Evaluation of dronedarone use in the US patient population between 2009 and 2010: a descriptive study using a claims database.

BACKGROUND: The utilization pattern of dronedarone was unknown, especially regarding prescribers' compliance with the product's prescribing information (PI) following its availability and the implementation of the Food and Drug Administration-approved risk evaluation and mitigation strategy for the drug in the United States. OBJECTIVE: This study was designed to evaluate the dronedarone prescribers' adherence to PI regarding the following contraindications: (1) patients with heart failure (HF) with a recent decompensation requiring hospitalization or referral to a specialist, (2) concomitant use of potent CYP3A4 inhibitors, and (3) concomitant use of QT-prolonging drugs. METHODS: Patients prescribed dronedarone between July 2009 and August 2010 were identified through LabRx. The following rates surrounding dronedarone use were examined: (1) atrial fibrillation or atrial flutter in the past year, (2) worsening or hospitalization for HF within the month before prescription, and (3) concomitant prescription of potent CYP3A4 inhibitors and concomitant prescription of QT-prolonging drugs within the following month. RESULTS: A total of 4595 dronedarone prescriptions were filled by 1820 patients. More than 94% of the participants had ≥1 diagnosis of atrial fibrillation or atrial flutter in the previous year. Worsening of or hospitalization for HF was found in 61 (3.4%) patients within the month before receiving dronedarone, including 18 patients with HF as the primary cause for hospitalization. Potent CYP3A4 inhibitors were prescribed to 10 (0.6%) patients within a month following dronedarone initiation, 6 of whom received them for topical use only. QT-prolonging drugs were prescribed to 67 (3.7%) patients within a month following dronedarone initiation, among which >90% were other antiarrhythmics. CONCLUSIONS: Dronedarone was used mostly in compliance with PI and risk evaluation and mitigation strategy in the studied population. In the LabRx database, dronedarone was commonly dispensed to patients with cardiovascular risk factors and rarely dispensed to patients with contraindications such as worsening HF or hospitalization for HF or with concomitant prescriptions of potent CYP3A4 inhibitors, QT-prolonging drugs, or both.

Incidence rates of heart failure, stroke, and acute myocardial infarction among Type 2 diabetic patients using insulin glargine and other insulin.

PURPOSE: The aim of this study was to compare incidence rates of heart failure, stroke, and acute myocardial infarction (AMI) in Type 2 diabetic patients using different types of insulin. METHODS: Included were patients with a diagnosis of Type 2 diabetes and at least one insulin prescription from May 2001 to July 2007. Incidence rate ratios (RRs) of heart failure, stroke, and AMI were estimated using Poisson regression with adjustment for age, gender, history of hypertension, dyslipidemia history, days supply, and duration of diabetes. RESULTS: Incidence rates of heart failure, stroke, and AMI in the insulin glargine group were 306.9 (95%CI: [278.9, 334.8]), 174.8 (95%CI: [153.7, 195.8]), and 105.2 (95%CI: [88.9, 121.5]) cases per 10,000 person-years, respectively. After adjustment for covariates, the incidence rates of CVD events in the insulin glargine were comparable to those in the other long/intermediate acting insulin group (reference), except for AMI, which tended to be lower in the insulin glargine group (RR = 0.81, 95%CI: [0.65, 1.02]). Using the same reference, the incidence rate of stroke was higher in patients taking rapid/short acting insulin, premixed insulin, or mixed use of insulin except insulin glargine (RR = 1.20, 95%CI: [1.04, 1.40]). CONCLUSION: This study suggested that insulin glargine use might be associated with a lower risk of AMI, compared to the other long/intermediate acting insulin use, and that insulin regimen of rapid/short acting insulin, premixed insulin, or mixed use of insulin except insulin glargine was associated with a higher risk of stroke using the same reference.

The incidence rate of seizures in relation to BMI in UK adults.

