Publications

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    ABSTRACT: Biologics are the fastest growing segment of annual United States (US) drug expenditure. Biologics are complex proteins derived from living sources that are important therapy for a variety of diseases. The US is now poised to introduce biosimilars, which are copies of biologics that are not manufactured by the innovator company and are approved under an abbreviated regulatory process. Biosimilars are intended to offer comparable safety and efficacy to the reference biologic at a lower cost. Because of the complexity of producing biologics, the manufacturing process for biosimilars may differ from that of the reference biologic, which may result in subtle changes in biological characteristics and clinical activity. Questions exist regarding whether these slight differences allow the products to be interchanged with the reference product and if unique adverse events will occur with use. While the Biologics Price Competition and Innovation Act outlined the abbreviated approval pathway for biosimilars, guidance from the US Food and Drug Administration (FDA) is needed on specific details of the approval process. The FDA has recently provided guidance about the scientific and quality requirements for demonstrating biosimilarity, but a number of unanswered questions still remain, including concerns about immunogenicity, product naming, and the exact cost savings from biosimilars. Emergency Medicine practitioners must have a sound understanding of these issues to ensure patient safety and avoid complications in care.
    Current Emergency and Hospital Medicine Reports. 12/2013; 1(4).
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    John Fanikos
    Journal of Medical Economics 08/2013;
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    ABSTRACT: 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). Single-center prospective cohort study with a historical control group. Large academic medical center. A total of 672 patients assessed for HIT. 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). 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. 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.
    Pharmacotherapy 06/2013; · 2.31 Impact Factor
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    ABSTRACT: Anticoagulants remain the primary strategy for the prevention and treatment of thrombosis. Unfractionated heparin, low molecular weight heparin, fondaparinux, and warfarin have been studied and employed extensively with direct thrombin inhibitors typically reserved for patients with complications or those requiring intervention. Novel oral anticoagulants have emerged from clinical development and are expected to replace older agents with their ease of use and more favorable pharmacodynamic profiles. Hemorrhage is the main concerning adverse event with all anticoagulants. With their ubiquitous use, it becomes important for clinicians to have a sound understanding of anticoagulant pharmacology, dosing, and toxicity.
    Current emergency and hospital medicine reports. 06/2013; 1(2):83-97.
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    ABSTRACT: Rivaroxaban is the first agent available within a new class of anticoagulants called direct factor Xa inhibitors. Rivaroxaban is approved for use in the United States for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the prevention of deep vein thrombosis in patients undergoing total hip replacement and total knee replacement, for the treatment of deep vein thrombosis and pulmonary embolism, and for the reduction in risk of recurrence of deep vein thrombosis and pulmonary embolism (with additional indications under review). Rivaroxaban dose and frequency of administration vary depending on the indication. As of result of predictable pharmacokinetics and pharmacodynamics, a fixed dose of rivaroxaban is administered without routine coagulation testing. Rivaroxaban has a short half-life, undergoes a dual mode of elimination (hepatic and renal), and is a substrate for P-glycoprotein. Rivaroxaban has a lower potential for drug interactions compared with warfarin. Despite the advantages of a once/day fixed-dose oral agent, in many clinical situations limited evidence is available to guide optimal management of rivaroxaban therapy. In this article, we review the available evidence and provide recommendations where possible for such situations including the desire to monitor the anticoagulation intensity, use in special patient populations, managing drug interactions, and transitioning across anticoagulant agents. Potential strategies for reversing rivaroxaban's anticoagulant effect are reviewed. Health systems will need to perform a systematic safety evaluation and ensure that numerous hospital policies related to anticoagulation are updated to include rivaroxaban. A comprehensive approach to education is needed for clinicians, patients, and technical support personnel involved in patient interactions to ensure safe use.
