bluuebunny/crossref_metadata_2025_split huggingface dataset:
Niacin-ER and Lovastatin Treatment of Hypercholesterolemia and Mixed Dyslipidemia
Authors: Yim Barbara T , Chong Pang H 
Published: June 2003

OBJECTIVE To review the currently available information on the once-daily combination of niacin extended-release (ER)/lovastatin in the treatment of patients with hypercholesterolemia and mixed dyslipidemia at high risk for cardiovascular events. DATA SOURCES MEDLINE (1966–July 2002) was searched for primary and review articles. Data from the manufacturer were also included. STUDY SELECTION/DATA EXTRACTION All articles and product labeling deemed relevant to the combination of niacin and statins (i.e., lovastatin) were included for review. English-language studies selected for inclusion were limited to those with human subjects. DATA SYNTHESIS The Food and Drug Administration approved a new fixed-dose combination of niacin-ER/lovastatin, which is administered once daily. The efficacy and safety of the combined agent have been proven to be similar to either component used alone or in combination for management of hyperlipidemia and mixed dyslipidemia. CONCLUSIONS Elevated low-density lipoprotein cholesterol (LDL-C) is independently associated with a higher risk for cardiovascular events. Lowering of elevated LDL-C concentrations with statin monotherapy may be insufficient in patients at high risk for cardiovascular events. In fact, consideration of elevated triglycerides (TGs) and/or low concentrations of high-density lipoprotein cholesterol (HDL-C) in patients with elevated LDL-C places them at greater risk. The addition of niacin may enhance or improve the lipid profile of those who require a further decrease of TGs and/or increase of HDL-C even after stable statin therapy. Niacin-ER offers efficacy similar to that of immediate-release niacin, but minimal myopathy and hepatotoxicity (compared with sustained-release niacin). Although no clinical outcomes are available, current evidence shows that the combination product offers adequate lowering of LDL-C and TGs and increasing HDL-C. The data suggest that therapy with the niacin-ER and lovastatin combination product is safe and does not increase the incidence of adverse effects. THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-03-003-H01
Fluoroquinolone Treatment of Community-Acquired Pneumonia: A Meta-Analysis
Authors: Salkind Alan R , Cuddy Paul G , Foxworth John W 
Published: June 2003

OBJECTIVE: To determine the role of newer fluoroquinolones (FQs) for adults with community-acquired pneumonia (CAP) whose level of illness allows treatment with an oral antibiotic. METHODS: Meta-analysis of randomized controlled trials comparing a macrolide, β-lactam, or doxycycline antibiotic with a newer oral FQ for the treatment of CAP. RESULTS: Patients (5118), most of whom were <60 years of age and free of coexisting diseases, were enrolled in 13 studies comparing an oral macrolide or β-lactam antibiotic with an FQ for the treatment of CAP. No previous study compared doxycycline with an FQ. In the intention-to-treat (ITT) population, no trial demonstrated significant differences between FQs or alternative therapies. Summary estimates showed a statistically significant advantage in favor of the FQs in both the ITT (OR 1.22; 95% CI 1.02 to 1.47; p = 0.03) and evaluable populations (OR 1.37; 95% CI 1.11 to 1.68; p = 0.003). The number needed to treat for an FQ advantage was 33 (95% CI 17 to 362) in the ITT population and 37 (95% CI 22 to 121) in the evaluable population. Treatment failures represented slow symptom resolution; no deaths were reported. CONCLUSIONS: The newer oral FQs showed modest therapeutic benefit compared with the studied alternative antibiotics in adults with CAP. Based on the number needed to treat from the ITT population as a measure of treatment effect, clinicians must decide whether treating 33 patients with an FQ to prevent a single therapeutic failure with another studied antibiotic warrants use of an agent from that class for an illness with a generally favorable outcome regardless of antibiotic selection, and at a time when FQ resistance may be increasing.
Fluorouracil for Allergic Reactions to Capecitabine
Authors: Liu Chin Y 
Published: June 2003

