bluuebunny/crossref_metadata_2025 huggingface dataset:
Reboxetine: A Selective Norepinephrine Reuptake Inhibitor for the Treatment of Depression
Authors: Scates Ann C , Doraiswamy P Murali
Published: June 2003

OBJECTIVE:

To review the pharmacology, pharmacokinetics, efficacy, and tolerability of reboxetine in the treatment of major depressive illness.

DATA SOURCES:

A MEDLINE search restricted to English-language literature was conducted (1966 to July 1999). Abstracts and posters presented at meetings were also reviewed.

DATA EXTRACTION/STUDY SELECTION:

Studies currently available were conducted in Europe. Data from clinical trials were reviewed to gather information specific to efficacy analysis, pharmacokinetic parameters, tolerability profiles, and drug—drug interactions. Information on reboxetine was compared with other antidepressant therapies when appropriate data were available.

DATA SYNTHESIS:

Reboxetine is a selective norepinephrine reuptake inhibitor shown to be an effective agent in the treatment of major depressive illness. In clinical trials, reboxetine was effective in decreasing mean total scores of the Hamilton Rating Scale for Depression in adult populations. Improvements were similar between reboxetine and desipramine and imipramine, as well as fluoxetine. Reboxetine is relatively well tolerated, with insomnia, sweating, constipation, and dry mouth being commonly reported adverse events. Hypotension and urinary hesitancy occur at lower rates than with the tricyclics, and compared with fluoxetine, reboxetine is associated with lower rates of nausea, somnolence, and diarrhea. Dosage adjustments may be appropriate in elderly patients and those with renal and hepatic impairment.

CONCLUSIONS:

Reboxetine has received two letters of approval from the Food and Drug Administration for the treatment of major depression in adults. Upon completion of an additional US clinical study, reboxetine is likely to become a first-line agent in the management of depressive illness and a promising alternative for patients who have failed treatment with or do not tolerate serotonergic antidepressants.
Interaction between Warfarin and Trazodone
Authors: Small Nancy L , Giamonna Kathy A
Published: June 2003

BACKGROUND:

It is well known that there are many drug interactions involving warfarin. However, few data have been supplied to guide clinicians concerning the interaction between trazodone and warfarin.

CASE SUMMARY:

Three clinically significant cases of suspected trazodone and warfarin interactions were identified in a retrospective chart review based on changes in the prothrombin time (PT) and international normalized ratio (INR) that were not explained by other factors. In each of the cases, the INR changed by ≥1.0 after the initiation or discontinuation of trazodone. In the patients who started trazodone, a subsequent decrease in the PT and INR resulted; conversely, the PT and INR increased in the patient who stopped trazodone therapy. Although none of the patients experienced adverse effects due to the marked changes in PT and INR, the warfarin dosages had to be adjusted accordingly on initiation and discontinuation of trazodone.

DISCUSSION:

These cases show that there is a potentially clinically significant interaction between trazodone and warfarin. The time to onset of the interaction is variable; the mechanism behind it is not known, but it may involve substrate or protein-binding competition.

CONCLUSIONS:

The use of trazodone on an as-needed basis for sleep is strongly discouraged in patients who are receiving warfarin, due to the difficulty of achieving a therapeutic PT and INR. Until more is known, patients and clinicians should be educated about this potential interaction and monitor for changes in the anticoagulant effects when trazodone is initiated or stopped.
Skin Discoloration with Blue Food Coloring
Authors: Zillich Alan J , Kuhn Robert J , Petersen Thomas J
Published: June 2003

OBJECTIVE:

To describe a pediatric patient who developed a clinical cyanotic appearance after receiving an excessive amount of blue food coloring.

CASE SUMMARY:

An 11-year-old white girl with cerebral palsy was admitted for unresolving aspiration pneumonia and dehydration. Antibiotics and intravenous fluids were administered. During the hospital course, enteral nutrition containing blue food coloring was also administered. Twelve hours after the start of enteral nutrition, the patient appeared cyanotic despite a regular respiratory rate and normal oxygen saturation. The pediatric code response team was called. Enteral nutrition was stopped and then restarted without blue food coloring. Over the next 24 hours, the cyanotic appearance resolved and no further complications developed.

DISCUSSION:

At our institution, blue food coloring is used with enteral nutrition for detecting aspiration of stomach contents. The dietary department supplies food coloring to each nursing unit in pint-sized medicine bottles. Nurses place an unstandardized amount of blue food coloring into each enteral nutrition bag. This child received an unspecified amount of FD&C Blue No. 1 food coloring. No toxicity studies exist for acute or human ingestion, but the National Academy of Sciences lists 363 mg/d of FD&C Blue No. 1 as a safe level for humans. We estimated this child ingested 780–3940 mg of dye over a 12-hour period.

CONCLUSIONS:

This is the first known report of an adverse effect from blue food coloring. To prevent similar occurrences within our institution, the blue food coloring for tube feedings will be dispensed by the pharmacy department in standardized units.
Congruence of Three Self-Report Measures of Medication Adherence among HIV Patients
Authors: Gao Xin , Nau David P
Published: June 2003

OBJECTIVE:

To evaluate the accordance between three measures of self-reported medication adherence.

METHODS:

A survey was administered to HIV patients. The three adherence measures included a four-item Morisky-type scale (Measure1) and two measures defining adherence as the percentage of doses taken as prescribed during the past two days (Measure2) or past two weeks (Measure3).