    Pharmacotherapy 05/2013; · 2.31 Impact Factor
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    ABSTRACT: Dabigatran was expected to replace warfarin for stroke prevention in patients with nonvalvular atrial fibrillation (AF) who are warfarin naive, difficult to maintain in therapeutic range, or at risk of warfarin-related bleeding complications. We hypothesized that the number of patients with nonvalvular AF referred to Anticoagulation Management Services would decrease sharply and that most would switch from warfarin to dabigatran. We evaluated the number of patients with nonvalvular AF referred to 2 large services, Anticoagulation Management Service 1 and Anticoagulation Management Service 2, 12 months before and after market entry of dabigatran. We also evaluated the number of patients who switched from warfarin to dabigatran. Anticoagulation Management Service 1 follows 1,225 patients with nonvalvular AF with mean CHADS2 and CHA2DS2-VASc scores of 2.0 and 3.5, respectively. Anticoagulation Management Service 2 follows 1,137 patients with nonvalvular AF with mean CHADS2 and CHA2DS2-VASc scores of 2.0 and 3.3, respectively. In the 12 months preceding market entry of dabigatran, patients with nonvalvular AF constituted 537 (31.4%) of the referrals sent to Anticoagulation Management Service 1 and increased to 793 (32.3%) in the following 12 months. For Anticoagulation Management Service 2, patients with nonvalvular AF constituted 617 (30.7%) of referrals before market entry of dabigatran and decreased to 495 (25.2%) of referrals. Eighty-one patients (6.6%) from Anticoagulation Management Service 1 and 44 (3.9%) from Anticoagulation Management Service 2 have switched from warfarin to dabigatran. The frequency of initial prescription of dabigatran for stroke prevention in AF and the frequency of transition from warfarin to dabigatran have been less than expected.
    The American journal of cardiology 05/2013; · 3.58 Impact Factor
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    ABSTRACT: Venous thromboembolism (VTE) is a common complication of cancer and chemotherapy. We evaluated the baseline clinical characteristics, thromboprophylaxis patterns, frequency and timing of VTE, and clinical outcomes in 1000 adult hospitalized patients with active cancer. Overall, symptomatic VTE occurred in 5.4% of hospitalized patients with cancer. The VTE occurred in 2.3% of patients with cancer during hospitalization and in 3.4% between hospital discharge and day 90. Few (13.9%) hospitalized patients with cancer received extended duration pharmacological prophylaxis after hospital discharge. Cancer was the most frequent known cause of death in both the groups. In conclusion, VTE was common in hospitalized patients with cancer, especially after discharge. Inhospital death and death between discharge and day 90 were frequent in hospitalized patients with cancer who developed VTE.
    Clinical and Applied Thrombosis/Hemostasis 03/2013; · 1.02 Impact Factor
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    John R Fanikos, Julie K Atay, Jean M Connors
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    ABSTRACT: Three agents have recently been approved to reduce the risk of stroke and embolism, and one agent is in phase 3 trials. These drugs cause less serious bleeding and are simpler to manage, compared with warfarin, but they are not without their risks.
    P&T 03/2013; 38(3):173-7. · 1.07 Impact Factor
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    ABSTRACT: OBJECTIVE: Pulmonary embolism places a heavy economic burden on health care systems, but the components of hospital cost have not been elucidated. We evaluated hospitalized patients with the primary diagnosis of pulmonary embolism. Our goal was to determine the total and component costs associated with their hospital care. METHODS: We included patients hospitalized at Brigham and Women's Hospital from September 2003 to May 2010. Patient demographics, characteristics, comorbidities, interventions, and treatments were obtained from the electronic medical record. Costs were obtained using the hospital's accounting software and categorized into the areas providing direct patient supplies or care. RESULTS: We identified 991 hospitalized patients with acute pulmonary embolism. In-hospital mortality was 4.2%, and 90-day mortality after hospital discharge was 13.8%. The median length of hospital stay was 3 days, and the mean length of hospital stay was 4 days. The mean total hospitalization cost per patient was $8764. Nursing costs, which included room and board, were $5102. Pharmacy ($966) and radiology ($963) costs were similar. Pharmacy costs ($966) were dominated by the use of low-molecular-weight heparin ($232). Radiology costs ($963) were dominated by the use of diagnostic imaging examinations ($672). During the observation period, an average of 160 patients with pulmonary embolism were admitted each year, requiring an annual hospital expense ranging from $884,814 to $1,866,489. CONCLUSIONS: Pulmonary embolism has a high case fatality rate and remains an expensive illness to diagnose and treat. Nursing costs comprise the largest component of costs.