OBJECTIVE: To report the safe use of fluorouracil in a patient with breast cancer who had allergic reactions to capecitabine. CASE SUMMARY: A 42-year-old African American woman with metastatic breast cancer developed progressive disease. Capecitabine 1500 mg taken by mouth twice daily was prescribed as the salvage chemotherapy. She developed a generalized rash and itching, sore throat, and dizziness approximately 4 hours after the first dose of capecitabine. These reactions recurred immediately after the second dose. Capecitabine was discontinued and the allergic reactions resolved after the woman took diphenhydramine for 1 week. In view of limited therapeutic options for her progressive disease, a trial of fluorouracil 300 mg/m2/d continuous intravenous infusion over 5 days was initiated without any premedications. She did not experience any reactions. The dose of fluorouracil in the second cycle was increased to 400 mg/m2/d continuous infusion over 5 days. DISCUSSION: Capecitabine is not intrinsically cytotoxic, but is converted to fluorouracil in tumor tissues via a 3-step enzymatic pathway. Capecitabine reaches peak blood concentrations in about 1.5 hours, with peak fluorouracil concentrations occurring at 2 hours. The elimination half-life of both drugs is 0.5–0.7 hours. The patient tolerated the rechallenge with fluorouracil without complications. Objective causality assessment revealed that the adverse event was probably drug induced. It was postulated that the allergic reaction was most likely caused by capecitabine or the intermediate metabolites based on the immediate reappearance of symptoms from the rechallenge, pharmacokinetic data, and well-tolerance of fluorouracil. CONCLUSIONS: The use of fluorouracil treatment with careful monitoring can be considered in a patient with mild allergic reactions to capecitabine.
Fulminant Liver Failure Associated with Clarithromycin
Authors: Tietz Andreas , Heim Markus H , Eriksson Urs , Marsch Stephan , Terracciano Luigi , Krähenbühl Stephan 
Published: June 2003

OBJECTIVE To report a patient developing fulminant liver failure while being treated with clarithromycin for pneumonia. CASE SUMMARY A 58-year-old white woman developed fulminant liver failure while being treated with the macrolide antibiotic clarithromycin for pneumonia. Comedication included N-acetylcysteine, atenolol, and isradipine. Other causes of liver failure, such as viral hepatitis, autoimmune hepatitis, toxins, and heart failure, were excluded by appropriate diagnostic means. All drugs were stopped, and the patient was transferred to another hospital for liver transplantation. She recovered spontaneously within several days, making transplantation unnecessary. A liver biopsy obtained 10 days after the initial presentation revealed centroacinar necrosis and beginning fibrous reorganization, compatible with recent centroacinar damage. DISCUSSION Since no other cause could be identified, liver injury was considered to be drug related. Fulminant liver failure has not previously been described with concomitant use of atenolol and N-acetylcysteine. Although isradipine has been associated with hepatocellular injury, there are no reports of fulminant liver failure with this agent, and our patient had been treated for >2 years without signs of toxicity. The most likely cause of liver failure in this patient was, therefore, clarithromycin, which undergoes hepatic metabolism and has been reported to cause fulminant hepatic failure. A second possibility is an interaction between clarithromycin and isradipine, potentially increasing the hepatic toxicity of isradipine. CONCLUSIONS Clarithromycin may be a cause of fulminant liver failure either alone or by inhibiting the metabolism of other drugs.
Safety of Selegiline with Cold Medications
Authors: Jacob Jeena E , Wagner Mary L , Sage Jacob I 
Published: June 2003

OBJECTIVE: To evaluate the safety of the coadministration of selegiline with cold medications. DATA SOURCES: Clinical literature accessed through MEDLINE(1965–September 2002), IPA database, and Drug-Reax System. The following search terms were used: selegiline, pseudoephedrine, dextromethorphan, MAOI, and drug interactions. Somerset Pharmaceuticals, the marketers of Eldepryl (selegiline HCI), were also contacted. DATA SYNTHESIS: Despite a warning against its concomitant use with pseudoephedrine and dextromethorphan, interactions with selegiline have not been reported. However, there have been reports of patients experiencing adverse events with related agents. CONCLUSIONS: Patients taking selegiline should try to avoid pseudoephedrine and dextromethorphan or use drugs without interaction potential. If selegiline is used with these medications, watch for adverse events or replace selegiline with another drug.
Lactic Acidemia Associated with Metformin
Authors: Khan Jamshed K , Pallaki Muralidhar , Tolbert Sandra R , Hornick Thomas R 
Published: June 2003

