scholarly journals Pharmacogenetic Warfarin Dosing Algorithm in the Russian Population

2019 ◽  
Vol 4 (3) ◽  
pp. 40-44
Author(s):  
T. A. Bairova ◽  
A. Yu. Sambyalova ◽  
L. V. Rychkova ◽  
E. A. Novikova ◽  
F. I. Belyalov ◽  
...  
Keyword(s):  
Ethnic Groups ◽  
Predictive Accuracy ◽  
Warfarin Dose ◽  
Absolute Error ◽  
International Normalized Ratio ◽  
Russian Population ◽  
Asian Patients ◽  
Performance Limitation ◽  
The Mean ◽  
Warfarin Dosing

Background. To date, there are many pharmacogenetic algorithms for selecting the dose of warfarin. However, there is very little information about the predictive accuracy of the algorithms. We decided to evaluate the predictive accuracy of the Gage algorithm, using a calculator, located on the web site (http://www.warfarindosing.org) in two ethnic groups (Caucasians and Asians), living in Russia.Aim. To compare the actual warfarin dose (AWD) to the calculated warfarin dose (CWD), using the algorithm in two ethnic groups taking warfarin.Materials and methods. We included 114 patients (66 Caucasians and 48 Asians): the mean age was60.91 ± 12.34 years; 61 (53.51 %) men, and 53 (46.49 %) women. The comparative characteristics of the algorithm were tested using the mean absolute error (MAE) between AWD and CWD, and percentage of patients, whose CWD fell within 20 % of AWD (percentage within 20 %). Genotyping for CYP2C9*2, CYP2C9*3, CYP4F*2 and VKORC1 was performed by real-time polymerase chain reaction (RT-PCR) method using Pharmacogenetics Warfarin reagent kits (DNA technology, Russia).Results. The Gage algorithm produced the predictive accuracy with MAE = 1.02 ± 0.16 mg/day and percentage within 20 % for Asian patients was 39.6 %. We obtained MAE = 1.33 ± 0.16 mg/day and percentage within 20 % for Caucasian patients was 40.9 %. In two ethnic groups (Caucasians and Asians) of the Russian population, overall performance of warfarin pharmacogenetic dosing by the Gage algorithm was similar.Conclusions. Despite the performance limitation of the current warfarin pharmacogenetic dosing Gage algorithm, constant international normalized ratio monitoring is important.

scholarly journals Warfarin Interaction With Hepatic Cytochrome P-450 Enzyme-Inducing Anticonvulsants

2017 ◽  
Vol 24 (1) ◽  
pp. 172-178 ◽  
Author(s):  
Nathan P. Clark ◽  
Kim Hoang ◽  
Thomas Delate ◽  
John R. Horn ◽  
Daniel M. Witt
Keyword(s):  
Warfarin Therapy ◽  
Therapeutic Response ◽  
Warfarin Dose ◽  
Clinical Information ◽  
International Normalized Ratio ◽  
The Mean ◽  
Warfarin Dosing ◽  
Meaningful Interaction ◽  
Cytochrome P 450 ◽  
Hepatic Cytochrome

Initiation of cytochrome P-450 (CYP)-inducing anticonvulsant medications during warfarin therapy may decrease anticoagulant effect and necessitate frequent warfarin dose adjustments to maintain therapeutic response measured by the international normalized ratio (INR). Clinical information regarding interactions between warfarin and these medications is limited. This study investigated warfarin dose and INR response following CYP-inducing anticonvulsant initiation among chronic warfarin users. This retrospective, pre-post study included patients ≥18 years who were receiving chronic warfarin therapy and who initiated carbamazepine, oxcarbazepine, phenobarbital, or phenytoin between January 1, 2006, and December 31, 2013. Mean weekly warfarin dose/INR ratio and mean weekly warfarin dose were compared in the 90 days pre- and days post-anticonvulsant initiation periods. Of the 57 included patients, 34 (60%), 15 (26%), 6 (11%), and 2 (3%) patients purchased a prescription for carbamazepine, phenytoin, oxcarbazepine, and phenobarbital, respectively. Mean age was 70 years, 59% were female, and the majority were receiving chronic warfarin therapy for atrial fibrillation (39%) or venous thromboembolism (26%). The ratio of mean warfarin dose and INR increased significantly between the pre- and post-anticonvulsant initiation periods (from 13 mg/INR to 18 mg/INR, respectively, P ≤ .001) as did the mean weekly warfarin dose (from 33 mg to 37 mg, P = <.001). Warfarin dose and dose/INR ratio significantly increased after carbamazepine initiation (both P < .001), while oxcarbazepine, phenobarbital, and phenytoin initiation did not significantly affect warfarin dosing. Our results support the presence of a clinically meaningful interaction between warfarin and carbamazepine. Frequent INR monitoring and warfarin dose escalation are recommended in this setting.

