warfarin and Fatigue

Belinostat is a potent small molecule inhibitor that exerts its antitumor effect through inhibition of histone deacetylase. The purpose of this study was to evaluate the pharmacokinetics and pharmacodynamics of warfarin (as a reference drug metabolized by CYP2C9) in the presence and absence of belinostat.. We conducted a phase I, single-center, open-label, drug-drug interaction study between belinostat and warfarin. In part I, patients were given warfarin 5 mg orally (day-14 and 3) and belinostat 1000 mg/m(2) (days 1 through 5). Patients receiving benefit continued belinostat on days 1 through 5 every 21 days until disease progression, unacceptable toxicity, or per patient preference.. A total of 18 patients were treated. With belinostat, the least-squared means for maximum concentration (C max), area under the curve0-∞, and area under the curve0-t of R-warfarin were slightly increased. However, for the more potent S-warfarin isomer, the same parameters were primarily contained within the pre-specified equivalence limits of 0.80 and 1.25, indicating there was no statistically significant interaction between S-warfarin and belinostat. The most common adverse events were nausea, vomiting, and fatigue. Three grade 3 adverse events (diarrhea 5.6 %, nausea 5.6 %, and vomiting 5.6 %) were thought to be treatment related. Progression-free survival ranged from 0.2 to 13.8 months in all patients.. Belinostat did not significantly affect the pharmacokinetics and pharmacodynamics of warfarin, indicating no clinically relevant effect on the enzymatic activity of CYP2C9.

Topics: Adult; Aged; Anticoagulants; Area Under Curve; Cytochrome P-450 CYP2C9; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Interactions; Fatigue; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Middle Aged; Neoplasms; Sulfonamides; Treatment Outcome; Vomiting; Warfarin

Some patients develop fatigue while taking warfarin, but causality is uncertain.. To assess whether warfarin use is associated with fatigue.. This investigation was a substudy of a randomized double-blind trial in 13 outpatient thromboembolism clinics. Subjects who had received one month of open-label warfarin therapy for venous thromboembolism due to a transient risk factor were randomly assigned to receive warfarin or placebo for 2 months and followed for another 9 months after stopping the study drug. Fatigue was measured using a Likert scale, and change of fatigue was measured by the patient's global rating.. In 87 subjects, the overall ratings of fatigue were 0.1 unit lower (95% CI 0.6 units lower to 0.4 units higher) while taking warfarin. Global rating for change in fatigue intensity showed no increase of fatigue with warfarin use.. The short-term use of warfarin was not associated with symptoms of fatigue.

Topics: Analysis of Variance; Double-Blind Method; Fatigue; Female; Humans; Male; Middle Aged; Venous Thrombosis; Warfarin

Central venous catheter-associated bacteraemia caused by Nocardia species is very rare; the diagnosis of nocardiosis in patients with cancer is challenging because its clinical presentation is varied, sometimes mimicking metastases, and the high index of clinical suspicion is required for prompt institution of therapy. Herein, we report a case of nocardial sepsis with native aortic valve endocarditis in a patient with breast cancer in whom multidisciplinary team involvement and prompt initiation of therapy have led to successful outcome.

Topics: Amikacin; Anti-Bacterial Agents; Anticoagulants; Aortic Valve; Breast Neoplasms; Central Venous Catheters; Clopidogrel; Cough; Endocarditis, Bacterial; Fatigue; Female; Headache; Heart Valve Prosthesis Implantation; Humans; Meropenem; Middle Aged; Nocardia; Nocardia Infections; Platelet Aggregation Inhibitors; Radiography, Thoracic; Sepsis; Treatment Outcome; Warfarin

Topics: Anemia, Hemolytic; Antibodies, Monoclonal, Humanized; Diagnosis, Differential; Fatigue; Female; Headache; Hematologic Agents; Hemoglobinuria, Paroxysmal; Hemolysis; Humans; Middle Aged; Patient Care Management; Thrombosis; Warfarin

An 85-year-old man with persistent atrial flutter (AFL) with slow ventricular rate of 44/min, causing fatigue and presyncope, was referred for urgent treatment. In spite of thromboembolic risk scale value 4, he had not been treated with anticoagulants because of high risk of bleeding. The decision was made to perform urgent catheter ablation to interrupt and cure AFL. Intracardiac echocardiography probe was placed in the pulmonary artery and visualized left atrial appendage free from thrombus with its proper function. Heparin was administered and AFL stopped during energy application. Intracardiac echocardiography showed immediate thrombus formation in left atrial appendage owing to complete atrial standstill and no retrograde conduction during hemodynamically effective escape nodal rhythm. This case report shows that in patients with sinus node disease effective ablation of AFL with escape rhythm without retrograde conduction to the atria may result in complete 'electrically induced' atrial standstill and immediate thrombus formation.

