Evaluating Outcomes Associated with Alternative Dosing Strategies for Piperacillin/Tazobactam: A Qualitative Systematic Review (February).

Ann Pharmacother. 2012 Jan 24;

Authors: Mah GT, Mabasa VH, Chow I, Ensom MH

Abstract
OBJECTIVE:To perform a qualitative systematic review of the evidence comparing traditional strategies against prolonged intermittent or continuous infusion strategies for piperacillin/tazobactam, based on clinical and pharmacodynamic outcomes.DATA SOURCES:MEDLINE (1950-September 2011), EMBASE (1980-September 2011), and International Pharmaceutical Abstracts (1970-September 2011) were searched, using the terms piperacillin, tazobactam, pharmacokinetics, pharmacodynamics, dosing, and infusion. Reference lists from relevant publications were also reviewed.STUDY SELECTION AND DATA EXTRACTION:Articles evaluating the administration of piperacillin/tazobactam to adults and comparing at least 2 dosing regimens (1 of which included the traditional, manufacturer-recommended 30-minute infusion; the other, a prolonged or continuous infusion strategy) were included. Prespecified clinical outcomes of interest included mortality, clinical cures, and adverse events. The pharmacodynamic endpoint of interest was percent time of unbound drug concentration remaining above the minimum inhibitory concentration.DATA SYNTHESIS:Twelve studies were included in this review, 7 of which assessed clinical outcomes and 5 that assessed pharmacodynamic endpoints using Monte Carlo simulations. Prolonged or continuous infusions of piperacillin/tazobactam consistently achieved higher pharmacodynamic endpoints than did traditional infusions. The association of prolonged or continuous infusions with improved clinical outcomes, however, is unclear. Two retrospective studies found improved mortality rates with prolonged infusions (1 in a subgroup of patients with higher APACHE II [Acute Physiology and Chronic Health Evaluation II] scores), while another retrospective study found improved clinical cure rates with continuous infusions in patients with ventilator-associated pneumonia. These clinical benefits have not been substantiated in prospective randomized trials. No study has provided evidence of reduced adverse effects with prolonged or continuous infusions.CONCLUSIONS:The limited evidence available does not firmly support widespread adoption of administering piperacillin/tazobactam as prolonged intermittent or continuous infusions to improve clinical outcomes despite the achievement of higher pharmacodynamic targets in simulated studies. Retrospective studies indicate that critical care patients are the subgroup most likely to benefit from these dosing strategies. Well-designed prospective clinical trials are required to confirm potential benefits observed in retrospective studies.

PMID: 22274145 [PubMed - as supplied by publisher]

Ketamine in Adult Emergency Medicine: Controversies and Recent Advances (December).

Ann Pharmacother. 2011 Dec 6;

Authors: Sih K, Campbell SG, Tallon JM, Magee K, Zed PJ

Abstract
OBJECTIVE:To review the evidence for the use of ketamine in adult emergency medicine for procedural sedation and analgesia (PSA) and rapid sequence intubation (RSI), as well as to focus on the issues of recovery agitation, combination with propofol for PSA, and the use of ketamine as an induction agent in patients with acute head injury in need of definitive airway management.DATA SOURCES:PubMed (1949-July 2011), EMBASE (1980-July 2011), Google Scholar (to July 2011), International Pharmaceutical Abstracts (1964-July 2011), and Cochrane databases were searched independently. A manual search of references was also performed.STUDY SELECTION:English-language, full reports of experimental and observational studies evaluating ketamine in adults undergoing PSA and RSI in the emergency department (ED) were included if they reported efficacy or safety outcomes.DATA EXTRACTION:Two reviewers independently assessed each article for inclusion, data extraction, and study limitations.DATA SYNTHESIS:Six studies that used ketamine for PSA were included. The majority reported adequate sedation with high patient satisfaction and lack of pain and procedural recall. There is no evidence to support the superiority of a combination of ketamine and propofol compared to propofol alone for PSA in adults. Recovery agitation is common but can be minimized with premedicationwith midazolam (number needed to treat 6). Two studies were identified that evaluated the role of ketamine for induction during RSI in the ED. Although ketamine is not a first-line agent for RSI, it is an alternative and may be used as an induction agent in patients requiring endotracheal intubation.CONCLUSIONS:Ketamine is an effective agent in adults undergoing PSA and RSI in the ED. The best available evidence provides sufficient confidence to consider use of this agent in the ED.

