Dabigatran etexilate: appropriate use in patients with chronic kidney disease and in the elderly patients

2017 ◽  
Vol 12 (4) ◽  
pp. 425-435 ◽  
Author(s):  
Mauro Molteni ◽  
Mario Bo ◽  
Giovanni Di Minno ◽  
Giuseppe Di Pasquale ◽  
Simonetta Genovesi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Elderly Patients ◽  
Dabigatran Etexilate ◽  
The Elderly ◽  
Appropriate Use

scholarly journals MEDICATION BURDEN AND INAPPROPRIATE PRESCRIPTION RISK AMONG ELDERLY WITH ADVANCED CHRONIC KIDNEY DISEASE

2019 ◽  
Author(s):  
Clarisse Roux-Marson ◽  
Jean-Baptiste Baranski ◽  
Coraline Fafin ◽  
Guillaume Extermann ◽  
Cecile Vigneau ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Elderly Patients ◽  
Healthcare Providers ◽  
Antihypertensive Agents ◽  
The Elderly ◽  
Anticholinergic Drugs ◽  
Cross Sectional ◽  
French Study ◽  
Sectional Analysis

Abstract Background Elderly patients with chronic kidney disease (CKD) frequently present comorbidities that put them at risk of polypharmacy and medication-related problems. This study aims to describe the overall medication profile of patients aged ≥ 75 years with advanced CKD from a multicenter French study and specifically the renally (RIMs) and potentially inappropriate-for-the-elderly medications (PIMs) that they take. Methods This is a cross-sectional analysis of medication profiles of individuals aged ≥ 75 years with eGFR < 20 ml/min/1.73m2 followed by a nephrologist, who collected their active prescriptions at the study inclusion visit. Medication profiles were analyzed according to route of administration, therapeutic classification, and their potential inappropriateness for these patients, according to Beers' criteria. Results We collected 5196 individual medication prescriptions for 556 patients, for a median of 9 daily medications [7-11]. Antihypertensive agents, antithrombotics, and antianemics were the classes most frequently prescribed. Moreover, 88% of patients had at least 1 medication classified as a RIM, and 21% of those were contraindicated drugs. At least 1 PIM was taken by 68.9%. The prescriptions most frequently requiring reassessment due to potential adverse effects were for proton pump inhibitors and allopurinol. The PIMs for which deprescription is especially important in this population are rilmenidine, long-term benzodiazepines, and anticholinergic drugs such as hydroxyzine. Conclusion We showed potential drug-related problems in elderly patients with advanced CKD. Healthcare providers must reassess each medication prescribed for this population, particularly the specific medications identified here.

scholarly journals Quantification of CYP3A and Drug Transporters Activity in Healthy Young, Healthy Elderly and Chronic Kidney Disease Elderly Patients by a Microdose Cocktail Approach

2021 ◽  
Vol 12 ◽  
Author(s):  
Punyabhorn Rattanacheeworn ◽  
Stephen J Kerr ◽  
Wonngarm Kittanamongkolchai ◽  
Natavudh Townamchai ◽  
Suwasin Udomkarnjananun ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Elderly Patients ◽  
Half Life ◽  
Dabigatran Etexilate ◽  
Organic Anion ◽  
Maximum Plasma ◽  
Cyp3a Activity ◽  
Cancer Resistance ◽  
Healthy Elderly

