«Real-life»-Daten zur Asthmakontrolle mit Budesonid/Formoterol als Erhaltungs- und Bedarfstherapie: die Erfahrung in der Schweiz

Hintergrund: Die Asthmakontrolle ist bei vielen Patientinnen und Patienten nach wie vor unzureichend. Es hat sich gezeigt, dass ein neuer Ansatz in der Asthmabehandlung - nämlich der Einsatz von Budesonid/Formoterol als Erhaltungs- und Bedarfstherapie - gegenüber konventionellen Therapien eine bessere Asthmakontrolle herbeiführt. Die Schweiz war das erste europäische Land, in dem die Erhaltungs- und Bedarfstherapie mit Budesonid/Formoterol formal zugelassen wurde. Im Januar 2006 wurde daher ein Patienten-Beobachtungsprogramm gestartet, um die Wirksamkeit und Sicherheit dieses Therapieansatzes unter realen Bedingungen zu beurteilen. Methoden: In sämtlichen Sprachregionen der Schweiz wurde eine nicht-randomisierte, unkontrollierte Anwendungsbeobachtung durchgeführt, an der 420 Ärzte mitwirkten und in die 2035 Asthmapatienten aufgenommen wurden. Dabei erfolgte eine Erhebung von Daten zur gegenwärtigen Asthmabehandlung, zur Asthmakontrolle sowie zu ungeplanten Arztbesuchen wegen einer Verschlimmerung der Asthmasymptomatik. Die Asthmakontrolle wurde subjektiv von Ärzten und Patienten sowie objektiv anhand des validierten Asthma Control Questionnaire mit 5 Items (ACQ5) beurteilt. Ein ACQ-Score von 0.75 oder weniger entspricht einer guten Asthmakontrolle. Resultate: Es erfolgte eine Analyse der Daten von 2006 von insgesamt 2035 Patienten (mittleres Alter 44.9 ± 19.6 Jahre, 50.5% Frauen). Unter einer Erhaltungs- und Bedarfstherapie mit Budesonid/Formoterol verbesserte sich der mittlere ACQ5-Score um mehr als das Dreifache der definierten kleinsten relevanten Veränderung (minimal important difference; MID). Der Prozentanteil von Patienten mit einem ACQ-Score ≤0.75 stieg von 4.8% bei Studienbeginn auf 58.0% am Ende des Beobachtungsprogramms. Die Zufriedenheit der Patienten mit Budesonid/Formoterol als Erhaltungs- und Bedarfstherapie war hoch. Schlussfolgerungen: Die Erhaltungs- und Bedarfstherapie mit Budesonid/Formoterol verbessert die Asthmakontrolle in einem nicht-randomisierten «real-life-Setting». = Background: Asthma is not adequately controlled in many patients. A new approach in asthma treatment, known as Budesonide/Formoterol Maintenance and Reliever Therapy has shown improvement in asthma control compared to conventional therapy regimens. As Switzerland was the first European country to formally approve budesonide/formoterol maintenance and reliever therapy, a patient follow-up programme was commenced in January 2006 to investigate its efficacy and safety in a «real-life» environment. Methods: A non randomized uncontrolled post-marketing survey involving 420 physicians in all language regions in Switzerland was carried out. 2035 patients with asthma were enrolled. Data on current asthma treatment, asthma control and unscheduled visits due to worsening asthma were recorded. Asthma control was assessed subjectively by both the patients and the physicians as well as by means of the validated 5-item Asthma Control Questionnaire (ACQ5). An ACQ score of 0.75 or less indicates well-controlled asthma. Results: Data from 2006 out of 2035 patients were analysed (mean age 44.9 ± 19.6 years, 50.5% female). With budesonide/formoterol maintenance and reliever therapy the mean ACQ5 score improved by more than 3-fold the defined minimal important difference (MID). The percentage of patients with an ACQ score ≤0.75 increased from 4.8% at baseline to 58.0% at the end of the follow-up programme. Patient satisfaction with budesonide/formoterol for both maintenance and relief was high. Conclusions: Budesonide/formoterol maintenance and reliever therapy improves asthma control in a non randomised real-life setting

Roflumilast--a phosphodiesterase-4 inhibitor licensed for add-on therapy in severe COPD