PMID: 22147144 [PubMed - as supplied by publisher]

Takotsubo Cardiomyopathy as a Complication of Electroconvulsive Therapy (December).

Ann Pharmacother. 2011 Nov 24;

Authors: Sharp RP, Welch EB

Abstract
OBJECTIVE:To examine the evidence regarding takotsubo cardiomyopathy as a complication of electroconvulsive therapy (ECT).DATA SOURCES:Searches in MEDLINE, EMBASE, and International Pharmaceutical Abstracts (1966-August 2011) were conducted.STUDY SELECTION AND DATA EXTRACTION:Published studies and case reports that mentioned takotsubo cardiomyopathy following ECT were reviewed.DATA SYNTHESIS:Twelve case reports were available for review. There were 7 documented cases of takotsubo cardiomyopathy, 4 cases of myocardial stunning, and 1 case of cardiogenic shock following ECT. Although takotsubo cardiomyopathy was not mentioned in 5 of the cases, some clinical characteristics were consistent with this diagnosis. Left ventricular ejection fraction and the electrocardiogram returned to normal within a few days in the majority of the cases. All cases were in women, the majority of whom were postmenopausal (average age 64 years). Takotsubo cardiomyopathy developed after a single course of ECT in 6 of the cases, while the syndrome developed after more than 1 course in the other 6 cases. ECT was successfully readministered without syndrome recurrence in 4 of the cases, but only after 3 of the 4 patients received a ?-adrenergic receptor blocking agent prior to each subsequent therapy session. The ?-adrenergic blocking agents used were esmolol in 1 case and labetolol in the other 2.CONCLUSIONS:Takotsubo cardiomyopathy is a serious but transient potential complication of electroconvulsive therapy. Limited evidence indicates that ?-adrenergic receptor blocking agents may help prevent its reoccurrence in patients needing further electroconvulsive treatment. Health care providers in psychiatry should be aware of this potential complication of electroconvulsive therapy, especially in postmenopausal women. However, many questions remain regarding this issue.

PMID: 22116995 [PubMed - as supplied by publisher]

Beers Criteria as a Proxy for Inappropriate Prescribing of Other Medications Among Older Adults (November).

Ann Pharmacother. 2011 Oct 4;

Authors: Lund BC, Steinman MA, Chrischilles EA, Kaboli PJ

Abstract
BACKGROUND:The Beers criteria are a compilation of medications deemed potentially inappropriate for older adults, widely used as a prescribing quality indicator.OBJECTIVE:To determine whether Beers criteria serve as a proxy measure for other forms of inappropriate prescribing, as measured by comprehensive implicit review.METHODS:Data for patients 65 years and older were obtained from the Veterans Affairs Enhanced Pharmacy Outpatient Clinic (EPOC) and the Iowa Medicaid Pharmaceutical Case Management (PCM) studies. Comprehensive measurement of prescribing quality was conducted using expert clinician review of medical records according to the Medication Appropriateness Index (MAI). MAI scores attributable to non-Beers medications were contrasted between patients who did and did not receive a Beers criteria medication.RESULTS:Beers criteria medications accounted for 12.9% (EPOC) and 14.0% (PCM) of total MAI scores. Importantly, non-Beers MAI scores were significantly higher in patients receiving a Beers criteria medication in both studies (EPOC: 15.1 vs 12.4, p = 0.02; PCM:11.1 vs 8.7, p = 0.04), after adjusting for important confounding factors.CONCLUSIONS:Beers criteria utility extended beyond direct measurement of a limited set of inappropriate prescribing practices by serving as a clinically meaningful proxy for other inappropriate practices. Using prescribing quality indicators to guide interventions should thus identify patients for comprehensive medication review, rather than identifying specific medication targets for discontinuation. Future research should explore both the quality measurement and the intervention targeting applications of the Beers criteria, particularly when integrated with other indicators.

