Actas Urol Esp. 2018;42(6):375---380
Actas Urol´ ogicas Espa˜ nolas www.elsevier.es/actasuro
Review of the evidence on handling drugs and hazardous products in Urology Departments. Consensus document between the Spanish Urological Association and the Spanish Society of Hospital Pharmacy夽,夽夽 M. Unda-Urzaiz a,∗ , J.M. Alonso-Herreros b , J.M. Fernandez-Gomez c , no d , J.M. Cozar-Olmos e , A.C. Cercós Lleti f , M. Gaspar-Carre˜ Grupo Medicamentos Peligrosos SEFH a
Hospital Universitario Basurto, Bilbao, Vizcaya, Spain Hospital General Universitario Los Arcos del Mar Menor, Murcia, Spain c Complejo Universitario de Asturias, Oviedo, Asturias, Spain d Hospital Intermutual de Levante, Valencia, Spain e Hospital Universitario Virgen de las Nieves, Granada, Spain f Hospital Universitario Dr. Peset, Valencia, Spain b
Received 8 March 2018; accepted 13 March 2018 Available online 10 June 2018
KEYWORDS Occupational exposure; Dangerous substances; Safety; Safety devices; Vesical instillation; Mitomycin C
Abstract Background: The intravesical administration of hazardous drug products is a standard practice in the urology setting, which potentially exposing medical personnel to these drug products. It was deemed necessary to have a consensus document among the scientiﬁc societies involved (the Spanish Urological Association and the Spanish Society of Hospital Pharmacy) that collects the best available evidence on the safest handling possible of dangerous drug products in the setting of urology departments. Methods: We reviewed the legislation and recommendations on the handling of dangerous drug products, both at the national and international level.
夽 Please cite this article as: Unda-Urzaiz M, Alonso-Herreros JM, Fernandez-Gomez JM, Gaspar-Carre˜ no M, Cozar-Olmos JM, Cercós Lleti AC, et al. Revisión de la evidencia sobre el manejo de medicamentos y productos peligrosos en los servicios de Urología. Documento de consenso entre la Asociación Espa˜ nola de Urología y la Sociedad Espa˜ nola de Farmacia Hospitalaria. Actas Urol Esp. 2018;42:375---380. 夽夽 This article is published simultaneously in: Farm Hosp https://doi.org/10.7399/fh.11014 with the consent of the authors and editors. ∗ Corresponding author. E-mail address: [email protected]
2173-5786/© 2018 AEU. Published by Elsevier Espa˜ na, S.L.U. All rights reserved.
M. Unda-Urzaiz et al. Results: There is national legislation and regulations for protecting workers who handle dangerous drugs and products, as well as recommendations for handling to protect both the product and workers. Discussion: Following the strategic lines of the European Parliament for 2014---2020 in the chapter on occupational safety and health, the Spanish Urological Association and the Spanish Society of Hospital Pharmacy proposed a series of actions that decrease the risks of exposure for practitioners and caregivers involved in the handling of these products. Conclusions: After this review, 19 recommendations were established for handling dangerous drug products, which can be summarized as the need to train all individuals involved (from management teams to patients and caregivers), adopt systems that prevent contaminating leaks, implement exposure surveillance programs and optimize available resources. © 2018 AEU. Published by Elsevier Espa˜ na, S.L.U. All rights reserved.
