Primary care electronic medication record discrepancies in patients starting treatment at a hospital-based ambulatory care pharmacy and impact on prevalence of potential drug-drug interactions.

OBJECTIVE: Our objective was to evaluate the prevalence of discrepancies between primary care electronic medication records (EMR) and patient reported medication (PRM) in ambulatory patients starting a hospital dispensing treatment (HDT) at a hospital-based ambulatory care pharmacy (HACPh). Our secondary aims were to analyse factors associated with the presence of discrepancies and their impact on the prevalence of potential drug-drug interactions (DDIs) with the HDT. METHODS: Retrospective study including 230 patients starting a HDT at the HACPh. Pharmacists interviewed patients and PRM was compared with EMR. Discrepancies were classified as omissions (medication in the PRM not present in the EMR) and commissions (medication active in the EMR that the patients were not taking). Potential DDIs with the HDT were screened, and univariate and multivariate analyses were performed to detect factors associated with the presence of discrepancies. RESULTS: We identified 221 discrepancies in 116 (50.4%) patients. Being visited by three or more medical specialties (OR 1.93, 95% CI 1.11 to 3.37) and attending private healthcare (OR 4.36, 95% CI 1.14 to 16.72) in the 12 months before the study inclusion were the factors independently associated with the presence of discrepancies. Among patients with commissions (n=91), 15.4% had a potential DDI between the HDT and one medication from the EMR that they were not taking at that moment. Among patients with omissions (n=45), 11.1% had a potential DDI between the HDT and a medication in the PRM not present in the EMR. CONCLUSIONS: About 40% of patients had one or more medications in the EMR which they were not taking and one fifth used medications that were not listed in the EMR. EMR should not be used as the only source of information when screening for DDIs, especially in patients followed by different medical specialties or combining private and public healthcare.

Impact of HCV cure with drug-acting antivirals in the use of concomitant medication and lipid profile: follow-up data 2 years after the sustained virological response.

BACKGROUND AND AIM: Patients with chronic hepatitis C (CHC) frequently associated comorbidities and concomitant medication. Sustained virological response (SVR12) has been related to an increase in cholesterol serum levels and in peripheral vascular resistance. Our aim was to evaluate the impact of SVR12 on the use of concomitant medication and serum lipid profile. METHODS: Prospective study including patients treated with direct-acting antivirals who had achieved the SVR12. Clinical data and concomitant drugs were analysed at baseline and at least 1 year after SVR12. Differences from baseline to follow-up in the concomitant medication were evaluated by Stuart-Maxwell test and lipid profile by Wilcoxon signed-rank test. Patients were categorized according to the increase/decrease in the number of drugs included in each class (Anatomical Therapeutic Chemical classification system). RESULTS: Two hundred twenty-six patients with SVR12 were included, 73.5% were receiving concomitant drugs (49.6% with antihypertensive effect, 30.5% antacids, 16.4% anti-diabetic drugs, and 7.1% lipid-lowering agents). One year after SVR12, total cholesterol serum levels increased from 161 to 179 mg/dl (P < 0.001) and, after a median time of 25.7 months, the use of lipid-lowering drugs increased from 7.8 to 11.5% (P = 0.009). In addition, we observed a trend to use more antihypertensive drugs in older patients (P = 0.06), especially in those with cirrhosis. Anxiolytics decreased after SVR12 from 13.7 to 10.6% (P = 0.035). CONCLUSION: CHC cure is associated with a significant increase in cholesterol serum levels and the use of lipid-lowering agents, as well as the use of drugs with antihypertensive effect in older patients.

Linezolid Dosing in Patients With Liver Cirrhosis: Standard Dosing Risk Toxicity.

BACKGROUND: Limited data regarding altered linezolid pharmacokinetics in patients with liver cirrhosis are available. The objective of this study was to evaluate the pharmacokinetics, efficacy and safety of linezolid in cirrhotic patients. METHODS: A case-control 1:1 study of patients undergoing linezolid therapeutic drug monitoring was conducted between January 2015 and June 2017. Cases with liver cirrhosis were matched with controls by age, body weight, comorbidities, renal function, and intensive care unit (ICU) admission. RESULTS: Fifty-two patients were included, 26 in each group. Patients with Child-Pugh Scores A, B, and C were 1 (3.8%), 13 (50.0%), and 12 (46.2%), respectively. Cases had higher median linezolid trough plasma concentrations than controls [20.6 (17.4) versus 2.7 (11.3); P < 0.001)] and more frequently achieved an optimal pharmacodynamic index [26 (100%) versus 16 (61.5%); P = 0.002]. In addition, potentially toxic concentrations and treatment discontinuation due to overexposure and hematological toxicity were also more frequently seen in cirrhotic patients. Overall clinical cure rate was high (67.4%), and in-hospital mortality was 28.8%. No differences in clinical outcomes were observed between both groups. CONCLUSIONS: Linezolid showed a high clinical cure rate. Nevertheless, plasma concentrations and treatment discontinuation due to hematological toxicity were higher in cirrhotic patients. Liver cirrhosis may influence linezolid pharmacokinetics and question the use of standard doses. Therapeutic drug monitoring of linezolid would be valuable in these patients.

