Andexanet Alfa (Andexxa) Formulary Review.

Andexanet alfa, a recombinant modified human "decoy" factor Xa (FXa) protein, is the first and only available antidote approved by the Food and Drug Administration to manage life-threatening or uncontrolled bleeding associated with the anti-Xa agents. It binds to direct and indirect anti-Xa oral anticoagulants with high specificity to reverse their inhibitory effects and restore the activity of FXa. Andexanet alfa is administered via two different dosing regimens, standard and high dose, based on the specific FXa inhibitor, dose, and time since the patient's last dose of FXa inhibitor. The approval for andexanet alfa is supported by data from two phase 3 studies (ANNEXA-A, ANNEXA-R) and preliminary data from the phase 3b/4 ANNEXA-4 trial. The first study found that andexanet alfa rapidly reduced anti-Xa activity by 92%-94% in healthy volunteers taking apixaban or rivaroxaban. The ANNEXA-4 study found that the median anti-Xa activity decreased by 89%-93% in patients with major bleeding taking apixaban or rivaroxaban. However, thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up in ANNEXA-4. Additionally, only 40% of patients had restarted anticoagulation and, in this group, the rate of thrombotic events was 12%. Four patients had a thrombotic event within 3 days after andexanet alfa treatment. The wholesale acquisition cost of the standard dose regimen is $24,750, and the high-dose regimen is $49,500. The estimated annual drug budget of treating 10-100 patients ranges from $248K to $495M. Effective October 1, 2018, Medicare will provide an add-on payment for andexanet alfa of up to $14,063 per qualifying case to Inpatient Prospective Payment System-participating acute care hospitals. In this formulary review for a health system's pharmacy and therapeutics committee, andexanet alfa clinical trials and medication package insert were summarized and, after consulting with clinical experts from our institutions, practical recommendations for use were generated to ensure appropriate and safe use of this agent.

Ceftaroline for Severe Methicillin-Resistant Staphylococcus aureus Infections: A Systematic Review.

Ceftaroline is approved by the Food and Drug Administration for acute bacterial skin and skin-structure infections and community-acquired bacterial pneumonia, including cases with concurrent bacteremia. Use for serious methicillin-resistant Staphylococcus aureus (MRSA) infections has risen for a multitude of reasons. The aim of this article is to review the literature evaluating clinical outcomes and safety of ceftaroline prescribed for serious MRSA infections. We conducted a literature search in Ovid (Medline) and PubMed for reputable case reports, clinical trials, and reviews focusing on the use of ceftaroline for treatment of MRSA infections. Twenty-two manuscripts published between 2010 and 2016 met inclusion criteria. Mean clinical cure was 74% across 379 patients treated with ceftaroline for severe MRSA infections. Toxicities were infrequent. Ceftaroline treatment resulted in clinical and microbiologic cure for severe MRSA infections. Close monitoring of hematological parameters is necessary with prolonged courses of ceftaroline.

Evaluation of an institution-wide guideline for hyperglycemic emergencies at a tertiary academic medical center.

BACKGROUND: No previous studies exist examining implementation of an institution-wide guideline and order set for hyperglycemic emergencies (diabetic ketoacidosis [DKA] and hyperosmolar hyperglycemic state [HHS]). OBJECTIVE: Evaluate the impact of an institutional guideline and order set for hyperglycemic emergencies. METHODS: This retrospective descriptive study evaluated patients with a diagnosis of DKA or HHS. Two time periods were evaluated: phase 1 (PRE) assessed practice preguideline implementation, and phase 2 (POST) assessed practice postguideline and order set introduction. RESULTS: A total of 172 patients (91 PRE and 81 POST) were included in the analysis. There was no difference in the mean hospital length of stay (LOS) in the PRE versus POST groups (5.2 ± 4 vs 5.9 ± 8.6 days, P = .49). The mean intensive care unit (ICU) LOS was shorter in the POST group (64.8 ± 19 vs 37.1 ± 74.8 hours, P < .01). The POST group had an increase in frequency of assessments for clearance of urinary ketones (18 vs 33.3%, P = .03) and ß-hydroxybutyrate (16 vs 37%, P < .01). Frequency of point-of-care glucose testing (12.5 ± 4.6 vs 15.1 ± 4.7, P < .01) and time to anion gap closure (13 ± 9 vs 9.3 ± 7.4 hours, P < .01) improved in the POST group. There was no difference in the number of patients experiencing hypoglycemia or hypokalemia between both groups. CONCLUSIONS: Implementation of an institutional guideline and order set for hyperglycemic emergencies decreased ICU LOS and time to anion gap closure, with no difference in rates of hypoglycemia.

Impact of an immunoglobulin G-specific enzyme-linked immunosorbent assay on the management of heparin-induced thrombocytopenia.

STUDY OBJECTIVE: To evaluate whether using an immunoglobulin G (IgG)-specific platelet factor 4 (PF4) test reduces the rate of positive PF4 results and has an impact on prescribing practices of nonheparin anticoagulants (direct thrombin inhibitors and fondaparinux) in patients assessed for heparin-induced thrombocytopenia (HIT). DESIGN: Single-center prospective cohort study with a historical control group. SETTING: Large academic medical center. PATIENTS: A total of 672 patients assessed for HIT. INTERVENTION: Patients were assessed for HIT by using either an IgG-specific PF4 enzyme-linked immunosorbent assay (ELISA; 336 patients) or a nonspecific PF4 ELISA (336 patients; historical control group). MEASUREMENTS AND MAIN RESULTS: No significant difference was noted in the proportion of patients with a low, intermediate, or high risk of HIT based on the 4Ts pretest clinical scoring system. The PF4 ELISA was positive in 6.9% versus 11.3% of patients (p=0.04) in the IgG-specific and nonspecific cohorts, respectively. A smaller proportion of patients were prescribed a direct thrombin inhibitor in the IgG-specific cohort (19.4% vs 25.9%; p=0.04). No significant difference in fondaparinux use was noted between the cohorts. The duration of direct thrombin inhibitor therapy, bleeding events, hospital length of stay, and in-hospital mortality was similar in both cohorts. CONCLUSION: Use of an IgG-specific PF4 ELISA was associated with a lower rate of positive PF4 test results. Direct thrombin inhibitor prescribing was also significantly lower during the time period where the IgG-specific PF4 ELISA was used, with no significant differences noted in safety outcomes.