Meta-analysis: ribavirin-induced haemolytic anaemia in patients with chronic hepatitis C

AIM: To use meta-analysis to study the risk of anaemiarelated to ribavirin therapy for chronic hepatitisC. METHODS: The MEDLINE database up to January 2001 was searched for randomized controlled trials of ribavirin (monotherapy or combined with interferon) for chronic hepatitis C. The outcomes evaluated were withdrawal from the study due to anaemia, ribavirin dosage reduction due to a decrease in haemoglobin and haemoglobin levels below 10 g/dL. RESULTS: Based on 17 studies, the overall risk difference (ribavirin vs. no ribavirin) for anaemia was 0.09 [95% confidence interval (CI), 0.04-0.13]. Two Asian studies reported risk differences of 0.29 and 0.22, greater than the pooled risk difference of 0.07 (95% CI, 0.03-0.12) for 15 non-Asian studies. The risk associated with 1 g or more of ribavirin per day was higher (risk difference, 0.09; 95% CI, 0.04-0.14) than that for 0.8 g of ribavirin per day (risk difference, 0.01; 95% CI, - 0.04-0.06). CONCLUSIONS: Chronic hepatitis C patients treated with 1 g or more of ribavirin per day were at a higher risk of developing anaemia. Reported risks were higher among Asian studies, which may be due to differences in study entrance criteria, dosage titration strategy or ethnic vulnerability.     

Epoetin delta is effective for the management of anaemia associated with chronic kidney disease

ABSTRACT

Objective: To demonstrate the efficacy and safety of epoetin delta for the treatment of anaemia in dialysis patients with chronic kidney disease (CKD).

Research design and methods: This was a 12‐week, randomized, double-blind, active-comparator study. CKD patients who were naïve to epoetin treatment and had haemoglobin < 10?g/dL were randomized to epoetin delta 15, 50, 150, or 300 IU/kg or epoetin alfa 50 IU/kg. Patients initially entered a correction phase until they recorded haemoglobin of ≥ 11.5?g/dL for two consecutive weekly measurements or one haemoglobin measurement of ≥ 13?g/dL (correction success). A maintenance phase followed where the dose was adjusted to maintain haemoglobin ≥ 10.5?g/dL. Maintenance success was defined as haemoglobin > 10.5?g/dL at Week 12. Total success was defined as achieving maintenance and correction success.

Main outcome measures: The primary objective was to demonstrate that the proportion of patients achieving total success was greater in the pooled 150?IU/kg and 300?IU/kg groups compared with the 15?IU/kg dose group.

Results: Total success was achieved in 55.6% of patients in the pooled highest epoetin delta group compared with 4.5% in the lowest dose group. There was no significant difference in total success for the epoetin delta and epoetin alfa 50?IU/kg groups. Significant increases in haemoglobin and haematocrit levels were observed in the 150 and 300?IU/kg dose groups. Adverse events occurred at frequencies expected for this patient group.

Conclusions: Epoetin delta was effective in increasing haemoglobin levels in patients with baseline haemoglobin of < 10?g/dL.     

Recombinant human erythropoietin for the treatment of renal anaemia in children: no justification for bodyweight-adjusted dosage