Roflumilast is a selective phosphodiesterase 4 inhibitor which has been licensed in the European Union since 2010 and in Switzerland since November 2011 as an add-on treatment for patients with chronic obstructive pulmonary disease (COPD) in GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages 3 and 4 (FEV(1) <50% predicted after bronchodilatation) and frequent exacerbations despite correctly-dosed therapy with a long-acting bronchodilator. Roflumilast is designed to target both the systemic and pulmonary inflammation associated with COPD. In this review roflumilast's chemistry, pharmacodynamics, pharmacokinetics, clinical efficacy, safety and tolerability and the current ongoing clinical trials involving roflumilast are outlined. Information has been sourced from the Swiss and US product information monographs, peer-reviewed published literature (identified from a PubMed MEDLINE search 1966 - March 2012 using the term "roflumilast"), the COPD GOLD international guidelines for the management of COPD (Revised 2011) and an independent analysis of phase 3 clinical trial data by FDA staff physicians. Clinical efficacy in terms of a modest gain in FEV(1)% and a reduction in exacerbation rate has been demonstrated in phase 3 clinical trials and roflumilast has been recently incorporated into international treatment guidelines. However data examining roflumilast as add-on therapy to long-acting bronchodilators and ICS (standard therapy) is currently awaited and phase 4 post-marketing studies are required to determine the incidence and severity of adverse events and the long-term beneficial effects of roflumilast as a maintenance therapy for COPD in every-day clinical practice

Lactic acidosis and hyperlactatemia associated with lamivudine accumulation and sepsis in a kidney transplant recipient-a case report and review of the literature

BACKGROUND: We report a case of sudden, lethal metabolic acidosis in a 70-year-old man on long-term nucleoside reverse transcriptase inhibitor (NRTI) -based antiretroviral therapy (ART) who had developed atypical necrotizing fasciitis 1 month after kidney transplantation. CASE PRESENTATION: The HIV infection of the patient was treated for the last four months with an integrase strand inhibitor (dolutegravir 50 mg/d) plus a NRTI backbone including lamivudine (150 mg/d) and abacavir (600 mg/d). In this renal transplant patient we hypothesize that the co-existence of sepsis, renal failure and an accumulation of lamivudine led to the development of fatal metabolic acidosis and hyperlactatemia. Although lamivudine is only rarely associated with hyperlactatemia, there is evidence that overdose may be a risk factor for developing it. In our patient the lamivudine concentration two days after stopping and during hemodiafiltration was more than 50 times higher than therapeutic target trough concentrations. Likely reasons for this were renal impairment and concurrent treatment with trimethoprim, known to inhibit the renal elimination of lamivudine. CONCLUSIONS: NRTIs could trigger the development of hyperlactatemia in septic patients. The use of NRTI sparing regimens might be considered in the presence of this critical condition

Cardiovascular adverse effects of lopinavir/ritonavir and hydroxychloroquine in COVID-19 patients: Cases from a single pharmacovigilance centre

In this article we summarize the cardiovascular adverse events that were observed in three patients during their treatment for COVID-19 and discuss their association with lopinavir/ ritonavir (LPV/r) and hydroxychloroquine (HCQ). The cases were reported to our regional pharmacovigilance centre in April 2020. All three patients were above 75 years in age, male and multimorbid, and had been hospitalized for treatment of COVID-19. As part of their treatment, all of them received a very strictly monitored off-label therapy with LPV/r and HCQ, for which they had given their prior, written, informed consent. In one patient, erythromycin was also administered. All three patients developed a significant QTc time prolongation during or shortly after therapy with the above drugs. On account of this, the treatment had to be discontinued early in each case and QTc time recovered in all three patients

Supplementary Material for: C-Reactive Protein and Procalcitonin in Case Reports of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome

<b><i>Background:</i></b> The spectrum of inflammatory marker response in DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome has not been systematically characterized. <b><i>Methods:</i></b> An epidemiological biomarker study of C-reactive protein (CRP) and procalcitonin (PCT) values in patients with DRESS syndrome reported at 2 regional pharmacovigilance centers in Switzerland or published in the medical literature 2008–2016 was performed. <b><i>Results:</i></b> Ninety-four DRESS cases were studied. All cases showed a CRP value > 10 mg/L (the upper limit of normal). The mean CRP value was 109.2 ± 79.4 mg/L. CRP values were significantly higher in 22 cases where a cause of inflammation besides DRESS could not be excluded (mean 162.1 vs. 92.9 mg/L; <i>p</i> = 0.003). Receiver operator characteristics curve analysis showed a moderate performance with a CRP cut-off value of 99.4 mg/L (AUC 0.717) to distinguish between patients with and without a possible additional cause of inflammation. The mean and median PCT values were 2.44 ± 5.94 and 0.69 ng/mL, respectively (<i>n</i> = 25 patients). Patients in whom an additional cause of inflammation besides DRESS could not be excluded showed a median PCT of 1.37 ng/mL (<i>n</i> = 9) versus 0.67 ng/mL (<i>n</i> = 16) in patients with DRESS only. PCT values were above the normal cut-off of 0.1 ng/mL, suggestive of bacterial infection in all but 1 case. Furthermore, there was a correlation between PCT values and hepatic enzyme measurements. <b><i>Conclusions:</i></b> Evaluating CRP and PCT values might be of use in helping physicians to distinguish between cases of DRESS syndrome with and without concurrent infection or other causes of inflammation. Further prospective investigation is required to define the use of these inflammatory markers in the management of DRESS