Role of {alpha}2-Agonists in the Treatment of Acute Alcohol Withdrawal (May).
Ann Pharmacother. 2011 Apr 26;
Authors: Muzyk AJ, Fowler JA, Norwood DK, Chilipko A
OBJECTIVE: To evaluate literature reporting on the role …

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Terlipressin in Hepatorenal Syndrome (March).

Ann Pharmacother. 2011 Mar 8;

Authors: Mazur JE, Cooper TB, Dasta JF

OBJECTIVE: To compare the pharmacology, dosing, and adverse reactions of vasopressin and terlipressin for the treatment of hepatorenal syndrome (HRS) and assess the efficacy of the investigational drug terlipressin for HRS. DATA SOURCES: Articles evaluating prospective studies for vasopressin and terlipressin were discussed after being identified through PubMed (1966-November 2010), International Pharmaceutical Abstracts (1970-November 2010), and EMBASE (1985-November 2010) with combinations of the following terms: vasopressin, terlipressin, and hepatorenal syndrome. In addition, reference citations from publications identified were reviewed. Thirteen studies were identified for terlipressin, along with 4 meta-analyses and 1 case report. For vasopressin, 2 studies were identified. STUDY SELECTION AND DATA EXTRACTION: Prospective clinical studies directly comparing terlipressin and vasopressin were evaluated, as well as prospective clinical studies and meta-analyses for terlipressin in HRS. DATA SYNTHESIS: No randomized, placebo-controlled trials using vasopressin for the treatment of type I HRS have been published, and 4 randomized studies involving 197 patients provide the most current outcome data for use of terlipressin in HRS. Terlipressin differs significantly from vasopressin with regard to its pharmacology, dosing, and adverse drug reaction profile. There is a paucity of data on vasopressin for HRS. CONCLUSIONS: No definitive recommendations can be made for the use of terlipressin for this indication until further, well-conducted studies are performed.

PMID: 21386023 [PubMed - as supplied by publisher]

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Evaluation of Contraindicated Drug-Drug Interaction Alerts in a Hospital Setting (March).

Ann Pharmacother. 2011 Mar 8;

Authors: Hatton RC, Rosenberg AF, Morris CT, McKelvey RP, Lewis JR

BACKGROUND: Risks associated with contraindicated drug-drug interaction alerts (CDDIAs) should always outweigh benefits. Misclassified CDDIAs should be eliminated. OBJECTIVE: To review CDDIAs and determine if they are contraindicated according to Food and Drug Administration-approved product labeling and if there are circumstances in which contraindicated interactions are acceptable. METHODS: A cross-sectional observational and quality improvement study was conducted over two 1-year periods. The 20 most common CDDIAs from May 2007 to May 2008 and all CDDIAs from April 2008 to April 2009 were collected at a large teaching hospital. Horizon Meds Manager used First DataBank as the knowledge base for decision support. Interactions were deemed truly contraindicated if listed in the contraindications section of the labeling of at least one of the interacting drugs. Alerts were grouped by drug and pharmacologic class to evaluate the evidence supporting the relevance of these interactions. An expert panel determined when an alert was misclassified. A medical advisory committee determined whether a contraindicated drug-drug combination was acceptable. RESULTS: Twelve (60%) of the most common 20 contraindicated interaction pairs from 2007 to 2008 were inappropriately classified. Half of the alerts were not truly contraindicated. The 8 truly contraindicated drug-drug pairs were ketorolac and other nonsteroidal antiinflammatory drugs or oral solid potassium products and anticholinergics. Half of these interactions were subsequently deemed acceptable under specific circumstances. Similar results were found in the second year, with only 55.1% of all CDDIAs being truly contraindicated despite eliminating some of the alerts that were misclassified in the first year. Nearly three fourths of legitimate CDDIAs were deemed acceptable under specific circumstances. CONCLUSIONS: Most contraindicated drug-drug interaction alerts from a commercial knowledge base were inappropriately categorized and could be downgraded. Some contraindicated drug combinations are permissible under specific circumstances. Alerts suggesting that certain drugs should never be used together, but their use together is sometimes acceptable, contribute to alert fatigue.

