Off-label and unlicensed use of medicinal products in the neonatal setting in the Slovak Republic.

BACKGROUND: Frequent prescription of medication in an unapproved manner (off-label or unlicensed) in the neonatal setting is a result of the limited availability of adequately studied drugs in the pediatric population. Given that little information is available on this issue from eastern European countries, the purpose of this study was to describe for the first time the extent and pattern of off-label or unlicensed use of medicines in newborns in the Slovak Republic. METHODS: Cross-sectional study was performed at the Department of Pathological Newborns of Children's University Hospital, Bratislava, and Unit of Pathological Newborns of Teaching Hospital Nitra. Data were collected on hospitalized neonates admitted between 1 April and 30 September 2012 who received pharmacotherapy. Label status of the administered drugs was determined according to the Slovak Summaries of Product Characteristics. RESULTS: A total of 962 prescriptions referring to 97 different medications was administered to 202 hospitalized newborns (46% premature). Anti-infectives and alimentary drugs were the most commonly prescribed. Of all prescriptions, 43% were identified as off-label and 4.8% as unlicensed. At least one off-label or unlicensed drug was given to 88.6% of patients. Ketoconazole was the most frequent drug used in an unapproved manner. A total of 13.8% of all prescriptions was administered despite contraindication. CONCLUSIONS: Administration of drugs to newborns in an unapproved manner was common in the participating Slovak neonatal wards, reflecting the lack of appropriate pediatric drug labeling.

Influence of hospitalisation on the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in elderly hypertensive patients.

BACKGROUND AND AIMS: The underutilization of beneficial cardiovascular medications such as angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) in the elderly patients continues to be a matter of concern. The aim of the presented study was to compare the prescription of ACEI and ARB in elderly hypertensive patients at the time of hospital admission and discharge and to identify patient-related factors which determine the prescription of ACEI/ARB. METHODS: The study sample (n = 1111) was selected from 2,157 patients hospitalised at long-term care departments of three municipal hospitals during the period between January 1, 2008 and December 31, 2009 and included hypertensive patients aged ≥65 years suffering from myocardial infarction, heart failure, atrial fibrillation, diabetes mellitus or nephropathy. RESULTS: In hypertensive patients with myocardial infarction, diabetes mellitus and nephropathy, a significant increase was found in the use of ACEI/ARB during hospitalisation. However, there was no similar change in the use of such medications during hospitalisation in patients with heart failure and atrial fibrillation. Age ≥85 years (OR = 0.59 and OR = 0.50 at hospital admission and discharge, respectively), depression (OR = 0.63 at hospital discharge) and the systolic blood pressure ≤115 mmHg (OR = 0.45 at hospital discharge) decreased the probability of ACEI/ARB prescription. On the other hand, increasing the number of evaluated co-morbid conditions increased the patient's likelihood of being an "ACEI/ARB user" (OR = 1.20 at hospital discharge). CONCLUSIONS: Our study has identified a subset of elderly hypertensive patients (with heart failure, atrial fibrillation) in whom the use of ACEI/ARB could be improved.

Naproxen and Diclofenac Attenuate Atorvastatin-induced Preconditioning of the Myocardium.

Statins reduce infarct size (IS) in ischemia-reperfusion injury of the myocardium. Inhibition of cyclooxygenase-2 (COX-2) attenuates this benefit. We investigated the effect of two widely used non-selective non-steroidal anti-inflammatory drugs (NSAIDs) with different degree of anti-COX-2 activity on atorvastatin-mediated preconditioning. Wistar rats received oral atorvastatin (10 mg∙kg-1∙day-1), naproxen (10 mg∙kg-1∙day-1), diclofenac (8 mg∙kg-1∙day-1), atorvastatin+naproxen, atorvastatin+diclofenac or water for three days. Hearts were then excised and perfused in the Langendorff system. Area at risk (AR) and IS were determined after 30 min of regional ischemia and 120 min of reperfusion. Atorvastatin reduced IS by 51.3% compared with controls (14.7 ± 3.9% vs. 30.2 ± 4.6% of the AR; P < 0.001). Naproxen and diclofenac alone did not alter IS compared to control. Diclofenac completely abrogated atorvastatin-mediated protection of the myocardium. Naproxen significantly attenuated but did not eliminate the IS reducing the effect of atorvastatin when compared with controls (P = 0.038). The difference in IS between the atorvastatin+naproxen group and the atorvastatin+diclofenac group showed a strong trend in reaching statistical significance (P = 0.058), but was not found to be significant. Our results suggest relatively small, but noticeable differences among non-selective NSAIDs in their potential to attenuate statin-mediated preconditioning.