Vincent J Colucci

Advanced-practice pharmacists: Practice characteristics and reimbursement of pharmacists certified for collaborative clinical practice in New Mexico and North Carolina

PURPOSE The results of a survey assessing the practice settings, clinical activities, and reimbursement experiences of pharmacists with advanced-practice designations are reported. METHODS A questionnaire was sent to all certified Pharmacist Clinicians in New Mexico and all Clinical Pharmacist Practitioners in North Carolina (a total of 189 pharmacists at the time of the survey in late 2008) to elicit information on practice settings, billing and reimbursement methods, collaborative drug therapy management (CDTM) protocols, and other issues. RESULTS Of the 189 targeted pharmacists, 64 (34%) responded to the survey. On average, the reported interval from pharmacist licensure to certification as an advanced practitioner was 11 years. The majority of survey participants were practicing in community or institutional settings, most often hospital clinics or physician offices. About two thirds of the respondents indicated that their employer handled the billing of their services using standard evaluation and management codes, with estimated total monthly billings averaging

Heart Failure Worsening and Exacerbation After Venlafaxine and Duloxetine Therapy

6500. At the time of the survey, about 80% of the respondents were engaged in a CDTM protocol. The survey results suggest that pharmacists with advanced-practice designations are perceived favorably by patients and physicians and their services are in high demand, but more than one third of respondents indicated a need to justify their advanced-practice positions to administrators. CONCLUSION Pharmacists with advanced-practice designations are providing clinical services in various settings under collaborative practice arrangements that include prescribing privileges. Despite growing patient and physician acceptance, reimbursement challenges continue to be a barrier to wider use of CDTM programs.

Increase in International Normalized Ratio Associated with Smoking Cessation

Objective: To report 2 cases of worsened heart failure (HF) after the introduction of venlafaxine or duloxetine therapy in patients with previously stable disease. Case Summaries: Two patients, a 39-year-old female and a 68-year-old male, both diagnosed with HF of left ventricular systolic dysfunction, had worsening symptoms in the presence of the serotonin and norepinephrine reuptake inhibitors (SNRIs) venlafaxine 75 mg twice daily and/or duloxetine 30–60 mg/day. Both patients developed tachycardia, which remitted after the discontinuation of these agents. The woman was rechallenged with duloxetine 60 mg daily after her HF worsened with venlafaxine, only to have the tachycardia and HF symptoms return. Other iatrogenic causes and metabolic disturbances (eg, anemia) were ruled out. Discussion: increased levels of norepinephrine secondary to reuptake inhibition may be potentially deleterious in patients with chronic HF of left ventricular dysfunction owing to the “progressive HF model” and neurohormonal compensatory responses. Use of the Naranjo probability scale showed a probable relationship between venlafaxine/duloxetine use and these adverse outcomes. Venlafaxine and duloxetine were discontinued. Conclusions: Use of drugs that increase serum norepinephrine levels, such as the SNRIs, may be potentially deleterious in individuals with unstable or advanced HF. These medications should be avoided or used with caution and monitored regularty in this patient population.

Tolterodine–Warfarin Drug Interaction:

TO THE EDITOR:The clearance of warfarin and international normalized ratio (INR) assessments must take into account the effect of various factors including diet, concomitant drugs, and comorbidities. 1 We report a patient whose INR increased after smoking cessation. Case Report.An 80-year-old white man had received Coumadin for the past five years for secondary prevention following a cerebral vascular accident. His anticoagulation regimen was directed by a multidisciplinary anticoagulation management service, which included a clinical pharmacist. Concurrent medical history included chronic stable angina, hyperlipidemia, and mild but chronic psoriasis on his hands and knees. Other medications included simvastatin 20 mg/d, isosorbide mononitrate 60 mg/d, and topical mometasone furoate for psoriasis. His INR check was routinely performed (Figure 1), and the warfarin dosage had been stabilized over the previous 10 months at 5 mg/d (35 mg/wk), with INRs ranging between 2.0 and 2.8 (target range 2.0–3.0). Approximately three months after smoking cessation, his INR value was discovered to be slightly elevated (3.0) on routine INR check. The patient was instructed to take a modified dose of warfarin (2.5 mg/d) for the next two days, then resume his routine regimen and return for evaluation in two weeks. At the time of the recheck, his INR was 3.7. The patient had experienced no apparent clinical bleeding, and the rest of the assessment was unremarkable. He was instructed to omit a single dose of warfarin and modify the warfarin dose over the next two days by taking only 2.5 mg/d, then return to his usual regimen with follow-up in two weeks. The INR 15 days later revealed a value of 3.7, possibly suggesting a new but elevated steady-state concentration of warfarin. There was no clinically evident bleeding or ecchymoses. At this time, a single dose of warfarin was omitted, and the weekly maintenance dose of warfarin was decreased by 14% to 30 mg/wk. Other factors that may have been affecting warfarin pharmacokinetics and clearance could not be discerned. The patient was cordial and compliant, and the information gleaned from him was evaluated to be reliable. Diet, including consumption of two to three beers per day, had remained constant over at least the past six years, as did his activity, which included daily walking. The medication regimen was unchanged. He denied the use of any herbal or over-the-counter product. The patient reported no recent illnesses or febrile events and no changes in bowel movements or obvious absorption issues; there also were no changes in his cardiovascular status and hemodynamics per cardiologist evaluation during this time frame. Liver function studies included only aspartate transaminase (AST), which was 24 IU/dL, but this had remained relatively stable and within normal limits (8–37 IU/dL) for the previous six years. Further inquiry revealed that the patient had been a 50-pack/year smoker (1 1/2–2 packs/d for >30 y) but had quit smoking approximately three months before this episode, which suggested that the lack of induction of hepatic isoenzymes CYP1A1 and CYP1A2 secondary to smoking cessation 2,3 could have led to a decreased clearance of warfarin and subsequent increases in the INR surrogate marker. After warfarin dosage reduction, the INRs have decreased to 2.3–2.8 for the past nine months. The patient remains smoke free; no further changes in the INR have occurred. Discussion.Using the Naranjo scale 4 for assessing the validity and causality of the smoking–warfarin interaction results in a possible reaction rating. The literature 2,3,5-11on the effects of smoking with regard to warfarin clearance is scarce, dated, and inconsistent, with most sources concluding that there is an insignificant effect; however, this is not a universal consensus. 2,9

