Andexanet alfa: A Novel Factor Xa Inhibitor Reversal Agent.

Objective: The purpose of this article is to review the available clinical trial data for andexanet alfa and its role in clinical practice. Data Sources: A MEDLINE/PubMed search was conducted (January 2000 to January 2019) using the keyword andexanet alfa for clinical trials. References of identified articles were searched by hand for additional citations. Study Selection and Data Extraction: We included English-language articles related to the Food and Drug Administration (FDA) approval of andexanet alfa or provided novel information regarding this drug entity. Data Synthesis: The findings of the review show that andexanet alfa may be a safe and effective option for the reversal of apixaban and rivaroxaban. Relevance to Patient Care and Clinical Practice: With the approval of this reversal agent, patients and providers can feel safer when using apixaban and rivaroxaban, which in turn may increase the use of these anticoagulant agents. Conclusions: The new FDA approval of andexanet alfa will allow safer use of oral anticoagulants and will likely further the use of direct oral anticoagulants for anticoagulant needs. Reversing enoxaparin-/edoxaban-induced bleeding with this agent should be limited because there is no FDA approval owing to the fact that only phase II trial data available.

Erenumab: A First-in-Class Monoclonal Antibody for Migraine Prevention.

Objective: To review the pharmacology, efficacy, and safety of the calcitonin gene-related peptide (CGRP) inhibitor erenumab for migraine preventive therapy. Data Sources: A MEDLINE/PubMed search (January 2000 to January 2019) was conducted using the keywords erenumab-aooe, erenumab, migraine, migraine prophylaxis, migraine prevention, and chronic migraine. Additional articles were identified by hand from references. Study Selection and Data Extraction: We included English-language articles (excluding poster presentations) evaluating erenumab pharmacology, efficacy, or safety in humans for migraine prevention. Data Synthesis: Erenumab is a CGRP inhibitor that inhibits vasodilation in response to acute migraines, which decreases pain perception during the migraine. Erenumab efficacy and safety has only been compared with placebo, but its reduction in monthly migraine days (MMDs) and medication response (≥50% reduction in MMDs) are comparable to current recommended off-label therapies for migraine prevention in short-term treatment studies. Additionally, erenumab is associated with low adverse event burden with no difference found compared with placebo per published clinical trials. Relevance to Patient Care and Clinical Practice: Erenumab is the first medication approved in the United States for the prevention of migraines in adults. No head-to-head data are available, but existing data suggest that erenumab is at least as effective as current off-label products and with reduced adverse effects. Conclusion: Erenumab is an effective once-monthly injectable agent for migraine prevention in patients with chronic or episodic migraine. It is also effective for patients who have previously failed migraine preventive therapy. Erenumab has a favorable adverse effect profile, which may improve patient adherence.

Ertugliflozin: A New Option in the SGLT-2 Inhibitor Market for the Treatment of Type 2 Diabetes Mellitus.

OBJECTIVE: The purpose of this article is to review the pharmacological aspects of ertugliflozin and its clinical trials, which led to Food and Drug Administration (FDA) approval for the treatment of type 2 diabetes mellitus (T2DM). DATA SOURCES: A MEDLINE/PubMed (May 2013 to October 2018) search was conducted using the following keywords: ertugliflozin, sodium glucose co-transporter 2 inhibitor, SGLT2 inhibitor, type 2 diabetes mellitus, hyperglycemia. Study Selection and Data Extraction Quantify: We included English-language articles evaluating ertugliflozin pharmacology, pharmacokinetics, efficacy, and safety in humans for blood glucose reduction in human subjects. DATA SYNTHESIS: Ertugliflozin has been FDA approved and considered both safe and efficacious for the treatment of T2DM with hemoglobin A1C reductions ranging from -0.6% to -1.16%. Safety outcomes appear to be similar to that of other SGLT2 inhibitors. Relevance to Patient Care and Clinical Practice: With this approval, patients and clinicians now have another oral option for treating this difficult disease while minimizing hypoglycemia and other unwanted adverse drug reactions. CONCLUSIONS: With the number of patients with diabetes growing, additional safe and effective treatment options available for clinicians and patients is important. Ertugliflozin appears to be an effective and safe therapy as both single and add-on therapy.

Betrixaban: A New Oral Factor Xa Inhibitor for Extended Venous Thromboembolism Prophylaxis in High-Risk Hospitalized Patients.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of the factor Xa (FXa) inhibitor betrixaban for extended-duration prophylaxis of acute medically ill patients with venous thromboembolism (VTE) risk factors. DATA SOURCES: A MEDLINE/PubMed (January 1990 to October 2017) search was conducted using the following keywords: betrixaban, PRT054021, FXa inhibitor, novel oral anticoagulant, NOAC, direct oral anticoagulant, DOAC, and target specific oral anticoagulant, TSOAC. References of identified articles were searched by hand for additional relevant citations. STUDY SELECTION AND DATA EXTRACTION: We included English-language articles evaluating betrixaban pharmacology, pharmacokinetics, efficacy, or safety in human subjects for VTE prophylaxis. DATA SYNTHESIS: Betrixaban is a FXa inhibitor that decreases prothrombinase activity and thrombin generation. Betrixaban efficacy and safety has been compared with that of enoxaparin for prophylaxis of VTE in acutely ill medical patients. In the APEX trial and substudies, extended-duration betrixaban was superior in efficacy to standard-duration enoxaparin in patients at high risk for VTE, including those with elevated D-dimer levels (≥2× upper limit of normal) and of older age (≥75 years). Betrixaban is noninferior to enoxaparin in rates of major bleeding, but the former is associated with more clinically relevant nonmajor bleeding events. CONCLUSION: Betrixaban is the first oral agent approved for extended-duration VTE prophylaxis in acutely ill hospitalized patients. Extended-duration thromboprophylaxis with betrixaban reduces the risk of VTE compared with standard-duration thromboprophylaxis with enoxaparin but is associated with increased risk of bleeding.