PMID: 21972251 [PubMed - as supplied by publisher]

Clinical outcomes of a collaborative, home-based postdischarge warfarin management service.

Ann Pharmacother. 2011 Mar;45(3):325-34

Authors: Stafford L, Peterson GM, Bereznicki LR, Jackson SL, van Tienen EC, Angley MT, Bajorek BV, McLachlan AJ, Mullan JR, Misan GM, Gaetani L

Abstract
BACKGROUND: Warfarin remains a high-risk drug for adverse events, especially following discharge from the hospital. New approaches are needed to minimize the potential for adverse outcomes during this period.
OBJECTIVE: To evaluate the clinical outcomes of a collaborative, home-based postdischarge warfarin management service adapted from the Australian Home Medicines Review (HMR) program.
METHODS: In a prospective, nonrandomized controlled cohort study, patients discharged from the hospital and newly initiated on or continuing warfarin therapy received either usual care (UC) or a postdischarge service (PDS) of 2 or 3 home visits by a trained, HMR-accredited pharmacist in their first 8 to 10 days postdischarge. The PDS involved point-of-care international normalized ratio (INR) monitoring, warfarin education, and an HMR, in collaboration with the patient's general practitioner and community pharmacist. The primary outcome measure was the combined incidence of major and minor hemorrhagic events in the 90 days postdischarge. Secondary outcome measures included the incidences of thrombotic events, combined hemorrhagic and thombotic events, unplanned and warfarin-related hospital readmissions, death, INR control, and persistence with therapy at 8 and 90 days postdischarge.
RESULTS: The PDS (n=129) was associated with statistically significantly decreased rates of combined major and minor hemorrhagic events to day 90 (5.3% vs 14.7%; p=0.03) and day 8 (0.9% vs 7.2%; p=0.01) compared with UC (n=139). The rate of combined hemorrhagic and thrombotic events to day 90 also decreased (6.4% vs 19.0%; p=0.008) and persistence with warfarin therapy improved (95.4% vs 83.6%; p=0.004). No significant differences in readmission and death rates or INR control were demonstrated.
CONCLUSIONS: This study demonstrated the ability of appropriately trained accredited pharmacists working within the Australian HMR framework to reduce adverse events and improve persistence in patients taking warfarin following hospital discharge. Widespread implementation of such a service has the potential to enhance medication safety along the continuum of care.

PMID: 21386021 [PubMed - indexed for MEDLINE]

Incidence of Hospitalized Rhabdomyolysis with Statin and Fibrate Use in an Insured US Population (October).

Ann Pharmacother. 2011 Sep 13;

Authors: Amend KL, Landon J, Thyagarajan V, Niemcryk S, McAfee A

Abstract
BACKGROUND:The incidence of hospitalized rhabdomyolysis is not well characterized among patients taking statin-fibrate combination therapies.OBJECTIVE:To estimate and compare the rates of hospitalized rhabdomyolysis during periods of exposure to different statins and fibrates.METHODS:We retrospectively identified a cohort of patients who initiated a statin or fibrate between January 1, 1998, and December 31, 2007, using a database of a large US health insurer. Patients were followed for the occurrence of hospitalized rhabdomyolysis, determined by clinical review of medical records. Exposure status during the study period was determined by electronic records of statin and fibrate dispensing. Incidence rates (IRs) and incidence rate ratios (IRRs) for various combinations of fibrate and statin exposure were modeled, using Poisson regression.RESULTS:There were 1,116,805 patients who initiated statin and/or fibrate therapy, with 2.4 million person-years of observation. Seventy cases of hospitalized rhabdomyolysis were confirmed. Adjusted analyses showed a persistent increased risk of rhabdomyolysis with combination therapy, while statin and fibrate therapy alone showed similar, nonsignificant increases in risk. The adjusted IRR for a statin and fenofibrate was 3.26 (95% CI 1.21 to 8.80), while the adjusted IRR for a statinand gemfibrozil was 11.93 (95% CI 3.96 to 35.93) versus statin therapy alone. The individual IRs for statin monotherapy ranged from 0.00 to 3.34 per 100,000 person-years. The number needed to harm was lower for combination statin-gemfibrozil therapy (2753) compared with that for statin therapy alone (454,545).CONCLUSIONS:The incidence of hospitalized rhabdomyolysis is rare, but higher in patients with concomitant statin-fibrate treatment than in patients on statin therapy alone. The rate found in this study is consistent with the known profile of the statin-fibrate treatment option for mixed dyslipidemia.

