- Comparative risk/benefit profile of biosimilar and originator erythropoiesis-stimulating agents (ESAs): data from an Italian observational study in nephrology. [Journal Article]
- EJEur J Clin Pharmacol 2018 Feb 10
- CONCLUSIONS: Biosimilar ESAs have similar risk/benefit profile compared to originators. Our data are in agreement with relevant scientific literature and, on the other hand, they are in contrast with common thought that considers biosimilar less efficacious and less safe than originators.
- Hyporesponsiveness to Darbepoetin Alfa in Patients With Heart Failure and Anemia in the RED-HF Study (Reduction of Events by Darbepoetin Alfa in Heart Failure): Clinical and Prognostic Associations. [Journal Article]
- CHCirc Heart Fail 2018; 11(2):e004431
- CONCLUSIONS: A poor response to darbepoetin alfa was associated with worse outcomes in heart failure patients with anemia. Patients with a poor response were difficult to identify using clinical and biochemical biomarkers.
- Change in Hemoglobin Trajectory and Darbepoetin Dose Approaching End-Stage Renal Disease: Data from the Trial to Reduce Cardiovascular Events with Aranesp Therapy Trial. [Journal Article]
- AJAm J Nephrol 2017; 46(6):488-497
- CONCLUSIONS: Our analyses provide descriptive insights regarding the temporal changes of Hb, darbepoetin dose, and related parameters as ESRD approaches in participants of TREAT. Hb declined as much as 1-2 years prior to the development of ESRD, without biochemical evidence of iron deficiency. The most precipitous decline occurred in the months immediately prior to ESRD, despite administration of escalating doses of darbepoetin and in parallel with an increase in CRP.
- Comparative Assessment of the Effect of Hyper-glycosylation on the Pattern and Kinetics of Degradation of Darbepoetin Alfa using a Stability-Indicating Orthogonal Testing Protocol. [Journal Article]
- JCJ Chromatogr B Analyt Technol Biomed Life Sci 2018 Jan 01; 1072:405-414
- Darbepoetin alfa (DA); hyper-glycosylated Erythropoietin alfa (EPO) is an essential treatment of anemia in patients with chronic kidney failure and cancer. In this study, DA and EPO were subjected to...
Darbepoetin alfa (DA); hyper-glycosylated Erythropoietin alfa (EPO) is an essential treatment of anemia in patients with chronic kidney failure and cancer. In this study, DA and EPO were subjected to physicochemical stress factors that might be encountered during production, transport and storage (pH, temperature, agitation, repeated freeze-thaw and oxidation). An orthogonal stability-indicating assay protocol comprised of SE-HPLC, RP-HPLC, ELISA and SDS-PAGE was developed and validated to investigate the effect of further glycosylation of DA on the pattern and kinetics of degradation. Results showed a relatively higher stability and lower tendency to form high molecular weight aggregates in the case of DA when compared to EPO, under equivalent stress conditions. Dimers and aggregates were formed for both drugs across the whole pH range and following incubation at temperatures higher than 2-8°C or repeated freeze/thaw. The same observation was noted upon agitation of standard samples prepared in the formulation buffers at high speed and upon oxidation with hydrogen peroxide. The agreement between SE-HPLC, supported with spectral purity data and ELISA confirmed the specificity of both techniques for the intact drugs. Results of RP-HPLC and SDS-PAGE indicated that dimerization occurred through disulfide and bi-tyrosine covalent bonds in the case of pH and oxidation, respectively. It was evident that aggregation was significantly suppressed upon increasing the glycan size and under any of the studied stress factors loss of the glycan has not been observed. These observations supported with the slow kinetics of degradation confirmed the superiority of glyco-engineering over chemical pegylation to enhance the stability of EPO. Formation of such potentially immunogenic product-related impurities at all tested stress factors confirmed the need for orthogonal testing protocols to investigate the complex pattern of degradation of such sensitive products.
- [The role of pharmacological preconditioning in renal ischemic and reperfusion injury]. [Review]
- UUrologiia 2017; (5):139-144
- Renal ischemic and reperfusion injury resulting in acute renal failure is a multidisciplinary problem at the junction of pathophysiology, transplantology, urology, nephrology, cardiac surgery and pha...