Potential drug-drug interactions of OMBITASVIR, PARITAPREVIR/ritonavir ± DASABUVIR ± ribavirin in clinical practice.

BACKGROUND & AIMS: Drug-drug interactions (DDIs) with ombitasvir/paritaprevir/ritonavir with or without dasabuvir and with or without ribavirin (OBV/PTV/r ± DSV ± RBV) are common in clinical trials. Our aim was to analyze the prevalence and management of potential DDIs and adverse events (AEs) related to DDIs in patients with chronic hepatitis C (CHC) receiving OBV/PTV/r ± DSV ± RBV in clinical practice. METHODS: 177 CHC patients started OBV/PTV/r ± DSV ± RBV in 4 Spanish hospitals and were screened for potential DDIs using the University of Liverpool database. Patients were classified according to the most serious potential DDIs at baseline and AEs during therapy. RESULTS: At least one potential DDI was found in 110 (62.1%) patients: 100 (56.5%) had at least one manageable potential DDI and 10 (5.6%) at least one contraindicated. Patients with potential DDIs were receiving a higher number of concomitant drugs (4 vs. 2, P < 0.001). Routine medication was modified at baseline due to potential DDIs in 49 (27.7%) patients. During antiviral treatment, 67 (37.9%) patients presented at least one AE. In 9 (4.5%) patients, a DDI was suspected between OBV/PTV/r ± DSV ± RBV and the concomitant drug, requiring antiviral discontinuation in 4 patients. CONCLUSIONS: Potential DDIs are frequent with OBV/PTV/r ± DSV ± RBV, although a change in baseline medication is made in only one-quarter of patients. More than half of potential DDIs were only followed, and only 5% of patients developed AEs in which the implication of DDIs could not be excluded.

Drug-drug interactions of telaprevir and boceprevir in HCV-monoinfected and HIV/HCV-coinfected patients can modify the adherence.

BACKGROUND & AIMS: The first generation protease inhibitors, boceprevir (BOC) and telaprevir (TVR), are both CYP3A4 inhibitors, which predispose drug-drug interactions (DDIs). The aim of this study was to evaluate the prevalence of potential DDIs, the management of outpatient medication and its impact on adherence and efficacy to antiviral treatment in hepatitis C virus (HCV)-monoinfected and human immunodeficiency virus (HIV)/HCV-coinfected patients receiving BOC and TVR. METHODS: The usual medication starting with BOC or TVR was screened by the pharmacist of the multidisciplinary support programme (MSP) for potential DDIs. Recommendations were made to avoid significant DDIs, and changes in the baseline medication were recorded. Adherence to antiviral treatment was considered as 80/80/95% of total doses. Sustained virological response was assessed at week 12 (SVR12). RESULTS: At least one potential DDI was found in 70 (64.8%) patients, 45 (54.2%) being HCV-monoinfected and 25 (100%) HIV/HCV-coinfected (P < 0.01). Baseline treatment modifications were required in 38 (35.2%) patients. Adherence and SVR12 were higher in patients without DDIs (86.8%) and (67.6%) compared to those with DDIs (62.8%) (P = 0.021) and (47.2%) (P = 0.097) respectively. CONCLUSIONS: More than half of the patients were at risk of presenting DDIs, leading to changes in the baseline medication in one-third of the patients. Drug interactions are frequent in patients with lower adherence.

A multidisciplinary support programme increases the efficiency of pegylated interferon alfa-2a and ribavirin in hepatitis C.

