatment of cardiac arrest or periarrest due to suspected pulmonary embolism.

When a previously healthy adult experiences atraumatic cardiac arrest, providers must quickly identify the etiology and implement potentially lifesaving interventions such as advanced cardiac life support. A subset of these patients develop cardiac arrest or periarrest due to pulmonary embolism (PE). For these patients, an early, presumptive diagnosis of PE is critical in this patient population because administration of thrombolytic therapy may significantly improve outcomes. This article reviews thrombolysis as a potential treatment option for patients in cardiac arrest or periarrest due to presumed PE, identifies features associated with a high incidence of PE, evaluates thrombolytic agents, and systemically reviews trials evaluating thrombolytics in cardiac arrest or periarrest. Despite potentially improved outcomes with thrombolytic therapy, this intervention is not without risks. Patients exposed to thrombolytics may experience major bleeding events, with the most devastating complication usually being intracranial hemorrhage. To optimize the risk-benefit ratio of thrombolytics for treatment of cardiac arrest due to PE, the clinician must correctly identify patients with a high likelihood of PE and must also select an appropriate thrombolytic agent and dosing protocol.

Local antimicrobial administration for prophylaxis of surgical site infections.

Despite a lack of consensus guidelines, local antibiotic administration for prophylaxis of surgical site infections is used during many surgical procedures. The rationale behind this practice is to provide high antibiotic concentrations at the site of surgery while minimizing systemic exposure and adverse effects. Local antibiotic administration for surgical site prophylaxis has inherent limitations in that antibiotics are applied after the incision is made, rather than the current standard for surgical site prophylaxis that recommends providing adequate antibiotic concentrations at the site before the incision. The efficacy and safety of local application of antibiotics for surgical site prophylaxis have been assessed in different types of surgery with a variety of antibiotic agents and methods of application. We identified 22 prospective, randomized, controlled trials that evaluated local application of antibiotics for surgical site prophylaxis. These trials were subsequently divided and analyzed based on the type of surgical procedure: dermatologic, orthopedic, abdominal, colorectal, and cardiothoracic. Methods of local application analyzed included irrigations, powders, ointments, pastes, beads, sponges, and fleeces. Overall, there is a significant lack of level I evidence supporting this practice for any of the surgical genres evaluated. In addition, the literature spans several decades, and changes in surgical procedures, systemic antibiotic prophylaxis, and microbial flora make conclusions difficult to determine. Based on available data, the efficacy of local antibiotic administration for the prophylaxis of surgical site infections remains uncertain, and recommendations supporting this practice for surgical site prophylaxis cannot be made.