Efficacy of four cleaning solutions for the decontamination of selected cytotoxic drugs on the different surfaces of an automated compounding system

The automated aseptic preparation of ready-to-administer antineoplastic drug solutions with robotic systems reduces the risk of occupational exposure. However, the surfaces in the preparation area of the robot are to be cleaned by wiping with an appropriate cleaning solution. The aim of the study was to evaluate the cleaning efficacy of four cleaning solutions on four surface materials installed in the APOTECAchemo robot. Predefined amounts of cisplatin (Cis), 5-fluorouracil (5-FU), and cyclophosphamide (CP) were intentionally spread on test plates made of stainless steel, aluminium, polyoxymethylene, and polycarbonate just as installed in the robotic system APOTECAchemo. After drying, the …

H2-Antihistaminika, 28. Mitt. Synthese und H2-antagonistische Wirkung 3-(3-piperidinomethyl-phenoxy)propyl-substituierter Kohlensäurederivate und Analoge

Es wurden 3-(3-piperidinomethyl-phenoxy)propyl-substituierte Kohlensaurederivate wie Harnstoffe, Thioharnstoffe, Guanidine und Cyanoguanidine sowie analoge Nitroethendiamine dargestellt und am isolierten Meerschweinchenvorhof und zum Teil an der histaminstimulierten Sauresekretion der narkotisierten Ratte auf H2-antagonistische Wirkung untersucht. H2-Antihistaminics, XXVIII: Syntheses and H2-Antagonistic Activity of Derivatives of Carbonic Acid and Analogues Carrying a 3-[3-(Piperidinomethyl)phenoxy]propyl Substituent Derivatives of carbonic acid such as ureas, thioureas, guanidines, and cyanoguanidines as well as the analogous nitroethenediamines were prepared with a 3-[3-(piperidinomethyl…

Compatibility of epirubicin-loaded DC bead™ with different non-ionic contrast media

Purpose The aim of this study was to determine the compatibility of epirubicin-loaded DC bead™ with different non-ionic contrast media over a period of seven days when stored light protected under refrigerated conditions. Methods DC bead™ (2 ml) (Biocompatibles UK Ltd) of the bead size 70–150 µm ( = DC bead M1) or bead size 100–300 µm were loaded with 75 mg epirubicin powder formulation (Farmorubicin® dissolved in 3 ml water for injection to a concentration of 25 mg/ml) or 76 mg epirubicin injection solution (Epimedac® 2 mg/ml) within 2 h or 6 h, respectively. After removal of the excess solution, the epirubicin-loaded beads were mixed in polypropylene syringes with an equal volume (∼1.5 ml…

Loading, release and stability of epirubicin-loaded drug-eluting beads.

Purpose The aim of this study was to determine the loading efficiency, physico-chemical stability and release of epirubicin-loaded DC Bead™ (Biocompatibles UK Ltd, a BTG International group company) (bead size 70–150 µm (=DC Bead M1™) and 100–300 µm) after loading with epirubicin solution (2 mg/ml) or reconstituted powder formulation (25 mg/ml) and controlled storage. Methods DC Bead™ were loaded with 76 mg epirubicin solution (Epimedac™, Medac GmbH) or 75 mg epirubicin powder formulation (Farmorubicin™, Pharmacia Pfizer GmbH) per 2 ml of beads. Drug loading efficiency and stability were determined by measuring the epirubicin concentration in the excess solution after predetermined interval…

Physicochemical stability of cabazitaxel containing premix solution and diluted infusion solutions

Objectives This study was conducted to investigate the extended physicochemical stability of cabazitaxel containing premix solution and diluted infusion solutions in either 0.9% sodium chloride (NaCl) or 5% glucose (G5) vehicle solution. Methods A stability indicating, reverse phase, high performance liquid chromatography assay with ultraviolet detection was developed and validated. Premix solutions of cabazitaxel were prepared in the original vials. Infusion solutions were prepared in prefilled polypropylene/polyethylene (PP/PE) infusion bags (0.9% NaCl, G5) to achieve the recommended minimum and maximum cabazitaxel concentrations (0.1 mg/mL, 0.26 mg/mL). Test solutions were stored refrige…