PMID: 21917557 [PubMed - as supplied by publisher]

Evaluation of the Accuracy of a Pharmacokinetic Dosing Program in Predicting Serum Vancomycin Concentrations in Critically Ill Patients (October).

Ann Pharmacother. 2011 Sep 6;

Authors: Aubron C, Corallo CE, O Nunn M, Dooley MJ, Cheng AC

Abstract
BACKGROUND:Optimization of the timing of appropriate antibiotics is crucial to improve the management of patients in severe sepsis and septic shock. Vancomycin is commonly used empirically in cases of nosocomial infections in critically ill patients. Therefore, early optimization of vancomycin pharmacokinetics is likely to improve outcomes.OBJECTIVE:To evaluate a pharmacokinetic program to predict serum vancomycin concentrations in accordance with administered dose, weight, height, and creatinine clearance in a critically ill population.METHODS:We conducted a prospective observational single-center study in a 45-bed intensive care unit (ICU). All patients hospitalized in the ICU requiring intravenous treatment with vancomycin for a suspected infection were enrolled. The modalities of vancomycin therapy and the monitoring of serum concentrations were left to the discretion of the treating clinician. We compared the measured serum vancomycin concentrations with those predicted by the MM-USCPACK program and analyzed the factors influencing the prediction.RESULTS:Fifty-four intravenous vancomycin courses were administered in 48 critically ill patients over the 3-month study. The precision was considered acceptable, based on a relative precision equal to 8.9% (interquartile range 3.5-18.9%) and the relative bias for all predictions was equal to -1.3%. Overall, 77.3% of predictions were within 20% of observed concentrations; factors correlating with a poorer prediction were a change in renal function, obesity, and the magnitude of organ dysfunction on initiation of vancomycin (expressed by a Systemic Organ Failure Assessment score >11).CONCLUSIONS:The MM-USCPACK program is a useful and reliable tool for prediction of serum vancomycin concentrations in patients hospitalized in ICU and likely reflects the close monitoring of renal function in this setting. For some patients (more severely ill, obese, or significant change in renal function during vancomycin therapy), predictions were less precise.

PMID: 21896920 [PubMed - as supplied by publisher]

Treating Hypertension in the Very Elderly (September).

Ann Pharmacother. 2011 Aug 18;

Authors: Charpentier MM, Bundeff A

Abstract
OBJECTIVE: To review the evidence for strict blood pressure (BP) management in the very elderly, defined as patients aged 80 years and older. DATA SOURCES: A literature search was performed using PubMed (1950 through November 2010) for the MeSH terms hypertension and elderly; subterms of identified MeSH terms (Ie, explosioN) for the elderly were also searched. A broader search was conducted of PubMed articles published in the past 4 years. Searches were conducted for additional primary literature referenced in identifiedarticles; an updated Cochrane Database review was also performed. STUDY SELECTION AND DATA EXTRACTION: All identified studies that specifically included very elderly patients and BP were reviewed. DATA SYNTHESIS: The BP goal established in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) is less than 140/90 mm Hg, regardless of age, unless a compelling indication exists. Although evidence suggests that lowering BP will lower the risk of stroke, lower BP in the very elderly may result in higher mortality. Many physicians are reluctant to treat BP in accordance with the JNC 7 goal in very elderly patients for a variety of reasons, including concerns about fall risk, lack of benefit in mortality reduction, and concerns about drug interactions andadverse effects. Results from a randomized controlled trial and meta-analysis have demonstrated reductions in stroke, heart failure, and cardiovascular events in the very elderly. The American College of Cardiology Foundation/American Heart Association recently published guidelines for elderly patients that suggest treating the very elderly carefully and with different BP goals than previously recommended. CONCLUSIONS: Optimal management of hypertension in the very elderly remains a concern. Few studies have evaluated hypertension in this population, and studies that included patients over 80 enrolled too few to draw conclusions. Although the HYVET (Hypertension in the Very Elderly Trial) study did have adequate power to evaluate the very elderly, because this study was stopped early because of significant findings in mortality, unanswered questions remain regarding optimal BP targets.