RESULTS:

For Measure1, 29.2% of the patients were categorized as high adherence and 61.5% as medium adherence. For Measure2 and Measure3, the mean scores were 93.6% and 96.5%, respectively. Using 90% as cutoff values, 78.5% and 95.4% of the patients were classified as adherent by Measure2 and Measure3, respectively (k = 0.30; p = 0.001). When 80% was used, 90.8% of the patients were classified as adherent for Measure2 and 96.9% for Measure3 (k = 0.48; p < 0.001). When using 90% and 80% as cutoff values to categorize Measure2 and Measure3 as three levels, there was no agreement between Measure1 and the other two measures. The accordance of Measure2 and Measure3 was significant albeit not high (k = 0.31; p < 0.001).

CONCLUSIONS:

The accordance between a Morisky-type adherence scale and measures of missed doses is unsatisfactory. However, “missed-dose” measures using two-day or two-week time periods yield fairly similar results. Researchers should be cautious when comparing adherence rates between studies that use different methods for assessing adherence.
Possible Serotonin Syndrome Associated with Buspirone Added to Fluoxetine
Authors: Manos Gail H
Published: June 2003

OBJECTIVE:

To report the development of a possible serotonin syndrome in a patient taking buspirone and fluoxetine.

CASE SUMMARY:

A 37-year-old white man taking fluoxetine 20 mg/d for generalized anxiety disorder developed confusion, diaphoresis, incoordination, diarrhea, and myoclonus after buspirone was added to the drug regimen.

DISCUSSION:

Serotonin syndrome is a potentially lethal condition of serotonin hyperstimulation, which may develop rapidly or over the course of several weeks. Symptoms of serotonin syndrome typically occur following additions or increases of serotonin-enhancing drugs. Although buspirone has variable effects on post- and presynaptic 5-HT1A receptors that may reduce the risk of serotonin syndrome when administered as a single agent, it may cause an adverse reaction when given with other serotonergic drugs.

CONCLUSIONS:

Symptoms consistent with serotonin syndrome may develop with the concurrent administration of buspirone and fluoxetine.
Zanamivir in the Treatment and Prevention of Influenza
Authors: Chapple Kevin J , Hendrick Anne E , McCarthy Michelle W
Published: June 2003

OBJECTIVE:

To evaluate the efficacy of zanamivir in the prevention and treatment of influenza.

DATA SOURCES:

Medical literature was accessed through MEDLINE (1966–June 1999). Key search terms included zanamivir, GG167, and influenza. Additional information was obtained from GlaxoWellcome, Inc.

DATA SYNTHESIS:

Zanamivir is the first in a new class of drugs to be developed for the treatment of influenza. An evaluation of clinical trials using inhaled zanamivir was conducted to determine its efficacy.

CONCLUSIONS:

Zanamivir appears to shorten the median duration of influenza symptoms by up to 2.5 days when compared with placebo. It was well tolerated in clinical trials, with mild adverse effects occurring in a small percentage of subjects.
Treatment Options for Rheumatoid Arthritis: Celecoxib, Leflunomide, Etanercept, and Infliximab
Authors: Luong Brigitte T , Chong Barbara S , Lowder Dionne M
Published: June 2003

OBJECTIVE:

To review new pharmacologic agents approved for use in the management of rheumatoid arthritis (RA).

DATA SOURCES:

A MEDLINE search (1966–January 2000) was conducted to identify English-language literature available on the pharmacotherapy of RA, focusing on celecoxib, leflunomide, etanercept, and infliximab. These articles, relevant abstracts, and data provided by the manufacturers were used to collect pertinent data.

STUDY SELECTION:

All controlled and uncontrolled trials were reviewed.

DATA EXTRACTION:

Agents were reviewed with regard to mechanism of action, efficacy, drug interactions, pharmacokinetics, dosing, precautions/contraindications, adverse effects, and cost.

DATA SYNTHESIS:

Traditional pharmacologic treatments for RA have been limited by toxicity, loss of efficacy, or both. Increasing discoveries into the mechanisms of inflammation in RA have led to the development of new agents in hopes of addressing these limitations. With the development of celecoxib, a selective cyclooxygenase-2 inhibitor, the potential exists to minimize the gastrotoxicity associated with nonsteroidal antiinflammatory drugs. Leflunomide has been shown to be equal to or less efficacious than methotrexate, and may be beneficial as a second-line disease-modifying antirheumatic drug (DMARD). The biologic response modifiers, etanercept and infliximab, are alternatives that have shown benefit alone or in combination with methotrexate. However, they should be reserved for patients who fail to respond to DMARD therapy. Further studies should be conducted to evaluate the long-term safety and efficacy of these agents as well as their role in combination therapy.

CONCLUSIONS:

Celecoxib, leflunomide, etanercept, and infliximab are the newest agents approved for RA. Clinical trials have shown that these agents are beneficial in the treatment of RA; however, long-term safety and efficacy data are lacking.
The Use of ACE Inhibitors as Renoprotective Agents in Medicaid Patients with Diabetes
Authors: Scarsi Kimberly K , Bjornson Darrel C
Published: June 2003

OBJECTIVE:

To establish a relationship between angiotensin-converting enzyme (ACE) inhibitor therapy and renal outcomes in Medicaid patients with diabetes, and compare the use of ACE inhibitors between 1994 and 1998.