PMID: 21386026 [PubMed - as supplied by publisher]

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Subcutaneous unfractionated heparin for treatment of venous thromboembolism in end-stage renal disease.

Ann Pharmacother. 2010 Dec;44(12):2023-7

Authors: Metzger NL, Chesson MM

To report 3 cases of venous thromboembolism (VTE) in patients with end-stage renal disease (ESRD) treated with subcutaneous unfractionated heparin (UFH) bridged with warfarin.

PMID: 21098749 [PubMed - indexed for MEDLINE]

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Medication reconciliation during internal hospital transfer and impact of computerized prescriber order entry.

Ann Pharmacother. 2010 Dec;44(12):1887-95

Authors: Lee JY, Leblanc K, Fernandes OA, Huh JH, Wong GG, Hamandi B, Lazar NM, Morra D, Bajcar JM, Harrison J

Internal hospital transfer is a vulnerable time during which patients are at high risk of medication discrepancies that can result in clinically significant harm, medication errors, and adverse drug events.

PMID: 21098753 [PubMed - indexed for MEDLINE]

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Impact of a Pharmacist-Directed Anticoagulation Service on the Quality and Safety of Heparin-Induced Thrombocytopenia Management (February).

Ann Pharmacother. 2011 Feb 8;

Authors: To L, Schillig JM, Desmet BD, Kuriakose P, Szandzik EG, Kalus JS

BACKGROUND: The use of anticoagulant medications is complex and prone to error in the inpatient setting. Patients with heparin-induced thrombocytopenia (HIT) must receive treatment with alternative anticoagulant agents to ensure optimal patient outcomes. OBJECTIVE: To evaluate the impact of an inpatient pharmacist-directed anticoagulation service (PDAS) on the safety and efficiency of direct thrombin inhibitor use in patients with HIT. METHODS: This was a quasi-experimental pre/postintervention study comparing patients with HIT managed with usual care to patients managed with a focused inpatient anticoagulation service. The primary endpoints of the study were the percent of time that the activated partial thromboplastin time (aPTT) remained within the therapeutic range and time to achievement of a therapeutic aPTT. Bleeding and appropriateness of warfarin initiation were evaluated as secondary endpoints. RESULTS: A total of 193 patients were included in the study. Percent of time that aPTT was in the therapeutic range was 32% higher with the PDAS (p < 0.001) and time to therapeutic aPTT was shortened by approximately 12.5 hours in patients managed by the PDAS (p < 0.001). There was a trend for more bleeding events, regardless of severity, among control patients (p = 0.130). Rate of TIMI (Thrombolysis in Myocardial Infarction) major bleeding was lower in the PDAS group (p = 0.006), but there was no significant difference between groups in GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate/severe bleeding (p = 0.679). Appropriateness of warfarin initiation was also similar between groups. CONCLUSIONS: Implementation of a focused inpatient PDAS was associated with improved efficiency of dosing, improved monitoring, and low bleeding risk.

PMID: 21304024 [PubMed - as supplied by publisher]

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A Comparative Look at the Safety Profiles of Intravenous Iron Products Used in the Hemodialysis Population (February).

Ann Pharmacother. 2011 Feb 8;