Chapter 4: Requirements Concerning Antiseptics for Periorbital, Orbital and Intraorbital Application. 4.5.: Formulation Requirements for the Ophthalmic Use of Antiseptics

Pharmazeutische Betreuung von Epilepsie-Patienten: Betreuung im ambulanten und stationären Sektor

Epileptiker mussen gut auf ihr Medikament eingestellt sein – allerdings erfolgt haufig nach einer medikamentosen Ersteinstellung eine Umstellung auf ein anderes Antiepileptikum. Leider wird hier nur in den seltensten Fallen auch ein Apotheker zu Rate gezogen.

H2-Antihistaminika, 25. Mitt. Synthese und H2-antagonistische Wirkung monosubstituierter 1,2,4-Oxadiazol-3,5-diamine

Es wurden die N3- bzw. N5-substituierten 1,2,4-Oxadiazol-3,5-diamine 4a-e und 5a-e dargestellt und auf Histamin-H2-antagonistische Aktivitat untersucht. H2-Antihistaminics, XXV: Synthesis and H2-Antagonistic Activity of Monosubstituted 1,2,4-Oxadiazole-3,5-diamines The N3-or N5-substituted 1,2,4-Oxadiazole-3,5-diamines 4a-e and 5a-e were prepared and tested for histamine H2-antagonistic activity.

Compatibility of irinotecan-loaded DC Bead with different volumes and types of non-ionic contrast media.

Objectives Irinotecan-loaded microspheres are used for simultaneous embolisation and chemotherapy of liver metastases of colorectal carcinoma. The aim of the study was to evaluate the compatibility of recently introduced DC Bead M1 (bead size 70–150 µm) loaded with irinotecan after admixture with different types and volumes of non-ionic contrast media over a maximum period of 24 h and storage at room temperature. Methods Test suspensions were prepared by loading 2 mL DC Bead M1 with 100 mg irinotecan within 2 h. The loading efficiency was determined by measuring the concentrations of irinotecan in the excess solutions via a reversed phase high pressure liquid chromatography (RP-HPLC) assay …

Aerosolization Performance of Jet Nebulizers and Biopharmaceutical Aspects

In this work, 13 jet nebulizers, some of which in different configurations, were investigated in order to identify the biopharmaceutical constraints related to the quality attributes of the medicinal products, which affect their safety, efficiency, compliance, and effectiveness. The aerosolization parameters, including the aerosol output, aerosol output rate, mass median aerodynamic diameter, and fine particle fraction, were determined according to the European Standard EN 13544-1, using sodium fluoride as a reference formulation. A comparison between the aerosol output nebulization time and the fine particle fraction displayed a correlation between the aerosol quality and the nebulization …

How to select a biosimilar

In the past few years biosimilars have penetrated the market following the expiry of patents of originator variants. This offers the opportunity to apply high-tech protein products at a lower cost. In contrast to small-molecule generics, clinicians and pharmacists have found it difficult to judge the efficacy and safety profiles of complex protein products. In recent years, the European Medicines Agency (EMA) has gained knowledge on assessing comparability between biosimilars and originator products in scientific and legal areas. This article provides an overview of an extensive set of 31 previously drawn biosimilar selection criteria and describes how several of these criteria are covered …

Physico-chemical stability of eribulin mesylate containing concentrate and ready-to-administer solutions.