Comparison of the prediction performance of different warfarin dosing algorithms based on Chinese patients

2020 ◽  
Vol 21 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Cheng Xie ◽  
Ling Xue ◽  
Yuzhen Zhang ◽  
Jianguo Zhu ◽  
Ling Zhou ◽  
...  
Keyword(s):  
Mean Absolute Error ◽  
Warfarin Dose ◽  
Predictive Performance ◽  
Absolute Error ◽  
Prediction Performance ◽  
Chinese Patients ◽  
Geographical Populations ◽  
The Mean ◽  
Warfarin Dosing

Aim: To compare the prediction performance of different warfarin dosing algorithms based on Chinese patients. Materials & methods: A total of 18 algorithms were tested in 325 patients. The predictive efficacy of selected algorithms was evaluated by calculating the percentage of patients whose predicted dose fell within ±20% of their actual stable warfarin dose and the mean absolute error. Results: The percentage within ± 20% and the mean absolute error of the algorithms ranged from 11.9 to 41.2% and -0.20 (-0.29 to -0.11) mg/d to -1.63 (-1.75 to -1.50) mg/d. The algorithms established by Miao et al. and Wei et al. had optimal predictive performance. Conclusion: Algorithms based on geographical populations might be more suitable for the prediction of stable warfarin doses in local patients.

scholarly journals PCA Forecast Averaging—Predicting Day-Ahead and Intraday Electricity Prices

Energies ◽  
2020 ◽  
Vol 13 (14) ◽  
pp. 3530
Author(s):  
Katarzyna Maciejowska ◽  
Bartosz Uniejewski ◽  
Tomasz Serafin
Keyword(s):  
Predictive Accuracy ◽  
Expert Knowledge ◽  
Predictive Ability ◽  
Principal Component ◽  
Absolute Error ◽  
Electricity Prices ◽  
Short Term ◽  
White Test ◽  
The Mean ◽  
Short Term Forecasting

Recently, the development in combining point forecasts of electricity prices obtained with different length of calibration windows have provided an extremely efficient and simple tool for improving predictive accuracy. However, the proposed methods are strongly dependent on expert knowledge and may not be directly transferred from one to another model or market. Hence, we consider a novel extension and propose to use principal component analysis (PCA) to automate the procedure of averaging over a rich pool of predictions. We apply PCA to a panel of over 650 point forecasts obtained for different calibration windows length. The robustness of the approach is evaluated with three different forecasting tasks, i.e., forecasting day-ahead prices, forecasting intraday ID3 prices one day in advance, and finally very short term forecasting of ID3 prices (i.e., six hours before delivery). The empirical results are compared using the Mean Absolute Error measure and Giacomini and White test for conditional predictive ability (CPA). The results indicate that PCA averaging not only yields significantly more accurate forecasts than individual predictions but also outperforms other forecast averaging schemes.

