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Warfarin, a commonly prescribed anticoagulant, has many potential drug interactions. We describe a case of intravaginal miconazole potentiating the effects of warfarin in a patient previously stable on a consistent dose of 8.5 mg warfarin daily. Following a course of intravaginal miconazole and a dosage increase to 9 mg daily, her international normalized ratio (INR) increased from 2.0 to 5. After the course of miconazole was complete, the patient was stable with a therapeutic INR (mean INR 2.9) on 9 mg warfarin daily. Clinicians should consider the possibility of systemic absorption of intravaginal miconazole, and a resultant increase in warfarin's anticoagulant effect.
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We reviewed medical records from 2264 patients with isolated CABG performed during a period when our institution had no policy on anticoagulation for postoperative atrial fibrillation. The outcome was ischemic stroke within 30days postoperatively and verified with computed tomography (CT) in patients with new postoperative atrial fibrillation for more than 48h.
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In conclusion, using the stroke prevention guidelines, thrombotic therapy protocols and familiarity with patients' diagnosis and risk factors in the experimental group led to more patients' stability time (The time that patients could remain stable within the INR therapeutic range) in their therapeutic range of INR as the best indicator of clinical performance.
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In clinical trials new oral anticoagulants (NOAC) have proved to be as effective as warfarin for thromboprophylaxis in atrial fibrillation. The aim of this study was to evaluate the efficacy and safety of these drugs in clinical practise.
Findings suggest that an online PSM registry is feasible, accurate and acceptable to patients. These findings require confirmation in a larger cohort of PSM patients. An online self-report registry could provide a valuable resource for gathering real world evidence of clinical effectiveness and safety of these developing models of care.
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Novel oral anticoagulants including the factor Xa inhibitor rivaroxaban are important alternatives to warfarin for the prevention of thromboembolic stroke in patients with nonvalvular atrial fibrillation. The pharmacology and metabolism of these agents differ from those of the vitamin K antagonists used over the decades preceding their introduction. We present a case of spontaneous hemopericardium and cardiac tamponade following administration of rivaroxaban. A review of the patient's medications revealed a total of seven agents known to be metabolized through cytochrome P450 3A4 (CYP3A4), the major pathway for rivaroxaban metabolism. While most physicians are familiar with recommendations to monitor renal function in patients prescribed rivaroxaban, we suspect that many fail to evaluate possible interactions with other agents having CYP3A4 inhibitory or inducer activity.
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The new oral anticoagulants (NOACs), which include dabigatran, rivaroxaban, apixaban, and edoxaban, are poised to replace warfarin for treatment of the majority of patients with venous thromboembolism (VTE). With a rapid onset of action and the capacity to be administered in fixed doses without routine coagulation monitoring, NOACs streamline VTE treatment. In phase 3 trials in patients with acute symptomatic VTE, NOACs have been shown to be noninferior to conventional anticoagulant therapy for prevention of recurrence and are associated with less bleeding. Rivaroxaban and dabigatran are already licensed for VTE treatment in the United States, and apixaban and edoxaban are under regulatory consideration for this indication. As the number of approved drugs increases, clinicians will need to choose the right anticoagulant for the right VTE patient. To help with this decision, this review (1) compares the pharmacologic profiles of the NOACs, (2) outlines the unique design features of the phase 3 trials that evaluated the NOACs for VTE treatment, (3) reviews the results of these trials highlighting similarities and differences in the findings, (4) provides perspective about which VTE patients should receive conventional treatment or are candidates for NOACs, and (5) offers suggestions about how to choose among the NOACs.
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The study was an observational self-controlled study from 1998 to 2012 leveraging data on INR measurements on patients treated with warfarin from primary care and outpatient clinics and their use of prescription drugs. Data were analyzed in 2015. We assessed INR, warfarin dose, and dose/INR ratio before and after initiating PPI treatment using the paired student's t-test.