Authors: Coppol E, Shelly J, Cheng S, Kaakeh Y, Shepler B

OBJECTIVE: To review clinical trials conducted in hemodialysis patients of the 4 intravenous iron products available in the US in an attempt to discern strengths and inferiorities between products and evaluate current safety data that can be used to assist the clinician in selecting the most appropriate agent. DATA SOURCES: Literature was accessed through PubMed (January 2000-October 2010). In some cases, reference citations from selected review articles were evaluated as well. STUDY SELECTION AND DATA EXTRACTION: Clinical trials published in the English language were selected using the search terms iron dextran, iron sucrose, sodium ferric gluconate, and ferumoxytol. Studies were further pared down to include only those enrolling hemodialysis patients. DATA SYNTHESIS: There are currently 4 intravenous iron formulations in the US used to treat iron-deficiency anemia in hemodialysis patients. Ferumoxytol has not yet been directly compared to the other 3 agents. Eight studies have been conducted in hemodialysis patients directly comparing iron dextran, iron sucrose, and/or sodium ferric gluconate. These studies were further categorized for evaluation based on iron products compared. Four studies directly compared iron dextran to iron sucrose, 1 study compared iron dextran to sodium ferric gluconate, 1 study compared iron sucrose to sodium ferric gluconate, and 2 studies compared all 3 agents. Of the 3 agents, iron dextran appears to have the least favorable safety profile, while iron sucrose appears most favorable. CONCLUSIONS: The newest intravenous iron product, ferumoxytol, has not been directly compared to the other 3 agents. Large well-controlled studies of these products specifically in the hemodialysis population would further help clinicians determine appropriate therapy. Iron sucrose appears to offer the most favorable safety profile when compared to iron dextran and sodium ferric gluconate in treating hemodialysis patients. Oxidative stress and hypersensitivity reactions are common problems encountered when administering intravenous iron.

PMID: 21304025 [PubMed - as supplied by publisher]

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Intestinal Necrosis Associated with Orally Administered Calcium Polystyrene Sulfonate Without Sorbitol (February).

Ann Pharmacother. 2011 Feb 8;

Authors: Goutorbe P, Montcriol A, Lacroix G, Bordes J, Meaudre E, Souraud JB

OBJECTIVE: To describe a case of extensive intestinal necrosis with oral intake of calcium polystyrene sulfonate without sorbitol. CASE SUMMARY: A 73-year-old woman was admitted to the emergency department with abdominal pain. Abdominal computed tomography (CT) scan showed widespread dilatation of the bowel. The diagnosis of acute colonic pseudoobstruction was made. On day 3, her serum potassium level rose to 5.6 mEq/L. It was treated with hydrocortisone 100 mg/day and calcium polystyrene sulfonate 15 g/day via jnasogastric tube from day 3 to day 6. On day 6, the severe abdominal pain recurred, with abdominal tenderness. CT scan showed pneumoperitoneum and peritoneal effusion. At surgery, 2 lenticular jejunal perforations and an ischemic cecum were found. Microscopic findings indicated that the transmural abscess contained massive inflammatory infiltrate and the cecal mucosa showed ulceration and inflammation with a fibrinous and purulent coating. Small gray-purple or blue angulated crystals were embedded in the cecal and most of the jejunal mucosal ulcers. On day 19, the patient died of multiple organ failure after her third laparotomy. DISCUSSION: Ion-exchanging resins are given orally or by retention enema for the treatment of hyperkalemia. The most commonly used and best-established resin is sodium polystyrene sulfonate. However, it is known to promote colonic necrosis when sorbitol is also given or especially in patients with renal failure or postoperative ileus. Calcium polystyrene sulfonate is another ion-exchange resin. There are few reports of adverse effects in the literature. Our case is interesting for 2 reasons: the resin given was calcium polystyrene sulfonate and sorbitol was not used. CONCLUSIONS: Like sodium polystyrene sulfonate, calcium polystyrene sulfonate is an ion-exchanging resin that can promote bowel necrosis. We believe that it should not be used with sorbitol or when bowel transit time is slowed.

PMID: 21304040 [PubMed - as supplied by publisher]

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Thienopyridines in Acute Coronary Syndrome (February).