METHODS:

One thousand patients with either type 1 or type 2 diabetes were randomly selected from the Iowa Medicaid database and followed retrospectively from 1994 through 1998. Data on medication use (insulin, oral antidiabetic agents, or both) and medical services were collected from prescription claims and diagnostic codes. Differences were evaluated with nonparametric statistics.

RESULTS:

Overall, 402 patients (40.2%) were prescribed an ACE inhibitor during the study period before any adverse renal outcomes occurred; 25 of the patients in this group (6.2%) had a subsequent adverse renal outcome. One hundred patients (16.7%) not receiving an ACE inhibitor had an adverse renal outcome (p = 0.006). We evaluated four subgroups and found that patients with hypertension had fewer adverse renal outcomes if they were receiving ACE inhibitors whether they were taking (p = 0.0006) or not taking insulin (p = 0.047). There was no difference in adverse renal outcomes and ACE inhibitor use in normotensive patients who were taking (p = 0.15) or not taking insulin (p = 0.96). The pattern of use of ACE inhibitors in this population increased more than twofold between 1994 and 1998 (38.1% vs. 80.1%; p < 0.001). Of those patients who had adverse renal outcomes, almost one-half (43.2%) were not taking an ACE inhibitor in 1998.

CONCLUSIONS:

ACE inhibitors were renoprotective in patients with diabetes in the Iowa Medicaid population. All patients with diabetes who had hypertension had fewer renal outcomes when taking an ACE inhibitor. ACE inhibitors were used more frequently in 1998 than in 1994. The use of ACE inhibitors in this population is improving, but remains less than optimal.
Clinical Pharmacology of Encapsulated Sustained-Release Cytarabine
Authors: Murry Daryl J , Blaney Susan M
Published: June 2003

BACKGROUND:

The therapeutic effectiveness of chemotherapy is often limited by the inability to sustain cytotoxic concentrations at the tumor site. Cytarabine liposome injection (DepoCyt), a sterile, injectable suspension of the antimetabolite cytarabine, encapsulated into multivesicular, lipid-based particles, has been developed to improve the treatment of neoplastic meningitis (NM) through sustained release of cytarabine.

OBJECTIVE:

To review the pharmacokinetics, efficacy, and safety of intrathecal DepoCyt for the treatment of NM secondary to lymphoma or solid tumors.

RESULTS:

In preclinical and clinical studies, DepoCyt markedly extended the duration of tumor exposure to cytotoxic concentrations of cytarabine compared with administration of unbound cytarabine. Data from recent clinical studies demonstrate that DepoCyt improves complete response rates among patients with NM secondary to lymphoma. Trends in time to neurologic progression and median survival also favored DepoCyt over unbound cytarabine in these studies. Data have also been presented that suggest that patients with NM secondary to solid tumors benefit more from DepoCyt than from conventional treatment approaches. Chemical arachnoiditis (i.e., headache, fever, nausea, vomiting) was common in patients receiving DepoCyt; however, symptoms were manageable with oral dexamethasone.

CONCLUSIONS:

Encapsulation of cytarabine into liposomes for sustained release prolongs tumor exposure to cytotoxic concentrations of cytarabine, which may improve therapeutic efficacy in patients with NM secondary to lymphoma or solid tumors.
Phenytoin and Enteral Feedings: Does Evidence Support an Interaction?
Authors: Yeung Sam CS Au , Ensom Mary HH
Published: June 2003

OBJECTIVE:

To systematically review the reported interaction between oral dosage forms of phenytoin and enteral feeding formulations with respect to the evidence supporting or refuting its existence, proposed mechanism(s) underlying the interaction, and recommended interventions.

DATA SOURCES:

We conducted a MEDLINE search (1966–April 2000) for English-language articles on phenytoin–enteral feeding interactions; the search terms used were phenytoin, enteral feeding, and/or interaction, and/or in vitro. This search was supplemented by a bibliographic review of all relevant articles.

STUDY SELECTION:

Prospective, randomized, controlled studies; prospective, nonrandomized, controlled studies; prospective, nonrandomized, uncontrolled studies; retrospective studies; clinical experience reports; case reports; in vitro studies; and letters were evaluated for relevant information.

DATA EXTRACTION:

Data elements abstracted from these articles were study design, type (patients or healthy volunteers) and number of subjects involved, method of administration of phenytoin and enteral feeding, formulation of phenytoin, type of feeding (and whether it was continuous or interrupted), major findings, and proposed mechanisms of the interaction.

DATA SYNTHESIS:

Although four prospective, randomized, controlled trials in healthy human volunteers refute the existence of the interaction, there are numerous reports and studies showing dramatic decreases of serum phenytoin concentrations in patients when it is coadministered with enteral feeding formulations. Therefore, evidence supports the existence of this interaction in patients and in vitro studies, but not in healthy volunteers. Unfortunately, the exact mechanisms underlying this interaction remain unknown. Many methods have been devised to prevent and treat the interaction once it has occurred; however, a single, generally accepted, and practical intervention strategy is still lacking.