    The American journal of medicine 02/2013; 126(2):127-132. · 5.30 Impact Factor
  • Deborah Cios, John Fanikos
    Circulation 04/2012; 125(14):e542-4. · 15.20 Impact Factor
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    ABSTRACT: Up to 15% of clinician-ordered doses of injectable pharmacological prophylaxis to prevent venous thromboembolism are not administered. Patient refusal accounts for nearly 50% of these omitted doses. We conducted a prospective cohort study to determine whether a patient education program would improve medication adherence to clinician-ordered injectable prophylactic anticoagulation. We identified 528 hospitalized patients ordered to receive injectable pharmacological venous thromboembolism prophylaxis. We evaluated the impact of pharmacist-led patient education sessions on medication adherence (defined as the ratio of doses administered to doses scheduled) compared with our historical cohort. Individualized patient education sessions were conducted within 24 hours of the initial order for prophylactic anticoagulation in 99% of patients. Adherence to clinician-ordered pharmacological venous thromboembolism prophylaxis was higher after the patient education program than in our historical cohort (94.4% vs 89.9%, P <.0001). The proportion of patients receiving 100% of scheduled doses of injectable pharmacological venous thromboembolism prophylaxis was higher after our novel patient education program than in our historical cohort (73.7% vs 62.4%, P=.001). Patient refusal as a reason for omitted doses was less frequent after the patient education program (29.3% vs 43.7%, P=.001). Pharmacist-led individualized patient education sessions were associated with higher medication adherence to clinician-ordered injectable pharmacological venous thromboembolism prophylaxis and a reduction in patient refusal as a reason for omitted doses. A randomized controlled trial to evaluate the impact of a patient education program on medication adherence to pharmacological venous thromboembolism prophylaxis is warranted.
    The American journal of medicine 03/2012; 125(3):258-64. · 5.30 Impact Factor
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    ABSTRACT: Many hospitalized Medical Service patients remain at high risk for venous thromboembolism (VTE) after hospital discharge. Our aim was to compare the effect of the use or omission of extended pharmacologic VTE prophylaxis after hospital discharge among Medical Service patients on the incidence of symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) over the ensuing 3 months. In this case-control study, we identified a case population of 461 patients for whom parenteral pharmacological VTE prophylaxis was prescribed to continue after discharge and matched them according to age, sex, and VTE risk score to a control group of 922 patients for whom VTE prophylaxis was not continued after discharge. The primary endpoint of symptomatic DVT or PE at 90 days occurred in 5.0% of patients receiving extended prophylaxis compared with 4.3% of patients who received no prophylaxis after discharge (P=.58). Fewer patients were alive at 90 days in patients receiving extended pharmacologic VTE prophylaxis, compared with those who received no prophylaxis after discharge (56.8% vs 68.4%, P <.001). Major bleeding, defined as those events requiring blood transfusion, medical, or surgical intervention, occurred more frequently in patients receiving extended VTE prophylaxis after discharge than in those patients who received no prophylaxis after discharge (3.9% vs 1.9%, P=.03). Extended pharmacologic thromboprophylaxis in high-risk Medical Service patients did not reduce symptomatic DVT and PE in the ensuing 90 days after hospital discharge. There was a higher incidence of all-cause death and major bleeding episodes in patients receiving extended prophylaxis. Our observations do not support the routine use of extended VTE prophylaxis in Medical Service patients. Further research is needed to identify patients who may benefit from extended pharmacologic VTE prophylaxis and those who may have too great a bleeding risk.
