Clinical Therapeutics In the comparisons, Chi-square and Kruskal-Wallis tests were used and P< 0.05 was considered as significant. Results: Patients were aged 18–87 years (40.6 ± 15.2). Of them, 54.4% were male. Most of them (61.3%) had epilepsy. Forty-nine (30.6%) were on LEV monotherapy and valproic acid (22.5%) and carbamazepine (16.2%) were the most common AED comedication. Median LEV concentration was 14.3 (7.8–27.6) vs. 20.0 (11.6–32.5) in monotherapy and polytherapy groups, respectively (P > 0.05). LEV concentration was within reference range in 79.6% and 77.5% of the patients in monotherapy and polytherapy groups, respectively (P > 0.05). Influence of concomitant AED use on LEV concentrations was evaluated in patients using only one additional AED (n = 68). Median LEV concentration was 18.0 (11.7-32.3), 18.3 (8.2-31.1), 21.4 (14.6-26.3) in patients using enzyme inducer (carbamazepine, phenytoin), enzyme inhibitor (valproic acid) and neutral AEDs, respectively (P > 0.05). Of the patients, 51.1% in monotherapy and 28.7% in polytherapy groups were seizure-free. Conclusions: Concomitant AED use, whether being enzyme inducer or inhibitor, resulted in no significant change in LEV serum concentration.
The use of Antihypertensive Medication in Hospitalised Elderly Patients M. Wawruch; J. Murin; Z. Kallay; J. Luha; J. Papincak; P. Mikes; and T. Leitmann 1 Faculty of Medicine, Comenius University, Bratislava, Slovakia; and 2Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia Background: Despite the importance of hypertension as a risk factor for adverse outcomes, elderly patients have the lowest rate of adequate blood pressure control. The antihypertensive therapy in elderly patients requires special attention because of questions which remain still unresolved from the evidence based medicine point of view as well as regarding the safety aspects. The aim of the presented work was to evaluate the antihypertensive treatment in a sample of hospitalised patients aged ≥ 65 years. Methods: Patients aged ≥ 65 years with arterial hypertension treated with at least one antihypertensive drug at hospital admission were included in our study (n = 1233). We analysed following patients’ characteristics as possible factors influencing the prescription of antihypertensive agents: socio-demographic signs (age, gender), living alone, immobilisation and comorbid conditions. Results: In the evaluated group women were prevailing over men (64.7% vs. 35.3%). The mean age of patients was 78.3 ± 6.7 years. In the group of patients aged ≥ 80 years a significantly lower prevalence of following antihypertensives was found: antagonists of AT1 receptors, dihydropyridine calcium channel blockers, betablockers and agonists of I1 receptors. On the other hand, in this age group the highest prevalence of furosemide prescription was revealed. Patients living alone were at higher chance (OR = 2.38) and those aged 80 years or more at lower chance (OR = 0.57) for administration of urapidil at discharge. A significant increase in the use of antihypertensive drug combinations was observed comparing their prevalence at the time of hospital admission and discharge, respectively (76.2% vs. 83.3%; P < 0.001). Conclusions: The results of the presented work showed the compliance of antihypertensive therapy with guidelines for treatment of arterial hypertension. The study indicates certain areas in which the use of antihypertensive medications could be improved in elderly patients. This study was supported by grants VEGA 1/0886/14 and VEGA 1/0939/14.
Concentrations and Activity of Amphotericin B in Bile achieved by Lipid-Formulations R. Welte1; S. Eschertzhuber2; S. Leitner-Rupprich1; M. Aigner1; C. Lass-Flörl1; S. Weiler1; E. Stienecke1; R. Bellmann-Weiler1; M. Joannidis1; and R. Bellmann1 1 Innsbruck Medical University, Innsbruck, Austria; and 2 Innsbruck General Hospital, Innsbruck, Austria Background: Amphotericin B (AMB) has a broad antifungal spectrum, but also a considerable toxicity. Its lipid-formulations are safer. As fungal cholangitis is a life-threatening disease, we assessed biliary AMB penetration in patients treated with lipid-formulated AMB and biliary AMB activity by in-vitro and ex-vivo-simulations. Methods: Biliary and plasma AMB levels were measured by highpressure-liquid-chromatography in two patients on liposomal AMB and in two on AMB colloidal dispersion. AMB kinetics in bile and plasma was determined in three of these patients. In-vitro simulation was performed with isolates of Candida (C.) albicans, C. tropicalis, C. glabrata and C. krusei incubated in porcine bile or in RPMI medium at relevant AMB concentrations for up to 48 hours. For ex-vivo simulation, patient bile samples were inoculated with the same Candida strains. Results: Biliary AMB concentrations were lower and displayed a slower rise and decline than plasma levels. Growth of C. albicans and C. tropicalis in porcine bile was similar to that in RPMI medium. Proliferation of C. glabrata was diminished, and C. krusei displayed no proliferation in bile. AMB activity was lower in porcine bile than in medium. In most of the patient bile samples, fungal growth was delayed or lacking, even in the absence of AMB. AMB concentrations of up to 1.28 mg/L had no fungicidal effect in patient bile. Conclusion: Biliary AMB concentrations were similar to or below the MIC values of relevant fungi. Fungal growth and AMB activity were impaired by bile. Treatment of fungal cholangitis with AMB lipid formulations is not supported by these pharmacokinetic and pharmacodynamic data.