Background: Ageing and chronic kidney disease (CKD) affect pharmacokinetic (PK) parameters. Since mechanisms are related and remain unclear, cytochrome P450 (CYP) 3A and drug transporter activities were investigated in the elderly with or without CKD and compared to healthy adults using a microdose cocktail.Methods: Healthy young participants (n = 20), healthy elderly participants (n = 16) and elderly patients with CKD (n = 17) received, in study period 1, a single dose of microdose cocktail probe containing 30 µg midazolam, 750 µg dabigatran etexilate, 100 µg atorvastatin, 10 µg pitavastatin, and 50 µg rosuvastatin. After a 14-day wash-out period, healthy young participants continued to study period 2 with the microdose cocktail plus rifampicin. PK parameters including area under the plasma concentration-time curve (AUC), maximum plasma drug concentration (Cmax), and half-life were estimated before making pairwise comparisons of geometric mean ratios (GMR) between groups.Results: AUC and Cmax GMR (95% confidence interval; CI) of midazolam, a CYP3A probe substrate, were increased 2.30 (1.70–3.09) and 2.90 (2.16–3.88) fold in healthy elderly and elderly patients with CKD, respectively, together with a prolonged half-life. AUC and Cmax GMR (95%CI) of atorvastatin, another CYP3A substrate, was increased 2.14 (1.52–3.02) fold in healthy elderly and 4.15 (2.98–5.79) fold in elderly patients with CKD, indicating decreased CYP3A activity related to ageing. Associated AUC changes in the probe drug whose activity could be modified by intestinal P-glycoprotein (P-gp) activity, dabigatran etexilate, were observed in patients with CKD. However, whether the activity of pitavastatin and rosuvastatin is modified by organic anion transporting polypeptide 1B (OATP1B) and of breast cancer resistance protein (BCRP), respectively, in elderly participants with or without CKD was inconclusive.Conclusions: CYP3A activity is reduced in ageing. Intestinal P-gp function might be affected by CKD, but further confirmation appears warranted.Clinical Trial Registration:http://www.thaiclinicaltrials.org/ (TCTR 20180312002 registered on March 07, 2018)

scholarly journals Pacemaker Therapy in the Elderly and Very Elderly

2021 ◽  
pp. 1-3
Author(s):  
Alexander Marschall ◽  
Alexander Marschall ◽  
Andrea Rueda Liñares ◽  
Belen Biscotti Rodil ◽  
Montserrat Torres Lopez ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Prognostic Factors ◽  
Kidney Disease ◽  
Elderly Patients ◽  
Cox Regression ◽  
The Elderly ◽  
Very Elderly ◽  
Pacemaker Therapy ◽  
All Cause Mortality

Background: The number of elderly patients undergoing pacemaker (PM) implantation is constantly growing. However, information on survival and prognostic factors of this particular patient group is scarce. The objective of this study was to determine the survival of elderly and very elderly patients undergoing PM implantation, as well as to investigate prognostic factors of mortality. Methods: This is a retrospective observational study of a single center. Patients ≥ 80 years of age, that underwent PM implantation between January 2017 and December 2018 in our center, were included for chart review. Very elderly patients were defined as those with ≥ 90 years of age. Results: A total of 269 patients were included in the study with a mean age of 85 (±4.1) years. 53 patients were ≥ 90 years of age. 52% of the patients were male. 24.5% of the elderly patients and 41.5% of the very elderly patients received a single chamber PM. Median follow-up time was 28 (14-30) months, with no significant differences between the two groups of patients. The mortality rate for elderly patients was 15.7% for the elderly and 32.1% for the very elderly (p = 0.002). Generating multivariate Cox regression models, the following parameters showed to be significant predictors of all-cause mortality: Age (1.37 (1.02-1.29), p = 0.005), chronic kidney disease (5.57 (2.47-12.56), p<0.001), COPD (3.74 (1.19-11.55), p = 0.023) and cancer (3.57 (1.02-12.51), p = 0.046). In the group of the very elderly only age (1.58 (1.10-2.27), p = 0.014) and cancer (3.76 (2.38-4.18), p = 0.003) significantly predicted mortality. Conclusion: Our study shows a good life expectancy of elderly and very elderly patients that underwent PM implantation, with a survival rate that is comparable to the general population. The primary prognostic factors were non-cardiological and comorbidities, such as chronic kidney disease, cancer and COPD, had a stronger association with mortality than age.

scholarly journals Pacemaker therapy in the elderly and very elderly: survival and prognostic factors