Objectives The aim of this study was to determine the stability of commercially available eribulin mesylate containing injection solution as well as diluted ready-to-administer solutions stored under refrigeration or at room temperature. Methods Stability was studied by a novel developed stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) assay with ultraviolet detection (detection wavelength 200 nm). Triplicate test solutions of eribulin mesylate containing injection concentrate (0.5 mg/mL) and with 0.9% sodium chloride solution diluted ready-to-administer preparations (0.205 mg/mL eribulin mesylate in polypropylene (PP) syringes, 0.020 mg/mL eribulin mesyl…

The new world of biosimilars: what diabetologists need to know about biosimilar insulins

Biosimilar pharmaceuticals are emerging as patent protection on the original biopharmaceutical products expires. However, biopharmaceuticals are particularly complex molecules, and biosimilar insulins present special challenges. In part this reflects their structure and chemical modification after synthesis to attain a biologically active form. Their therapeutic window is narrow and the accuracy of their dosing is highly dependent on the formulation and quality of the administration device. For these reasons, the European Medicines Agency has issued stringent guidelines that must be fulfilled in order to receive approval as a biosimilar soluble insulin. Prescribers should therefore consider…

Plasticizer extraction of Taxol infusion solution from various infusion devices.

Taxol solution extracts the plasticizer DEHP (di(2-ethylhexyl)phthalate) from polyvinyl chloride (PVC) materials. In order to minimize patient exposure to DEHP, Taxol solutions should be prepared and administered in PVC-free materials. Particulate matter may form in Taxol infusion solution over time, so that in-line filtration with microporous membranes not greater than 0.22 microns is advisable. The purpose of this study was to evaluate the suitability of various administration- and in-line filter-sets for Taxol application. The extent of leached DEHP was determined using a Reversed Phase HPLC assay specific for DEHP. The four tested administration-sets, labeled as PVC-free, were all found…

Physicochemical compatibility of nebuliser solution admixtures containing colistimethate and hypertonic saline or colistimethate, fluticasone-17-propionate, ipratropium bromide and salbutamol sulfate

Objectives For practical reasons, patients with cystic fibrosis (CF) tend to mix different inhalation solutions for concomitant inhalation instead of inhaling the different medications consecutively. A study was undertaken to examine the compatibility of colistimethate dissolved in 5.85% hypertonic sodium chloride (NaCl) solution and the quadripartite mixtures of colistimethate, fluticasone-17-propionate, ipratropium bromide and salbutamol sulfate. Methods The test solutions were prepared by mixing ordinary doses of the inhalation products and analysed immediately. Microbiological assays of antibiotics and high-performance liquid chromatography assays were used to determine chemical compati…

OHP-041 Formulary Decision-Making For Biosimilars: Considerations For Hospital Pharmacists

Background It has been 6 years since the first biosimilar was approved for use in the European Union (EU). Given the likelihood that biosimilar monoclonal antibodies will be approved in Europe in the near future, it is timely to review the formulary selection criteria for biologicals and biosimilars. The European Medicines Agency (EMA) has issued guidelines that define the regulation of biosimilars in Europe and recommend approaches to establish biosimilarity. However, several questions regarding the assessment of biosimilars for formulary inclusion remain unanswered, including those related to manufacturing and drug supply. Purpose To aid hospital pharmacists in developing evaluation crite…

Pharmakoökonomische Aspekte der Therapie mit Bisphosphonaten: Preiswert und effizient!?

Physicochemical stability of irinotecan injection concentrate and diluted infusion solutions in PVC bags

Purpose. To determine the physicochemical stability of irinotecan injection concentrate and irinotecan infusion solutions after dilution in two commonly used infusion fluids (0.9% sodium chloride, 5% dextrose) in PVC bags, stored under refrigeration (2-8°C) or at room temperature either light protected or exposed to light. Methods. Stability of irinotecan injection concentrate was determined in the original amber glass vials. Diluted irinotecan infusion solutions were aseptically prepared by further dilution of irinotecan stock solution with either 0.9% sodium chloride or 5% dextrose in PVC bags, in amounts yielding irinotecan concentrations of 0.4, 1.0, or 2.8 mg/ml. Test solutions were s…

Robotic i.v. medication compounding: Recommendations from the international community of APOTECAchemo users.