CONCLUSIONS:

The exact role of enteral feeding in this interaction is unclear due to the lack of prospective, randomized, controlled trials performed in patients. However, decreased serum phenytoin concentrations associated with enteral feeding may increase the risk of seizures. Clinicians should be aware of this potential drug–nutrient interaction and design a patient-specific care plan that includes consideration of the enteral feeding formulation and method of administration, as well as the phenytoin dosage fo rm, schedule of administration, and monitoring.
Safety and Tolerability of Bolus Intravenous Colistin in Acute Respiratory Exacerbations in Adults with Cystic Fibrosis
Authors: Conway Steven P , Etherington Christine , Munday James , Goldman Martin H , Strong Joanna J , Wootton Mandy
Published: June 2003

OBJECTIVE:

To assess the safety and tolerability of bolus intravenous doses of colistin during acute respiratory exacerbations in adults with cystic fibrosis and chronic Pseudomonas aeruginosainfection.

METHODS:

Twelve patients with acute exacerbations of cystic fibrosis were enrolled in a Phase I open-label study. On day 1, patients received three doses of colistin 2 mega-units (160 mg), reconstituted in 50 mL of NaCl 0.9%, by infusion over 30 minutes three × daily. On days 2, 3, and 4, the same dose of colistin was administered by bolus injection three × a day over five minutes after reconstitution in 20, 15, and 10 mL of NaCl 0.9%, respectively. The injection was given by a nurse or physician using a hand-held syringe. If the latter dose was tolerated, it was continued for the remaining eight days of the study. If any dose was not tolerated, treatment reverted to the previously tolerated concentration, which was continued throughout the remainder of the study.

RESULTS:

No serious adverse events occurred during the course of the trial. Patients without total indwelling venous access systems experienced mild to moderate injection pain. There were no clinically significant changes in renal function.

CONCLUSIONS:

This study indicates that the administration of bolus intravenous colistin as 2 mega-units (160 mg) in 10 mL of NaCl 0.9% three × a day is safe. It is well-tolerated by patients with total indwelling venous access systems.
Soy Protein in the Management of Hyperlipidemia
Authors: Costa Rebecca L , Summa Maria A
Published: June 2003

OBJECTIVE:

To review the effects of soy on blood lipids and to provide guidance on the clinical relevance of soy's health effects with respect to hyperlipidemia.

DATA SOURCES:

Clinical literature accessed through MEDLINE and EMBASE (1966–November 1999). Key search terms included soy, isoflavone, phytoestrogen, cholesterol, and blood lipids.

DATA SYNTHESIS:

A review of studies evaluating the effects of soy protein on blood lipids was undertaken. Soy may be an alternative for patients seeking modest reductions in low-density lipoprotein cholesterol (<10%).

CONCLUSIONS:

Soy can improve blood lipid parameters in both normocholesterolemic and hypercholesterolemic subjects, although the use of soy alone may not allow patients with hyperlipidemia to achieve target lipid parameters, as indicated by the National Cholesterol Education Program. Further study is warranted for the use of soy in combination with traditional hyperlipidemic medications.
Publication Rates of Abstracts from Two Pharmacy Meetings
Authors: Byerly Wesley G , Rheney Catherine C , Connelly Julie F , Verzino Kelly C
Published: June 2003

OBJECTIVE:

To determine the rate of publication of abstracts presented at the 1994 American Society of Health-System Pharmacists (ASHP) Midyear Clinical Meeting and the 1994 American College of Clinical Pharmacists (ACCP) Annual Meeting.

METHODS:

Abstracts presented at the 1994 ASHP Midyear Clinical Meeting and the 1994 ACCP Annual Meeting were evaluated for subsequent publication as full articles in journals indexed in MEDLINE, International Pharmaceutical Abstracts, and Current Contents.

RESULTS:

Five hundred one abstracts presented at the 1994 ASHP Midyear Clinical Meeting were evaluated; 55 (11%) of these had been published. Two hundred fifteen abstracts presented at the 1994 ACCP Annual Meeting were evaluated; 71 (33%) of these had been published.

CONCLUSIONS:

The publication rates for abstracts presented at ASHP and ACCP meetings were found to be lower than many of those for other medical groups. The presentation of research abstracts at professional meetings is an integral part of the exchange of scientific information; however, many of the presented abstracts are not subsequently published as full research reports. The failure to publish the results of the studies may limit the ability of a reader to judge the validity, reliability, and generalizability of the research. This could affect the use of the findings in clinical practice and in supporting or refuting other research findings.
Sirolimus: Continuing the Evolution of Transplant Immunosuppression
Authors: Ingle Gordon R , Sievers Theodore M , Holt Curtis D
Published: June 2003

OBJECTIVE:

To review the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and economic issues associated with sirolimus, the most recent immunosuppressive agent approved for kidney transplantation.

DATA SOURCES:

A MEDLINE search (1966–June 2000) was completed to identify primary and review articles. In addition, abstracts from recent meetings on transplantation were reviewed for information and research on sirolimus.

STUDY SELECTION AND DATA EXTRACTION:

Blinded, randomized, controlled studies were the goal, but, as with most newly approved immunosuppressive agents, a significant amount of information on sirolimus is not available in this optimal form. All articles were assessed and all pertinent information was incorporated in this review.

DATA SYNTHESIS:

Sirolimus is structurally related to the immunosuppressive agent tacrolimus, and retains a pharmacokinetic and drug interaction profile similar to that of the calcineurin inhibitors, cyclosporine and tacrolimus. However, the novel mechanism of action of sirolimus differs significantly from these agents, as does its adverse effect profile. The most significant adverse reaction is hyperlipidemia. Clinical experience with sirolimus has allowed transplant centers to expand its use into other areas of transplantation as well as certain autoimmune disorders.