PMID: 21852597 [PubMed - as supplied by publisher]

Intensity of Anticoagulation with Warfarin and Risk of Adverse Events in Patients Presenting to the Emergency Department (July/August).

Ann Pharmacother. 2011 Jul 12;

Authors: Anthony CJ, Karim S, Ackroyd-Stolarz S, Fry A, Murphy NG, Christie R, Zed PJ

BACKGROUND: The ability of patients receiving warfarin to maintain an international normalized ratio (INR) within the desired therapeutic range is important for both efficacy and risk of adverse events. It is unclear whether the desired INR is maintained in patients receiving warfarin who present to the emergency department (ED) and whether they have a higher rate of adverse events. OBJECTIVE To evaluate the intensity of anticoagulation with warfarin and the risk of bleeding and thromboembolic complications in patients in the ED. METHODS: A prospective observational study was performed using a convenience sample of patients receiving warfarin and presenting to the ED over an 18-week period. Data were collected using a standardized form that included chief complaint, history of present illness, past medical history, medication history, and allergy status. Information from the physical examination, laboratory results, and other diagnostic tests obtained as part of routine assessment in the ED, was used as necessary. The primary outcome was the proportion of patients whose INR was within, above, or below the desired therapeutic range. Bleeding complications and thromboembolic events were recorded in an attempt to determine the relationship between the intensity of anticoagulation and adverse outcomes. RESULTS: Two hundred one patients were included, with a mean (SD) age of 74.0 (13.2) years; 53.7% were female. Primary indications for warfarin were atrial fibrillation (75.6%) and venous thromboembolic disease (14.9%). A therapeutic INR was observed in 88 patients (43.8%; 95% CI 37.1 to 50.7), while 45 patients (22.4%; 95% CI 17.2 to 28.7) and 68 patients (33.8%; 95% CI 27.6 to 40.6) had subtherapeutic and supratherapeutic INRs, respectively. Overall, there were 28(18 major and 10 minor) bleeding complications (13.9%; 95% CI 9.8 to 19.4) and 4 thromboembolic events (2.0%; 95% CI 0.6 to 5.2). Among patients with ableeding complication, 14 (50.0%) had a supratherapeutic INR, while 2 patients who experienced a thromboembolic event (50.0%) had a subtherapeutic INR. CONCLUSIONS: The majority of patients receiving warfarin on presentation to the ED had INRs outside the desired therapeutic range. By establishing the impact of warfarin-related adverse events in this population, focused interventions can be established in this setting to address factors that can be targeted to reduce these events.

PMID: 21750309 [PubMed - as supplied by publisher]

Activated Partial Thromboplastin Time Versus Antifactor Xa Heparin Assay in Monitoring Unfractionated Heparin by Continuous Intravenous Infusion (July/August).