Purpose The development of recommendations for advancing automated i.v. medication compounding is described. Summary Managing the shift from manual to robotic compounding of i.v. therapies requires an awareness of how automation affects practice and how to best implement robotics into current practice. An international panel of pharmacy professionals, researchers, and technology leaders with experience in i.v. robotics collaborated during a two-day meeting in August 2014 to define a general set of principles to broaden the understanding of the fundamental elements of robotic compounding worldwide. Participants were divided into four working groups (technology and safety; drugs and products;…

Implementation and microbiological stability of dose-banded ganciclovir infusion bags prepared in series by a robotic system.

Objectives The implementation of dose-banding (DB) in centralised, pharmacy-based cytotoxic drug preparation units allows the preparation of standardised doses in series. The aim of this study was to evaluate the feasibility of DB for the prescribing of ganciclovir (GV) infusion solutions and to investigate the microbiological stability of dose-banded, automatically prepared ready-to-administer GV infusion bags by media-fill simulation tests and sterility tests. Methods The frequency of prescription of GV doses was retrospectively analysed before and after implementing the DB scheme. Four dose-ranges or ‘bands’ and the corresponding standard doses (250, 300, 350, 400 mg) were identified. Th…

Physicochemical stability of human insulin 1 I.U./mL infusion solution in 50 mL polypropylene syringes

Abstract Objectives The objective of this study was to investigate the physicochemical stability of human insulin 1 I.U./mL injection solutions (Insuman® Rapid) diluted with 0.9% NaCl solution in 50 mL disposable three-piece polypropylene syringes and stored refrigerated or at room temperature. Methods 1 I.U./mL test solutions were prepared with Insuman® Rapid and 0.9% sodium chloride infusion solution in 50 mL Original-Perfusor® syringes and BD® Perfusion syringes. Test solutions were stored for 90 days at 2–8 °C/dark or 48 h at 20–25 °C/diffuse room light in order to determine chemical stability. Additional test solutions were stored 28 days at 2–8 °C/dark followed by 24 h at 20–25 °C/dif…

Environmental and Product Contamination during the Preparation of Antineoplastic Drugs with Robotic Systems

Abstract Background Robotic systems are designed to minimize the exposure to antineoplastic drugs during automated preparation. However, contamination cannot be completely excluded. The aim of the study was to evaluate the contamination with antineoplastic drugs on the working surfaces and on the outer surface of the ready-to-use products (infusion bags and syringes) during automated preparation with different versions of a robot and manual preparation. Methods Surface contamination with platinum (Pt) and 5-fluorouracil (5-FU) was measured by wipe sampling and quantified by voltammetry for Pt and GC-MS for 5-FU. Sampling was performed on pre-defined locations in the working areas before and…

Physicochemical stability of carfilzomib (Kyprolis®) containing solutions in glass vials, ready-to-administer plastic syringes and infusion bags over a 28-day storage period.

Centralized aseptic preparation of ready-to-administer carfilzomib containing parenteral solutions in plastic syringes and polyolefine (PO) infusion bags needs profound knowledge about the physicochemical stability in order to determine the beyond-use-date of the preparations. Therefore, the purpose of this study was to determine the physicochemical stability of carfilzomib solution marketed as Kyprolis® powder for solution for infusion. Reconstituted solutions and ready-to-administer preparations of Kyprolis® stored under refrigeration (2–8℃) or at room temperature (25℃) were analyzed at predetermined intervals over a maximum storage period of 28 days. Chemical stability of carfilzomib wa…

Betasympathomimetika und andere Arzneimittel zur Feuchtinhalationstherapie

Stability of topotecan infusion solutions in polyvinylchloride bags and elastomeric portable infusion devices