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
HA Del Castillo-Carnevali ◽  
A Marschall ◽  
M Torres-Lopez ◽  
E Basabe-Velasco ◽  
I Gomez-Sanchez ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Prognostic Factors ◽  
Kidney Disease ◽  
Elderly Patients ◽  
Cox Regression ◽  
The Elderly ◽  
Very Elderly ◽  
Pacemaker Therapy ◽  
Funding Sources

Abstract Funding Acknowledgements Type of funding sources: None. Background The number of elderly patients undergoing pacemaker (PM) implantation is constantly growing. However, information on survival and prognostic factors of this particular patient group is scarce. Objective The objective of this study was to determine the survival of elderly and very elderly patients undergoing PM implantation, as well as to investigate prognostic factors of mortality. Methods This is a retrospective observational study of a single centre. Patients ≥ 80 years of age, that underwent PM implantation between January 2017 and December 2018 in our centre, were included for chart review. Very elderly patients were defined as those with ≥ 90 years of age. Results A total of 269 patients were included in the study with a mean age of 85 (±4.1) years. 53 patients were ≥ 90 years of age. 52% of the patients were male. 24.5% of the elderly patients and 41.5% of the very elderly patients received a single chamber PM. Median follow-up time was 28 (14-30) months, with no significant differences between the two groups of patients. The mortality rate for elderly patients was 15.7% for the elderly and 32.1% for the very elderly (p = 0.002). Generating multivariate Cox regression models, the following parameters showed to be significant predictors of all-cause mortality: Age (1.37 (1.02-1.29), p = 0.005), chronic kidney disease (5.57 (2.47-12.56), p &lt; 0.001), COPD (3.74 (1.19-11.55), p = 0.023) and cancer (3.57 (1.02-12.51), p = 0.046). In the group of the very elderly only age (1.58 (1.10-2.27), p = 0.014) and cancer (3.76 (2.38-4.18), p = 0.003) significantly predicted mortality. Conclusions Our study shows a good life expectancy of elderly and very elderly patients, that underwent PM implantation, with a survival rate that is comparable to the general population. The primary prognostic factors were non-cardiological and co-morbidities, such as chronic kidney disease, cancer and COPD, had a stronger association with mortality than age.

scholarly journals Medication Burden And Inappropriate Prescription Risk Among Elderly With Advanced Chronic Kidney Disease

2019 ◽  
Author(s):  
Clarisse Roux-Marson ◽  
Jean-Baptiste Baranski ◽  
Coraline Fafin ◽  
Guillaume Extermann ◽  
Cecile Vigneau ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Elderly Patients ◽  
Healthcare Providers ◽  
Antihypertensive Agents ◽  
The Elderly ◽  
Anticholinergic Drugs ◽  
Cross Sectional ◽  
Dose Modification ◽  
Severe Impairment

Abstract Background Elderly patients with chronic kidney disease (CKD) frequently present comorbidities that put them at risk of polypharmacy and medication-related problems. This study aims to describe the overall medication profile of patients aged ≥ 75 years with advanced CKD from a multicenter French study and specifically the renally (RIMs) and potentially inappropriate-for-the-elderly medications (PIMs) that they take. Methods This is a cross-sectional analysis of medication profiles of individuals aged ≥ 75 years with eGFR < 20 ml/min/1.73m2 followed by a nephrologist, who collected their active prescriptions at the study inclusion visit. Medication profiles were first analyzed according to route of administration, therapeutic classification. Second, patients were classified according to their risk of potential medication-related problems, based on whether the prescription was a RIM or a PIM. RIMs and PIMs have been defined according to renal appropriateness guidelines and to Beer’s criteria in the elderly. RIMs were subclassified by 4 types of category : (a) contraindication; (b) dose modification is recommended based on creatinine clearance (CrCl); (c) dose modification based on CrCl is not recommended but a maximum daily dose is mentioned, (d) no specific recommendations based on CrCl : “use with caution”, “avoid in severe impairment”, “careful monitoring of dose is required” “reduce the dose”. Results We collected 5196 individual medication prescriptions for 556 patients, for a median of 9 daily medications [7-11]. Antihypertensive agents, antithrombotics, and antianemics were the classes most frequently prescribed. Moreover, 77.0% of patients had at least 1 medication classified as a RIM. They accounted 31.3% of the drugs prescribed and 9.25% was contraindicated drugs. At least 1 PIM was taken by 57.6% and 45.5% of patients had at least one medication classified as RIM and PIM. The prescriptions most frequently requiring reassessment due to potential adverse effects were for proton pump inhibitors and allopurinol. The PIMs for which deprescription is especially important in this population are rilmenidine, long-term benzodiazepines, and anticholinergic drugs such as hydroxyzine. Conclusion We showed potential drug-related problems in elderly patients with advanced CKD. Healthcare providers must reassess each medication prescribed for this population, particularly the specific medications identified here.