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Introduction. The safety of vitamin K antagonists (VKA) use can be compromised by many popular herbal supplements taken by individuals. The literature reports that 30% of warfarin-treated patients self-medicates with herbs. Possible interactions represent an health risk. We aimed to identify all herbs-oral anticoagulants interactions collected in the Italian database of suspected adverse reactions to "natural health" products. Methods. The Italian database of spontaneous reports of suspected adverse reactions to natural products was analyzed to address herb-VKAs interactions. Results. From 2002 to 2009, we identified 12 reports with 7 cases of INR reduction in patients treated with warfarin (n = 3) and acenocoumarol (n = 4), and 5 cases of INR increase (all warfarin associated). It was reported 8 different herbal products as possibly interacting. Discussion. Our study confirms the risk of interactions, highlighting the difficulty to characterize them and their mechanisms and, finally, prevent their onset. The reported data underline the urgent need of healthcare providers being aware of the possible interaction between natural products and VKA, also because of the critical clinical conditions affecting patients. This is the first step to have the best approach to understand possible INR alterations linked to herb-VKA interaction and to rightly educate patients in treatment with VKA.
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Different patient-level factors predicted unidirectional below-target and 'erratic' patterns of INR control. Distinct interventions are necessary to address these two separate pathways to poor anticoagulation.
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A chart review of VTE cases at two tertiary, urban hospitals from January 1, 2010 to December 31, 2012 was performed to capture historical practice in VTE management, using LMWH/warfarin. This historical data were compared against data derived from clinical trials, where a DOAC was used. Cost minimization analyses comparing the two modes of anticoagulation were completed from hospital and patient perspectives.
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The functional and structural performance of a 5cm synthetic small diameter vascular graft (SDVG) produced by the copolymerization of polyvinyl alcohol hydrogel with low molecular weight dextran (PVA/Dx graft) associated to mesenchymal stem cells (MSCs)-based therapies and anticoagulant treatment with heparin, clopidogrel and warfarin was tested using the ovine model during the healing period of 24 weeks. The results were compared to the ones obtained with standard expanded polyetetrafluoroethylene grafts (ePTFE graft). Blood flow, vessel and graft diameter measurements, graft appearance and patency rate (PR), thrombus, stenosis and collateral vessel formation were evaluated by B-mode ultrasound, audio and color flow Doppler. Graft and regenerated vessels morphologic evaluation was performed by scanning electronic microscopy (SEM), histopathological and immunohistochemical analysis. All PVA/Dx grafts could maintain a similar or higher PR and systolic/diastolic laminar blood flow velocities were similar to ePTFE grafts. CD14 (macrophages) and α-actin (smooth muscle) staining presented similar results in PVA/Dx/MSCs and ePTFE graft groups. Fibrosis layer was lower and endothelial cells were only detected at graft-artery transitions where it was added the MSCs. In conclusion, PVA/Dx graft can be an excellent scaffold candidate for vascular reconstruction, including clinic mechanically challenging applications, such as SDVGs, especially when associated to MSCs-based therapies to promote higher endothelialization and lower fibrosis of the vascular prosthesis, but also higher PR values.
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A 35-year-old man developed priapism with the use of low-molecular-weight heparin and warfarin following repair of left brachial artery sustained after gunshot injury. Priapism progressed to penile gangrene despite decompression and distal shunt procedure leading to total penectomy and perineal urethrostomy. We describe the mechanism of anticoagulant (heparin and warfarin)-induced penile gangrene and the possible methods to avert such a devastating complication.
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Most drug interaction resources suggest that levothyroxine can dramatically potentiate the effect of warfarin. However, the mechanistic basis of the interaction is speculative, and little evidence supports a meaningful drug interaction. We conducted a population-based nested case-control study to examine the risk of hospitalization for hemorrhage following the initiation of levothyroxine in a cohort of 260,076 older patients receiving warfarin. In this group, we identified 10,532 case subjects hospitalized for hemorrhage and 40,595 controls. In the primary analysis, we found no association between hospitalization for hemorrhage during warfarin therapy and initiation of levothyroxine in the preceding 30 days (adjusted odds ratio 1.11, 95% confidence interval 0.67-1.86). Secondary analyses using more remote initiation of levothyroxine also found no association. These findings suggest that concerns about a clinically meaningful levothyroxine-warfarin drug interaction are not justified. Drug interaction resources that presently characterize this interaction as important should reevaluate this classification.