BACKGROUND: Drug doses for children are usually calculated by reducing adult doses in proportion to bodyweight. The clinically effective dose of recombinant human erythropoietin (epoetin) in children, however, seems to be higher than predicted by this calculation. OBJECTIVE: To determine the quantitative relationship between epoetin dose, bodyweight and response in children with end-stage renal disease. PATIENTS AND METHODS: The time-course of haemoglobin in 52 children during long-term treatment with epoetin beta was analysed by population pharmacodynamic modelling. Patients were 5-20 years old and weighed 16-53kg at the beginning of treatment. Epoetin beta was given intravenously three times per week after haemodialysis. Doses ranged from 110 to 7500IU (3-205 IU/kg). Haemoglobin versus time was described by assuming that the haemoglobin level rises after each dose due to the formation of new red blood cells, which then survive according to a logistic function. The initial rise after each dose was modelled in terms of absolute dose (not dose/kg). A parametric analysis was done with NONMEM, followed by a nonparametric analysis with NPAG. RESULTS: Dose-response was best described by a sigmoid maximum-effect (E(max)) model with median E(max) = 0.29 g/dL, median 50% effective dose (ED(50)) = 2400IU and shape parameter gamma = 2. The estimated median survival time of the epoetin-induced red blood cells, tau, was 76 days. Neither of the dose-response parameters E(max) and ED(50) showed dependence on bodyweight. The median haemoglobin response to a standard dose, 0.042 g/dL for 1000IU, was similar to that reported for adults with intravenous administration. CONCLUSIONS: Doses for children in this age range should be specified as absolute amounts rather than amounts per unit bodyweight. Initial doses can be calculated individually, based on haemoglobin level before treatment, the desired haemoglobin at steady state and the median population parameters E(max), ED(50) and tau.     

Should all patients with unexplained anaemia be screened for chronic lead poisoning?

The global prevalence of lead poisoning is declining. However, the prevalence of lead poisoning in patients with either microcytic or normocytic anaemia is unknown. Blood samples from anaemic patients residing in south-east London without an obvious cause for anaemia had their blood lead concentration (BLC) analysed. A batch of 988 samples was analysed for BLC using atomic absorption spectroscopy. Median haemoglobin was 10.3 g/dL (range: 4.2-10.9) in females, 10.6 g/dL (range: 5.2-11.4) in males and 10.7 g/dL (range: 6.7-10.9) in children. Median BLC was 2.63 microg/dL (0.21-24.0 microg/dL; 95th centile 7.54 microg/dL). Fifteen samples (1.5%) had a BLC > 10.0 microg/dL, five samples (1%) > 15.0 microg/dL and one sample (0.1%) > 20.0 micrg/L. In the 106 children, median BLC was 2.34 microg/dL (0.5-14.5 microg/dL; 95th centile 6.12 microg/ dL). Only one child (14.5 microg/L) had a BLC > 10.0 pg/dL. There was a poor correlation between haemoglobin and BLC (r2 = 0.08). Routine screening for lead poisoning cannot be justified in all patients with unexplained anaemia, unless there is a history or clinical features to suggest lead toxicity. Additionally, we have shown that in this former high-risk area for lead exposure, there is a low point prevalence of significant lead poisoning, even in an anaemic population.     

Anti-viral therapy in haemodialysed HCV patients: efficacy, tolerance and treatment strategy

Aliment Pharmacol Ther 2011; 34: 454–461

Summary

Background In end‐stage renal disease (ESRD) patients, hepatitis C virus (HCV) eradication improves patient and graft survival. Aim To determine optimal use of erythropoietin (EPO) and ribavirin, to compare ribavirin concentrations with those of HCV patients having normal renal function and to evaluate sustained virological response (SVR) in a prospective observatory of ESRD candidates for renal transplantation. Methods Thirty‐two naïve patients were treated with Peg‐IFN‐α2a and ribavirin. Two different schedules of ribavirin and EPO administration were used: starting ribavirin at 600 mg per week and adapting EPO when haemoglobin (Hb) fell below 10 g/dL (adaptive strategy) or starting ribavirin at 1000 mg per week while increasing EPO from the start of treatment (preventive strategy). Results Patients treated with the adaptive strategy had lower median Hb levels (9.6 vs. 10.9 g/dL, P = 0.02) and more frequent median Hb levels below 10 g/dL (58 vs. 5%, P = 0.0007) despite lower median ribavirin doses (105 vs. 142 mg/day, P < 0.0001) than patients treated with the preventive strategy. There was a trend for more frequent transfusion in patients treated with the adaptive strategy than in patients treated with preventive strategy (50 vs. 20%, P = 0.08). Compared to patients with normal renal function, ESRD patients had lower ribavirin concentrations during the first month (0.81 vs. 1.7 mg/L, P = 0.007) and similar concentrations thereafter. SVR was reached in 50%. Conclusions Pegylated interferon (Peg‐IFN) and an adapted schedule of ribavirin are effective in ESRD patients. Increasing EPO from the start of treatment provides better haematological tolerance. The optimal dosage of ribavirin remains unresolved, in light of frequent side effects.     