Drug Dosing in the Elderly Patients with Chronic Kidney Disease

2009 ◽  
Vol 25 (3) ◽  
pp. 459-527 ◽  
Author(s):  
Ali J. Olyaei ◽  
William M. Bennett
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Elderly Patients ◽  
The Elderly ◽  
Drug Dosing

scholarly journals Quantification of CYP3A and drug transporters activity in healthy young, healthy elderly and chronic kidney disease elderly patients by a microdose cocktail approach

2021 ◽  
Author(s):  
Punyabhorn Rattanacheeworn ◽  
Stephen Kerr ◽  
Wonngarm Kittanamongkolchai ◽  
Natavudh Townamchai ◽  
Suwasin Udomkarnjananun ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Half Life ◽  
Dabigatran Etexilate ◽  
Geometric Mean ◽  
The Elderly ◽  
Maximum Plasma ◽  
Cancer Resistance ◽  
Time Curve ◽  
Healthy Elderly

Aims: Ageing and chronic kidney disease (CKD) are known to affect pharmacokinetics (PK) parameters. Since mechanisms are related and remain unclear, cytochrome P450 (CYP)3A and drug transporter activity were investigated in the elderly with or without CKD and compared to healthy adults using a microdose cocktail. Methods: Healthy young volunteers (n = 20), healthy elderly volunteers (n = 16) and elderly with CKD (n = 17) received a single dose of microdose cocktail probe containing 30 µg midazolam, 750 µg dabigatran etexilate, 100 µg atorvastatin, 10 µg pitavastatin, and 50 µg rosuvastatin. After a 14-day washout period, healthy young volunteers continued to study period 2 with the microdose cocktail plus rifampicin. PK parameters including area under the concentration-time curve (AUC), maximum plasma drug concentration (Cmax) and half-life were estimated before making pairwise comparisons of geometric mean ratios between groups. Results: AUC and Cmax of midazolam, a CYP3A probe substrate, were increased 2.30 and 2.90 fold in healthy elderly and elderly with CKD, respectively, leading to a prolonged half-life. AUC and Cmax of atorvastatin, another CYP3A4 probe substrate, was increased 2.14 fold in healthy elderly and 4.15 fold in elderly with CKD, indicating decreased CYP3A4 activity related to ageing. Association with PK changes in probe drugs representing activity of OATP1B1, intestinal P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP) transporters was noticed, but were inconclusive. Conclusions: CYP3A activity is reduced in ageing. There is a trend in changes of OATP1B1, P-gp, and BCRP activity measured by microdose cocktail probe drugs.

scholarly journals Medication Burden and Inappropriate Prescription Risk Among Elderly With Advanced Chronic Kidney Disease

2020 ◽  
Author(s):  
Clarisse Roux-Marson ◽  
Jean-Baptiste Baranski ◽  
Coraline Fafin ◽  
Guillaume Extermann ◽  
Cecile Vigneau ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Elderly Patients ◽  
Healthcare Providers ◽  
Antihypertensive Agents ◽  
The Elderly ◽  
Anticholinergic Drugs ◽  
Cross Sectional ◽  
Dose Modification ◽  
Severe Impairment