Ann Pharmacother. 2011 Feb 8;

Authors: Goodwin MM, Desilets AR, Willett KC

OBJECTIVE: To evaluate the safety and efficacy of the thienopyridines in order to identify their current place in therapy for the treatment of acute coronary syndrome (ACS). DATA SOURCES: Literature was accessed through MEDLINE (1966-October 2010 week 1), EMBASE (1980-2010 week 40), and a bibliographic review of published articles using the search terms acute coronary syndrome, clopidogrel, and prasugrel. Articles were limited to clinical trials conducted in humans and published in the English language. STUDY SELECTION AND DATA EXTRACTION: Head-to-head clinical trials evaluating the safety and efficacy of the thienopyridines in patients with ACS were critically reviewed. Trials evaluating ticlopidine were excluded due to its limited clinical use. DATA SYNTHESIS: Thienopyridines are an integral part of the treatment of ACS. Prior to the approval of prasugrel, clopidogrel was considered the agent of choice due to safety concerns associated with ticlopidine. A randomized controlled trial comparing prasugrel and clopidogrel has demonstrated superior efficacy with prasugrel, and post hoc analyses suggest additional benefit with prasugrel is derived in patients with ST-segment elevation myocardial infarction and patients with diabetes. However, safety concerns exist linking prasugrel with an increased risk of bleeding, which diminishes its advantage in elderly patients, underweight patients, and those with a history of stroke. Pharmacokinetic and pharmacodynamic studies discussing differences in response variability, platelet inhibition, interactions with proton pump inhibitors, and genetic factors between the thienopyridines are numerous, although more clinical data are needed to determine clinical implications. CONCLUSIONS: Clinical trial data have suggested prasugrel is superior to clopidogrel at preventing ischemic events in patients with ACS undergoing percutaneous coronary intervention. However, this coincides with an increased risk of bleeding. Clinicians must carefully interpret the current evidence, including limitations in study design and pharmacologic differences between agents, in order to balance the risks and benefits as new data become available.

PMID: 21304037 [PubMed - as supplied by publisher]

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Prescriber Compliance with a New Computerized Insulin Guideline for Noncritically Ill Adults (February).

Ann Pharmacother. 2011 Jan 18;

Authors: Clemens E, Cutler T, Canaria J, Pandya K, Parker P

BACKGROUND: In March 2008, the University of California, Davis Medical Center(UCDMC), implemented a guideline for the inpatient management of diabetes in noncritically ill adults. In accordance with national guidelines, all patients with type 2 diabetes are prescribed basal, nutritional, and correctional insulin. The guideline was added to the electronic medical record as a standardized physician order set in April 2008 and provider training on the insulin guideline occurred in May 2008. OBJECTIVE: To evaluate provider compliance with a new electronic standardized insulin order set in a hospital setting. METHODS: All patients with insulin orders admitted to the general internal medicine service between June 1, 2008, and November 1, 2008, were evaluated in this single-center retrospective chart review at UCDMC in Sacramento. Patients older than 18 years with a history of type 2 diabetes were included in the analysis. Insulin orders were categorized as preferred (followed the guideline) or nonpreferred regimens (did not follow all components of the guideline). RESULTS: A total of 265 patients were identified during the study period. The preferred regimen was ordered in 82 (30.9%) of the evaluated patient admissions. Of the 183 (69.1%) nonpreferred regimens, more than half (54.6%) contained correctional insulin alone; 84.2% of patient admissions prescribed nonpreferred regimens lacked nutritional insulin. Average admission blood glucose readings were higher in the preferred versus nonpreferred regimen group (224.4 vs 164.8 mg/dL, p < 0.001). CONCLUSIONS: The preferred regimen was not prescribed for the majority of patients admitted with a history of type 2 diabetes, despite computerized decision support. Nutritional insulin was the most common missing component in the nonpreferred regimens. Baseline clinical factors, educational modalities, and guideline content may have influenced prescribing patterns.

PMID: 21245289 [PubMed - as supplied by publisher]

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Medication history reconciliation by clinical pharmacists in elderly inpatients admitted from home or a nursing home.

Ann Pharmacother. 2010 Oct;44(10):1596-603

Authors: Steurbaut S, Leemans L, Leysen T, De Baere E, Cornu P, Mets T, Dupont AG

Accurate medication histories at hospital admission are an important element of medication safety. Discrepancies may have clinically significant consequences, especially in the elderly population.