BACKGROUND & AIMS: Adherence to antiviral treatment is important to achieve sustained virological response (SVR) in chronic hepatitis C (CHC). We evaluated the efficiency of a multidisciplinary support programme (MSP), based on published HIV treatment experience, to increase patient adherence and the efficacy of pegylated interferon alfa-2a and ribavirin in CHC. METHODS: 447 patients receiving antiviral treatment were distributed into 3 groups: control group (2003-2004, n=147), MSP group (2005-2006, n=131), and MSP-validation group (2007-2009, n=169). The MSP group included two hepatologists, two nurses, one pharmacist, one psychologist, one administrative assistant, and one psychiatrist. Cost-effectiveness analysis was performed using a Markov model. RESULTS: Adherence and SVR rates were higher in the MSP (94.6% and 77.1%) and MSP-validation (91.7% and 74.6%) groups compared to controls (78.9% and 61.9%) (p<0.05 in all cases). SVR was higher in genotypes 1 or 4 followed by the MSP group vs. controls (67.7% vs. 48.9%, p=0.02) compared with genotypes 2 or 3 (87.7% vs. 81.4%, p=n.s.). The MSP was the main predictive factor of SVR in patients with genotype 1. The rate of adherence in patients with psychiatric disorders was higher in the MSP groups (n=95, 90.5%) compared to controls (n=28, 75.7%) (p=0.02). The cost per patient was € 13,319 in the MSP group and € 16,184 in the control group. The MSP group achieved more quality-adjusted life years (QALYs) (16.317 QALYs) than controls (15.814 QALYs) and was dominant in all genotypes. CONCLUSIONS: MSP improves patient compliance and increases the efficiency of antiviral treatment in CHC, being cost-effective.

Levofloxacin versus clarithromycin in a 10 day triple therapy regimen for first-line Helicobacter pylori eradication: a single-blind randomized clinical trial.

BACKGROUND: There is growing evidence that the standard triple therapy against Helicobacter pylori infection is losing clinical effectiveness. A triple therapy regimen with levofloxacin, amoxicillin and a proton pump inhibitor has been reported to be effective and well tolerated, and this regimen has been suggested as an alternative first-line treatment. The aim of this single-blind randomized clinical trial was to compare the eradication success of two first-line triple therapy regimens in the north of Spain: clarithromycin, amoxicillin and omeprazole (CAO) versus levofloxacin, amoxicillin and omeprazole (LAO). MATERIALS AND METHODS: A total of 250 consecutive patients diagnosed by conventional methods with H. pylori infection were randomized into one of two 10 day therapeutic regimens: standard CAO (n = 128) or LAO (n = 122). Eradication was confirmed by the (13)C-urea breath test. Adverse effects and compliance were also assessed. The clinical trial registration number was HPL08001HCLAD (EudraCT: 2008-001892-31). RESULTS: Intention-to-treat cure rates were: CAO, 75.0% (96/128; 95% CI: 66.6%-82.2%) and LAO, 82.8% (101/122; 95% CI: 74.9%-89.0%). Per-protocol cure rates were: CAO, 78.0% (96/123; 95% CI: 69.7%-85.0%) and LAO, 83.1% (98/118; 95% CI: 75.0%-89.3%). There were no statistically significant differences in effectiveness between the two regimens. In addition, no relevant differences in compliance or adverse effects were demonstrated. CONCLUSIONS: Levofloxacin-based treatment for H. pylori infection did not improve upon the eradication rate of the standard clarithromycin-based triple therapy in this study. This may reflect the progressive increase in in vitro resistance rates to levofloxacin observed in our region.

Antimicrobial susceptibility of Helicobacter pylori to six antibiotics currently used in Spain.

BACKGROUND: Antibiotic resistance is directly related to the loss of efficacy of currently accepted Helicobacter pylori therapies. Knowledge of the antibiotic susceptibility in a local area can contribute to the design of specific 'à la carte' treatments. The aim of this study was to analyse the susceptibility of H. pylori isolates to six conventional antibiotics currently used in a northern region of Spain. METHODS: Seventy-one isolates were obtained from gastric biopsies of 76 consecutive adult patients suffering from peptic ulcer disease, dyspepsia or familial gastric cancer and known to be infected with H. pylori by conventional methods. Susceptibility testing was performed for amoxicillin, ciprofloxacin, levofloxacin, clarithromycin, metronidazole and tetracycline using the Etest method. RESULTS: The prevalence rates of resistance were as follows: amoxicillin, 1.4% [95% confidence interval (CI) 0.0-7.6]; clarithromycin, 14.7% (95% CI 7.3-25.4); ciprofloxacin, 14.3% (95% CI 7.1-24.7); levofloxacin, 14.5% (95% CI 7.2-25.0); metronidazole, 45.1% (95% CI 33.2-57.3); and tetracycline, 0% (95% CI 0.0-5.1). CONCLUSIONS: Our study confirms an increasing rate of resistance to levofloxacin that equals that of clarithromycin in our healthcare area. This fact may reflect a wide and indiscriminate use of the former antibiotic and could account for a loss of clinical effectiveness of levofloxacin-containing regimens. Moreover, clarithromycin resistance rates remain stable, which could allow us to maintain its use in our area.