CONCLUSIONS:

The definitive role of sirolimus will continue to be determined; however, sirolimus offers an excellent addition to the transplant immunosuppression armamentarium.
The Origin of the “Ideal” Body Weight Equations
Authors: Pai Manjunath P , Paloucek Frank P
Published: June 2003

OBJECTIVE:

To provide a historical perspective on the origin and similarity of the “ideal” body weight (IBW) equations, and clarify the terms ideal and lean body weight (LBW).

DATA SOURCES:

Primary and review literature were identified using MEDLINE (1966–November 1999) and International Pharmaceutical Abstracts (1970–November 1999) pertaining to ideal and lean weight, height–weight tables, and obesity. In addition, textbooks and relevant reference lists were reviewed.

DATA EXTRACTION:

All articles identified through the data sources were evaluated. Information deemed to be relevant to the objectives of the review were included.

DATA SYNTHESIS:

Height–weight tables were generated to provide a means of comparing a population with respect to their relative weight. The weight data were found to correlate with mortality and resulted in the use of the terms desirable or ideal to describe these weights. Over the years, IBW was interpreted to represent a “fat-free” weight and thus was used as a surrogate for LBW. In addition, the pharmacokinetics of certain drugs were found to correlate with IBW and resulted in the use of IBW equations published by Devine. These equations were consistent with an old rule that was developed from height–weight tables to estimate IBW. Efforts to improve the IBW equations through regression analyses of height–weight data resulted in equations similar to those published by Devine.

CONCLUSIONS:

The similarity between the IBW equations was a result of the general agreement among the various height–weight tables from which they were derived. Therefore, any one of these equations may be used to estimate IBW.
Docetaxel as an Alternative to Paclitaxel after Acute Hypersensitivity Reactions
Authors: Bernstein Bridget J
Published: June 2003

OBJECTIVE:

To review the mechanism involved in paclitaxel-induced hypersensitivity reactions and to evaluate the potential use of docetaxel after acute hypersensitivity reactions (HSRs) to paclitaxel.

DATA SOURCES:

Literature identified through a MEDLINE search (1966–September 2000) and through secondary sources.

DATA SYNTHESIS:

HSRs to paclitaxel can be life-threatening. The exact etiology involved in paclitaxel-induced HSRs has not been fully elucidated; the reactions may be due to the Cremophor EL vehicle or to paclitaxel itself. Options for treatment following HSRs are limited. A rechallenge attempt can be made, but is not always successful. Docetaxel, a semisynthetic taxane, may have a role in therapy for patients unable to tolerate paclitaxel therapy. This review examines the etiology of paclitaxel-induced HSRs and the potential role of docetaxel following these acute reactions.

CONCLUSIONS:

Docetaxel may be a viable alternative for patients who experience HSRs to paclitaxel.
High-Flux Hemodialysis without Hemoperfusion is Effective in Acute Valproic Acid Overdose
Authors: Kane Sandra L , Constantiner Marigel , Staubus Alfred E , Meinecke Curt D , Sedor John R
Published: June 2003

OBJECTIVE:

To report a case of valproic acid overdose treated successfully with high-flux hemodialysis without the addition of charcoal hemoperfusion. CASE SUMMARY: A 25-year-old white woman with a history of multiple suicide attempts and schizophrenia presented after ingesting an unknown amount of valproic acid. She became comatose and developed hypotension and lactic acidosis as valproic acid concentrations increased to >1200 μg/mL (therapeutic concentration 50–100). High-flux hemodialysis was performed for four hours; the calculated elimination rate constant (kel) during the procedure was 0.2522 h−1 with a half-life (t1/2) of 2.74 hours compared with posthemodialysis kel of 0.0296 h−1 and t1/2 of 23.41 hours, suggesting that high-flux hemodialysis effectively eliminates valproic acid. The patient's hemodynamic status and mental function improved in conjunction with the acute reduction in valproic acid concentrations. Her subsequent hospital course was complicated only by transient thrombocytopenia. DISCUSSION: Most literature reports of valproic acid overdose have described the use of charcoal hemoperfusion alone or in combination with hemodialysis to accelerate valproic acid clearance at toxic concentrations. However, the pharmacokinetic properties of valproic acid indicate that hemodialysis alone would be effective therapy for an acute valproic acid overdose.

CONCLUSIONS:

We suggest that toxic concentrations of valproic acid can be effectively reduced with high-flux hemodialysis without the addition of charcoal hemoperfusion and its attendant risks.
Olanzapine-Induced Acute Pancreatitis
Authors: Doucette Douglas E , Grenier JPM Sylvain , Robertson Patrick S
Published: June 2003

OBJECTIVE:

To report the first published case of olanzapine-induced acute pancreatitis. CASE SUMMARY: A 72-year-old white woman was admitted to the intensive care unit (ICU) with acute hemorrhagic pancreatitis and unintentional verapamil overdose. The patient did not consume alcohol and had undergone a cholecystectomy in the past; other medical causes of pancreatitis had been ruled out. She was taking several medications chronically, but olanzapine was started six days prior to the onset of acute abdominal symptoms. According to the Naranjo probability scale, olanzapine was considered the probable cause of acute pancreatitis in this patient. Following a 12-day stay in the ICU, the patient was transferred to the ward where she died a few days later of unrelenting peritonitis secondary to acute pancreatitis. DISCUSSION: A literature search (1966–July 2000) and contact with the manufacturer failed to detect any published reports of acute pancreatitis associated with olanzapine. The contribution of concomitant medications taken prior to ICU admission in initiating or worsening the pancreatitis was deemed unlikely. More common causes of acute pancreatitis, such as ethanol consumption and gallstones, were also ruled out in this patient. Therefore, olanzapine was rated as a probable cause for acute pancreatitis in our patient. The mechanism of this adverse reaction is unknown.

