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Farmacia Hospitalaria

versión On-line ISSN 2171-8695versión impresa ISSN 1130-6343

Farm Hosp. vol.42 no.5 Toledo sep./oct. 2018 


Review of evidence on handling hazardous drugs and Products in Urology Services; consensus document between the Spanish Urology Association and the Spanish Society of Health-System Pharmacists

Miguel Unda-Urzáiz1  , Jose María Alonso-Herreros2  , Jesus Maria Fernández-Gómez3  , Marisa Gaspar-Carreño4  , Jose Manuel Cozar-Olmos5  , Ana Cristina Cercós-Lleti6 

1Basurto University Hospital, Bilbao. Spain.

2Los Arcos del Mar Menor General University Hospital, Murcia. Spain.

3Asturias University Complex, Oviedo. Spain.

4Levante Intermutual Hospital, Valencia. Spain.

5Virgen de las Nieves University Hospital, Granada. Spain.

6Dr. Peset University Hospital, Valencia Spain.



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.


We reviewed the legislation and recommendations on the handling of dangerous drug products, both at the national and international level.


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.


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.


After this review, 19 recommendations were established for handling dangerous drug products, which can be summarised as the need to train all individuals involved (from management teams to patients and caregivers), adopt systems that prevent contaminating leaks, implement exposure surveillance programmes and optimise available resources.

KEYWORDS: Occupational exposure; Hazardous drugs; Closed system transfer device; Intravesical instillation; BCG; Mitomycin C



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 Española de Urología y Sociedad Española 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.


Se ha realizado una revisión de la legislación y de las recomendaciones sobre el manejo de medicamentos peligrosos tanto a nivel estatal como internacional.


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.


Siguiendo las líneas estratégicas del Parlamento Europeo para el período 2014-2020 en el capítulo de seguridad y salud laboral, la Asociación Española de Urología y la Sociedad Española de Farmacia Hospitalaria proponen una serie de actuaciones que hagan disminuir los riesgos de exposición de los profesionales y cuidadores implicados en su manejo.


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 los equipos directivos hasta los pacientes y cuidadores), la adopción de sistemas que no permitan fugas contaminantes, programas de vigilancia de las exposiciones y optimización de los recursos disponibles.

PALABRAS CLAVE: Exposición ocupacional; Drogas peligrosas; Sistemas cerrados; Instilación vesical; BCG; Mitomicina C


The term “Hazardous drugs” was introduced for the first time by the American Society of Health-System Pharmacists (ASHP) in 19901 and later adopted by the Occupational Safety and Health Administration (OSHA), designated for the first time by the National Institute for Occupational Safety and Health (NIOSH) in 20042. The hazardous nature of these medicines lies in the chemical risk, related to carcinogenic, teratogenic, genotoxic and toxic activity on the reproductive process or on a specific organ in low doses, or because this is a new drug similar to others with this type of risk.

El United States NIOSH lists potentially hazardous treatments to be chemotherapy, antivirals, hormones, and others, mentioning endovesical instillations for chemotherapy and BCG in patients with non muscular invasive bladder cancer as a source of potential contamination involving hazardous substances3.

The Spanish Urology Association (AEU) ensures that the standard referring to this speciality is disseminated and applied, and the Spanish Society of Health-System Pharmacists (SEFH) ensures appropriate, safe and effective use of the drugs and healthcare products.

The Technical Document for the National Institute of Occupational Health and Safety (INSHT) on preparation and administration of hazardous drugs4 recommends a consensus document between the two societies compiling recommendations for handling hazardous drugs in the field of Urology Services.

Exposure to hazardous drugs in the workplace and health risks for healthcare personnel have been documented over the last four decades2. The number of health workers exposed to these substances has risen due to greater use, new drugs and longer use as life expectancy has risen, representing a challenge for healthcare centres5 that have to adapt their procedures to handling these drugs6.

The European Union has acknowledged this concern through the European Union Occupational Safety and Health Agency (EUOSHA)7, raising the alarm on lack of legislation harmonisation on risk prevention for healthcare workers.