PALABRAS CLAVE Exposición ocupacional; Sustancias peligrosas; Seguridad; Dispositivos de seguridad; Instilación vesical; Mitomicina C
Revisión de la evidencia sobre el manejo de medicamentos y productos peligrosos en los servicios de Urología. Documento de consenso entre la Asociación Espa˜ nola de Urología y la Sociedad Espa˜ nola de Farmacia Hospitalaria Resumen Introducción: La administración intravesical de medicamentos peligrosos es una práctica habitual en el ámbito de la urología, con posible exposición del personal sanitario a dichos medicamentos. Se considera necesario disponer de un documento de consenso entre las sociedades cientíﬁcas implicadas ----Asociación Espa˜ nola de Urología y Sociedad Espa˜ nola de Farmacia Hospitalaria---- que recoja la mejor evidencia disponible para el manejo, de la forma más segura posible, de medicamentos peligrosos en el ámbito de los servicios de Urología. Métodos: Se ha realizado una revisión de la legislación y de las recomendaciones sobre el manejo de medicamentos peligrosos tanto a nivel estatal como internacional. Resultados: Se dispone de legislación nacional y de normativas para la protección de los trabajadores que manipulen medicamentos y productos peligrosos, así como recomendaciones de manipulación para la protección tanto del producto, como de los trabajadores. Discusión: Siguiendo las líneas estratégicas del Parlamento Europeo para el período 2014-2020 en el capítulo de seguridad y salud laboral, la Asociación Espa˜ nola de Urología y la Sociedad Espa˜ nola de Farmacia Hospitalaria proponen una serie de actuaciones que hagan disminuir los riesgos de exposición a los profesionales y cuidadores implicados en su manejo. Conclusiones: Tras esta revisión se establecen 19 recomendaciones para el manejo de medicamentos peligrosos que pueden resumirse en la necesidad de formación de todas las personas implicadas (desde equipos directivos hasta los pacientes y cuidadores), adopción de sistemas que no permitan fugas contaminantes, programas de vigilancia de las exposiciones y optimización de los recursos disponibles. © 2018 AEU. Publicado por Elsevier Espa˜ na, S.L.U. Todos los derechos reservados.
Introduction The term ‘harzardous drugs’ was introduced for the ﬁrst time by the American Society Hospital Pharmacy (ASHP) in 19901 and later adopted by the Occupational Safety and Health Administration (OSHA), being named for the ﬁrst time by the National Institute for Occupational Safety and Health (NIOSH) in 2004.2 The dangerousness of these drugs is due to chemical risk related to carcinogenic, teratogenic, genotoxic, and toxic activity on the reproductive process or on a speciﬁc organ at low doses, or because it is a new drug similar to others with this type of risk. The NIOSH of the United States includes, among the potentially dangerous treatments, chemotherapy agents, antivirals, hormones, and others, mentioning endovesical instillations of chemotherapy agents and BCG in patients
with non-muscle-invasive bladder cancer as a source of potential contamination of dangerous substances.3 The Spanish Association of Urology (AEU) ensures that the regulations affecting the specialty itself are known and applied, and the Spanish Society of Hospital Pharmacy (SEFH) ensures proper, safe, and effective use of medicines and health products. The technical document of the National Institute for Safety and Hygiene at Work (INSHT) on the preparation and administration of dangerous drugs4 makes it advisable to have a consensus document between both societies, which includes recommendations for the handling of dangerous drugs in the ﬁeld of Urology services. Exposure to dangerous drugs in the workplace and health risks for health personnel have been documented in the last 4 decades.2 The number of health workers exposed to
Review on handling drugs and hazardous products in Urology Departments these substances has increased due to increased use, new medicines, and increased use as life expectancy increases, which is a challenge for health centers,5 which must adapt their procedures in the handling of these medications.6 The European Union has recognized this concern through the European Agency for Safety and Health at Work (EU-OSHA),7 warning about the lack of harmonization of legislation in the prevention of risk to health workers. The aim of this document is to disseminate among health professionals the best available evidence for the safe management of medicines and dangerous products (MDP) in the ﬁeld of Urology.
Methods A review of the legislation and scientiﬁc literature was conducted on November 3, 2016 by consulting the electronic databases of Medline and The Cochrane Library Plus. The following search terms were used: occupational exposure, hazardous drugs, closed system transfer device, and intravesical instillation. The most relevant articles and works on this topic of the last 5 years were selected. Finally, an additional manual search was performed among the references of the selected articles.