Evaluation of dosing and safety outcomes of low-dose prophylactic warfarin in children after cardiothoracic surgery

2020 ◽  
Vol 77 (13) ◽  
pp. 1018-1025
Author(s):  
Maura Harkin ◽  
Brittany Powers Shaddix ◽  
Stephen B Neely ◽  
Leigh A Peek ◽  
Katy Stephens ◽  
...  
Keyword(s):  
Low Dose ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Primary Objective ◽  
Cardiothoracic Surgery ◽  
Entire Study Period ◽  
Entire Study ◽  
Frequent Monitoring ◽  
Safety Outcomes ◽  
Warfarin Dosing

Abstract Purpose Prophylactic warfarin with an International Normalized Ratio (INR) goal of 1.5 to 2.0 is one antithrombotic therapy utilized in children after cardiothoracic surgery (CTS); published sources suggest a dose of 0.1 mg/kg per day to achieve this goal. However, few studies have evaluated dosing in this population. The purpose of this study was to evaluate dosing and safety outcomes in children receiving warfarin after CTS. Methods A descriptive, retrospective review was conducted to evaluate warfarin dosing and INR outcomes in patients 18 years of age or younger who underwent CTS and received prophylactic warfarin with an INR goal of 1.5 to 2.0 from January 2014 through December 2018. The primary objective was to determine the median initial warfarin dose. Secondary objectives included identifying the percentage of documented INR values that were outside the therapeutic range, the percentage of patients with therapeutic INRs at discharge, and the 30-day readmission rate. Results Twenty-six patients were included in the review. The median initial warfarin dosage was 0.07 mg/kg/d (interquartile range [IQR], 0.05-0.10 mg/kg/d). Of the total of 177 INR values collected during the entire study period, 67 (37.9%) were therapeutic, 64 (36.2%) were subtherapeutic, and 46 (26.0%) were supratherapeutic. Eighteen patients (69.2%) had at least 1 supratherapeutic INR at any point during the study period, most frequently on days 2 through 4 of therapy. At discharge, 11 patients (42.3%) had therapeutic INRs. Four patients (15.4%) were readmitted within 30 days, with bleeding documented in 2 patients during their readmission. Conclusion The majority of patients received an initial warfarin dose less than that specified in published recommendations but still had a supratherapeutic INR at least once during the study period. When initiating warfarin after CTS, a dosage of &lt;0.1 mg/kg per day and frequent monitoring may be needed to achieve an INR goal of 1.5 to 2.0.

scholarly journals Preliminary outcomes of preemptive warfarin pharmacogenetic testing at a large rural healthcare center

2019 ◽  
Vol 76 (6) ◽  
pp. 387-397 ◽  
Author(s):  
Emili Leary ◽  
Murray Brilliant ◽  
Peggy Peissig ◽  
Sara Griesbach
Keyword(s):  
Care Service ◽  
Anticoagulation Therapy ◽  
Warfarin Dose ◽  
Standard Of Care ◽  
International Normalized Ratio ◽  
Preliminary Evaluation ◽  
Thromboembolic Events ◽  
Rural Healthcare ◽  
Pharmacogenetic Testing ◽  
Warfarin Dosing

Abstract Purpose As a preliminary evaluation of the outcomes of implementing pharmacogenetic testing within a large rural healthcare system, patients who received pre-emptive pharmacogenetic testing and warfarin dosing were monitored until June 2017. Summary Over a 20-month period, 749 patients were genotyped for VKORC1 and CYP2C9 as part of the electronic Medical Records and Genomics Pharmacogenetics (eMERGE PGx) study. Of these, 27 were prescribed warfarin and received an alert for pharmacogenetic testing pertinent to warfarin; 20 patients achieved their target international normalized ratio (INR) of 2.0–3.0, and 65% of these patients achieved target dosing within the recommended pharmacogenetic alert dose (± 0.5 mg/day). Of these, 10 patients had never been on warfarin prior to the alert and were further evaluated with regard to time to first stable target INR, bleeds and thromboembolic events, hospitalizations, and mortality. There was a general trend of faster time to first stable target INR when the patient was initiated at a warfarin dose within the alert recommendation versus a dose outside of the alert recommendation with a mean (± SD) of 34 (± 28) days versus 129 (± 117) days, respectively. No trends regarding bleeds, thromboembolic events, hospitalization, or mortality were identified with respect to the pharmacogenetic alert. The pharmacogenetic alert provided pharmacogenetic dosing information to prescribing clinicians and appeared to deploy appropriately with the correct recommendation based upon patient genotype. Conclusion Implementing pharmacogenetic testing as a standard of care service in anticoagulation monitoring programs may improve dosage regimens for patients on anticoagulation therapy.