CONCLUSIONS:

This is believed to be the first published report suspecting olanzapine, an atypical antipsychotic agent, to have caused acute hemorrhagic pancreatitis in a patient, leading to admission to the ICU and, eventually, death secondary to unrelenting peritonitis.
Pentoxifylline for Sickle-Cell Disease
Authors: Sherer Jeffrey T , Glover Pheophilus H
Published: June 2003

OBJECTIVE:

To review the use of pentoxifylline for the prevention and treatment of acute vasoocclusive episodes (VOEs) in sickle-cell disease (SCD).

DATA SOURCES:

Searches of MEDLINE (1965–April 2000), International Pharmaceutical Abstracts (1970–April 2000), and Science Citation Index Expanded (1989–April 2000) were performed using the key search terms sickle-cell disease, pentoxifylline, oxypentifylline, and Trental.

DATA SYNTHESIS:

Patients with SCD commonly suffer from painful VOEs. Pentoxifylline may be useful in this condition due to its ability to increase red blood cell deformability and inhibit platelet aggregation. Laboratory evidence, an animal model, and case reports suggest a benefit, but available clinical studies are methodologically poor, and data analysis is often inappropriate or absent. Limited data suggest that pentoxifylline is beneficial for treatment of a VOE in progress, but no data exist demonstrating a reduction in the number of VOEs with chronic pentoxifylline therapy.

CONCLUSIONS:

Documentation of the efficacy of pentoxifylline for VOE prevention and treatment of SCD is poor; further studies are needed before its routine use is recommended.
Antiretroviral Prescribing Errors in Hospitalized Patients
Authors: Purdy Bonnie D , Raymond Alesa M , Lesar Timothy S
Published: June 2003

OBJECTIVE:

To quantify error type and frequency and to identify factors associated with antiretroviral prescribing errors in hospitalized HIV-infected patients.

DESIGN:

Systematic evaluation of all medication prescribing errors involving antiretroviral medications between January 1, 1996, and October 31, 1998. Each error was concurrently evaluated for the potential to result in adverse patient consequences. Each error was retrospectively evaluated by three pharmacists and assigned a “likely related factor.”

SETTING:

A 631-bed tertiary care teaching hospital.

PARTICIPANTS:

All physicians prescribing antiretroviral medications during the study period and all staff pharmacists involved in the routine review of medication orders.

MAIN OUTCOME MEASURES:

Type and frequency of prescribing errors involving antiretroviral medications and frequency of association of likely related factors to errors.

RESULTS:

A total of 108 clinically significant prescribing errors involving antiretrovirals were detected during the 34-month study period. The most common errors were overdosing and underdosing. Overall, errors occurred in 5.8% of admitted patients prescribed antiretroviral medications. The rate of error increased from 2% of admissions in 1996 to 12% of admissions in 1998. The most common likely related factors associated with errors were confusion/lack of familiarity regarding appropriate dosing frequency (30.3%) or dosage (25.5%), and confusion due to need for multiple dosage units per dose (13%).

CONCLUSIONS:

Hospitalized patients taking antiretrovirals are at risk for adverse outcomes due to prescribing errors. This risk has increased with the rising complexity of antiretroviral drug regimens. A limited number of factors are associated with a large proportion of antiretroviral prescribing errors. This information should be considered in the development of medication error prevention strategies necessary to prevent adverse patient outcomes resulting from such errors.
Syncope Associated with Concurrent Amitriptyline and Fluconazole Therapy
Authors: Robinson Renee F , Nahata Milap C , Olshefski Randall S
Published: June 2003

OBJECTIVE:

To report on a 12-year-old white male with prostatic rhabdomyosarcoma who experienced episodes of syncope attributed to concurrent amitriptyline and fluconazole therapy, confirmed by readministration.

CASE REPORT:

The patient began experiencing syncopal episodes periodically over a seven-month period. These repeated episodes occurred when fluconazole was administered for periodic mucositis secondary to chemotherapy. The patient had received fluconazole in the past with no difficulty and had been receiving a stable dose of amitriptyline for neuropathic pain. On discontinuation of amitriptyline, no further episodes were noted.

DISCUSSION:

Concurrent administration of fluconazole with amitriptyline likely resulted in the decreased metabolism of amitriptyline. Three case reports presented in the literature of adults receiving concurrent amitriptyline and fluconazole have shown an increase in serum amitriptyline concentrations with concurrent administration of fluconazole; however, none of these patients were rechallenged. Literature available on amitriptyline overdose confirms that syncope and the adverse events noted in the case studies may result from elevated amitriptyline plasma concentrations.

CONCLUSIONS:

The consistent presentation of syncope in our patient during readministration of amitriptyline and fluconazole strongly suggests a drug—drug interaction.
Cefdinir: An Expanded-Spectrum Oral Cephalosporin
Authors: Guay David RP
Published: June 2003

OBJECTIVE:

To review the antimicrobial activity, pharmacokinetics, clinical efficacy, and tolerability of cefdinir, an expanded-spectrum oral cephalosporin.

