Concomitant use of levofloxacin and fluconazole leading to possible torsades de pointes.

Prolongation of the corrected QT interval can lead to the deadly arrhythmia torsades de pointes. There are many risk factors for corrected QT prolongation, one being medication. The goal of this case report is to add to the limited literature surrounding the possibility of torsades de pointes when levofloxacin and fluconazole are used concomitantly. Additionally, provide guidance for patient factors that need to be assessed when prescribing the two drugs.

Automatic Errors: A Case Series on the Errors Inherent in Electronic Prescribing.

The adoption of electronic prescribing is on the rise, as it reduces medication errors compared to handwritten orders. The inadvertent dispensing of discontinued medications is a type of medication error that is less well described, but one that can lead to adverse events. Software for electronic prescriptions transmits orders for refills or new prescriptions, but not discontinuations, to the pharmacy. Medications that have been stopped are displayed only at the prescribing facility's electronic medical record (EMR). This report describes five cases in which the pharmacy dispensed electronically discontinued medications, two of which contributed to adverse outcomes.

Association of beta-blocker dose with serum procollagen concentrations and cardiac response to spironolactone in patients with heart failure.

STUDY OBJECTIVE: To determine whether beta-blocker dose influences cardiac collagen turnover and the effects of spironolactone on cardiac collagen turnover in patients with heart failure. DESIGN: Prospective clinical study. SETTING: Two heart failure centers. PATIENTS: Eighty-eight spironolactone-naïve patients with heart failure who were taking beta-blockers. INTERVENTION: In a subset of 29 patients, spironolactone was started at 12.5 mg/day, with the dosage titrated to 25 mg/day if tolerated. MEASUREMENTS AND MAIN RESULTS: Venous blood samples were collected from each patient. Serum procollagen type I and type III aminoterminal peptides (PINP and PIIINP) were determined by radioimmunoassay and compared between the 25 patients receiving low doses (< 50% of recommended target dose) and the 63 patients receiving high doses (> or = 50% of recommended target dose) of beta-blockers. Patients receiving low-dose beta-blockers had higher mean +/- SD PIIINP concentrations (6.6 +/- 3.5 vs 4.9 +/- 2.6 microg/L, p=0.03) and tended to have higher PINP concentrations (74.0 +/- 44.1 vs 57.1 +/- 28.6 microg/L, p=0.10) compared with those receiving high doses. A repeat blood sample was collected from the 29 patients who received spironolactone after 6 months of therapy. Changes in procollagen peptides also were compared in this subset between low-dose (9 patients) and high-dose (20 patients) beta-blocker groups. Low beta-blocker doses were associated with greater reductions in concentrations of PINP (median [intraquartile range] -14.3 microg/L [-9.8 to -19.3 microg/L] vs -2.5 microg/L [5.9 to -9.8 microg/L], p=0.02) and PIIINP (-1.4 microg/L [-0.9 to -2.4 microg/L] vs 0.1 microg/L [0.9 to -1.3 microg/L], p=0.045) with spironolactone therapy than high beta-blocker doses. In addition, 100% of the patients in this subset taking low-dose beta-blockers versus only 35% taking higher doses had reductions in both markers of cardiac fibrosis. CONCLUSION: Spironolactone may benefit patients with heart failure who cannot tolerate upward titration of beta-blocker dosages, at least in terms of its effects on cardiac remodeling.

Markers of cardiac collagen turnover are similar in patients with mild and more severe symptoms of heart failure.

Cardiac fibrosis plays an important role in the pathophysiology of heart failure. The authors sought to determine whether biomarkers of cardiac fibrosis for milder clinical degrees of heart failure are comparable to those of more advanced disease. Procollagen types I and III amino-terminal peptides (PINP and PIIINP) and type I collagen telopeptide (ICTP) were compared between aldosterone-antagonistnaive patients with heart failure and New York Heart Association class I or II (n=22/23) and class III or IV (n=42/3) symptoms. Median (interquartile) range concentrations of PINP (63.3 [44.2-88.8] vs 48.6 [37.8-74.9] microg/L), ICTP (7.0 [5.4-16.8] vs 6.5 [4.7-12.7] microg/L), and PIIINP (4.7 [3.2-7.0] vs 4.7 [2.9-7.3] microg/L) were comparable between patients with mild and moderate to severe disease, respectively. These data suggest that patients with mild heart failure may have similar degrees of cardiac fibrosis to patients with more severe disease and support the examination of antifibrotic therapy, including aldosterone antagonists, in milder degrees of heart failure.

Racial differences in potassium response to spironolactone in heart failure.

Evidence of racial differences in aldosterone concentrations and K+ disposition suggests that response to aldosterone antagonism might vary by race. The authors sought to determine whether K+ response to spironolactone differs between African Americans and Caucasians with heart failure. Heart failure patients of African-American (n = 34) or Caucasian (n = 17) race were started on spironolactone 12.5 mg/d, with up-titration as tolerated. Laboratory values and drug therapy were similar between racial groups at baseline. Spironolactone was titrated to a median dose of 25 mg/d in both groups. Neither concomitant medications nor serum creatinine changed significantly in either group during spironolactone dose titration. Median serum K+ concentrations increased by 0.5 mEq/L (range, -0.7 to 1.6 mEq/L) in Caucasians, but only 0.1 mEq/L (range, -0.8 to 0.9 mEq/L) in African Americans; p < 0.01. These data suggest that African Americans with heart failure may be less responsive to the renal effects of spironolactone.

Racial differences in patients' potassium concentrations during spironolactone therapy for heart failure.