    The American journal of medicine 12/2011; 124(12):1143-50. · 5.30 Impact Factor
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    ABSTRACT: Anticoagulant drugs are among the most common medications that cause adverse drug events (ADEs) in hospitalized patients. We performed a 5-year retrospective study at Brigham and Women's Hospital to determine clinical characteristics, types, root causes, and outcomes of anticoagulant-associated ADEs. We reviewed all inpatient anticoagulant-associated ADEs, including adverse drug reactions (ADRs) and medication errors, reported at Brigham and Women's Hospital through the Safety Reporting System from May 2004 to May 2009. We also collected data about the cost associated with hospitalizations in which ADRs occurred. Of 463 anticoagulant-associated ADEs, 226 were medication errors (48.8%), 141 were ADRs (30.5%), and 96 (20.7%) involved both a medication error and ADR. Seventy percent of anticoagulant-associated ADEs were potentially preventable. Transcription errors (48%) were the most frequent root cause of anticoagulant-associated medication errors, while medication errors (40%) were a common root cause of anticoagulant-associated ADRs. Death within 30 days of anticoagulant-associated ADEs occurred in 11% of patients. After an anticoagulant-associated ADR, most hospitalization expenditures were attributable to nursing costs (mean $33,189 per ADR), followed by pharmacy costs (mean $7451 per ADR). Most anticoagulant-associated ADEs among inpatients result from medication errors and are, therefore, potentially preventable. We observed an elevated 30-day mortality rate among patients who suffered an anticoagulant-associated ADE and high hospitalization costs following ADRs. Further quality improvement efforts to reduce anticoagulant-associated medication errors are warranted to improve patient safety and decrease health care expenditures.
    The American journal of medicine 12/2011; 124(12):1136-42. · 5.30 Impact Factor
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    ABSTRACT: A number of novel anticoagulants are moving through various stages of drug development. Recently, the United States Food and Drug Administration approved the oral direct thrombin inhibitor dabigatran etexilate to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Although dabigatran offers a number of advantages over existing oral and parenteral anticoagulants, challenges exist for clinicians who must ensure its safe and effective use. Limited data are available on dabigatran use in patients with renal dysfunction and in obese patients, or in combination with other drugs. Clinical experience is lacking in populations for whom anticoagulants are routinely used, such as patients with a previous stroke, acute coronary syndromes, or pregnancy-associated thrombosis, or those requiring ablation therapy. More important, clinicians will be faced with incorporating dabigatran into hospital guidelines for transitioning between oral and parenteral anticoagulants, measuring anticoagulant intensity, managing anticoagulant-related hemorrhage, ensuring safe use around neuraxial anesthesia, and implementing computer-based alert or warning systems. Since anticoagulants are ubiquitously used in the prevention or treatment of venous and arterial thrombosis, both clinicians and patients must be provided structured education on dabigatran's benefits and limitations. In this article, our goal was to provide practical advice to enhance clinician understanding of dabigatran, identify clinical and operational challenges to its use, and offer system improvements that can ensure safe and effective use of dabigatran.
    Pharmacotherapy 12/2011; 31(12):1232-49. · 2.31 Impact Factor
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    ABSTRACT: The study objective was to determine whether higher antiplatelet factor 4 (PF4)/heparin antibody levels using an enzyme-linked immunosorbent assay are associated with more frequent thrombotic events in patients with clinically suspected heparin-induced thrombocytopenia. Heparin-induced thrombocytopenia is an immune-mediated adverse drug reaction. An enzyme-linked immunosorbent assay detects anti-PF4/heparin antibodies to support a suspected clinical diagnosis of heparin-induced thrombocytopenia. The utility of quantitative enzyme-linked immunosorbent assay results is uncertain. Our single-centered study evaluated quantitative anti-PF4/heparin antibody levels using an enzyme-linked immunosorbent assay in consecutive hospitalized patients with a clinical suspicion of heparin-induced thrombocytopenia and positive anti-PF4/heparin antibody levels between July 2003 and December 2006. Overall, anti-PF4/heparin antibody values were available for 318 patients with clinically suspected heparin-induced thrombocytopenia. The median level was 0.85 optical density units (range 0.31-4.0). The overall rate of arterial or venous thrombosis was 23.3%. A 1-unit increase in anti-PF4/heparin antibody level was associated with an approximate doubling in the odds of thrombosis by 30 days (odds ratio, 1.9; 95% confidence interval, 1.5-2.6; P=.0001). The proportion of patients with pulmonary embolism increased with higher anti-PF4/heparin antibody levels. Higher levels of anti-PF4/heparin antibody are associated with increased thrombosis risk among patients with clinically suspected heparin-induced thrombocytopenia and might have clinical utility for prediction of true heparin-induced thrombocytopenia and the development of thrombosis.