OBJECTIVE To report 2 cases of lactic acidemia associated with the use of metformin in patients with normal renal function. CASE SUMMARY An 82-year-old African American man and a 76-year-old white man developed an elevated serum lactic acid concentration a few weeks after initiation of metformin therapy for type 2 diabetes. After the patients discontinued metformin, the serum lactic acid concentration normalized in both cases. An objective causality assessment revealed that the adverse drug event was probably related to the use of metformin. DISCUSSION Metformin interferes with the production and elimination of lactic acid by a variety of mechanisms that are not well understood. Few systematic data are available on changes in plasma lactic acid concentrations in patients with type 2 diabetes and normal renal function. Clinical significance of a high serum lactic acid concentration needs clarification. CONCLUSIONS Metformin therapy can be associated with subclinical elevation of lactic acid concentration in the absence of renal insufficiency or other contraindications to using this agent in patients with type 2 diabetes. Periodic monitoring of basic metabolic panels may prevent this potentially serious complication of metformin therapy.
Adverse Reaction to a Dietary Supplement in an Elderly Patient
Authors: Sleeper Rebecca B , Kennedy Shalyn M 
Published: June 2003

OBJECTIVE To describe the case of an elderly patient who experienced hepatic enzyme elevations and symptoms of hepatitis associated with the administration of a dietary supplement. CASE SUMMARY A 92-year-old white woman with no history of hepatic disease developed jaundice and increased confusion associated with increased hepatic enzymes. The hepatitis panel, abdominal ultrasound, and antinuclear antibody screen indicated no abnormalities. A drug regimen review revealed that the patient was receiving a dietary supplement, Nutrilite Double X Multivitamin–Multimineral. Following discontinuation of the supplement, the patient's symptoms resolved and the hepatic enzymes decreased or returned to the reference range at evaluations occurring 1 week and 1 month after intervention. An objective causality assessment revealed this to be a probable adverse drug event. DISCUSSION While the association of certain herbal preparations with hepatotoxicity has been demonstrated, the potential for this adverse effect is easily overlooked. In this patient, infectious or autoimmune causes of acute hepatitis were ruled out, and drug-induced causes were considered. The resolution of symptoms and laboratory values following discontinuation of the supplement support a relationship between the dietary supplement and this episode of hepatitis. CONCLUSIONS Our case indicates that there was a probable relationship between the dietary supplement Nutrilite Double X Multivitamin–Multimineral and the development of acute hepatitis. Due to the multiingredient formulation of the product, as well as lack of data describing manufacturing procedures, it is difficult to determine which component may be associated with this effect. Over-the-counter supplements should be considered as a part of the differential diagnosis in patients presenting with increased liver enzymes and related symptoms.
Olmesartan Medoxomil: The Seventh Angiotensin Receptor Antagonist
Authors: Gardner Stephanie F , Franks Amy M 
Published: June 2003

OBJECTIVE To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of olmesartan medoxomil, an angiotensin II receptor antagonist for the treatment of hypertension. DATA SOURCES Information was obtained from MEDLINE searches (1996–April 2002) of English-language medical literature. Search terms included CS-866, olmesartan, olmesartan medoxomil, RNH-6270 (active metabolite of olmesartan), Benicar, angiotensin receptors, and antihypertensive agents. In addition, references from relevant articles were reviewed for additional citations. The authors independently reviewed literature identified in the searches. Studies evaluating olmesartan (i.e., abstracts, clinical trials, data on file with manufacturer) were considered for inclusion. STUDY SELECTION All articles identified from data sources with pertinent information regarding olmesartan medoxomil were evaluated, and all information deemed relevant was included in this review. DATA SYNTHESIS Olmesartan medoxomil is a competitively priced addition to the class of angiotensin II receptor antagonists. Monotherapy with olmesartan medoxomil in once-daily doses of 20–40 mg has produced significant reductions in systolic and diastolic blood pressure in hypertensive patients. Adverse effects have been minimal with olmesartan medoxomil, with dizziness being the only adverse effect occurring more often than with placebo in clinical trials. Additionally, animal studies indicate that olmesartan medoxomil may prove to be useful treatment for diabetic nephropathy, as well as atherosclerosis. CONCLUSIONS Olmesartan medoxomil has a favorable safety and efficacy profile, with blood pressure–lowering effects comparable to those of other angiotensin receptor blockers (i.e., losartan, valsartan, irbesartan). At this time, formulary decisions will be driven primarily by economic issues. Theoretical benefits of olmesartan medoxomil in reducing atherogenesis and lowering angiotensin II concentrations better than the alternative agents will be determined only with more extensive research. THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-03-002-H01
Aztreonam Treatment of Pasteurella Multocida Cellulitis and Bacteremia
Authors: Winner Jamie S , Gentry Chris A , Machado Linda J , Cornea Paul 
Published: June 2003