Ann Pharmacother. 2011 Jun 28;

Authors: Guervil DJ, Rosenberg AF, Winterstein AG, Harris NS, Johns TE, Zumberg MS

BACKGROUND Unfractionated heparin (UFH) has been used clinically for 5 decades. Despite being a cornerstone of anticoagulation, UFH is limited by its unpredictable pharmacokinetic profile, which makes close laboratory monitoring necessary. The most common methods for monitoring UFH are the activated partial thromboplastin time (aPTT) and antifactor Xa heparin assay (anti-Xa HA), but both present challenges, and the optimal method to monitor UFH remains unclear. OBJECTIVE To compare the performance of the aPTT with the anti-Xa HA for efficiency and safety of monitoring intravenous UFH infusions. METHODS This was a single-center, retrospective, observational cohort study conducted in an 852-bed academic medical center. RESULTS One hundred patients receiving intravenous UFH for a variety of indications were enrolled in the study; 50 were assigned to each group. The mean (SD) time to achieve therapeutic anticoagulation was significantly less in the anti-Xa HA group compared with the aPTT group (28 [16] vs 48 [26] hours, p < 0.001). In addition, a greater percentage of anti-Xa HA patients compared to aPTT patients achieved therapeutic anticoagulation at 24 hours (OR 3.5; 95% CI 1.5 to 8.7) and 48 hours (OR 10.9; 95% CI 3.3 to 44.2). Patients in the anti-Xa HA group also had more test values within the therapeutic range (66% vs 42%, p < 0.0001). A significant difference was seen between the 2 groups in the number of aPTT or anti-Xa HA tests performed per 24 hours (p < 0.0001) and number of infusion rate changes per 24 hours (p < 0.01), both favoring the anti-Xa HA group. CONCLUSIONS Monitoring intravenous UFH infusions with the anti-Xa HA, compared to the aPTT, achieves therapeutic anticoagulation more rapidly, maintains the values within the goal range for a longer time, and requires fewer adjustments in dosage and repeated tests.

PMID: 21712506 [PubMed - as supplied by publisher]

Evaluation of a Simplified N-Acetylcysteine Dosing Regimen for the Treatment of Acetaminophen Toxicity (June).

Ann Pharmacother. 2011 May 17;

Authors: Johnson MT, McCammon CA, Mullins ME, Halcomb SE

BACKGROUND: Acetaminophen overdose is the most common pharmaceutical poisoning in the US. The labeled dosing regimen for Acetadote, the only intravenous N-acetylcysteine (IV-NAC) product approved by the Food and Drug Administration (FDA) for treatment of acetaminophen toxicity, is a complex 3-step process that produces frequent medication errors. We have been using an off- label, uncomplicated dosing regimen consisting of a standard preparation of IVNAC 30 g in 1 L of 5% dextrose in water, with a 150-mg/kg loading dose administered over 1 hour followed by an infusion of 14 mg/kg/h for 20 hours. OBJECTIVE: To evaluate the frequency of medication errors, resolution of hepatotoxicity, and tolerability of the protocol used in our institution for treatment of acetaminophen toxicity. METHODS: This single-center, retrospective chart review evaluated patients receiving IV-NAC for acetaminophen toxicity from August 2006 to August 2008. Charts were reviewed for prescribing practices, dosing errors, and clinical outcomes. RESULTS: Among 70 patients who met inclusion criteria, 35 medication errors occurred, including 22 administration errors and 13 protocol initiation errors. The frequency of administration errors was 13.5 errors per 100 administration interventions. Loading dose errors were most common with 11 rate-related and 8 dose-related errors. Interruptions longer than 60 minutes occurred in only 3 patients. No adverse outcomes were associated with medication errors. The mean (SD) duration of therapy was 25.6 hours (n = 60 pts. [17.8], range 1-76.5), and mean length of stay was 2.99 days ([3.82], range 0.1-25.7). All patients with hepatotoxicity (aspartate aminotransferase >1000 units/L) due to acute acetaminophen toxicity had resolution of the toxicity and were successfully discharged. CONCLUSIONS: This single intravenous bag protocol is effective and well tolerated, and there is infrequent interruption of therapy. The overall rate of administration errors is similar to that in reports on the FDA regimen; thus, our protocol may be an acceptable alternative.

PMID: 21586653 [PubMed - as supplied by publisher]

Pancreatic Enzyme Products: Digesting the Changes (May).