Guidelines and recommendations for the management of anaemia in patients with lymphoid malignancies

Patients with lymphoid malignancies frequently require repetitive and intensive anticancer treatments to induce and maintain disease remission. Anaemia (haemoglobin [Hb] <12 g/dL) is a common and debilitating problem associated with both the malignancy itself and its treatment burden. Anaemia negatively impacts on all aspects of patient quality of life (QOL) and treatment outcomes and survival, particularly in this disease setting.Widely acknowledged goals of anaemia treatment include Hb correction to approximately 12 g/dL, reduction in transfusion requirements and optimisation of patient QOL. Since the introduction of recombinant human erythropoietic therapy, transfusion (once the only anaemia treatment option available) is now primarily reserved for non-responders or those with severe or life-threatening anaemia. Data from randomised, double-blind, placebo-controlled studies, and large, non-randomised, open-label, community-based studies, along with almost 15 years of practical experience, support the assertion that epoetin alfa administered at a dosage of 150-300 U/kg three times weekly or 40,000-60,000U once weekly, both of which are US FDA-approved dose administration schedules, can effectively and safely achieve anaemia treatment goals for the majority of patients with lymphoid malignancies. Data and practical experience collected over the last 5 years on another erythropoietic agent with a slightly longer half-life but lower binding affinity, darbepoetin alfa, show that this agent when administered according to the FDA-approved dose administration schedules (2.25-4.5 microg/kg once weekly or 500microg once every 3 weeks) or according to a commonly-administered dose in clinical practice (3.0-5.0 microg/kg once every 2 weeks) can also effectively and safely correct anaemia, reduce transfusion requirements and improve QOL in many patients with lymphoid malignancies. One comparative head-to-head trial suggested that epoetin alfa might be superior to darbepoetin alfa in anaemic cancer patients receiving chemotherapy with respect to timing and magnitude of Hb correction, although further study is necessary, especially concerning optimal dose administration. Alternative dose administration schedules, such as epoetin alfa 80,000U every 2 weeks from initiation or 80,000U every 3 weeks following initiation with once weekly administration and darbepoetin alfa 4.5 microg/kg every 3 weeks following initiation with once weekly administration, are being actively investigated with the goal of increased flexibility for patients and healthcare providers.The treatment of anaemia in patients with lymphoid malignancies is an important part of overall disease management, as evidenced by continuous investigation of existing erythropoietic agents and new agents. Although treatment guidelines issued by organisations such as the National Comprehensive Cancer Network (NCCN) and American Society of Hematology (ASH)/American Society of Clinical Oncology (ASCO) suggest intervention with erythropoietic therapy when Hb falls below 10-11 g/dL or based on clinical symptoms, data suggest that anaemia is vastly under-recognised and under-treated. Clearly, an update on the definition, identification and optimal management of anaemia in patients with lymphoid malignancies is warranted.     

Large hiatal hernia in patients with iron deficiency anaemia: a prospective study on prevalence and treatment

BACKGROUND: Although large hiatal hernia may cause bleeding from Cameron erosions, its role in iron deficiency anaemia has been debated, and no data are available on the treatment of these patients with proton pump inhibitors. Aims : To determine the prevalence of large hiatal hernia in out-patients with iron deficiency anaemia and the role of proton pump inhibitors in the prevention of recurrence of anaemia. METHODS: Two hundred and twenty-eight out-patients underwent upper/lower endoscopy. Those with large hiatal hernia were given an oesophagogram, discontinued iron supplementation and received proton pump inhibitor treatment with (group 1) or without (group 2) surgery. Anaemia was re-assessed during 1 year of follow-up. RESULTS: Large hiatal hernia was the likely cause of anaemia in 21 patients (9.2%). The median haemoglobin and ferritin values at the diagnosis of anaemia were 7.9 g/dL and 6 micro g/L, respectively. Cameron erosions were found in 33% of patients. Ten and eleven patients were included in groups 1 and 2, respectively. Haemoglobin values were 13.8 g/dL and 13.4 g/dL at 3 months of follow-up, and 13.4 g/dL and 13.8 g/dL at 1 year of follow-up, in groups 1 and 2, respectively. CONCLUSIONS: Large hiatal hernia may cause iron deficiency anaemia, even without Cameron erosions. Surgery in combination with proton pump inhibitor therapy is no better than proton pump inhibitor therapy alone in preventing the recurrence of anaemia.     

