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BackgroundIn the University Medical Center Mainz standard concentrations are defined for medicinal products to be administered by continuous injection with syringe pumps in adult intensive care patients. Patient-individual doses are provided by adjusting the injection rate. Various medicines are aseptically prepared in the pharmacy department as ready-to-use products. Batch preparation of the products and keeping them in stock is only possible if stability of the products is tested using a validated method. Purpose The purpose of this study was to test the stability of ready-to-administer epinephrine solutions for injection 20 µg/ml in 50 ml plastic syringes. Materials and Methods Epinephrine bulk solution 20 µg/ml was prepared aseptically by diluting Suprarenin 25 mg/25 ml SanofiAventis with 5% glucose infusion solution in empty infusion bags (PP/PE). The solution was filled with the NeoCare Compounder into 50 ml BD Perfusion Syringes, Luer Lock Tip, protected from light. The syringes were stored at 2-8°C in the refrigerator. Epinephrine concentration was determined by using a validated HPLC method with UV detection at 280 nm and an innovative HPLC column Nucleodur which contains sulfonyl groups. Results The concentration of epinephrine in the 50 ml syringes remained unchanged over a period of 2 months. After 28 days and 2 months of refrigerated storage the concentration amounted to 100.5% and 100.8% of the nominal concentration, respectively. Neither adrenochrome (detection wavelength 480 nm) nor any other degradation products were detected during the study period. With regard to these results batch production is feasible. Stability over 2 months is assured. Conclusions Epinephrine solution for injection 20 µg/ml, aseptically prepared by diluting the marketed injection concentrate with 5% glucose infusion solution in 50 ml light-protected plastic syringes, is stable under refrigerated storage conditions for at least 2 months.No conflict of interest.

BackgroundSimeprevir, sofosbuvir and daclatasvir are new drugs for the treatment of hepatitis C virus (HCV) and are apparently safer than preceding treatments. Due to the limited patient profiles in clinical trials as well as limited length, adverse events (AEs) in patient groups with special characteristics and low incidence or long term AEs have not been defined.PurposeTo learn about the safety aspects of simeprevir, sofosbuvir and daclatasvir, and to detect AEs not previously described.Material and methodsRetrospective study from August 2014 to April 2015 of AEs registered in a cohort of patients diagnosed with chronic hepatitis C treated with simeprevir, sofosbuvir and/or daclatasvir. Recorded data were: age, sex, baseline laboratory values and FibroScan, viral genotype, pharmacotherapeutic information and referred AEs. The information was obtained from Farmatools software and medical records.Results39 patients were included (average age 52.2 years, 22/39 male) and 66.6% had a FibroScan value exceeding 12 kPa. HCV genotypes were: 1b (53.8%), 1a (15.4%) and other (30.8%). Pretreated patients comprised 49.7%. Treatments included ribavirin and/or peginterferon (61.5%); 38.5% were not treated.53 different AEs were detected in 152 patient, all of which were mild in severity. 92.3% of patients reported an AE. No patient had to be hospitalised or discontinue therapy because of AEs. Detected disorders were: 19.6% gastrointestinal, 12.4% skin and subcutaneous tissue, 12.4% nervous system, 11.1% blood and lymphatic system, 11.1% musculoskeletal and connective tissue, 10.5% psychiatric and 22.9% other disorders. The most prevalent AEs were anaemia (41.1%), pruritus (38.5%) and fatigue (28.2%). 97.4% of anaemia cases were grade 1 and associated with ribavirin included treatments; 2.6% were grade 2. Anaemia was also registered in a patient treated with sofosbuvir and daclatasvir. Patients reported AEs not previously described for these drugs: bone pain (2/39), urinary retention (2/39) and osteochondritis (1/39). A higher incidence of anticholinergic AEs were observed with co-administration of simeprevir and sofosbuvir.ConclusionSimeprevir, sofosbuvir and daclatasvir seem to be safer than previous direct acting antivirals used to treat HCV. The most frequent and severe AEs were mainly due to ribavirin. Due to the low sample size, infrequent or rare AEs could not be detected. It would be useful to extend the study to detect new AEs.No conflict of interest.