Ann Pharmacother. 2011 May 3;

Authors: Giuliano CA, Dehoorne-Smith ML, Kale-Pradhan PB

OBJECTIVE: To review the pharmacology, dosage regimens, efficacy, and safety of currently marketed pancreatic enzyme products (PEPs). DATA SOURCES: Studies were identified by PubMed (1966-January 2011), clinicaltrials.gov, fda.gov, and International Pharmaceutical Abstracts. Search terms included pancreatic enzyme, lipase, Creon, Zenpep, Pancreaze, and exocrine pancreatic insufficiency (EPI). STUDY SELECTION AND DATA EXTRACTION: All human studies evaluating the efficacy of currently approved or potential PEPs were reviewed. DATA SYNTHESIS: PEPs are composed of porcine lipase, amylase, and protease and are used in patients with EPI secondary to cystic fibrosis, chronic pancreatitis, and pancreatectomy. In 1938, PEPs were exempted from the Food, Drug, and Cosmetic Act of 1938 and never underwent a formal Food and Drug Administration (FDA) review process. In response to reports of treatment failures during product interchange, the FDA conducted a review of available PEP products. This review found a large variability of response between the unapproved PEP products, which resulted in the FDA requiring approval of all PEP products by April 2010. The 3 delayed-release, enteric-coated PEPs currently approved by the FDA (Creon, Zenpep, and Pancreaze) have demonstrated efficacy and safety in EPI secondary to cystic fibrosis. Creon has also demonstrated safety and efficacy in EPI secondary to chronic pancreatitis and pancreatectomy. Cost difference between the 3 products is minimal. Treatment-related adverse events in clinical studies for all PEPs were less than or similar to those with placebo. CONCLUSIONS: At this time, Creon is an appropriate first-line agent, as it has been approved for chronic pancreatitis, pancreatectomy, and cystic fibrosis.

PMID: 21540403 [PubMed - as supplied by publisher]

Dabigatran Etexilate: A Novel Oral Thrombin Inhibitor for Thromboembolic Disease (May).

Ann Pharmacother. 2011 May 3;

Authors: Bovio JA, Smith SM, Gums JG

OBJECTIVE: To evaluate the efficacy and safety of dabigatran etexilate, approved by the Food and Drug Administration (FDA) in October 2010 for the prevention of cardioembolic stroke in patients with atrial fibrillation; potential off-label use is treatment and prevention of venous thromboembolic disorders. DATA SOURCES: Literature was accessed through MEDLINE (1977-April 2011) and International Pharmaceutical Abstracts (1977-April 2011) using the terms dabigatran, dabigatran etexilate, BIBR 1048, direct thrombin inhibitor, anticoagulant, and thromboembolism. In addition, US government Web sites, including clinicaltrials.gov and fda.gov, were reviewed for pertinent information. Lastly, reference citations from publications identified in the initial search were reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were evaluated. For the evaluation of clinical efficacy and safety, only Phase 2 and 3 studies are included in this review. DATA SYNTHESIS: In 6 published Phase 3 trials to date, dabigatran has exhibited a similar efficacy and safety profile to that of comparator drugs, including dose-adjusted warfarin and enoxaparin, at various dosages. In the largest of these trials, RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy), dabigatran was at least as effective as dose-adjusted warfarin in reducing stroke or systemic embolism. Overall bleeding risks were similar; however, dabigatran may be associated with a lower incidence of intracranial bleeding and hemorrhagic stroke but a higher incidence of gastrointestinal bleeding. Although dabigatran is not approved for venous thromboembolism (VTE) prevention or treatment, results of the RE-MODEL and RE-NOVATE trials suggest similar efficacy to once-daily dosing of enoxaparin 40 mg but inferior efficacy to the FDA-approved twice-daily dosing of enoxaparin 30 mg in the RE-MOBILIZE trial. CONCLUSIONS: Dabigatran is an effective and safe alternative to oral vitamin K antagonists for stroke prevention in patients with nonvalvular atrial fibrillation, with fewer drug interactions and monitoring requirements. Additionally, dabigatran may be a viable alternative to enoxaparin in VTE prevention and warfarin in VTE treatment, although current trial data are limited.