Short report: the effect of misoprostol on the anaemia of NSAID enteropathy

Background: Small bowel ulceration is an increasingly recognised complication of therapy with non-steroidal anti-inflammatory drugs (NSAID). The ulceration is a potent site of blood loss contributing to unexplained iron deficiency anaemia in patients with arthritis. No drug is currently available to treat NSAID small bowel ulcers. Methods: We have retrospectively examined the effect of therapy with the prostaglandin El analogue misoprostol on the anaemia of patients with enteroscopically proven NSAID small bowel enteropathy. Results: All of the patients had proven iron deficiency anaemia. Eleven patients received misoprostol and ten received no treatment. Haemoglobin in the misoprostol-treated group rose significantly from median (range) 9.1 (6.2–10.6) g/dL (95% confidence intervals 8.76, 10.13) to 10.6 (6.5–16.8) g/dL (95% confidence intervals 10.06, 11.82); P= 0.004). Those patients who did not receive misoprostol had no significant change in their haemoglobin: 9.1 (7.5–10.6) g/dL to 8.1 (5.6–14.7) g/dL (P= N.S.). Conclusion: Misoprostol therapy was associated with an improvement in the anaemia in patients with proven NSAID enteropathy.     

Epoetin delta,erythropoietin produced in a human cell line,in the management of anaemia in predialysis chronic kidney disease patients

ABSTRACT

Objective: To demonstrate safety and efficacy of epoetin delta for the management of anaemia in predialysis patients with chronic kidney disease (CKD).

Research design and methods: This was a multicentre, open-label, uncontrolled study with predialysis CKD patients who had previously received subcutaneous epoetin therapy. Patients were switched to epoetin delta from their previous therapy, at an identical dose. Dose was subsequently titrated to maintain haemoglobin at 10.0–12.0?g/dL. Study duration was 52 weeks.

Main outcome measures: The primary endpoint was average haemoglobin levels over Weeks 12, 16, 20 and 24. Secondary analyses were performed on the proportion of patients with haemoglobin and haematocrit levels over preset target levels, haemoglobin and haematocrit levels through to study end and dosing levels.

Results: Haemoglobin levels were maintained at 11.3 ± 1.2?g/dL over Weeks 12–24. Over 80% of the haemoglobin measurements and 95% of the haematocrit measurements were above the predefined target level (haemoglobin ≥ 10?g/dL; haematocrit ≥ 30%). Weekly dose levels did not change significantly over the course of the trial. Epoetin delta was well tolerated, with adverse events occurring at frequencies expected for this patient population; no patient developed neutralizing anti-erythropoietin antibodies.

Conclusions: Epoetin delta was an effective and well-tolerated agent for the management of anaemia in a subgroup of predialysis CKD patients.     

A prospective observational study of the effectiveness,safety, and effect on fatigue of darbepoetin alfa for the treatment of chemotherapy-induced anaemia

ABSTRACT

Objective: Anaemia is common in cancer patients treated with chemotherapy. Darbepoetin alfa (DA) is the only erythropoiesis-stimulating protein approved for administration at weekly and every-three-week intervals in cancer patients receiving chemotherapy. This article investigates the effectiveness, tolerability and effect on fatigue of DA.

Methods: Prospective, observational study performed in 30 Spanish centres. Eligible patients were ≥?18?years of age, anaemic (haemoglobin [Hb] ≤?11?g/dL), with non-myeloid malignancies, receiving chemotherapy. DA (150?μg) was administered weekly for a maximum of 16?weeks (dosage doubled if Hb increased <?1?g/dL after 4?weeks).