Abstract Background Elderly patients with chronic kidney disease (CKD) frequently present comorbidities that put them at risk of polypharmacy and medication-related problems. This study aims to describe the overall medication profile of patients aged ≥ 75 years with advanced CKD from a multicenter French study and specifically the renally (RIMs) and potentially inappropriate-for-the-elderly medications (PIMs) that they take. Methods This is a cross-sectional analysis of medication profiles of individuals aged ≥ 75 years with eGFR < 20 ml/min/1.73m2 followed by a nephrologist, who collected their active prescriptions at the study inclusion visit. Medication profiles were first analyzed according to route of administration, therapeutic classification. Second, patients were classified according to their risk of potential medication-related problems, based on whether the prescription was a RIM or a PIM. RIMs and PIMs have been defined according to renal appropriateness guidelines and to Beer’s criteria in the elderly. RIMs were subclassified by 4 types of category : (a) contraindication; (b) dose modification is recommended based on creatinine clearance (CrCl); (c) dose modification based on CrCl is not recommended but a maximum daily dose is mentioned, (d) no specific recommendations based on CrCl : “use with caution”, “avoid in severe impairment”, “careful monitoring of dose is required” “reduce the dose”. Results We collected 5196 individual medication prescriptions for 556 patients, for a median of 9 daily medications [7-11]. Antihypertensive agents, antithrombotics, and antianemics were the classes most frequently prescribed. Moreover, 77.0% of patients had at least 1 medication classified as a RIM. They accounted 31.3% of the drugs prescribed and 9.25% was contraindicated drugs. At least 1 PIM was taken by 57.6% and 45.5% of patients had at least one medication classified as RIM and PIM. The prescriptions most frequently requiring reassessment due to potential adverse effects were for proton pump inhibitors and allopurinol. The PIMs for which deprescription is especially important in this population are rilmenidine, long-term benzodiazepines, and anticholinergic drugs such as hydroxyzine. Conclusion We showed potential drug-related problems in elderly patients with advanced CKD. Healthcare providers must reassess each medication prescribed for this population, particularly the specific medications identified here.

scholarly journals Structural and functional changes in the kidneys and their effect on cardiovascular risk in elderly patients

2020 ◽  
Vol 43 (4) ◽  
pp. 539-548
Author(s):  
Natalya I. Golovina ◽  
◽  
Yury A. Lykov ◽  
Keyword(s):  
Chronic Kidney Disease ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Elderly Patients ◽  
Structural Changes ◽  
Interstitial Fibrosis ◽  
The Elderly ◽  
Functional Changes ◽  
Age Related ◽  
Organ Systems

Like other organ systems, the kidneys also go through process of normal senescence, including both anatomical and physiological changes. Normal physiological aging is characterized by the expected age-related changes in the kidneys. With age, the kidneys are subject to structural changes, for example, there is a decrease in the number of functional glomeruli due to an increase in the prevalence of nephrosclerosis (atherosclerosis, glomerulosclerosis, atrophy of the tubules with interstitial fibrosis) and to some extent compensatory hypertrophy of the remaining nephrons. Older age is also associated with reduced cortical volume, increased medullary, and larger and more numerous renal cysts. Changes in normal aging are important in clinical practice. Against the background of suppression of reparative capabilities, the elderly are more prone to acute damage and chronic kidney disease, aggravation of the course of chronic kidney disease. The elderly have less renal functional reserve when they do actually develop chronic kidney disease and they are also at higher risk for acute kidney injury. Cardiovascular disease is a leading cause of death and a common comorbidity among patients with kidney disease. In this review, we have identified the most characteristic structural and functional changes in the kidneys in elderly patients and their impact on cardiovascular risk.

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