PMID: 20736427 [PubMed - indexed for MEDLINE]

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Octreotide for Symptomatic Treatment of Diarrhea due to Cytomegalovirus Colitis (January).

Ann Pharmacother. 2010 Dec 28;

Authors: Bartels MC, Mergenhagen KA

OBJECTIVE: To report the improvement of diarrhea in a patient with cytomegalovirus (CMV) colitis who was treated with octreotide after failure of loperamide. CASE SUMMARY: An 84-year-old male presented with chronic diarrhea and CMV colitis; he had been experiencing protracted diarrhea since 2006. In October 2009 he failed a 21-day course of valgancyclovir 900 mg orally twice daily. Several months later, due to continuing diarrhea and progressive malnutrition, a colonoscopy and subsequent biopsy again showed CMV. In March 2010 he was started on a 28-day course of intravenous ganciclovir 130 mg daily. Three weeks into treatment he continued with copious amounts of diarrhea, with no relief from loperamide, which was titrated from 2 mg/day to 2 mg every 6 hours. On day 20 of ganciclovir treatment he was started on octreotide 50 ?g subcutaneously every 8 hours; within a few days, the patient began to experience decreased stool frequency and consistency. He completed the full 28-day course of ganciclovir, with octreotide continuing unchanged, with much improvement in his diarrheal symptoms and improvement in appetite, nutritional status, and quality of life. DISCUSSION: Studies regarding the treatment of CMV colitis-associated diarrhea are scarce, and are typically limited to treating the underlying cause with antiviral medications and with the addition of antimotility agents. Three cases have been reported in the literature in which octreotide was used for the symptomatic treatment of diarrhea, none of which was refractory to loperamide. CONCLUSIONS: This is the first known case of a patient with chronic diarrhea due to CMV colitis that was unresponsive to loperamide, required protracted antiviral treatment (valgancyclovir and gancyclovir), and subsequently experienced relief by the use of octreotide 50 ?g subcutaneously every 8 hours.

PMID: 21189368 [PubMed - as supplied by publisher]

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Central Nervous System Toxicity Associated with Ertapenem Use (January).

Ann Pharmacother. 2010 Dec 21;

Authors: Duquaine S, Kitchell E, Tate T, Tannen RC, Wickremasinghe IM

OBJECTIVE: To report stroke-like symptoms and unusual central nervous system adverse effects in 2 elderly patients receiving ertapenem. CASE SUMMARY: Two patients ?70 years of age experienced unusual mental status changes while receiving ertapenem. Patient 1 developed garbled speech and miosis 1 week after starting appropriately dosed ertapenem (1 g/day) for sacral osteomyelitis. Symptoms resolved upon ertapenem discontinuation but recurred upon rechallenge. Patient 2, a cachectic male with acute renal insufficiency, became delirious and progressively obtunded 5 days after starting ertapenem 1 g/day. Nine days after initiation of therapy, he required intubation and mechanical ventilation; ertapenem was discontinued at that time. Within 2 days of ertapenem discontinuation, his mental state cleared and the ventilator was removed. DISCUSSION: Carbapenems, including ertapenem, have been implicated in causing central nervous system toxicity, including hallucinations and seizures. However, published reports of other, nonseizure-related central nervous system events are limited. Considerable resources were expended on extensive medical interventions before ertapenem was identified as a potential cause of the delirium in our patients. When applied to our patients, the Naranjo probability scale indicated a highly probable relationship for patient 1 and a probable relationship for patient 2 between the adverse effects and ertapenem use. CONCLUSIONS: Clinicians should be cognizant of ertapenem’s potential to induce profound changes in mental status that may mimic other conditions in elderly patients.

PMID: 21177419 [PubMed - as supplied by publisher]

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Treatment of Meningitis Caused by Vancomycin-Resistant Enterococcus faecium: High-Dose and Combination Daptomycin Therapy (December).