Purpose. The purpose of this study was to determine the physicochemical stability of topotecan after reconstitution and after further dilution in two commonly used infusion fluids (0.9% sodium chloride, 5% dextrose) in both polyvinylchloride (PVC) bags and elastomeric portable infusion devices. Methods. Each vial of topotecan (Hycamtin®) was reconstituted with sterile water for injection, yielding a nominal concentration of 1 mg/mL. Topotecan infusion solutions were aseptically prepared by further dilution of reconstituted topotecan solutions with either 0.9% sodium chloride or 5% dextrose in both PVC bags and portable elastomeric infusion devices, in amounts yielding topotecan concentrati…

Long-term stability study of clofarabine injection concentrate and diluted clofarabine infusion solutions

Purpose: The aim of this study was to investigate the physicochemical stability of clofarabine (CAFdA) injection concentrate and ready-to-use CAFdA infusion solutions over a prolonged period of 28 days. Methods: To determine the stability of CAFdA infusion solutions, the injection concentrate (Evoltra®, 1 mg/mL, Genzyme) was diluted either with 0.9% sodium chloride or 5% glucose infusion solution. The resulting concentrations of 0.2 mg/mL or 0.6 mg/mL, respectively, were chosen to represent the lower and upper limit of the ordinary concentration range. Test solutions were stored under refrigeration (2–8°C) or at room temperature either light protected or exposed to light. CAFdA concentrati…

Multi-center observational study on the adherence, quality of life, and adverse events in lung cancer patients treated with tyrosine kinase inhibitors.

Introduction Cancer patients tend to prefer oral instead of parenteral chemotherapy. To date, there is little evidence on the medication adherence in cancer patients. We investigated medication adherence to tyrosine kinase inhibitors in patients suffering from non-small cell lung cancer. Methods Tyrosine kinase inhibitor adherence was measured electronically by MEMS® (medication event monitoring system) over at least six months. Adherence rates were calculated in terms of Dosing Compliance, Timing Compliance, Taking Compliance, and Drug Holidays. Patients were dichotomized as adherent when Dosing Compliance and Timing Compliance were ≥80%, Taking Compliance ranged between 90 and 110%, and &…

Viability of microorganisms in novel antineoplastic and antiviral drug solutions

Introduction. In determining the expiration-dates of ready-to-use antineoplastic and antiviral drug solu tions, microbiological aspects must be considered. This is especially true because many antineoplastic drugs introduced into the market are already known to lack antimicrobial activity. The purpose of this study is to evaluate the growth of four different microorganisms in ready-to-use solutions of 14 differ ent novel antineoplastic and antiviral drugs. Methods. The lowest concentrations of 14 dif ferent antineoplastic and antiviral drugs prescribed in our hospital were prepared in polyvinyl chloride bags or a polyethylene container (paclitaxel) containing 0.9% sodium chloride or 5% dex…

Glucocorticoids in Graves’ orbitopathy: mechanisms of action and clinical application

Background:Graves’ orbitopathy (GO) is the most frequent extrathyroidal manifestation of the autoimmune Graves’ disease. GO significantly impacts quality of life and has a psycho-social morbidity. Inflammation and swelling of the orbital tissue often leads to proptosis, diplopia, and decrease of visual acuity. Due to the inflammatory background of the disease, glucocorticoids (GC) have been used as a first-line treatment for decades.Methods:PubMed and MeSH database were searched for original articles, clinical trials, reviews, and meta-analyses published between 1 January 2000 and 31 March 2020 and pertaining to both the mechanism of action and immunological effects of GC as well as to the …

In-use physicochemical and microbiological stability of biological parenteral products

Pharmaceutical scientists in the biotechnology industry have traditionally focused on achieving acceptable shelf lives of drug products in their original, unopened product unit configuration (e.g., two years stored at 2–8 °C). However, it is now clear that stability considerations extend beyond