Main outcome measures: Haematopoietic response (Hb increase ≥?2?g/dL or Hb ≥?12?g/dL in the absence of transfusions in the previous 28?days), transfusion required between Weeks 5 and 16 and fatigue measured by the Fatigue subscale of the Functional Assessment of Cancer Therapy.

Results: 293 adults were recruited (56.4% women), with lymphoproliferative malignancies (44.3%) or solid tumours (55.7%). Baseline Hb was 9–11?g/dL in 83.7% of patients. Sixty-four per cent (95% CI: 58.1–69.4%) had a haematopoietic response and 12% required transfusions. After adjusting for performance status, concomitant diseases and chemotherapy type, an increase in Hb level was significantly associated with an improvement in Fatigue subscale (+1.9 points per 1?g/dL). Only 2% of patients had treatment-related adverse events: thromboembolic pulmonary disease (0.3%); hypersensitivity reaction (0.3%); local pain following DA administration (0.3%); insomnia (0.3%); thrombocytosis (0.3%) and deep vein thrombosis (0.3%).

Conclusions: Fixed-dose DA administered once weekly seems to be an effective, well-tolerated treatment for chemotherapy-induced anaemia in patients with non-myeloid malignancies, and there is an indication of a possible benefit on fatigue in the clinical practice.     

Predicting sustained virological response and anaemia in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) plus ribavirin

AIM: To assess the likelihood of a sustained virological response (SVR) vs. the likelihood of anaemia in patients with chronic hepatitis C. METHODS: Data from 1732 patients treated with peginterferon alfa-2a (40KD) plus ribavirin in two randomized, multinational studies were pooled. Probabilities of SVR and anaemia were modelled using the generalized additive logistic model, with numerous clinical variables considered for entry into the model. Baseline haemoglobin was only considered in the analysis for anaemia. RESULTS: The probability of anaemia increased from 6 to 16% as a function of the ribavirin dose kg(-1) (12-16 mg kg(-1)), whereas the relationship between SVR and ribavirin dose kg(-1) was influenced by hepatitis C virus (HCV) genotype. The probability of an SVR was not influenced by the ribavirin dose kg(-1) in patients with HCV genotype 2 or 3 infection, but increased as a function of ribavirin dose kg(-1) in patients with HCV genotype 1 infection (40-50% increase in probability of SVR for 12-16 mg kg(-1) dose ribavirin increase). The probability of an SVR in patients included with HCV genotype 1 decreased with increasing HCV RNA level to about 3 million copies ml(-1), but was relatively independent of increasing HCV RNA level thereafter. In addition, older age, a higher ribavirin apparent oral clearance and cirrhosis had a negative impact on achieving an SVR, but improved with increasing alanine aminotransferase (ALT) quotient. Sex and ribavirin dose kg(-1) were the most important prognostic factors for anaemia, followed by baseline haemoglobin, age, baseline ALT quotient and cirrhosis. CONCLUSION: This study supports individualizing ribavirin dosages by HCV genotype and body weight, and highlights several clinical variables that influence the likelihood of an SVR compared with anaemia in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) plus ribavirin.     

A study of the response of elderly patients with end-stage renal disease to epoetin alfa or beta