Ann Pharmacother. 2010 Nov 30;

Authors: Le J, Bookstaver PB, Rudisill CN, Hashem MG, Iqbal R, James CL, Sakoulas G

OBJECTIVE: To report 3 successful treatments of vancomycin-resistant Enterococcus faecium meningitis in adults using daptomycin and either linezolid or gentamicin. CASE SUMMARY: Three case reports involving males (aged 58-78 years) are presented; in each case (trigeminal nerve microvascular decompression and subdural hygroma; paraspinal abscess; and hydrocephalus with subsequent craniotomy and ventriculo-peritoneal shunt placement) CSF examination revealed vancomycin-resistant Enterococcus (VRE) susceptible to daptomycin, gentamicin, and/or linezolid. Three- to four-week treatment regimens with daptomycin 6-12 mg/kg and either gentamicin or linezolid led to clinical resolution and microbiological clearance of infection. DISCUSSION: Daptomycin has previously been shown to be successful in treating methicillin-resistant Staphylococcus aureus-associated meningitis and other serious VRE and enterococcal infections. Higher than approved doses of daptomycin were used in 2 cases where in theory higher CSF concentrations would thus be obtained. Gentamicin and linezolid were added to daptomycin therapy based on in vitro data synergy results and because of documented successful treatment for VRE meningitis, respectively. CONCLUSIONS: The difficulty in treating VRE CSF infections involves both drug kinetics and microbial resistance factors, as well as external factors such as foreign bodies like shunts. This report highlighted 3 cases where daptomycin use in concert with either gentamicin or linezolid was successful in treating this infection. Additional controlled trials will be helpful in identifying the best strategies when using daptomycin to treat CSF infections.

PMID: 21119097 [PubMed - as supplied by publisher]

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Thrombolytics for Cardiac Arrest: Case Report and Systematic Review of Controlled Trials (December).

Ann Pharmacother. 2010 Nov 30;

Authors: Perrott J, Henneberry RJ, Zed PJ

OBJECTIVE: To describe a successful case involving the use of tenecteplase during cardiac arrest for presumed pulmonary embolism (PE) and to systematically review the evidence from controlled trials supporting the efficacy and safety of thrombolysis during cardiac arrest. CASE SUMMARY: A 48-year-old male presented to the emergency department with an acute onset of shortness of breath that began approximately 2 hours prior to presentation. Prior to undergoing a computed tomography (CT) scan to rule out PE, the patient went into cardiac arrest, with an initial rhythm of pulseless electrical activity at a rate of 140 beats/min. Cardiopulmonary resuscitation (CPR) was initiated and, due to suspected PE, a bolus dose of tenecteplase 50 mg was administered immediately following a single 1-mg dose of epinephrine. CPR was continued and 4 additional 1-mg doses of epinephrine and three 1-mg doses of atropine were given. After 13 minutes of CPR, return of spontaneous circulation (ROSC) was achieved, with a blood pressure of 144/50 mm Hg. After the patient was stabilized, a CT scan demonstrated extensive bilateral pulmonary emboli in most segmental arteries. He was admitted to the intensive care unit where he was sedated, paralyzed, and treated with induced hypothermia for 24 hours. He was discharged from the hospital 2 weeks later on warfarin, with no noted neurologic deficits. DISCUSSION: A systematic search of MEDLINE (1950-August 2010), Embase (1980-August 2010), and Google Scholar (to August 2010) was conducted to identify prospective controlled trials that investigated the use of thrombolytic medications to treat cardiac arrest. Five trials involving 1544 undifferentiated cases of cardiac arrest were found. Overall, some trials reported an improved rate of ROSC following administration of thrombolytics, but there was no overall mortality reduction in any trial. There was, however, an increased risk of bleeding events following administration of a thrombolytic drug. CONCLUSIONS: Controlled trials demonstrate that there is a lack of benefit and potential harm in administering thrombolysis in an undifferentiated patient with cardiac arrest. However, the case we present provides evidence that fibrinolysis may benefit selected patients with cardiac arrest in whom PE is confirmed or in whom there is high index of suspicion of PE.

PMID: 21119096 [PubMed - as supplied by publisher]

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