Physicochemical compatibility of mixtures of dornase alfa and tobramycin containing nebulizer solutions

Patients suffering from cystic fibrosis (CF) often need to inhale multiple doses of different nebulizable drugs per day. Patients attempt to shorten the time consuming administration procedure by mixing drug solutions/suspensions for simultaneous inhalation. The objective of this experimental study was to determine whether mixtures of the nebulizer solution dornase alfa (Pulmozyme) with tobramycin nebulizer solutions (TOBI and GERNEBCIN 80 mg) are physico-chemically compatible. Drug combinations were prepared by mixing the content of one respule Pulmozyme with either one respule TOBI or one ampoule GERNEBCIN 80 mg. Test solutions were stored at room temperature and exposed to light. Dornase…

Busulfan systemic exposure after oral administration of extemporeanously prepared high-dose busulfan capsules.

Purpose. The aim of the study was to analyze patients’ busulfan (BU) exposure after oral administration of extemporeanously prepared BU capsules prior to blood stem cell transplantation. Methods. Patients were treated with 1 mg/kg body weight BU administered orally every 6h on each of 4 consecutive days prior to blood stem cell transplantation. Each BU dose was administered in 1 gelatine capsule to be swallowed and containing the individually calculated dose of pure BU active substance. Blood samples were obtained from 6 adult patients 0, 30, 60, 90, 120, 180, 240, 300, and 360 min after the 1st, 5th, and 13th BU dose, frozen and analyzed subsequently by using a HPLC assay with UV detectio…

Stability of irinotecan-loaded drug eluting beads (DC BeadTM) used for transarterial chemoembolization

Purpose. The aim of this study was to determine the loading efficiency, physicochemical stability, and release of irinotecan-loaded DC BeadsTM (bead size 100—300 μm, 300—500 μm) before and after mixing with nonionic contrast medium (Accupaque® 300, Imeron® 300, Ultravist ® 300) during a prolonged period of time (28 days) when stored at room temperature or refrigerated. Methods. DC Beads TM were loaded with 50 mg irinotecan (Campto®) per milliliter beads in a 2 h loading period. Drug loading efficiency and stability were determined by measuring the irinotecan concentration in the excess solution. A free-flowing in vitro elution method for a period of 2 h and phosphate buffered solution (PBS…

Media-fill simulation tests in manual and robotic aseptic preparation of injection solutions in syringes

Objective The purpose of this study was to evaluate the contamination rate of media-fill products either prepared automated with a robotic system (APOTECAchemo™) or prepared manually at cytotoxic workbenches in the same cleanroom environment and by experienced operators. Media fills were completed by microbiological environmental control in the critical zones and used to validate the cleaning and disinfection procedures of the robotic system. Methods The aseptic preparation of patient individual ready-to-use injection solutions was simulated by using double concentrated tryptic soy broth as growth medium, water for injection and plastic syringes as primary packaging materials. Media fills w…

H2-Antihistaminika, 32. Mitt. Synthese und H2-antagonistische Wirkung von N-[3-(3-Piperidino-methyl-phenoxy)propyl]-1.3.4-oxadiazol-2-aminen

Es wird uber die Synthese und H2-antagonistische Wirksamkeit von N-[3-(3-Piperidinomethyl-phenoxy)-propyl]-1.3.4-oxadiazol-2-amin und dessen 5-substituierte Derivate berichtet. H2-Antihistaminics, XXXII: Synthesis and H2-Antagonistic Activity of N-[3-(3-(Piperidinomethyl)phenoxy)propyl]- 1.3.4-oxadiazol-2-amines The synthesis and H2-antagonistic activity of N-[3-(3-(piperidinomethyl)phenoxy)propyl]-l.3.4-oxadiazol-2-amine and its 5-substituted derivatives are reported.