BACKGROUND: Anaemia correction in patients with end-stage renal disease has been enhanced following the use of epoetin alfa or beta and there are a number of studies detailing its application. Dialysis centres are dealing with greater numbers of elderly patients and anaemia correction in these individuals may differ by virtue of co-existing comorbidity and their age. OBJECTIVE: The aim of this study was to examine the response of the elderly patients to anaemia correction using a locally devised anaemia correction protocol while receiving dialysis. METHODS: An incident, non-randomised, cohort observational study in a single centre was used to compare the correction of anaemia in a population of elderly (> or =65 years of age) and young dialysis patients. All incident patients starting peritoneal dialysis and haemodialysis (HD) between January 1998 and December 2000 were selected and treated using a locally devised anaemia correction protocol and observed for at least 1 year. Anaemia correction following adjustments for factors such as age, comorbidity, dialysis type, dialysis access type and predialysis nephrological care was assessed. RESULTS: 198 patients commenced dialysis with 86 elderly patients (mean age +/- SD 73.7 +/- 4.9 years). The elderly patients had similar periods of predialysis nephrological care as the younger patients. Most patients received HD and required a tunnelled dialysis catheter (TC) as vascular access. Equivalent numbers of elderly patients received peritoneal dialysis. Comorbid scores were greater in the elderly and patient survival was dependent upon these comorbid factors. Following the strict use of TCs, patient survival was similar to those patients commencing HD with arterio-venous fistulae.Anaemia correction in the elderly was similar to the younger patients, with a median haemoglobin of 11.3 g/dL. By 6 months of dialysis, most patients achieved the UK Renal Association anaemia correction standard (haemoglobin above 10 g/dL). The elderly patients maintained significantly higher serum ferritin levels throughout (median 209 microg/L) and required less epoetin alfa or beta (median 91.6 units/kg/wk), indicating that functional iron deficiency in the elderly dialysis patients is less. Intravenous iron sucrose doses were similar in both age groups and iron overload (serum ferritin above 800 microg/L) had been avoided following the use of the intravenous iron protocol. CONCLUSION: The study has noted that elderly patients responded to anaemia corrective therapies as well as the younger patients, despite greater levels of comorbidity while requiring less epoetin alfa or beta.     

High-dose vitamin E supplementation does not diminish ribavirin-associated haemolysis in hepatitis C treatment with combination standard alpha-interferon and ribavirin

BACKGROUND: Ribavirin is associated with haemolytic anaemia. Antioxidants have been reported to decrease severity of this anaemia. AIM: To determine effect of vitamin E supplementation on ribavirin-associated haemolysis in chronic hepatitis C treated with standard alpha-interferon and ribavirin. METHODS: Fifty-one naive chronic hepatitis C patients were randomized to receive either alpha-interferon/ribavirin therapy (control) or therapy plus vitamin E 800 IU b.d. with 24-week follow-up. Alanine aminotransferase ALT, haemoglobin and reticulocyte percentage were monitored. Symptoms and health-related quality of life were also monitored at each visit. RESULTS: Forty-seven subjects were treated (27 vitamin E /20 controls). Thirteen withdrew because of adverse effects or non-compliance. Groups were similar in demographics, genotype and baseline lab indices. Comparison with baseline, treatment and follow-up values showed a significant haemoglobin and ALT reduction in both groups. There was no significant difference in haemoglobin and reticulocyte percentage between groups. Sustained viral response was not significantly different between vitamin E (11/18) and control (6/16) groups. Three patients required ribavirin dose-reduction in the vitamin E group compared with two controls. Health-related quality of life during and end-of-treatment was not different between groups. CONCLUSIONS: Vitamin E supplementation alone during standard alpha-interferon and ribavirin therapy does not appear to diminish ribavirin-associated haemolysis.     

Comparison of the therapeutic effects of epoetin zeta to epoetin alfa in the maintenance phase of renal anaemia treatment

ABSTRACT

Objective: To evaluate the therapeutic efficacy and safety of epoetin zeta, compared with epoetin alfa, in maintaining target haemoglobin (Hb) concentrations in patients with anaemia and chronic kidney disease (CKD) maintained on haemodialysis.

Methods: Patients received epoetin zeta or epoetin alfa intravenously, 1–3 times/week for 12 weeks, then the alternative treatment for 12 weeks, in this double-blind, crossover, phase III trial. Eligible patients were 18–75 years old with CKD stage 5 maintained on haemodialysis. Patients had received epoetin for ≥ 3 months upon study entry and had achieved a target Hb level of 10.5–12.5?g/dL with a stable epoetin dose.

Main outcome measures: Primary efficacy endpoints were intra-individual differences (test–reference) in mean Hb levels and mean weekly dose/kg of body weight. Safety endpoints included occurrence of neutralizing anti-erythro­poietin antibodies, tolerability, and adverse events (AEs).