Prediction Model of Serum Lithium Concentrations

2017 ◽  
Vol 51 (03) ◽  
pp. 82-88 ◽  
Author(s):  
Kazunari Yoshida ◽  
Hiroyuki Uchida ◽  
Takefumi Suzuki ◽  
Masahiro Watanabe ◽  
Nariyasu Yoshino ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Prediction Model ◽  
Predictive Accuracy ◽  
Compartment Model ◽  
Absolute Error ◽  
Oral Dosage ◽  
Therapeutic Drug ◽  
Suitable Model ◽  
Blood Draw ◽  
The Mean

Abstract Introduction Therapeutic drug monitoring is necessary for lithium, but clinical application of several prediction strategies is still limited because of insufficient predictive accuracy. We herein proposed a suitable model, using creatinine clearance (CLcr)-based lithium clearance (Li-CL). Methods Patients receiving lithium provided the following information: serum lithium and creatinine concentrations, time of blood draw, dosing regimen, concomitant medications, and demographics. Li-CL was calculated as a daily dose per trough concentration for each subject, and the mean of Li-CL/CLcr was used to estimate Li-CL for another 30 subjects. Serum lithium concentrations at the time of sampling were estimated by 1-compartment model with Li-CL, fixed distribution volume (0.79 L/kg), and absorption rate (1.5/hour) in the 30 subjects. Results One hundred thirty-one samples from 82 subjects (44 men; mean±standard deviation age: 51.4±16.0 years; body weight: 64.6±13.8 kg; serum creatinine: 0.78±0.20 mg/dL; dose of lithium: 680.2±289.1 mg/day) were used to develop the pharmacokinetic model. The mean±standard deviation (95% confidence interval) of absolute error was 0.13±0.09 (0.10–0.16) mEq/L. Discussion Serum concentrations of lithium can be predicted from oral dosage with high precision, using our prediction model.

scholarly journals Mean Stable Warfarin Doses Versus CYP2C9*2 and VKORC11639G>A Genotypes in Sudanese Population

2016 ◽  
Vol 9 (1) ◽  
pp. 34
Author(s):  
Azza A. M. H. Swar Aldahab ◽  
Abdalla O. Elkhawad ◽  
Ahmed S. A. Elsayed ◽  
Hanan B. Eltahir
Keyword(s):  
Warfarin Dose ◽  
Therapeutic Index ◽  
Target Range ◽  
Wild Type ◽  
Genotype 3 ◽  
Pcr Rflp ◽  
Homozygous Mutant ◽  
Variant Genotype ◽  
The Mean ◽  
Warfarin Dosing

Warfarin is a potent anticoagulant with a confirmed effectiveness when anticoagulation targets are attained, an issue, that is troublesome to reach due to the fact that warfarin has a narrow therapeutic index (NTI), that means they have a narrow window between their effective doses and those at which they produce adverse toxic effects. However, oral anticoagulation throughout genetics recommended a genotype guided dosing, but is it favourable over clinical based dosing? Objectives: To analyze the mean stable warfarin doses attained clinically within CYP2C9*2 and VKORC11639G&gt;A wild-type and variant genotype status in Sudanese patients. Method: Genotyping for the CYP2C9*2 and VKORC1-1639G&gt;A polymorphisms were accomplished with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) technique. The mean stable warfarin dose per genotype was defined as the mean stable warfarin dose related to the stable INR within target range within a genotype of each of CYP2C9*2 or VKORC11639G&gt; Agenes, using Analysis of Variance (ANOVA) as the statistical method. Results: Fifty-three stable patients with wild-type CYP2C9*1*1 genotype had a mean stable warfarin dose of 4.9 ± 2.1 mg, 5 patients who were heterozygous CYP2C9*1*2 genotype, had a mean stable warfarin dose of 5.0 ± 0.71mg, and 2 patients were homozygous mutant CYP2CP*2*2 genotype had a mean stable warfarin dose of 4.8 ± 0.3 mg. The results were statistically insignificant, P = 0.992.Sixteen unstable patients were of wild-type CYP2C9*1*1 genotype, 40 patients with heterozygous CYP2C9*1*2 genotype, and 4 with homozygous mutant CYP2CP*2*2 genotype, had mean stable doses of 5.32 ± 2.9, 6.5 ± 2.7 and 4.5 ± 0.71 mg respectively. The result was statistically insignificant, P = 0.508. Fifty-two stable patients were having wild-type VKORC1G/G genotype, 3 patients had heterozygous VKORC1G/A genotype and 3 patients had homozygous mutant VKORC1/AA genotype, these patients had mean stable doses of 5.41 ± 1.63, 4.8 ± 2.19 and 5.4 ± 0.99 mg respectively. The mean warfarin stable dose among homozygous mutant VKORC1A/A genotype was lower than among wild-type and heterozygous genotype profiles. This result was statistically not significant, P = 0.729.In the unstable group, 8 patients of wild-type VKORC1G/G genotype, had a mean stable warfarin dose of 7.34 ± 3.9 mg, 40 patients of heterozygous VKORC1G/A genotype had a mean stable warfarin dose of 5.21 ± 2.76 mg, and 10 patients of homozygous VKORC1A/A genotype had a mean stable warfarin dose of 4.3 ± 1.83 mg. The result was statistically insignificant, P = 0.067.Conclusion: In our study, as there were no significant differences between warfarin mean stable doses related to different CYP2C9*2 and VKORC11639G&gt;A genotypes, the evidence is not satisfactory to conclude that the conventional use of genotype guided warfarin dosing will correct stable warfarin dose among Sudanese patients.