The aim of this document is inform healthcare professionals about the best possible evidence to safely handle Hazardous Drugs in the field of Urology.


The legislation and scientific literature was reviewed on 3 November 2016 by consulting the Medline and The Cochrane Library Plus electronic databases. The following search terms were used: occupational exposure, hazardous drugs, closed system transfer device, intravesical instillation. The most relevant complete text articles and works from the last 5 years on this topic were selected. Finally, an additional manual search was performed among the selected article references.


There is no clear evidence of the impact of these hazardous drugs on the healthcare population. However, some information might draw our attention to this potential risk. Several studies have demonstrated greater exposure to these products among this group of workers. There is epidemiological data supporting the fact that exposure to these drugs has an effect on embryo development and on reproductive functions8, although the methodology in these studies has been questioned9 and it has not been possible to confirm that this cancer risk is higher than among the rest of the population, so it is essential to take measures that help reduce this exposure, where preventive activity is the most appropriate10,11.

Exposure could take place by inhaling and cutaneous contact/absorption; ingestion or injection, are much less frequent. Environmental contamination, including air, gloves, clothing, work surfaces, floors, etc. can have different origins, from original contamination of the container or drips, to spills and splashes when handling them.

The probability that a worker will experience adverse effects due to a hazardous drug increases with the quantity and the frequency of exposure, affecting nurses, pharmacists and technicians but also nursing assistants or non healthcare staff such as cleaners, porters, laundry staff12-14. It is important to clean and decontaminate the place where work has involved hazardous substances.

One cause of contamination is using needles and conventional transfer systems that allow aerosol formation, vapour release or dripping medicines. In intravesical administration, the contamination risk is greater than in other clinical fields, as drug concentrations are greater than when administering intravenously. There are guides for handling hazardous drugs, including some for staff who carry out endovesical instillations with BCG and chemotherapy, adapted to the latest recommendations from the NIOSH15 or the SEFH16.

In 2004, Directive 2004/37/EC set a hierarchy of protection measures and the use of closed systems17. In 2007, the ISOPP (International Society of Oncology Pharmacy Practitioners) set level 1 for elimination, substitution or replacement of the product for a less toxic one (rarely possible in the healthcare field); level 2 with use of closed systems for complete isolation; level 3 with suitable control and ventilation systems and reduction of time and workers being exposed, and level 4, with Personal Protection Equipment (PPE) (lab coat, gloves, eye protection, breathing protection…) and staff training18.

The NTP 1051, uses the name Closed System Drug Transfer Devices (CSTD) to refer to devices to transfer drugs that prevent contaminants from entering and stops the release of the drug being handled, avoiding aerosols and vapours by equalling out the pressure inside and outside the vial. In Spain, these devices are considered to be healthcare products. In the United States, the FDA (Food and Drug Administration) has established the ONB product code for CSTD devices, thereby defining the quality of the systems, although they do not substitute work in the Biosafety Cabinets.

The choice of a CSTD should consider sterility of the prepared solution, safety for use (easy to transport, handle and transfer liquids), total transfer of the solutions, avoiding product losses, universal use (suitable for connections, sealing)19. The cost estimation is relevant (having published that CSTD systems can be cost-effective, even at times and in places with limited resources20,21.

In 2013, the European Commission published the Prevention and Best Practice Guide specifying that a risk should be avoided rather than reduced, or the drug should be replaced with another less hazardous substance22. Preventive measures should follow an order: starting with technical solutions, then organisational and, finally, personal/individual.

The United States Pharmacopoeia (USP) on handling hazardous drugs (USP 800) from 2016 indicates that contamination should be controlled to a limit that is “As Low As Reasonably Achievable” (ALARA), forcing the use of closed systems in preparation and administration of hazardous drugs although it does not recommend which to use23.