Results: In total, 313 patients were randomized to receive epoetin zeta (n = 155) or epoetin alfa (n = 158); 146 and 145 patients (respectively) switched treatment after 12 weeks. Mean (range) Hb levels were 11.35 (8.96–14.22) g/dL and 11.54 (8.74–13.84) g/dL for patients receiving epoetin zeta and epoetin alfa, respectively (95% confidence interval [CI] [test–reference]: 0.09–0.28?g/dL, within the predefined equivalence range of ±?0.6?g/dL). Mean (range) weekly doses were 92.68 (12.74–398.41) IU/kg/wk and 92.58 (10.53–393.07) IU/kg/wk for patients receiving epoetin zeta and epoetin alfa, respectively (95% CI [test–reference]: –4.67 and 4.29 IU/kg/wk, within the equivalence range of ±?45.00?IU/kg/wk). Patients underwent minor nominal dose adjustments during treatment crossover. AE profile was similar for both products; the most commonly reported AEs were infections and infestations (in 26.5% of patients receiving epoetin zeta and 23.6% receiving epoetin alfa). No patients developed neutralizing anti-erythropoietin antibodies.

Conclusions: Epoetin zeta is therapeutically equivalent to epoetin alfa in the maintenance of target Hb levels in patients with renal anaemia. No unexpected AEs were seen.     

Epoetins and [symbol: see text] darbepoetin alfa in malignant disease

Anaemia is common in people with cancer, and may reduce their quality of life and life expectancy. Blood transfusion can increase haemoglobin levels but is usually reserved for those with moderate anaemia (haemoglobin level below 10 g/dL). A potential alternative is treatment with one of the human recombinant forms of erythropoietin, epoetin alfa (Eprex--Janssen-Cilag) or epoetin beta (NeoRecormon--Roche), or their hyperglycosylated derivative [symbol: see text] darbepoetin alfa (Aranesp--Amgen). These products have improved the management of patients with chronic renal failure who are anaemic. Here we assess the place of the epoetins and darbepoetin alfa in managing anaemia in patients with cancer.     

Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) : a registry for characterizing anaemia management and outcomes in oncology patients

BACKGROUND AND OBJECTIVE: To report the design, methodology, implementation and initial results of the Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) Registry, the first US patient registry to collect and report on practice patterns and outcomes associated with erythropoiesis-stimulating therapy (EST) for anaemia management in oncology patients. METHODS: DOSE is a prospective ongoing registry of oncology patients treated with epoetin-alpha or darbepoetin-alpha. Patients from either community or academic centres who meet prespecified entry criteria are eligible for inclusion in the registry. Data collected include patient demographic and clinical characteristics, EST administration, haematological parameters, patient-reported outcomes and medical resource utilization. Patients are followed from EST initiation through to the end of therapy or 16 weeks, whichever is earlier. RESULTS: Initial results from 45 sites for 861 patients (epoetin-alpha, n = 312; darbepoetin-alpha, n = 549) showed that baseline demographic and disease characteristics were similar between the two treatment groups. Administration of EST at both weekly and > or =2-weekly intervals was observed in both groups, with similar numbers of haemoglobin determinations. However, the mean number of office visits was higher in the darbepoetin-alpha group despite more frequent administration of therapy at > or =2-weekly intervals in this group. Mean treatment duration was approximately 8 weeks for both groups. Mean post-baseline haemoglobin levels of 11-12 g/dL were achieved and maintained at all timepoints assessed with epoetin-alpha but not with darbepoetin-alpha. Both groups had similar rates of packed red blood cell transfusions. CONCLUSIONS: The DOSE Registry is a valuable source of data relating to anaemia management, practice patterns and outcomes in oncology patients from the perspective of actual clinical practice. Results from this registry should provide patients, clinicians and healthcare decision makers with a better understanding of the relationship between EST dosage and outcomes in the clinical setting.     

Haematopoietic effects of Angelica sinensis root cap polysaccharides against lisinopril-induced anaemia in albino rats

Context: Angelica sinensis L. (Umbelliferae) has medicinal properties.