DATA SOURCES:

Literature was identified by a MEDLINE search (January 1983–November 1999) of the medical literature, review of English-language literature and bibliographies of these articles, and product information.

STUDY SELECTION:

Clinical efficacy data were selected from all published trials mentioning cefdinir. Additional information concerning in vitro susceptibility, safety, chemistry, and pharmacokinetic profile of cefdinir was also reviewed.

DATA SYNTHESIS:

Cefdinir, an oral expanded-spectrum cephalosporin, has a broad spectrum of activity against many gram-negative and -positive aerobic organisms, including Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis. Cefdinir is stable to hydrolysis by many common β-lactamases. Cefdinir is rapidly absorbed from the gastrointestinal tract and is primarily eliminated via renal clearance of unchanged drug. The terminal disposition half-life of cefdinir is approximately 1.5 hours. Efficacy has been demonstrated in a number of clinical trials in adults and children with upper and lower respiratory tract infections (e.g., pharyngitis, sinusitis, acute otitis media, acute bronchitis, acute exacerbation of chronic bronchitis, community-acquired pneumonia) and skin and skin-structure infections. The adverse event profile is similar to that of comparator agents.

CONCLUSIONS:

Cefdinir is a second-line alternative to first-line antimicrobial agents, with convenient once- or twice-daily dosing in the treatment of upper and lower respiratory tract infections and skin and skin-structure infections. Similar to other oral expanded-spectrum cephalosporins, cefdinir has activity against common pathogens of the respiratory tract and skin and is stable in the presence of many β-lactamases. The clinical choice of an oral expanded-spectrum cephalosporin will be based on patient acceptance, frequency of administration, and cost.
Cilostazol: Treatment of Intermittent Claudication
Authors: Reilly Muredach P , Mohler Emile R
Published: June 2003

OBJECTIVE:

To review the pharmacology and clinical utility of cilostazol, an antiplatelet and vasodilator agent approved for the management of intermittent claudication.

DATA SOURCES:

Primary literature on cilostazol was identified from a comprehensive MEDLINE literature search (1980–February 2000). Selected meeting abstracts and manufacturer literature were also used as source material. Indexing terms included cilostazol, intermittent claudication, platelet inhibitors, and restenosis.

STUDY SELECTION:

Human clinical, pharmacokinetic and randomized comparative trials performed in the US and Asia were reviewed. Selected in vitro, ex vivo, and animal studies were evaluated when human data were not available.

DATA SYNTHESIS:

Intermittent claudication, defined as reproducible discomfort of a muscle group induced by exercise and relieved by rest, is the most common clinical manifestation of peripheral arterial disease (PAD). Cilostazol, a specific inhibitor of cyclic adenosine monophosphate phosphodiesterase in platelets and vascular smooth-muscle cells, is a potent antiplatelet agent and vasodilator that reduces vascular proliferation and has lipid-lowering effects in vivo. Recent multicenter, randomized, placebo-controlled trials have led to approval of cilostazol by the Food and Drug Administration for relief of intermittent claudication in patients with stable PAD. Cilostazol doubled walking distances and improved quality of life compared with placebo in these studies. One trial found that cilostazol was more effective than pentoxifylline, the only alternative pharmacologic therapy for claudication. Although frequent (∼50%) minor adverse effects, including headache, diarrhea, and palpitations, may occur in clinical practice, cilostazol has not been associated with major adverse events or increased mortality. Small, nonblind studies suggest that cilostazol may prove useful in preventing thrombosis and restenosis following percutaneous coronary interventions, although these remain unlabeled uses.

CONCLUSIONS:

The unique combination of antiplatelet, vasodilatory, and antiproliferative effects of cilostazol appear to make it an attractive agent for use in patients with PAD. Clinical trials demonstrating a significant improvement in walking distances with cilostazol therapy suggest that it will be an important tool in improving symptoms and quality of life in patients with intermittent claudication.
Computerized System for Outcomes-Based Antiemetic Therapy in Children
Authors: Holdsworth Mark T , Adams Val R , Raisch Dennis W , Wood Jim G , Winter Stuart S
Published: June 2003

OBJECTIVE:

To introduce a computerized data collection system used for an outcomes-based approach to antiemetic therapy in children, and to present data collected with this system in support of a new antiemetic dosing regimen.

METHODS:

A validated nausea/vomiting survey was used to collect data on nausea severity (NSEV), vomiting severity (VSEV), daily activity interference (DAI), and the number of vomiting episodes. NSEV, VSEV, and DAI were rated as 0 = none to 3 = severe. All children and/or their parents were surveyed following the completion of each highly emetogenic chemotherapy regimen. This survey was computerized and transferred to a handheld data entry unit. Time and motion studies were performed to compare the time required to collect nausea/vomiting data and transfer the data to a computerized database with the handheld system versus traditional paper (manual) surveys. The handheld technology was used to collect survey data for children receiving a new antiemetic regimen (daily ondansetron and dexamethasone [OD]), which was then compared with data obtained with a previously employed regimen (thrice-daily ondansetron and daily methylprednisolone [OM]). Statistical analysis and a cost-effectiveness analysis (CEA) were performed to compare the two antiemetic regimens.