Results There is no clear evidence of the impact of these MDPs on the health population. However, some data may raise awareness of this potential risk. Several studies have shown greater exposure to these products in this group of workers. There are epidemiological data that support that exposure to these drugs leads to effects on embryonic development and reproductive function,8 although the methodology of these studies is questioned9 and it has not been conﬁrmed that the risk of cancer is greater than in the rest of the population, so it is essential to adopt measures that help reduce this exposure, with preventive activity being the most appropriate.10,11 Exposure may occur through inhalation and skin contact/absorption; ingestion or injection are much less frequent. Environmental pollution, including air, gloves, clothes, work surfaces, ﬂoors, etc., can have different origins, from the original contamination of the container or dripping, to spills and splashes when handling them. The likelihood of a worker experiencing adverse effects due to MDP increases with the amount and frequency of exposure, affecting nurses, pharmacists and technicians, but also nursing assistants or non-health personnel such as cleaners, orderlies, laundry personnel.12---14 It is important to clean and decontaminate the place where it has been worked with hazardous substances. One cause of contamination is the use of needles and conventional transfer systems that allow for the formation of aerosols, release of vapors, or dripping of the medication. In intravesical administration, the risk of contamination is greater than in other clinical settings, because the concentrations of the drugs are higher than intravenously. There are guidelines for the management of MDPs, including some
aimed at personnel who perform endovesical instillations with BCG and chemotherapy, or adapted to the latest recommendations of the NIOSH15 or the SEFH.16 In 2004, Directive 2004/37/EC established a hierarchy of protection measures and the use of closed systems.17 In 2007, the International Society of Oncology Pharmacy Practitioners (ISOPP) established a level 1 of elimination, substitution, or replacement of the product with a less toxic one (in the health ﬁeld it is rarely possible); level 2 with use of closed systems of complete isolation; level 3 with adequate control and ventilation systems, and reduced time and exposed workers, and at level 4, with personal protective equipment (PPE) (gown, gloves, eye and respiratory protectors, etc.) and staff training.18 The NTP 1051 calls closed system drug transfer devices (CSTD) the devices for the transfer of drugs that prevent the entry of contaminants and the escape of the manipulated medication, avoiding aerosols and vapors equaling the pressures inside and outside the vial. In Spain, these equipments are considered sanitary products. In the United States, the Food and Drug Administration (FDA) has the ONB product code established for SCTM devices, thus deﬁning the quality of the systems, although they do not substitute work in biological safety cabinets. When choosing the SCTM, asepsis of the prepared solution, safety of use (easy transportation, handling, and transfer of liquids), total transfer of the solutions, avoiding product losses, universality of use (adaptation to connections, tightness) must be taken into account.19 The estimation of costs is relevant, having been published that SCTM systems can be cost-effective, even at times or places with limited resources.20,21 In 2013, the European Commission published the Prevention and Good Practices Guideline, which speciﬁes that a risk must be avoided rather than reduced, or replaced with a less dangerous one.22 Preventive measures must follow an order: start with technical solutions, then organizational and, ﬁnally, personal/individual ones. The United States Pharmacopoeia (USP) in the handling of dangerous drugs (USP 800) of 2016 indicates that contamination should be controlled to a limit ‘as low as reasonably achievable’ (ALARA), which requires the use of closed systems in the preparation and administration of dangerous drugs, although it does not give recommendations on which one to use.23 In Spain, the protection of workers against risks of exposure to carcinogens or mutagens is legislated by the RD 665/199724 and amended by the RD 1124/2000.25 The INSHT has published the technical notes on prevention (TNP) 74026 and TNP 1051,27 and the technical document on MDP that justiﬁes this consensus document.4 With regard to the drugs most commonly used in bladder instillations, Table 1 lists the MDPs most used in this area and Table 2 summarizes the INSHT recommendations. Taking into account the aforementioned aspects and following the strategic lines of the European Parliament for the period 2014---2020 in the chapter on occupational health and safety, the Spanish Association of Urology and the Spanish Society of Hospital Pharmacy propose a series of actions that reduce exposure risks to professionals and caregivers involved in their management.
378 Table 1
M. Unda-Urzaiz et al. Some of the most common MDPs in the ﬁeld of Urology.
Adriamycin/doxorubicin Mitomycin C BCG Epirubicin
2A (IARC) 2B (IARC) Biological risk D (FDA)
Probably carcinogenic in humans Possibly carcinogenic in humans There is clear evidence of teratogenic risk
FDA: Food and Drug Administration; IARC: International Agency for Research on Cancer.