Renal ischemic and reperfusion injury resulting in acute renal failure is a multidisciplinary problem at the junction of pathophysiology, transplantology, urology, nephrology, cardiac surgery and pharmacology. One of renal protection strategies is using the phenomenon of preconditioning. Preconditioning is one of the ways to adopt a tissue to repeated short-term effects of damaging factors to induce an enhanced tolerance to the long period of hypoxia and/or ischemia. There are multiple cellular and molecular mechanisms of the renal protective effects of preconditioning stimuli, but the key effectors and signaling molecules are ATP-dependent potassium channels, nitric oxide synthase, nitric oxide, and mitochondrial pore. Contradictory data on the protective effect of ischemic preconditioning allow searching for approaches to pharmacological correction of ischemic and reperfusion injuries. The article provides data on possible ways of using erythropoietin, darbepoetin and phosphodiesterase 5 inhibitors.
- Efficacy and Long-Term Safety of C.E.R.A. Maintenance in Pediatric Hemodialysis Patients with Anemia of CKD. [Journal Article]
- CJClin J Am Soc Nephrol 2018 Jan 06; 13(1):81-90
- CONCLUSIONS: Using a defined conversion factor, 4-weekly C.E.R.A. was efficacious in maintaining hemoglobin levels in pediatric patients with stable anemia of CKD undergoing hemodialysis, switching from maintenance treatment with epoetin alfa/beta or darbepoetin. Safety was consistent with the known C.E.R.A. safety profile in adults.
- Prognostic importance of emerging cardiac, inflammatory, and renal biomarkers in chronic heart failure patients with reduced ejection fraction and anaemia: RED-HF study. [Journal Article]
- EJEur J Heart Fail 2017 Sep 27
- CONCLUSIONS: Once NT-proBNP is included, only hsTnT moderately further improved risk stratification in this group of chronic heart failure with reduced ejection fraction patients with moderate anaemia. NT-proBNP and hsTnT far outperform other emerging biomarkers in prediction of adverse outcome.
- Erratum to: Rationale and design of oBservational clinical Research In chronic kidney disease patients with renal anemia: renal proGnosis in patients with Hyporesponsive anemia To Erythropoiesis-stimulating agents, darbepoetiN alfa (BRIGHTEN Trial). [Published Erratum]
- CEClin Exp Nephrol 2018; 22(1):85-86
- De novo weekly and biweekly darbepoetin alfa dosing in pediatric patients with chronic kidney disease. [Journal Article]
- PNPediatr Nephrol 2018; 33(1):125-137
- CONCLUSIONS: Darbepoetin alfa can be safely administered either QW or Q2W to ESA-naïve pediatric patients with CKD-related anemia to achieve Hb targets of 10.0-12.0 g/dl.
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- Real-world utilization of darbepoetin alfa in cancer chemotherapy patients. [Journal Article]
- JOJ Oncol Pharm Pract 2017 Jan 01; :1078155217725571
- Objectives To provide an understanding of darbepoetin alfa dose patterns in cancer patients undergoing myelosuppressive chemotherapy starting from 2011. Study design This is a retrospective cohort st...
Objectives To provide an understanding of darbepoetin alfa dose patterns in cancer patients undergoing myelosuppressive chemotherapy starting from 2011. Study design This is a retrospective cohort study using a proprietary outpatient oncology database. Methods Metastatic, solid tumor cancer patients receiving concomitant myelosuppressive chemotherapy and darbepoetin alfa with an associated hemoglobin <10 g/dL during 2011-2015 were identified. The analysis was restricted to the first continuous exposure to chemotherapy agents (maximum allowable gap of 90 days between consecutive exposures) with darbepoetin alfa for each eligible patient. Initial, maintenance, weekly, and cumulative doses of darbepoetin alfa were examined across all darbepoetin alfa users. Subgroup analyses were conducted by chemotherapy type, baseline hemoglobin level, year of chemotherapy, solid tumor type, and initial dosing schedule. Differences in weekly doses across subgroups were evaluated using Wilcoxon rank-sum tests. Results Among 835 eligible patients, over 90% were 50 years or older. Mean chemotherapy course duration was 248 days, and mean duration of darbepoetin alfa treatment was 106 days. The mean weekly darbepoetin alfa dose was 110 µg. Patients received a mean of 4.3 darbepoetin alfa injections in the first chemotherapy course. There were no statistically significant differences (all P values > .05) in weekly dose by chemotherapy type, baseline hemoglobin level, year of chemotherapy, or solid tumor type. Conclusion The average weekly darbepoetin alfa dose among metastatic cancer patients with chemotherapy-induced anemia from this study was 110 µg, which was lower than the labeled dosage for most adults. This estimate did not differ over time, across chemotherapy regimens, baseline hemoglobin levels, or solid tumor types.