Loading profile of topotecan into polyvinyl alcohol microspheres (DC Bead™) over a 7-day period

Purpose: DC Bead™ is successfully used for chemoembolization of various liver cancers. The purpose of this study was todetermine the loading capacity of the semi-synthetic topoisomerase-1 inhibitor topotecan into the DC Bead™ microspheres under static or agitated conditions and to assess the physicochemical stability over a period of 7 days. Methods: Commercially available topotecan hydrochloride powder (Hycamtin®) was reconstituted with water for injection to yield a nominal concentration of 1 mg/mL topotecan. Polyvinyl alcohol (PVA)-based microspheres (DC Bead™, 300–500 µm, 2 mL/vial) were mixed with 4 mL of the reconstituted topotecan solution. Vials were stored light protected at room …

European Databases on Stability and Compatibility of Injectable Medicinal Products in Europe

AbstractIn hospitals, the majority of medication therapy is administered intravenously. Especially, in intensive care units, simultaneous of various injectable drugs is a common practice Drug incompatibilities have been reported to be associated with up to 60 % of all serious and life-threatening adverse drug events. Several databases are used by hospital pharmacists to answer the questions of (in)compatibility of co-administered injectable drugs. The objective of this article is to present the European databases on compatibility and stability of injectable drugs. According to a questionnaire which was sent to the National Hospital Pharmacy Associations of the 28 countries of European Commu…

Aerosolcharakteristika ausgewählter Druckluftvernebler für Erwachsene in Simulationsmodellen und Verneblung von Salbutamol

Zusammenfassung Ziel Der Erfolg einer Inhalationstherapie wird durch Menge und Qualität des inhalierten Aerosols bestimmt. Die Auswahl eines Verneblers bedarf der Kenntnis der entsprechenden Aerosolcharakteristika. Methoden Die Aerosolperformance von 9 marktüblichen Druckluftverneblern wurde in vitro in 2 Simulationsmodellen geprüft. Salbutamol (Sultanol forte® Fertiginhalat 2,5 mg/2,5 ml; GSK) wurde über 4 Minuten vernebelt. Die Outputparameter wurden mit dem Atemzugsimulator PARI Compas II (Erwachsenenmanöver nach Ph.Eur.9.0; n = 5/6 Verneblungen) und die aerodynamische Partikelgrößenverteilung mit dem Next Generation Impaktor (Ph.Eur.9.0, Copley Scientific; n = 3 Verneblungen) per HPLC b…

H2-Antihistaminika, 34. Mitt. 1,3,4-Oxadiazol-2,5-diamine mit H2-antagonistischer Aktivität

Es wird uber die Synthese und H2-antagonistische Wirksamkeit von mono- und disubstituierten 1,3,4-Oxadiazol-2,5-diaminen mit Piperidinomethylphenoxypropylseitenkette sowie deren methylierte Derivate berichtet. H2-Antihistaminics, XXXIV: 1,3,4-Oxadiazole-2,5-diamines with H2-Antagonistic Activity Syntheses and H2-antagonistic activities of mono- and disubstituted 1,3,4-oxadiazole-2,5-diamines with a [(piperidinomethyl)phenoxy]propyl substituent and of their methyl derivatives are reported.

Assessing the risk to health care staff from long-term exposure to anticancer drugs--the case of monoclonal antibodies.

Today the occupational health and safety risk involved when handling most anticancer drugs is well recognized and, as a result of regulatory requirements, safety measures have been established. There is little knowledge about the occupational hazard posed by handling monoclonal antibodies assigned to ATC Class L01XC. The aim of our study was to evaluate the occupational risk of monoclonal antibodies. Using the information obtained in a systematic review of the literature, the potentially dangerous properties of the active drug substances were assessed using a specially devised algorithm. As a result, all monoclonal antibodies in question were categorized as substances with developmental to…

H2-Antihistaminika, 33. Mitt. Synthese und H2-antagonistische Aktivität heteroaromatischer (Thio)Carboxamide und Triazol(thi)on-Derivate des Piperidinomethylphenoxypropylamins