Objectives: The present study evaluates the haematopoietic effects of A. sinensis polysaccharides (ASP) against lisinopril-induced anaemia.

Materials and methods: Thirty healthy adult male albino rats were randomly divided into five groups (n?=?6). Group I was control group. Group II was treated with angiotensin-converting enzyme inhibitor (ACEI, 20?mg/kg/day) to induce anaemia. In group III, erythropoietin (EPO, 100?IU/kg/each) was administered in combination with ACEI. Group IV was treated with ASP (1?g/kg/day), extracted from A. sinensis root caps. In Group V, ASP (1?g/kg/day) was treated with ACEI. After 28 days, blood and tissue samples were collected for haematological and histopathological analysis, respectively.

Results: The results showed that ACEI significantly reduced the haemoglobin (Hb, 10.0?g/dL), packed cell volume (PCV, 39.5%), red blood cells (RBCs, 6.2 million/mm³), mean corpuscular volume (MCV, 53.5 fL) and mean corpuscular haemoglobin (MCH, 16.2?pg/cell) values. In the group treated with ASP, the Hb (13.7?g/dL) and RBCs (7.8 million/mm³) increased significantly (p?p?3), MCV (54.42 fL) and MCH (16.44?pg/cell) values. While histopathological examination of the liver and kidney cells showed a mild degree of toxicity in the ASP-treated group.

Conclusion: ASP has a potentiating effect on haematological parameters when given alone. However, when administered simultaneously with lisinopril, it showed an unfavourable effect with more complicated anaemia so it should not be used with ACEIs.     

Dosage adjustment of ribavirin based on renal function in Japanese patients with chronic hepatitis C

The daily dose of ribavirin is currently determined based on body weight. In the present study, the authors examined factors influencing total plasma clearance (CL(total)) and the toxic level on red blood cells of ribavirin in such body weight-based dosage adjustment in Japanese chronic hepatitis C patients (13 male and 6 female). Patients received ribavirin (600 or 800 mg/d) orally, depending on their body weights, together with interferon alpha-2b (6 million units) intramuscularly. A steady-state trough plasma concentration (C(pss)) was achieved approximately 4 weeks after the initiation of treatment, but the value was scattered among patients in a range from 1100 to 4200 ng/mL. The high C(pss) of ribavirin of approximately 4000 ng/mL decreased hemoglobin concentrations to less than 8.5 g/dL. The individual CL(total), estimated by dividing dose normalized by body weight by C(pss), of ribavirin correlated significantly with the patient's creatinine clearance. In contrast, no relationship was observed with other parameters such as age, body weight, serum creatinine concentration, alanine aminotransferase (ALT) concentration, or aspartate aminotransferase (AST) concentration, though ALT and AST concentrations decreased with ribavirin treatment in most patients. These results indicate that CL(total) of ribavirin is dependent on renal function (creatinine clearance), and hemolysis is induced by high ribavirin concentrations in plasma. Dosage adjustment of ribavirin based on renal function and body weight would provide effective and safer treatment without causing hemolysis.     

The role of ITPA and ribavirin transporter genes polymorphisms in prediction of ribavirin‐induced anaemia in chronic hepatitis C Egyptian patients

Few data are available concerning the roles of polymorphisms of inosine triphosphatase (ITPA) gene and ribavirin (RBV) transporter genes in the prediction of RBV‐induced anaemia among Egyptians with chronic hepatitis C (CHC). Genotyping of three ITPA gene variants and two variants of RBV transporter genes has been performed in 123 patients under pegylated interferon‐α/ribavirin treatment. The baseline haemoglobin and ITPA rs1127354 CA/AA have been found as predictors of anaemia at 4, 8 and 12 weeks of RBV therapy. In addition, ITPA rs7270101 AC/CC and age predicted anaemia after 12 weeks of therapy. In conclusion, the ITPA variant rs1127354C>A significantly predict RBV‐induced anaemia during the first 3 months of treatment and it is recommended to be assessed before RBV administration.