Terbinafine induced Erythema multiforme with Hepatitis R. Slim1; N. Fathallah1; S. larif1; A. Aounallah2; H. Zayani1; N. Ghariani2; and C. Ben Salem1 1 Faculty of Medicine of Sousse, Tunisia; and 2Farhat Hached University Hospital, Sousse, Tunisia Introduction: Terbinafine is an antifungal agent that is effective for the oral treatment of dermatophytes. Herein, we report a rare case of terbinafine induced erythema multiforme (EM) associated with hepatitis. Case Report: A 59-year-old woman was admitted with a generalized targetoid, pruritic eruption. Terbinafine for onychomycosis was started three weeks earlier. Clinical signs and skin biopsy were consistent with EM. Laboratory investigations showed liver dysfunction with elevated liver enzyme activities. Diagnostic tests for viral and autoimmune hepatitis were negative. Other well established causes of EM were ruled out. Terbinafine induced EM with hepatitis was suspected, the antifungal was stopped and oral corticosteroid treatment was started. Patient’s condition improved dramatically and liver tests returned to normal. Discussion: EM is an acute mucocutaneous hypersensitivity reaction with variety of etiologies. It is characterized by a skin eruption, with or without mucous membrane lesions. It can be induced by drug intake or several infections. Terbinafine is generally well tolerated and the most common cutaneous adverse effects are rash, pruritus and urticaria. In the literature a few cases of EM have been reported
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Poster Presentations following exposure to this drug. It had also reported that patients who have developed EM during terbinafine treatment suffered from a systemic autoimmune disease and no hepatic disorder was associated to the skin manifestation. Our case was diagnosed to be a suspected case of drug-induced EM with hepatitis on the basis of drug history, clinical presentation, improvement with dechallenge and exclusion of other likely causes of EM and hepatitis. According to the Naranjo probability scale, the adverse drug reaction was considered probable. Conclusion: Clinicians should be aware of the risk of EM associated with terbinafine, a generally well tolerated drug. The skin involvement may be also associated with liver disorder.
Off-Label use of Midazolam in randomized controlled trials 1
I. Duman ; O. Arun ; F. Arun ; and B. Oc Necmettin Erbakan University Faculty of Medicine, Konya, Turkey; 2Selcuk University Faculty of Medicine, Konya, Turkey; and 3Beyhekim State Hospital, Konya, Turkey Introduction: Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or form of administration (1). The goal of this study is to investigate the data regarding the off-label use of midazolam; a versatile benzodiazepine, in randomized controlled trials (RCTs). Material and Methods: RCTs of were identified retrospectively through a search of PubMed from March 2012 to the past (1981) using the search term ‘midazolam’. Identified articles were screened for purpose or indication of the midazolam use, on/off label use, age of patients, route and location of administration. On-label criteria were based on information provided by the manufacturer of midazolam. Results: A total of 1081 RCTs of midazolam were detected; 314 were off-label and 276 were conducted in children. Until 1989 the number of RCTs per year was under 20 and from 1990 to 2011 the average of RCTs was 43.4 (31-54) per year. Most common on-label indication was to provide sedation and induction of anesthesia. Common fields of research were induction of anesthesia and/or anesthetic effect/ technique, evaluation of pharmacokinetics and pharmacodynamics. The routes used for off-label administration were intranasal, intrathecal, sublingual and rectal route. The common subjects for off-label research were the anticonvulsant, antiemetic, anti-shivering effects of midazolam and the use as an adjunct to local anesthetics. Conclusions: Off-label use of midazolam occurs frequently in the RCTs. Although it is legal to prescribe drugs off-label, there may be 1
health risks and differences in legal liability. There is need to generate evidence-based and safe scientific basis regarding every aspects of clinical conditions during the processes of approving and labeling.
Reference 1. Stafford RS. Regulating off-label drug use- rethinking the role of FDA. N Engl J Med. 2008;358:1427–1429.
Effects of uncontrolled diabetes on LDL levels of patients undergoing carotid Endarterectomy on and off Statin Therapy: preliminary study M. Oc1; I. Duman2; B. Oc1; M. Simsek1; H. Vatansev1; O. Arun1; and A. Duman1 1 Selcuk University Faculty of Medicine, Konya, Turkey; and 2 Necmettin Erbakan University Faculty of Medicine, Konya, Turkey Introduction: This preliminary study aims to assess the effects of uncontrolled diabetes mellitus (DM) on LDL levels of atherosclerotic patients on long term statins and patients not on statins. Material and Methods: With institutional approval LDL levels of 40 patients undergoing carotid endarterectomy due to atherosclerosis were retrospectively analyzed. All statin users were on statins for > 1yr. Patients with HbA1C levels of > 6.4% were considered as uncontrolled DM (D+). All other patients were non diabetics (D-). Group1: D+, statin user (n = 9), group2: D- statin user (n = 10), group 3 D+ non statin user (n = 8), and group 4: D- non statin user (n = 13). LDL levels are given as mg/dl, Kruskal-Wallis and MannWhitney tests were used for statistics. P < 0.05 = significant. Results: Demographic data were similar. LDL levels for groups1, 2, 3 and 4 were 125.0 ± 8.7, 95.0 ± 7.0, 133.5 ± 10.0, and 114.0 ± 10.2 respectively. LDL levels of uncontrolled diabetic patients not on statins were significantly higher than all other groups (P < 0.05). LDL levels of uncontrolled diabetic patients on statins were also higher than non-diabetic patients (P < 0.05). LDL levels were similar in all non-diabetic patients (P > 0.05) Conclusions: Results of this preliminary study suggest that atherosclerotic patients with uncontrolled diabetes who are either on or off statin therapy have higher LDL results compared to non-diabetic atherosclerotic patients. A study recruiting higher number of patients is needed to clearly assess the effects of uncontrolled diabetes on LDL levels.