OBJECTIVE: To report a case of Pasteurella multocida cellulitis and bacteremia treated successfully with aztreonam. CASE SUMMARY: An 81-year-old white man with multiple antibiotic allergies was admitted with severe cellulitis of the left arm and bacteremia due to P. multocida. The patient was treated for 14 days with aztreonam and had complete resolution of the infection. DISCUSSION: To our knowledge, this is the first published case describing successful treatment of P. multocida cellulitis and bacteremia with aztreonam. Antimicrobials recommended for use in P. multocida infections include penicillin, ampicillin, amoxicillin, second- and third-generation cephalosporins, tetracyclines, fluoroquinolones, and trimethoprim/sulfamethoxazole. There is very little information in the current literature regarding the activity of aztreonam toward P. multocida. CONCLUSIONS: This case demonstrates the potential use of aztreonam for P. multocida cellulitis and bacteremia in those instances where antibiotics of choice cannot be given.
Warfarin and Amoxicillin/Clavulanate Drug Interaction
Authors: Davydov Liya , Yermolnik Marina , Cuni Lewis J 
Published: June 2003

OBJECTIVE: To report a case of warfarin–amoxicillin/clavulanate potassium (AM/CL) interaction resulting in an elevated international normalized ratio (INR) and hematuria. CASE SUMMARY: A 58-year-old Hawaiian/Asian/European woman developed an elevated INR and microscopic hematuria as a result of a drug–drug interaction between warfarin and AM/CL. DISCUSSION: Our report of an increased INR with bleeding complications as a result of an interaction between warfarin and AM/CL is consistent with those in the literature. Although the mechanism for this interaction is not fully known, it is suspected that a decrease in vitamin K–producing gut flora with resulting vitamin K deficiency would be the most likely contributing factor. An objective causality assessment revealed that this adverse drug event as a result of the warfarin and AM/CL interaction was possible. CONCLUSIONS: An increased INR secondary to warfarin interactions with various antibacterial agents is a known phenomenon. An increased awareness of warfarin–AM/CL interaction and appropriate monitoring are essential to control the INR levels and prevent bleeding complications.
Intrapleural Alteplase in a Patient with Complicated Pleural Effusion
Authors: Walker Charlotte A , Shirk Mary Beth , Tschampel Marva M , Visconti James A 
Published: June 2003

OBJECTIVE: To report the intrapleural use of alteplase in a patient diagnosed with complicated pleural effusion (CPE). CASE SUMMARY: A 62-year-old white woman admitted with respiratory distress and hypotension developed a right-sided multi-loculated pleural effusion. Thoracentesis and chest tube drainage were not successful in resolving the effusion. In an attempt to increase the drainage of the pleural effusion, alteplase 16 mg was administered into the pleural cavity via the chest tube on 6 consecutive days. As a result, the volume drained from the patient's chest tube increased, there was improvement on the chest X-ray, and she did not require surgical intervention. DISCUSSION: While streptokinase and urokinase have been shown to be useful adjuncts to chest tube drainage in the treatment of complicated pleural effusion and empyema, there have been no reports on the use of intrapleural alteplase. This report demonstrates that intrapleural administration of alteplase is a useful adjunct to tube drainage in resolving CPE. CONCLUSIONS: This patient's CPE resolved when intrapleural alteplase was used as an adjunct to chest tube drainage and antibiotics. Controlled trials need to be conducted to investigate fully the efficacy, dosing, and safety of intrapleural alteplase in the treatment of patients with CPE and empyema.
Hemodynamic and Electrocardiographic Effects of Short-Term Ginkgo Biloba
Authors: Kalus James S , Piotrowski Alexandria A , Fortier Christopher R , Liu Xinhcun , Kluger Jeffrey , White C Michael 
Published: June 2003