    The American journal of medicine 11/2011; 125(1):44-9. · 5.30 Impact Factor
  • American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists 10/2011; 68(19):1779-82. · 2.10 Impact Factor
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    ABSTRACT: The aim of our study was to assess hospital budget implications of substituting dabigatran for warfarin in patients enrolled in a large anticoagulation service. The study population was identified using criteria from randomized controlled trials of dabigatran. We obtained labor costs ($483 per patient) from the hospital's anticoagulation service budget, laboratory costs of international normalized ratio (INR) tests ($267 per patient), and wholesale costs of warfarin 5 mg tablets ($31 per patient) and dabigatran 150 mg capsules ($2464 per patient). A total of 1774 (93.5%) of 1898 patients were eligible to substitute dabigatran for warfarin. The annual projected hospital expense for anticoagulation with dabigatran was $4,371,136, attributable to drug cost alone. The annual projected cost of warfarin management was $1,385,494. This was comprised of $856,842 for labor, $473,658 for INR testing, and $54,994 for the drug cost of warfarin. Substitution will result in increased expense due to drug cost.
    Clinical and Applied Thrombosis/Hemostasis 08/2011; 18(2):181-4. · 1.02 Impact Factor
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    ABSTRACT: Venous thromboembolism (VTE) remains a common and life-threatening complication among patients with cancer. Thromboprophylaxis can be used to prevent the occurrence of VTE in patients with cancer who are considered at high risk for developing this complication. Therefore, it is critical to recognize the various risk factors for VTE in patients with cancer. Risk assessment tools are available to help identify patients for whom discussions regarding the potential benefits and risks of thromboprophylaxis would be appropriate. The NCCN Clinical Practice Guidelines in Oncology for VTE provide recommendations on risk evaluation, diagnosis, prevention, and treatment of VTE in patients with cancer.
    Journal of the National Comprehensive Cancer Network: JNCCN 07/2011; 9(7):714-77. · 5.11 Impact Factor
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    Charles E Mahan, John Fanikos
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    ABSTRACT: New and generic forms of widely used medications introduced in the antiplatelet, anticoagulant and fibrinolytic therapeutic classes will have a world-wide impact on prescribing, practice guidelines, and routine patient care. However, several uncertainties regarding these agents will remain even after the publication of their respective pivotal trials or regulatory approval. These questions include dosing in the frail, the elderly, and in those with renal and/or hepatic dysfunction, timing of administration in the peri-operative period, efficacy and safety in subgroup populations such as patients with cancer, the interchangeability of biosimilar products, and outcome differences between new agents in the absence of head-to-head clinical trials. Additionally, new generic forms of widely used agents have recently impacted the United States (US) and Canadian market place and more are under development. Clinicians should be vigilant concerning these agents and be prepared to inform patients and make decisions with their use.
    Thrombosis Research 06/2011; 127(6):518-24. · 3.13 Impact Factor
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    ABSTRACT: Dabigatran, rivaroxaban, and apixaban are novel oral anticoagulants that offer major advantages over existing agents. The onset of the anticoagulant effect of these agents is rapid. Each agent has a predictable anticoagulant response that eliminates the need for monitoring. Clinical trials have been completed with all three agents in the prevention and treatment of the three leading causes of cardiovascular death: myocardial infarction, stroke, and venous thromboembolism (VTE). Novel agents have shown reduced or similar rates of thrombosis, major bleeding, and adverse events when weighed against either low molecular weight heparin or warfarin. Additional trials are underway and more agents are in development. As a result, novel anticoagulants may impact physician prescribing practices and warrant consideration in patients requiring thrombosis management.
    Therapeutic advances in hematology. 06/2011; 2(3):175-95.

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