INSHT recommendations for the management of the most common dangerous drugs in urology.
Drug, pharmaceutical form (specialties)
FDA RP; IARC category
Bacillus Calmette-Guerin powder for intravesical suspension (Oncotice), powder and solvent for intravesical solution (Vejicur)
Administer with double glove, gown, eye, and respiratory protection
FDA RP C
Mitomicina polvo para solución inyectable (Mytomicin-C)
Prepare in BSC II or SI, with double glove, gown and mask. Use CDTS. Do not prepare in areas where parenteral medications are prepared to avoid cross contamination, or perform terminal cleansing later Prepare in BSC IIb or SI, with double glove, gown, and mask. Use CDTS
Administer with double glove and gown; use eye protection when there is a risk of splashing and respiratory if there is possibility of inhalation
IARC 2B; FDA RP D
SI: negative pressure sterile insulator; CSB IIb: class iib biological safety cabinet; FDA RP: category of the Food and Drug Administration of risk during pregnancy; IARC: classiﬁcation of carcinogenic risk in humans according to International Agency for Research on Cancer; CDTS: closed drug transfer system.
--- Health authorities and management teams must be aware of the danger of the exposed health personnel. --- Training should be provided to health professionals involved in any phase of the handling of dangerous drugs (from transport and storage, to preparation and administration), of the risks inherent in handling them, and the possible measures for their protection. --- The pollution levels by MDPs should be periodically monitored in the areas of preparation and administration. --- Occupational health surveillance programs should be established for health professionals involved in the management of MDPs. --- Information should be provided to patients and family members on ways to prevent exposure to MDPs. --- The management and Occupational Health teams of the hospitals must promote the adoption of the minimum standards for the preparation of MDPs, established in the Guideline of good practices for the preparation of medicines.21 --- Hospitals should promote the effective use of personal protective equipment (PPE) and closed systems for the preparation and administration of MDPs.
--- The sterile MDP preparation must be performed in class IIB or higher biological safety cabinets. --- A system that does not produce contamination during the whole process, preparation, transport, and bladder instillation should be sought. --- Transportation must be easy and safe, in sealed containers. The containers must be clearly labeled, legible, and with safety warnings. --- The personnel transporting it must be limited in number and well instructed in its management. --- Double glove or gloves should be used for the handling of cytostatics, waterproof gown, and measures of respiratory (mask type FFP3) and ocular protection. --- Rigorous cleanings and decontaminations of the place where the bladder instillation is performed must be carried out according to the procedure approved in each center by the Occupational Risk Prevention or Preventive Medicine Department. These procedures should have clear and speciﬁc instructions to be applied after the use of BCG. --- A system must be provided that is capable of transferring all the prepared solution in order to reduce the loss of
Review on handling drugs and hazardous products in Urology Departments
efﬁcacy that may result from not achieving it, especially with BCG. For this, the use of a 3-way valve key that allows the probe to be washed with a small volume of serum can be considered, without disconnection of the container from the dangerous medication being necessary. The system used must be compatible with the material used to perform bladder instillation, thus reducing the risks of exposure. The bladder catheter must be of the thinnest possible gauge, mainly free of latex and hydrophilic, to avoid urethral traumatism. To reduce exposure to the drug, the system with which the medication is administered and the system with which the probe is washed must remain attached to it during the entire process, including the removal of the bladder catheter. The collection and disposal of waste must be labeled appropriately and with safety warnings. Patients will be trained in the treatment of their excreta, adding bleach to the toilet in a volume approximately equal to that of urination, and leaving it to act for 15 minutes before ﬂushing the toilet, and making them aware of the importance of increasing hand hygiene.
Conclusions The review of the available evidence makes it possible to establish 19 recommendations for the management of dangerous drugs that can be summarized in the need for training of all the people involved (from management teams to patients and caregivers), adoption of systems that do not allow polluting leaks, programs of surveillance of exposures and optimization of available resources.
Conﬂict of interest The authors declare that they have no conﬂict of interest. 17.
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