RESULTS:

The mean time required for total data entry with the manual system was 5.2 minutes per survey versus 2.4 minutes with the handheld technology (p = 0.0026). A total of 376 nausea/vomiting surveys in 78 children receiving the OM antiemetic regimen were compared with 153 surveys in 38 children treated with the OD regimen. The mean survey scores were as follows: NSEV (1.2 vs. 0.8), VSEV (1.0 vs. 0.7), DAI (1.0 vs. 0.7), and number of vomiting episodes (4.3 vs. 2.1) for OM and OD, respectively; all were significantly lower with the OD regimen (p < 0.05). The percentage of patients with complete control of nausea and vomiting (19.2% vs. 39.2%) and good control (55.6% vs. 65.4%) were significantly greater with the OD regimen (p < 0.05). The CEA revealed that the OD resulted in a reduction of approximately $31 per patient for good protection and a $258 reduction for complete protection from nausea and vomiting.

CONCLUSIONS:

A computerized outcomes-based system aided by handheld technology allowed for more prompt and efficient collection of nausea/vomiting data. The OD antiemetic regimen was shown to be a more cost-effective alternative for children receiving severely emetogenic chemotherapy.
Role of Antimicrobial Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Russo René L , D'Aprile Michelle
Published: June 2003

OBJECTIVE:

To define the role of antimicrobial therapy in the treatment of acute bronchitic exacerbations of chronic obstructive pulmonary disease (COPD) through review of placebo-controlled clinical trials. Specifically, to determine the benefit of antimicrobial therapy on patient outcome.

DATA SOURCES:

Placebo-controlled clinical trials identified by MEDLINE search (1957–December 1999).

STUDY SELECTION AND DATA EXTRACTION:

All placebo-controlled clinical trials that included COPD patients with no evidence of pneumonia or underlying asthma were included in the evaluation.

DATA SYNTHESIS:

The role of antimicrobial agents in the treatment of acute exacerbations of COPD is controversial. Patients with COPD are often chronically colonized with bacteria, and many exacerbations are due to nonbacterial causes. Four placebo-controlled clinical trials and a meta-analysis have demonstrated significant improvements in outcome for patients treated with an antibiotic versus placebo. In contrast, six studies failed to demonstrate statistical differences, possibly due to the small sample size and the subjectivity of outcome measures. Overall, the data suggest that the benefit of antimicrobial therapy in acute exacerbations of COPD may be related to exacerbation severity.

CONCLUSIONS:

Antimicrobial agents may have a beneficial effect in the treatment of acute exacerbations of COPD in certain patients. Pending further research in this area, we recommend antimicrobial therapy only for COPD patients with acute bronchitic exacerbations characterized by increased dyspnea, sputum volume, and purulence.
Orlistat — A Novel Weight Loss Therapy
Authors: Lucas Kristy H , Kaplan-Machlis Barbara
Published: June 2003

OBJECTIVE:

To review the pharmacology, pharmacokinetics, clinical safety and efficacy, drug interactions, and therapeutic issues related to the use of orlistat for treatment of obesity.

DATA SOURCES:

English-language articles were identified from MEDLINE (1966–July 2000), Roche Laboratories, organizational guidelines, National Institutes of Health and Food and Drug Administration Web sites, and Doctor's Guide online. Key words included obesity, orlistat, and lipase inhibitors. References were also identified from reference sections of published articles.

STUDY SELECTION AND DATA EXTRACTION:

Prospective, randomized, double-blind, placebo-controlled, human trials were selected for review and discussion.

DATA SYNTHESIS:

Orlistat is the first agent in the lipase inhibitor class of antiobesity drugs. Orlistat is minimally absorbed and has been shown to reduce body weight by inhibiting absorption (by ∼30%) of ingested dietary fat. Safety and efficacy have been established in one- and two-year double-blind, placebo-controlled trials; adverse effects were primarily, and almost exclusively, gastrointestinal. Due to its ability to block fat absorption, orlistat also has the capability to inhibit absorption of fat-soluble vitamins. Therefore, a daily multiple vitamin is recommended while taking orlistat.

CONCLUSIONS:

By inhibiting fat absorption, orlistat offers a new treatment modality for weight loss and maintenance. Preliminary data from clinical trials suggest that orlistat may be beneficial in patients with comorbid conditions related to obesity, such as diabetes and hyperlipidemia. However, further studies during postmarketing surveillance are needed to fully establish orlistat's long-term benefits and safety. Orlistat should be considered a useful adjunctive therapy for weight loss and maintenance in obese patients (i.e., body mass index ≥30 kg/m2 or ≥27 kg/m2 if other risk factors are present) committed to lifestyle changes including diet, exercise, and behavioral modification.
Vitamin C in the Prevention of Nitrate Tolerance
Authors: Daniel Tamara A , Nawarskas James J
Published: June 2003

OBJECTIVE:

To evaluate the efficacy of vitamin C in preventing the development of nitrate tolerance. DATA SOURCES: A MEDLINE search (from 1966 to July 2000) was conducted to identify relevant articles, with additional references obtained from the bibliographies of these articles. DATA SYNTHESIS: One possible mechanism of nitrate tolerance involves superoxide-induced deactivation of nitric oxide, providing the rationale for the use of antioxidants. Most published research concerning deactivation of nitric oxide has involved vitamin C; a summary of this information is presented here.

CONCLUSIONS:

Preliminary studies seem to support the role of vitamin C in attenuating the development of nitrate tolerance. Considering these findings, larger, long-term trials are necessary to further establish the role of vitamin C in this situation.