Die Zyklisierung der (Thio)Semicarbazide la, b mit N-Cyan-diphenylimidocarbonat, N-Cyan-dimethyldithioimidocarbonat, Aminocrotonsaurenitril und Acetessigester gibt die heteroaromatischen (Thio)Carboxamide 5a, b und 7–9. Beim Einwirken von NaOH auf die (Thio)Biharnstoffe 12 und 13 sowie die (Oxa)Thiadiazoldiamine 19 und 20 werden die Triazol(thi)one 15 und 17 erhalten. Am Vorhof des Meerschweinchens zeigen 5a, 7 und 8 eine mit Cimetidin vergleichbare Histamin-H2-antagonistische Wirkung. H2-Antihistaminics, XXXIII: Synthesis and H2-Antagonistic Activity of Heteroaromatic (Thio)Carboxamides and Triazole(thi)one-Derivatives of Piperidinomethylphenoxypropylamine The (thio)semicarbazides la, b ar…

Inhalation solutions — Which ones may be mixed? Physico-chemical compatibility of drug solutions in nebulizers — Update 2013

AbstractMany patients suffering from chronic respiratory diseases rely on inhalation therapy with nebulizers. About 25% of patients who need to inhale several different drugs per day save time by mixing them for simultaneous inhalation. This review presents a comprehensive overview of the available data concerning physico-chemical compatibility of commonly mixed nebulizer solutions and suspensions. Information is based on our in vitro studies and a thorough literature search.Results indicate that many nebulizer solutions/suspensions are mixable without provoking incompatibilities. However, certain excipients contained in some of the tested drug products could be identified as a reason for i…

Inhalation solutions: which one are allowed to be mixed? Physico-chemical compatibility of drug solutions in nebulizers.

AbstractTherapy of chronic respiratory diseases often involves inhalation therapy with nebulizers. Patients often attempt to shorten the time consuming administration procedure by mixing drug solutions/suspensions for simultaneous inhalation. This article considers the issue of physico-chemical compatibility of admixtures of drug solutions/suspensions in nebulizers.A search of databases, prescribing information and primary literature was conducted to locate literature concerning the physico-chemical compatibility of inhalation solutions/suspensions. This was supplemented by telephone interviews.Admixtures of albuterol with ipratropium and/or cromolyn, of albuterol and budesonide, or tobramy…

Significant interaction between high-dose methotrexate and high-dose piperacillin-tazobactam causing reversible neurotoxicity and renal failure in an osteosarcoma patient.

Introduction Pharmacokinetic interaction of high-dose methotrexate (MTX) and other concomitantly administered renally secreted medicinal products may lead to insufficient methotrexate serum level decrease and significant MTX toxicity. Case report We report the case of an 18-year-old male patient treated with high-dose MTX for an osteosarcoma and with high-dose piperacillin-tazobactam at the same time. MTX serum levels were severely elevated 24 hours after the MTX infusion and did not decrease in accordance with the specific calcium folinate rescue protocol. The patient experienced renal failure accompanied by neurological symptoms, most consistent with MTX-related renal and CNS toxicity. Ma…

Physicochemical compatibility and stability of nebulizable drug admixtures containing Dornase alfa and tobramycin.

The objective of this in-vitro study was to determine whether admixtures of the inhalation solutions Pulmozyme(®) (Dornase alfa) and either Bramitob(®) or Tobi(®) (both containing Tobramycin) are physicochemically compatible and to analyze the aerodynamic parameters of these admixtures. After mixing, test solutions were stored at room temperature and under ambient light conditions over a period of 24 h. Tobramycin concentrations were determined by using a fluorescence immunoassay. Stability of dornase alfa was determined by size-exclusion high performance liquid chromatography, ultraviolet spectroscopy, sodium dodecyl sulfate polyacrylamide gel electrophoresis and tentacle strong cation-exc…