STUDY OBJECTIVE: To determine whether the effects of spironolactone on potassium homeostasis vary by race by comparing serum potassium concentrations and potassium supplement use in African-American and Caucasian patients receiving spironolactone for heart failure. DESIGN: Retrospective medical record review. SETTING: Two heart failure centers. PATIENTS: Fifty African-American and 67 Caucasian patients with heart failure who were receiving a stable dosage of spironolactone in addition to standard heart failure therapy with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker. MEASUREMENTS AND MAIN RESULTS: Medical records of eligible patients were reviewed by pharmacists and physicians who specialize in heart failure management. No significant differences were observed in diuretic therapy or renal function between racial groups; however, African-Americans were receiving higher doses of ACE inhibitors. African-Americans had lower serum potassium concentrations (4.2 +/- 0.4 vs 4.5 +/- 0.5 mEq/L, p<0.01) and a higher prevalence of potassium supplementation (48% vs 15%, p<0.01). In a subset of patients, spironolactone therapy was associated with a 2-fold greater increase in serum potassium concentration and a 3-fold greater reduction in potassium supplement use among Caucasians than African-Americans. CONCLUSION: Our findings suggest that a large percentage of patients with heart failure, particularly African-Americans, still require potassium supplementation despite treatment with spironolactone and standard vasodilator therapy.

Use of a simplified nomogram to individualize digoxin dosing versus standard dosing practices in patients with heart failure.

STUDY OBJECTIVES: To compare the frequency of achieving a therapeutic serum digoxin concentration (SDC), defined as 0.5-0.9 ng/ml, by using a simplified nomogram to individualize digoxin dosing with standard dosing practices in patients with heart failure, and to characterize the relationship between genetic polymorphisms of the ABCB1 gene and SDC. DESIGN: Prospective study with a historical control group. SETTING: Outpatient care center of an urban academic medical center. PATIENTS: A total of 131 adults with heart failure due to left ventricular dysfunction who were treated with digoxin. INTERVENTION: Digoxin doses were determined either by the dosing nomogram (65 patients) or standard care (SC; 66 patients) by using historical controls who were randomly selected from a list of SDCs obtained from laboratory records and who had their digoxin doses determined by standard dosing practices. MEASUREMENTS AND MAIN RESULTS: The primary end point was the proportion of patients achieving a steady-state SDC of 0.5-0.9 ng/ml; secondary end points were mean SDC and proportion of patients achieving a steady-state SDC lower than 1.0 ng/ml. Postdistributive steady-state SDCs were measured 2-4 weeks after digoxin dosage adjustment or initiation. Therapeutic SDCs were achieved with similar frequency in both groups (38.7% in the nomogram group vs 34.5% in the SC group, p=0.65); however, more patients in the nomogram group had SDCs lower than 1.0 ng/ml than in the SC group (85.0% vs 44.9%, p<0.001). Mean daily digoxin doses were lower in the nomogram group (149 ± 67 µg vs 177 ± 74 µg, p=0.02), resulting in lower mean SDCs compared with those in the SC group (0.52 ± 0.30 ng/ml vs 1.12 ± 0.58 ng/ml, p<0.001). Patients in the pharmacogenetic substudy provided blood samples for genotyping of three common ABCB1 single nucleotide polymorphisms: C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642). SDCs were not significantly associated with ABCB1 genotypes. CONCLUSION: Our simplified digoxin dosing nomogram resulted in lower SDCs compared with standard dosing practices but achieved therapeutic SDCs with similar frequency. A greater proportion of patients dosed according to our nomogram had SDCs lower than 1.0 ng/ml, consistent with consensus guidelines. Genetic polymorphisms of the ABCB1 gene were not associated with SDC.

Association of aldosterone concentration and mineralocorticoid receptor genotype with potassium response to spironolactone in patients with heart failure.

STUDY OBJECTIVE: To identify patient-specific factors associated with spironolactone-induced potassium level elevation in patients with heart failure. DESIGN: Prospective cohort study. SETTING: Two adult heart failure clinics. PATIENTS: Sixty-two adult (mean +/- SD age 54 +/- 16 yrs) aldosterone antagonist-naïve patients with heart failure. INTERVENTION: Patients received spironolactone 12.5 mg/day, titrated to 25 mg/day if tolerated. MEASUREMENTS AND MAIN RESULTS: Blood samples were obtained at baseline, 1 week after spironolactone initiation, and 1 week after spironolactone dose titration for assessment of baseline aldosterone level, serum chemistry, and angiotensinogen (AGT) c.-6G>A and p.M268T and mineralocorticoid receptor (NR3C2) c.215C>G and p.I180V genotypes. Patient characteristics, laboratory values, and genotypes were compared between those whose potassium levels increased by more than 0.5 mEq/L (15 patients) and those with lower potassium level elevations (47 patients) after spironolactone initiation and dose titration. Patients with a greater potassium level elevation had a higher mean +/- SD aldosterone concentration (178 +/- 92 vs 102 +/- 57 pg/ml, p=0.007) and NR3C2 215G allele frequency (50% vs 22%, p<0.01). Aldosterone concentrations positively correlated with diuretic dose (r=0.313, p=0.014) and negatively correlated with serum potassium level (r= -0.319, p=0.012). On regression analysis, factors predictive of potassium level increases greater than 0.5 mEq/L with spironolactone were aldosterone level greater than 150 pg/ml (odds ratio [OR] 30, 95% confidence interval [CI] 3.2-287] and NR3C2 215G carrier status (OR 17, 95% CI 1.6-167). CONCLUSION: Our data suggest that potassium should be monitored with particular caution when spironolactone is started in patients with heart failure who have evidence of elevated aldosterone levels, such as high diuretic requirements, or the NR3C2 215G allele.