A retrospective cohort study using the data from The Health Improvement Network (THIN) database in the United Kingdom was conducted to examine the incidence rates of seizures across different BMI levels in the adult population aged > or = 18 years. Poisson regression was used to examine the relationship between BMI and seizures. The overall incidence rate of seizures was found to be 31.2 cases per 100,000 person-years. The incidence rate of seizures (cases per 100,000 person-years) in obese patients (BMI > or = 30 kg/m2) was 34.8 (95% confidence interval (CI), 23.1, 46.4), comparable to that in patients with normal weight (BMI between 18.5 and 24.9 kg/m2) (35.8, 95% CI (26.6, 44.9)). In contrast, underweight patients (< 18.5 kg/m2) or extremely obese (> or = 40 kg/m2) patients tended to have higher incidence rates than those with normal weight. After adjustment for age, gender, and smoking status, compared to patients with normal weight, those who were underweight or extremely obese had a rate ratio (RR) for seizures of 1.6 (95% CI (0.7, 3.8)) and 1.7 (95% CI (0.7, 3.9)), respectively. To date, we have not found any study that examines the associations between BMI or obesity and seizures. In this study, the incidence rates of seizures in the extremely obese and underweight patients tended to be higher than that in the normal-weight patients.

The art and science of risk management: a US research-based industry perspective.

The research-based pharmaceutical industry in the US strongly supports the concepts of risk management and sees formal risk management as playing a major role in the development of safe medicines for the public, as well as providing a mechanism to ensure that decisions concerning individual drug benefit and risk are made based on scientific evidence. Safe medicines refer to those drugs whose benefits have been found to outweigh their risks when they are used according to the approved labelling. Risk management is the comprehensive and proactive application of scientifically based methodologies to identify, assess, communicate and minimise risk throughout the life cycle of a drug so as to establish and maintain a favourable benefit-risk balance in patients. Although there are certainly a number of global risk management initiatives in place or being undertaken, harmonisation has yet to be achieved. Industry is faced with a variety of different risk management approaches and tools. There is a need to move the focus of risk management from the post-approval arena to earlier in the development process and tools need to be developed to support risk management throughout the lifecycle of a drug. The focus in the US on risk minimalisation strategies will also be an area for methodological development. A key factor in the success of overall risk management is the dialogue between industry and regulators throughout the development, review and marketing of the product. It is through such dialogue that appropriate, efficient and effective risk management strategies will be developed and implemented and the best decisions regarding the safe use of pharmaceutical products will be made.

Patterns of health care resource utilization after macrolide treatment failure: results from a large, population-based cohort with acute sinusitis, acute bronchitis, and community-acquired pneumonia.

BACKGROUND: Macrolide antibiotics are used as first-line therapy for the treatment of respiratory tract infections. The recent emergence of macrolide-resistant pathogens is a major concern. OBJECTIVE: This study quantifies the frequency of macrolide treatment failure in respiratory infections and examines its impact on health care use. METHODS: Patients with respiratory infections treated with macrolides in outpatient clinics from January to December 2002 were identified from a health insurance claims database. Macrolide treatment failure was defined as the receipt of a second antibiotic, different from the first, within 4 weeks after the initial macrolide. The end points were numbers of hospitalizations and emergency department and office visits within 1 month after the initial macrolide. We examined diagnostic codes on claim forms for posttreatment hospitalizations and visits to identify those most likely to be related to treatment failure as opposed to other causes. Utilization data were analyzed by Poisson regression to control for confounding variables. RESULTS: The patients were divided into acute sinusitis (n = 111,135), acute bronchitis (n = 157,360), and community-acquired pneumonia (n = 36,212). Of these respective groups, 11,285 (10.2%), 15,498 (9.9%), and 4144 (11.4%) received a second antibiotic within 4 weeks. This subgroup with macrolide treatment failure was older, included more women, and had used more medical care before the index visit compared with patients with treatment success. After adjustment for age, sex, and previous health care use, patients experiencing treatment failure were more likely to be admitted to the hospital or to use emergency department or outpatient care after the index visit. This association was strongest for admissions and visits pertaining to the care of respiratory infections. CONCLUSIONS: By our definition, about 10% of patients with respiratory infections who were treated with macrolide antibiotics experienced treatment failure within 4 weeks. Macrolide treatment failure was associated with increased health care utilization.