A Probable Interaction between Warfarin and the Antiretroviral TRIO Study Regimen

2012 ◽  
Vol 46 (11) ◽  
pp. e34-e34 ◽  
Author(s):  
Michelle D Liedtke ◽  
Amulya Vanguri ◽  
R Chris Rathbun
Keyword(s):  
Drug Interaction ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Dose Requirement ◽  
Vein Thrombosis ◽  
Warfarin Dose Requirement ◽  
Recurrent Deep Vein Thrombosis ◽  
The Mean ◽  
Deep Vein ◽  
Probable Interaction

OBJECTIVE: To report a probable drug interaction between the antiretroviral TRIO regimen (ritonavir-boosted darunavir, etravirine, and raltegravir) and warfarin in an HIV-infected patient. CASE SUMMARY: In January 2010, a 50-year-old transgender female with HIV infection and recurrent deep vein thrombosis began treatment with the TRIO study regimen. Treatment had been maintained with warfarin for the past 5 years and emtricitabine monotherapy for the preceding 22 months. Emtricitabine was discontinued when the TRIO regimen was started. The mean weekly warfarin dose while the patient was receiving emtricitabine monotherapy was 13.3 mg (95% CI 12.7 to 13.8), with a mean international normalized ratio (INR) of 2.8 (95% CI 2.5 to 3.1). Following the initiation of the TRIO regimen, the mean weekly warfarin dose was increased to 19.3 mg (95% CI 18.5 to 20.1) and was maintained over the ensuing 71 weeks with a mean INR of 2.6 (95% CI 2.2 to 3.0). DISCUSSION: Information on the effect of newer antiretrovirals on warfarin metabolism, as well as the collective contribution of combination antiretroviral therapy including multiple agents that may alter warfarin metabolism, is limited. We predicted that warfarin dose requirements would change upon initiation of the TRIO regimen. Given the variability in INR that can occur with chronic warfarin treatment, weekly warfarin doses were averaged during emtricitabine monotherapy (90 weeks) and TRIO regimen (71 weeks) periods. Mean weekly warfarin doses increased by 45% (p < 0.001) following initiation of the TRIO regimen. Mean INR results for the 2 time periods were not significantly different, demonstrating that stable anticoagulation was maintained. The Horn drug interaction probability scale score to assess causation indicated a probable interaction. CONCLUSIONS: An increased weekly warfarin dose requirement is predicted when warfarin is used concurrently with the antiretroviral TRIO regimen. Increased INR monitoring is prudent when the combination is administered.