OBJECTIVE: To evaluate the immediate and short-term hemodynamic and electrocardiographic effects of Ginkgo biloba (ginkgo). METHODS: Healthy volunteers were randomized to receive ginkgo 120 mg or placebo twice daily for 7 days in this prospective, double blind trial. After at least a 7-day washout period, subjects were crossed over to an additional 7 days of alternate therapy. Blood pressure, heart rate, and 12-lead electrocardiograms were evaluated immediately before (baseline), and at 1, 3, and 5 hours after observed ingestion of study drug on days 1 and 7 of therapy. Electrocardiographic parameters (P wave and QRS complex duration; PR, QT, and QTc intervals) were measured in lead II by a blinded investigator. RESULTS: Ginkgo had no effect on any of the evaluated electrocardiographic parameters at any time point on days 1 or 7. Additionally, no changes in heart rate or systolic and diastolic blood pressure were found between the groups at any time point on any evaluative day. CONCLUSIONS: Commonly used doses of Ginkgo biloba do not have any immediate or short-term effects on blood pressure, heart rate, or electrocardiographic variables in young, healthy volunteers.
Bosentan for the Treatment of Pulmonary Arterial Hypertension
Authors: Kenyon Kenneth W , Nappi Jean M 
Published: June 2003

OBJECTIVE: To describe the pharmacology, pharmacokinetics, efficacy, and safety of bosentan in the treatment of pulmonary arterial hypertension (PAH). DATA SOURCES: A MEDLINE and Current Contents search (1966–June 2002) of the English-language literature was conducted to identify published dose-ranging, pharmacokinetic, pivotal efficacy trials and review articles of bosentan and endothelin antagonists. Additional references were identified from the bibliographies of the retrieved articles. DATA SYNTHESIS: Bosentan is the first orally active, nonpeptide endothelin receptor antagonist approved by the Food and Drug Administration for use in patients with World Health Organization (WHO) functional class III and IV PAH. Titrated to a dose of 125 mg twice daily, bosentan produces pulmonary vasodilation, improving cardiopulmonary hemodynamics leading to better outcomes for patients. It is metabolized primarily by the hepatic system via the cytochrome P450 enzyme pathway and eliminated by biliary excretion. Bosentan is an inducer of the isoenzymes CYP3A4 and 2C9. It possesses a unique pharmacokinetic profile with a terminal elimination half-life of approximately 5 hours, yet steady-state plasma concentrations are not achieved for 3–5 days as a result of enhanced drug clearance and autoinduction following multiple daily dosing. The major adverse effects of bosentan are the potential for birth defects and hepatotoxicity. CONCLUSIONS: The use of bosentan in patients with WHO functional class III and IV PAH is associated with improved exercise tolerance, cardiopulmonary hemodynamics, and increased time to clinical worsening when compared with placebo. It offers significant advantage in ease of administration and quality of life compared with epoprostenol therapy, with similar efficacy.
Voriconazole: A New Triazole Antifungal Agent
Authors: Pearson Margaret M , Rogers P David , Cleary John D , Chapman Stanley W 
Published: June 2003

OBJECTIVE: To review the pharmacology, in vitro susceptibility, pharmacokinetics, clinical efficacy, and adverse effects of voriconazole, a triazole antifungal agent. DATA SOURCES: A MEDLINE search, restricted to English language, was conducted from 1990 to June 2002. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 1996 to 2001 and manufacturer information available through the Food and Drug Administration's Web site. DATA EXTRACTION: All published and unpublished trials and abstracts citing voriconazole were selected. DATA SYNTHESIS: Voriconazole has shown in vitro activity against many yeasts and a variety of mold and dermatophyte isolates. Voriconazole can be administered either orally or parenterally. It exhibits good oral bioavailability, wide tissue distribution including distribution into the central nervous system, and hepatic metabolism. Drug interactions occur through inhibition of the CYP2C9, CYP2C19, and CYP3A4 isoenzymes, resulting in alterations in kinetic parameters of either voriconazole or the interacting agent. Efficacy has been illustrated in open, noncomparative studies of aspergillosis in immunocompromised patients. Human case reports describe successful treatment of rare fungal pathogens. The most commonly reported adverse events include visual disturbances and elevations in liver function tests. CONCLUSIONS: Voriconazole is at least as effective as amphotericin B in the treatment of acute invasive aspergillosis in immunocompromised patients. It has similar efficacy as fluconazole in treatment of esophageal candidiasis. Voriconazole did not achieve statistical non-inferiority to liposomal amphotericin B for empirical therapy in patients with neutropenia and persistent fever, diminishing enthusiasm for use in this indication until additional trials are completed. Based on case reports and in vitro efficacy, voriconazole may prove to be a clinically useful agent in the treatment of other fungal disease.