Topics: Aged, 80 and over; Anticoagulants; Atrial Flutter; Brugada Syndrome; Cardiac Conduction System Disease; Cardiomyopathies; Catheter Ablation; Echocardiography, Transesophageal; Fatigue; Genetic Diseases, Inborn; Heart Atria; Heart Block; Heart Ventricles; Heparin, Low-Molecular-Weight; Humans; Male; Syncope; Thrombosis; Warfarin

The cytochrome P450 enzyme CYP2C9 metabolizes several important drugs, such as warfarin and oral antidiabetic drugs. The enzyme is polymorphic, and all known alleles, for example, CYP2C9*2 and*3, give decreased activity. Ultra-high activity of the enzyme has not yet been reported.. We present a patient with Behçet's disease who required treatment with high doses of phenytoin. When fluconazole, a potent inhibitor of CYP2C9, was added to the treatment regimen, the patient developed ataxia, tremor, fatigue, slurred speech and somnolence, indicating phenytoin intoxication. On suspicion of ultra-high activity of CYP2C9, a phenotyping test for CYP2C9 with losartan was performed.. The patient was shown to have a higher activity of CYP2C9 than any of the 190 healthy Swedish Caucasians used as controls.. Our finding of an ultrarapid metabolism of losartan and phenytoin may apply to other CYP2C9 substrates, where inhibition of CYP2C9 may cause severe adverse drug reactions.

Topics: Alleles; Angiotensin II Type 1 Receptor Blockers; Anticonvulsants; Aryl Hydrocarbon Hydroxylases; Ataxia; Behcet Syndrome; Case-Control Studies; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Disorders of Excessive Somnolence; Dose-Response Relationship, Drug; Fatigue; Female; Fluconazole; Humans; Losartan; Middle Aged; Pharmaceutical Preparations; Phenotype; Phenytoin; Polymorphism, Genetic; Speech Intelligibility; Warfarin

Pulmonary arterial hypertension (PAH) remains a debilitating and life-threatening disease despite improvements in hemodynamics, exercise capacity and survival with recent therapeutic advances. Health-related quality of life (HRQOL) has, therefore, been proposed as an important outcome for evaluating care. Relatively little, however, is known regarding HRQOL or its determinants in PAH. The Minnesota Living with Heart Failure questionnaire was recently adapted and validated for HRQOL measurement in PAH. We applied this pulmonary hypertension-specific version (MLHF-PH) to a larger population of PAH patients.. Ninety-three consecutive outpatients with PAH completed the MLHF-PH. Scores were assessed for correlations with demographics, symptoms, hemodynamics and treatments.. Patients with PAH had significantly impaired HRQOL as assessed by the disease-specific MLHF-PH. Each physical and emotional component, as well as total scores on the MLHF-PH indicated severely depressed HRQOL. As compared to other diagnoses, PAH associated with scleroderma had the worst HRQOL. Patients with WHO functional Class II symptoms reported better HRQOL than Class III patients. Fatigue, weakness and abdominal discomfort were each associated with more severely depressed HRQOL, as was current epoprostenol use. With the sole exception of the right atrial pressure, hemodynamic measurements did not correlate with HRQOL scores. Simultaneous evaluation of HRQOL with a non-disease-specific questionnaire (SF-36) revealed a similarly impaired status, although identified fewer associations with patient-specific factors.. Severely impaired HRQOL is present in this population of patients with PAH evaluated with a disease-specific questionnaire. The availability of a pulmonary hypertension-specific HRQOL questionnaire may enable further targeted investigations of factors that might improve outcomes.

Topics: Activities of Daily Living; Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Chest Pain; Epoprostenol; Fatigue; Female; Health Status; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Quality of Life; Sickness Impact Profile; Warfarin; Young Adult

Topics: Anticoagulants; Atrial Fibrillation; Echocardiography, Doppler, Pulsed; Fatigue; Heart Atria; Heart Diseases; Humans; Imaging, Three-Dimensional; Male; Middle Aged; Pacemaker, Artificial; Pulmonary Embolism; Thrombolytic Therapy; Thrombosis; Tomography, Spiral Computed; Tricuspid Valve; Ventricular Dysfunction, Left; Warfarin

One of the standard treatments for cancer-associated thrombosis has been initial therapy with unfractionated heparin (UFH) followed by long-term therapy with an oral anticoagulant (i.e., warfarin). However, characteristics associated with these two agents may make them suboptimal for many cancer patients. This article will explore some of the considerations and limitations when using UFH and warfarin in the cancer population and will also utilize case studies to emphasize the importance of individualized care.. UFH is an effective anticoagulant when doses are adjusted to maintain the activated partial thromboplastin time (aPTT) within a specified therapeutic range. However, due to the complex pharmacokinetics of this agent, patients must undergo frequent monitoring to maintain a therapeutic aPTT. In addition, UFH can be associated with serious adverse events including osteoporosis, heparin-induced thrombocytopenia, and bleeding. Similar to UFH, warfarin requires frequent monitoring and dose adjustments to maintain the International Normalized Ratio (INR) within the therapeutic range of 2.0 to 3.0. Warfarin also has numerous drug-herbal, drug-food, and drug-drug interactions, including interactions with many commonly used anti-tumor therapies. Complications related to UFH and warfarin in the treatment of cancer-associated thrombosis have gradually been minimized with the increased use of low molecular weight heparins (LMWHs), which are associated with reduced incidence of bleeding, heparin-induced thrombocytopenia, and drug interactions. In addition, LMWHs allow for convenient daily dosing without requiring routine monitoring and the option of home therapy.. When deciding on the optimal anticoagulant strategy, pharmacists must take into account the unique characteristics and needs of each individual patient as well as the specifics of the various anticoagulant therapies. Future strategies for the initial and long-term treatment of cancer-associated thrombosis may increasingly incorporate LMWHs because of factors related to safety and convenience.

Topics: Anticoagulants; Bone Neoplasms; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Fatigue; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Thrombosis; Warfarin