Evaluation of an Initiation Regimen of Warfarin for International Normalized Ratio Target 2.0 to 3.0

2021 ◽  
pp. 875512252110341
Author(s):  
Sahimi Mohamed ◽  
Chan Mei Fong ◽  
Yew Jie Ming ◽  
Ahlam Naila Kori ◽  
Sopian Abdul Wahab ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Warfarin Therapy ◽  
Warfarin Dose ◽  
Asian Population ◽  
International Normalized Ratio ◽  
Efficacy And Safety ◽  
Risk Of Bleeding ◽  
Number Of Patients ◽  
Inpatient Settings ◽  
The Mean

Background: he number of patients on warfarin therapy is rising steadily. Although warfarin is beneficial, it carries a high risk of bleeding, especially if the international normalized ratio (INR) values exceed 3.0. Currently, no warfarin initiation regimens have been developed for the Asian population, especially for Malaysians. Objective: This article describes the efficacy and safety of a new initiation regimen for warfarin among warfarin-naive patients. Method: Data were retrospectively collected from the ambulatory and inpatient settings. Results: A total of 165 patients who each had a target INR of 2.0 to 3.0 were included in the study. The mean age was 57.2 years and 94 patients were male. A total of 108 patients used Regimen 1 (5 mg/5 mg/3mg) and the rest of the patients used Regimen 2 (5 mg/3 mg/3 mg). Most patients used warfarin either for atrial fibrillation (52.1%) or for venous thromboembolism (29.7%). Overall, 88 of the patients had INR values above 50% from the baseline on Day 4. Additionally, 13 patients had INR values of >3.2, which required withholding and lower dose of warfarin. The predicted weekly maintenance warfarin dose (23 ± 0.5 mg/week) was found to have correlated closely with the actual maintenance dose (22.8 ± 0.5 mg/week; r2 = 0.75). Nearly two thirds (70.3%) of the patients achieved the target INR on Day 11. Conclusion: The warfarin initiation regimens in this study was simple, safe, and suitable to be used in both ambulatory and inpatient settings for managing warfarin therapy.

scholarly journals Decreased warfarin sensitivity among patients treated with elbasvir and grazoprevir for hepatitis C infection

2019 ◽  
Vol 76 (17) ◽  
pp. 1273-1280
Author(s):  
Douglas D DeCarolis ◽  
Yi-Chieh Chen ◽  
Anders D Westanmo ◽  
Christopher Conley ◽  
Amy A Gravely ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Therapeutic Range ◽  
Antiviral Agents ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Sensitivity Index ◽  
Veterans Health ◽  
Health Administration ◽  
Hepatitis C Infection ◽  
The Mean

Abstract Purpose We previously reported an interaction with warfarin anticoagulation when initiating treatment with direct-acting antiviral agents for hepatitis C infection. A decreased warfarin sensitivity led to subtherapeutic anticoagulation. To study this interaction further, we expanded our research to include patients treated with the combination of elbasvir and grazoprevir concurrent with warfarin anticoagulation and investigated changes in warfarin sensitivity during and after treatment. Methods Using electronic health records of the Veterans Health Administration, patients starting treatment with elbasvir–grazoprevir for hepatitis C infection concurrent with warfarin anticoagulation were identified. Inclusion required stable warfarin anticoagulation prior to 12 weeks of treatment with elbasvir–grazoprevir. A warfarin sensitivity index (WSI) was calculated at the start and end of treatment and 12 weeks after treatment. The primary endpoint was the difference in WSI from pre- to end-treatment. The secondary endpoint was the WSI difference from pretreatment to 12 weeks posttreatment. Changes in International Normalized Ratio, warfarin doses, and time in therapeutic range were measured. Results In the final sample of 43 patients, the mean WSI decreased during treatment from 0.53 to 0.40, or 25.2%. After treatment, the mean WSI rose to 0.51. Although the mean weekly warfarin dose increased from 40.3 to 44.6 mg during treatment, the mean International Normalized Ratio decreased from 2.40 to 1.96, recovering to 2.59 after treatment. The time spent in therapeutic range decreased from 74.1% before treatment to 39.8% during treatment and back to 64.9% 12 weeks posttreatment. Conclusion When elbasvir–grazoprevir was added to stable warfarin anticoagulation, warfarin sensitivity decreased significantly during treatment and returned to baseline after treatment.

Sign in / Sign up

Export Citation Format

Share Document