In Spain, protection for workers against risks of exposure to carcinogenic agents or mutagens is legislated by RD 665/199724 and modified by RD 1124/200025, and the INSHT has published Technical Prevention Notes NTP 74026 and NTP 105127, and the Technical Document on hazardous drugs justifying this consensus document4.

With regard to the most used medication in vesical instillations, Table 1 shows the most used hazardous drugs in this field and Table 2 summarises the INSHT recommendations.

Table 1 Some of the most usual hazardous drugs in the field of Urology 

IARC:International Agency for Research on Cancer; FDA: Food and Drug Administration.

Table 2 INSHT recommendations for handling the most usual hazardous drugs in urology 

AE: negative pressure sterile insulator; CSB IIb: class IIb biosafety cabinet; FDA RE: pregnancy risk category from the Food and Drug Administration; IARC: carcinogenic risk for humans classification according to the International Agency for Research on Cancer; CSDT: closed system drug transfer.

Taking into account the aforementioned aspects and following the strategic lines from the European Parliament for the 2014-2020 period in the chapter on occupational health and safety, the AEU and the SEFH propose a series of actions that lower the risks of exposure for professionals and carers involved in handling these drugs.

- Health authorities and management teams should be aware of the danger to which healthcare staff are exposed.

- Training should be provided for healthcare professionals who work in any of the phases of handling hazardous drugs (from transport and storage to preparation and administration), regarding inherent risks for handling these drugs and possible protection measures.

- Contamination levels due to hazardous drugs should be monitored periodically in the preparation and administration areas.

- Surveillance programmes should be set up on occupational health for healthcare professionals involved in handling hazardous drugs.

- Information should be provided to patients and family members on how to prevent exposure to hazardous drugs.

- Management and occupational health teams at hospitals should promote basic standards for preparing hazardous drugs, laid down in the Medicine Preparation Best Practice Guide21.

- Hospitals should promote effective use of Personal Protection Equipment (PPE) and closed systems for preparation and administration of hazardous drugs.

- Sterile hazardous drugs should be prepared in Class IIb or higher biosafety cabinets.

- A system should be arranged that does not produce contamination during the entire process, preparation, transport and vesical instillation.

- Transport should be easy and safe, in sealed containers. Packaging should be labelled clearly, legibly and contain safety warnings.

- Only a small number of staff should transport hazardous drugs who are properly trained on how to handle them.

- Double gloves should be worn or gloves for handling cytostatics, waterproof lab coat plus breathing protection measures (FFP3 type mask) and eye protection.

- Rigorous cleaning and decontamination should be performed in the place where the vesical instillation takes place according to the procedure approved in each centre by the Occupational Risk Prevention and/or Preventive Medicine Service. These procedures should have clear and specific instructions to be applied after using BCG.

- A system should be arranged that can transfer the entire prepared solution to reduce any loss of efficacy resulting from incomplete transfer, particularly with BCG. A three-way valve might be considered to do this, washing the probe with a small amount of saline solution, without having to disconnect the hazardous medicine packaging.

- The system being used should be compatible with the material used to carry out the vesical instillation, thereby lowering exposure risks.

- The vesical probe should be the finest possible calibre, mainly latex-free and water-repellent to avoid urethral trauma.

- To reduce exposure to the drug, the system used to administer the medication and the system used to wash the probe should be joined throughout the process, even when the vesical probe is being removed.

- Collection and elimination of residue should be labelled properly and have safety warnings.

- Patients will be trained on how to deal with their excretions, adding bleach to the toilet in an approximately equal volume to their urination, and letting it act for 15 minutes before flushing the chain, and they will be informed of the importance of hand-washing hygiene.

The review of the available evidence made it possible to make 19 recommendations for handling hazardous medicines that can be summarised by the need to train the people involved (from management teams to patients and carers), adopting systems guarantee no contaminating leaks, surveillance programmes on exposure and optimisation of available resources.


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Received: March 05, 2018; Accepted: March 20, 2018

Autor para correspondencia. Correo electrónico: (Miguel Unda-Urzáiz).

Conflict of interests

No conflict of interest.

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