Relevant publications on the aetiopathogenesis, molecular biology, genetics and histopathology of Meniere's disease from 1861 to 2011 were analysed.
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VKA-naïve warfarin initiators had the highest overall bleeding rate. We found no evidence of marked excess of overall bleeding events when comparing dabigatran with warfarin users, irrespective of prior VKA experience.
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There were no gender differences in long-term mortality after stroke related to AF. Men were significantly more often prescribed anticoagulants before stroke, a finding that indicates the need for further studies.
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In terms of inconsistent conclusions across all relevant randomized controlled trials (RCTs) and available meta-analyses, we aimed to use a meta-analysis and trial sequential analysis (TSA) to evaluate whether clinical utility of a genotype-guided warfarin initiation dosing algorithm could be better than that of a standard therapy regimen, and whether currently relevant evidence could be reliable and conclusive. Overall, 11 eligible RCTs involving 2677 patients were included for further analyses. Compared with fixed dose or clinically adjusted warfarin initiation dosing regimens, genotype-guided algorithms significantly increased time in therapeutic range, shortened time to first therapeutic international normalized ratio (INR) and time to stable doses, but did not show any marked improvements in excessive anticoagulation, bleeding events, thromboembolism, or all-cause mortality. Subgroup analyses revealed that, genotype-guided algorithms showed better control in the outcomes of time in therapeutic range or excessive anticoagulation than fixed-dose regimens rather than clinically adjusted regimens. Except for excessive anticoagulation, currently available evidence of all other outcomes was unreliable and inconclusive as determined with TSA. Our findings suggest that genotype-guided warfarin initiation dosing algorithms have superiority in the improvement of surrogate quality markers for anticoagulation control, but that this does not translate into statistically significant differences in clinical outcomes, which is largely because of the insufficient sample size in the RCTs analyzed.
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Eighty-five percent of patients had a history of hypertension, and the 7.7% had heart failure, left ventricular dysfunction, or both. The mean CHADS2 score was 1.41±0.84. TE and major bleeding events were observed at a low incidence among the overall population at 1-year follow-up (0.97% and 0.81%, respectively). The univariate and multivariable analyses revealed no statistically significant differences in the incidence of TE, major bleeding events or mortality in paroxysmal and persistent AF patients. TE events were more common among women than men (p=0.02). The follow-up examination showed under- or overtreatment with warfarin in many patients, according to guideline suggestions. Warfarin was more frequently prescribed to patients with persistent AF (p<0.0001) and patients with AF recurrences (p<0.0001). AF recurrences were noninvasively detected in 632 (51.2%) patients. In patients without AF recurrences, the TE event rate was 0.5% versus 1.74%, 1.28%, and 1.18% for those with only symptomatic, only asymptomatic or both symptomatic and asymptomatic AF recurrences, respectively, but the difference was not statistically significant, even after adjusting for warfarin treatment and the CHADS2 score (HR 2.93; CI 95%; 0.8-10.9; p=0.11).
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Observational studies have overwhelmingly shown that variants in the genes CYP2C9 and VKORC1 are significant determinants of individual dose of coumarin anticoagulants needed to maintain a therapeutic international normalized ratio (INR).(1) Until recently, however, few randomized clinical trials had been performed relating to the use of genetic data to predict dosing. Three sucsh clinical trials have now reported their findings.
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Apixaban is likely to be a cost-effective alternative to warfarin for stroke prophylaxis in Chinese patients with NVAF in Hong Kong.
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The proportion of warfarin users among the population increased 3.6-fold from 0.68% in 1993 to 2.28% in 2008. Of a total of 982 patients with ICH, 182 (18.5%) had warfarin-related ICH. One-year survival rate after onset of stroke was 35.2% among warfarin users and 67.9% among nonusers. The annual incidence (P=0.062) and 28-day case fatality of warfarin-related ICHs (P=0.002) decreased during the observation period. Warfarin users were older (mean difference 6.6; 95% CI, 5.0 to 8.1; P<0.001) than nonusers. Admission international normalized ratio values above the therapeutic range (2.0 to 3.0) decreased through the observation period, suggesting improved control of anticoagulant therapy over time.