Drug Therapy Recommendations from the 2005 ACC/AHA Guidelines for Treatment of Chronic Heart Failure

OBJECTIVE: To report two cases of warfarin therapy in which the addition of tolterodine resulted in prolonged international normalized ratios (INRs). CASE SUMMARY: Two patients, each receiving warfarin for stroke prophylaxis in association with chronic atrial fibrillation, developed adverse effects after the initiation of tolterodine for urinary disorders. Other medications for concurrent medical diagnoses had remained unchanged. One patient had an episode of prostatitis, which was treated with levofloxacin immediately prior to tolterodine initiation. The warfarin dosage had remained constant for many weeks in both patients prior to and during the tolterodine trials. In each patient, the initiation of tolterodine was associated with a significant increase in the patients INR measured 10–14 days later. Thus, tolterodine was ineffective in both patients and was discontinued one to two days before the elevated INRs were determined during routine clinic visits. INRs determined approximately two weeks after tolterodine was discontinued were similar to those obtained during the period before the use of the drug; the warfarin dosage remained unchanged. Rechallenge with tolterodine was not attempted in either patient. DISCUSSION: Several aspects of the reported cases support the validity of a proposed drug interaction when tolterodine is initiated in a patient stabilized on warfarin therapy. The temporal association of the course of tolterodine with an elevated INR, the return to the previous warfarin dose–INR response relationship after tolterodine discontinuation, and the absence of other causes for the elevated INR were factors found in both patients. Possible mechanisms to explain the suggested drug interaction are explored. CONCLUSIONS: Until further data are available, clinicians should be vigilant for a possible drug interaction when tolterodine therapy is initiated in a patient maintained on warfarin therapy.

Vorapaxar in Atherosclerotic Disease Management

Objective: To review and discuss key aspects of the drug therapy recommendations in the American College of Cardiology (ACC)/American Heart Association (AHA) 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure (HF) in the Adult. Data Sources: Data were obtained from the ACC/AHA 2005 Guideline Update for Chronic HF. English-language clinical trials, observational studies, and pertinent review articles evaluating the pharmacotherapy of chronic HF were identified, based on MEDLINE searches through January 2006. Study Selection: Articles presenting information that impacts the evidence base for recommendations regarding the use of various drug therapies in patients with chronic HF were evaluated. Data Synthesis: The ACC/AHA 2005 Guideline Update for HF provides revised, evidence-based recommendations for the treatment of chronic HF. The new guidelines are based on a staging system that recognizes both the development and progression of HF. Recommendations are provided for 2 stages of patients (A and B) who do not yet have clinical HF but are clearly at risk and 2 stages (C and D) that include patients with symptomatic HF. The guidelines continue to emphasize the important role of neurohormonal blockade with angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-adrenergic blockers, and aldosterone antagonists. Based on recent trials, updated recommendations address the roles of combination therapy and the selective addition of hydralazine and isosorbide dinitrate. Along with specific drug recommendations, information on the practical use of various drugs is provided. Although the guidelines primarily focus on HF due to systolic dysfunction, general recommendations are also provided for patients with preserved systolic function. Conclusions: The ACC/AHA 2005 Guideline Update provides evidence-based recommendations for healthcare professionals involved in the care of adults with chronic HF. Recent clinical trial findings have further clarified the evolving role of neurohormonal-blocking drugs in the prevention and treatment of HF.