PMID: 21540406 [PubMed - as supplied by publisher]

Efficacy of Agents to Prevent and Treat Enteral Feeding Tube Clogs (May).

Ann Pharmacother. 2011 Apr 26;

Authors: Dandeles LM, Lodolce AE

OBJECTIVE: To review the efficacy and safety of agents used to prevent and treat clog formation in enteral feeding tubes. DATA SOURCES: A literature search was conducted through MEDLINE (1948-February 2011) and International Pharmaceutical Abstracts (1970-February 2011) using the search terms enteral feeding tube and occlusion. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language publications were reviewed for applicability. DATA SYNTHESIS: Occlusion is a common complication of enteral tube feeding. With Food and Drug Administration regulations, pancreatic enzymes have recently been reformulated and previously published reports can no longer be applied to currently available agents. This has led to concern over what available products have been shown to be efficacious. Three in vitro studies, 1 randomized in vivo trial, and 1 descriptive report were reviewed. In the prevention of tube clogging, it was concluded that water was comparable in efficacy, while being more readily available and cost effective, when compared to Coca-Cola, and both were superior to cranberry juice. For resolution of an existing clog, evidence of the efficacy of any individual agents is limited and has not been reproducible. New formulations of pancreatic enzymes, a new delivery system for enzymes, and products to mechanically dismantle clogs have become commercially available, but no studies have been completed to evaluate safety and efficacy. Comparative in vivo studies of currently available products are needed to evaluate possible methods for resolving an occlusion. CONCLUSIONS: Water flushes have shown to be the most effective method in preventing enteral feeding tube clogging. Well-designed trials are needed to establish the proper place in therapy of new commercially available agents marketed for resolving clogs. In addition, well-designed in vivo trials are needed to establish the role, dosage, and extemporaneous formulation of extended-release pancreatic enzymes in treating such clogs.

PMID: 21521858 [PubMed - as supplied by publisher]

Vancomycin-Induced Neutropenia: Is it Dose- or Duration-Related? (May).

Ann Pharmacother. 2011 Apr 26;

Authors: Black E, Lau TT, Ensom MH

OBJECTIVE: To systematically evaluate the literature to determine whether vancomycin-induced neutropenia is dose- or duration- related and provide clinicians with feasible treatment alternatives. DATA SOURCES: A literature search of PubMed (1949-November 2010), MEDLINE (1950-November 2010), EMBASE (1980-November 2010), and International Pharmaceutical Abstracts (1970-November 2010) was performed using the terms vancomycin, neutropenia, and leukopenia. Citations from publications were reviewed for additional references. STUDY SELECTION AND DATA EXTRACTION: Studies and case reports were included if they reported neutropenia with vancomycin administration and excluded if they did not describe vancomycin dosages and/or concentrations, or if neutropenia resolved while the patient was still receiving vancomycin. Cases with significant confounders and those in which authors provided minimal information about patients were also excluded. DATA SYNTHESIS: Seven retrospective chart reviews (ie, case series) and 33 case reports were identified. Of these, 3 retrospective reviews and 26 case reports met inclusion criteria. To our knowledge, no prospective studies have assessed this clinical complication. Data suggest that vancomycin-induced neutropenia may not be completely related to daily dosages, total cumulative dosage, or supra- therapeutic vancomycin concentrations. Furthermore, evidence suggests that neutropenia is more likely associated with therapy longer than 7 days, with the majority of episodes occurring beyond 20 days of therapy. Given these findings, a practical approach is to monitor white blood cell (WBC) count with a differential (including absolute neutrophil count) once a week in patients who are receiving vancomycin for more than 7 days. CONCLUSIONS: Vancomycin-induced neutropenia is most likely associated with prolonged vancomycin exposure. Patients receiving vancomycin for longer than 7 days should have WBC count, differential, monitored weekly. Vancomycin should be discontinued if there is a high clinical suspicion of it causing neutropenia, and an alternative agent should be initiated. Prospective case-controlled studies are needed to better characterize this adverse event.

PMID: 21521866 [PubMed - as supplied by publisher]