Effect of Patient Age, Dose, and Chronic Kidney Disease on the Risk of Adverse Reactions to Distigmine.

Although distigmine is known to sometimes cause severe adverse drug reactions (ADRs), such as cholinergic crisis, there are limited data on the risk factors for these ADRs. In this study, we defined a serum cholinesterase (sChE) cutoff level for early detection of ADRs to distigmine and sought to identify risk factors for these ADRs based on this value. This retrospective cohort study included all patients who were prescribed distigmine and underwent measurement of sChE over a period of 8 years at Kaetsu Hospital. Ninety-three patients were included. The sChE cutoff level below which there was an increase in risk of ADRs was defined as 129 U/L based on the levels in patients who had ADRs by receiver operating characteristic analysis. The percentage of ADRs tended to increase with advancing chronic kidney disease (CKD) stage. Multivariate logistic regression analyses showed that a distigmine dose >0.1 mg/kg/d (odds ratio 3.19, 95% confidence interval 1.24-8.19) and age >85 years (odds ratio 3.04, 95% confidence interval 1.18-7.82) were positively associated with an sChE level ≤129 U/L. An sChE cutoff level of 129 U/L is a useful predictor of the risk of an ADR to distigmine, and dose per body weight, age, and CKD progression may pose potential risk of an ADR to distigmine. Therefore, for patients taking distigmine who have these risk factors, the risk of a severe ADR to distigmine can be reduced by decreasing the dose of distigmine and close monitoring of the sChE level.

[Low Continuity Rate of Sucroferric Oxyhydroxide among Japanese Hemodialysis Patients with High Phosphate Binder Pill Burden].

This prospective observational study was conducted to evaluate the continuity, efficacy, and tolerability of sucroferric oxyhydroxide (SO) among hemodialysis (HD) patients who switched to SO from sevelamer hydrochloride (SH) or bixalomer (BX). Participants were 9 HD patients in Kaetsu Hospital who had been receiving more than 9 tablets/d of SH or BX and were switched to SO 750 mg/d. All the participants were men. Over a 6-month observational period, 6 of the 9 patients (67%) discontinued SO because of adverse events, including diarrhea, atheroma, and polycythemia. Although the diarrhea and atheroma were mild, the affected patients did not wish to restart SO. On the other hand, 3 of the 9 patients (33%) continued taking SO throughout the observation period. These patients tended to have increased levels of serum calcium, hematocrit, and serum ferritin; a decreased number of phosphate binder tablets (from 21 tablets/d to 8 tablets/d); and a decreased dosage of erythropoiesis-stimulating agents. Serum phosphate levels tended to decrease in continuers, but tended to increase in discontinuers. It may be preferable to increase the SO dosage gradually rather than switching from SH or BX all at once, and patients who switch to SO should be carefully monitored.

Comparison of Clinical Advantage between Topiroxostat and Febuxostat in Hemodialysis Patients.

To determine the response of hemodialysis (HD) patients to topiroxostat after a switch from febuxostat, we evaluated the efficacy, tolerability, and serum concentration of topiroxostat in HD patients after the switch. In this 16-month prospective observational study, we assessed the serum uric acid (UA) levels, other laboratory data, and serum topiroxostat concentrations of 10 HD patients who had been receiving febuxostat at a dose of 10 mg/d for over 1 year. No statistical difference was observed between the tolerability index at baseline and 16 months after the switch to topiroxostat. Serum UA after the switch in all patients (attained serum UA levels of ≤6 mg/dL) was 5.6±1.7 mg/dL (60%) at baseline, 4.9±0.5 mg/dL (100%) at 6 months and 5.7±0.4 mg/dL (50%) at 16 months (p=0.25), respectively. In patients with baseline serum UA levels >6 mg/dL, serum UA was significantly reduced at 6 and 16 months compared with baseline. Minimum serum concentrations of serum topiroxostat were lower than the limit of quantification (<25 ng/mL). Our results indicate that a switch from febuxostat 10 mg/d to topiroxostat 40 mg/d might reduce serum UA levels, with no change in other clinical laboratory data over the long term. These effects were more frequent in patients with high serum UA levels. Furthermore, topiroxostat therapy was more cost effective than febuxostat therapy. Thus, topiroxostat therapy could be a better treatment option for HD patients who develop high serum UA levels after febuxostat 10 mg/d administration.

Switching from allopurinol to febuxostat: efficacy and tolerability in hemodialysis patients.

BACKGROUND: Febuxostat is a novel xanthine oxidase inhibitor. However, few studies have examined the long-term efficacy and tolerability of febuxostat after switching from allopurinol in hemodialysis (HD) patients. Therefore, the present study evaluated the long-term efficacy and tolerability of febuxostat in HD patients after switching from allopurinol. FINDINGS: We monitored the levels of hemoglobin, hematocrit, platelet count, blood urea nitrogen, serum creatinine, serum sodium, serum potassium, serum chloride, serum calcium, serum inorganic phosphorus, aspartate transaminase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, and total protein that were considered overall as a tolerability index, while the serum uric acid (UA) level was considered an index of efficacy. All values were measured at baseline and at 1, 6, 12, and 16 months after the switch to febuxostat therapy. All subjects switched from allopurinol (100 mg/day) to febuxostat (10 mg/day) in August 2013. Clinical laboratory data were collected at baseline in July 2013 until December 2014. Nine patients were included in the study analysis. Results showed that clinical laboratory data at baseline versus those at 16 months were not significantly different. Serum UA levels, which represented the efficacy index, were significantly different between the baseline level (6.8 ± 1.4) and those at 1, 6, 12, and 16 months (5.2 ± 1.1, 5.1 ± 1.1, 4.6 ± 0.9, and 5.4 ± 1.8 mg/dL, respectively; all p < 0.05). CONCLUSION: Switching from allopurinol to febuxostat in HD patients reduced serum UA levels, with no changes in other clinical laboratory data in the long term.

Association between warfarin use and incidence of ischemic stroke in Japanese hemodialysis patients with chronic sustained atrial fibrillation: a prospective cohort study.

BACKGROUND: Although generally recommended for atrial fibrillation (AF) in the general population, the efficacy and safety of warfarin in hemodialysis patients remains controversial. Warfarin use in hemodialysis patients may confer an additional risk of bleeding that is not appreciated in patients without renal failure because hemodialysis patients have platelet defects and receive anticoagulation agents during dialysis. The incidence of major bleeding was reported to be higher in Japanese AF patients on warfarin therapy compared to patients in other countries, suggesting that racial differences may influence bleeding tendency. Thus, examining risks and benefits of warfarin therapy in Japanese hemodialysis patients with AF is important. METHODS: In order to determine associations between warfarin use and new ischemic stroke events, major bleeding, and all-cause mortality, a prospective cohort study of 60 Japanese hemodialysis patients with chronic sustained AF was conducted using Cox proportional modeling and propensity score matching. RESULTS: The mean patient age was 68.1 years. During 110 person-years of follow-up, 13 ischemic strokes occurred. After adjusting for CHADS2 score, warfarin use was not associated with a significant reduction in ischemic stroke events [hazard ratio (HR) 3.36; 95 % confidence interval (CI) 0.94-11.23]. Similar results were obtained after propensity score matching (HR 3.36; 95 % CI 0.67-16.66). Warfarin use was not associated with significant increases in major bleeding or all-cause mortality. CONCLUSIONS: These results suggest that warfarin may not prevent ischemic stroke in Japanese hemodialysis patients with chronic sustained AF. Adequately powered studies are needed to determine the risks and benefits of anticoagulation therapy in these patients.