Potential Contribution of Long-Term Rofecoxib in a Patient with Cardiogenic Syncope and Ischemic Stroke

Objective: To review the pharmacology, efficacy, and safety of vorapaxar, a protease activator receptor-1 (PAR-1) antagonist, in the management of atherosclerotic diseases. Data Sources: Peer-reviewed clinical trials and review articles were identified from MEDLINE and Current Content database (both 1966 to December 31, 2014) using the search terms vorapaxar and protease activator receptor antagonist. Study Selection and Data Extraction: A total of 30 clinical studies were identified (16 clinical trials, including subanalyses, 14 related to pharmacology, pharmacokinetics, and pharmacodynamics and drug interactions). Data Synthesis: Two phase III clinical trials with vorapaxar have been published. In patients with non–ST segment elevation myocardial infarction (MI), vorapaxar failed to significantly reduce the primary efficacy end point (composite of cardiovascular death, MI, stroke, recurrent ischemia with hospitalization, and urgent coronary revascularization). Conversely, in a study of secondary prevention for patients with cardiovascular disease, the composite end point of cardiovascular death, MI, or stroke was significantly reduced. In both trials, the safety end points of major/minor bleeding were increased compared with placebo. In the secondary prevention trial, an increased incidence of intracranial hemorrhage led to the exclusion of patients with a prior history of stroke. Conclusion: Vorapaxar is approved for use with aspirin and/or clopidogrel in the secondary prevention of cardiovascular events in stable patients with peripheral arterial disease or a history of MI. However, the addition of vorapaxar to other antiplatelets can significantly increase the risk of bleeding. It is, therefore, essential to balance the need for further reduction of risk of thrombotic event with patient’s individual bleeding risk.

Book Review: Sport and Exercise Pharmacology

Objective: To report a case of syncope followed by a cerebrovascular event in a patient receiving long-term therapy with rofecoxib. Case Summary: A 62-year-old man presented to a local rural hospital emergency department with loss of motor control in his left extremities. Neurologic workup confirmed a right hemispheric cerebrovascular accident. Carotid arteries were noncontributory, and cardiac workup was unrevealing except for thoracic aorta atherosclerosis. There was no history of hypertension, coronary artery disease, diabetes mellitus, left ventricular systolic dysfunction, or valvular stenotic disease. Cardiovascular risk factors included smoking and dyslipidemia with low high-density lipoprotein cholesterol and hypertriglyceridemia. Of importance was the patients 4 year history of rofecoxib use, 25 mg daily for a chronic back injury. Discussion: Recently published reports suggest that rofecoxib can contribute significantly to increased cerebrovascular events by an approximately twofold elevation in relative risk. An adverse drug reaction assessment, using the Naranjo probability scale, indicated a possible relationship of rofecoxib to the events. Rofecoxib was discontinued. Conclusions: Recent evidence of additive cardiovascular risk conveyed by cyclooxygenase-2 inhibitors and the temporal relationship between rofecoxib use and cerebrovascular events suggests that rofecoxib may be a potentially contributing factor to the unfavorable outcomes in our patient.

USING SERUM CREATININE CONCENTRATIONS TO SCREEN FOR INAPPROPRIATE DOSAGE OF RENALLY ELIMINATED DRUGS

Sports medicine, sports pharmacy, and exercise pharmacology continue to evolve at rapid paces, often outdistancing supporting evidence. Sport and Exercise Pharmacology has attempted to provide the clinician or therapist with an evidenced-based background for assessing and rendering drug therapy recommendations regarding physical activity and athletics. Reents provides a unique and useful method for examining and reviewing drugs and their role in exercise management. The book views drugs and pharmacotherapy in exercise from several different perspectives, including pharmacologic, pharmacokinetic, and ergogenic viewpoints. Further, the book explores the effect and impact drugs have on the exercising individual, as well as the results that exercise or physical activity have on drug pharmacology and kinetics. The chapters consist of specific drug classes, focusing primarily on cardiovascular agents, hormonal agents, metabolic agents, and social drugs. Each chapter addresses the results of exercise on the drug class, pharmacology and pharmacokinetics, and the effects of the drug on exercise or event performance. Additionally, each chapter discusses potential complications, summarizing guidelines for the practicing clinician or therapist, and the legal or banned status of the agents regarding governing sports bodies such as the United States Olympic Committee, the National Collegiate Athletic Association, and professional leagues. The references are broad, complete, and current. Although the paucity of data in many areas precludes consensus guidelines or conclusions, the author emphatically states this several times and, in fact, devotes an introductory chapter to this compromising element. The book is not designed as a secondary or tertiary reference text for drug pharmacology but, rather, is an evidenced-based, clinical application of drugs in an exercising or competing population. To that extent, the book serves as a valuable component in the armamentarium of resources regarding sports medicine and sports pharmacy. The author also nicely incorporates morality and ethics into his summations and guidelines.