Chapter 23: Administration of systemic anticancer therapies
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Safe handling of hazardous drugs
Evidence‐based approaches
There are hazards associated with many drugs but the highest risks are those associated with cytotoxic drugs because these chemicals can pose a risk to healthcare workers. Cytotoxic drug handling by nursing, pharmacy and other healthcare professionals is an occupational hazard (Weinstein and Hagle [265]). Cytotoxic drugs have been shown to be mutagenic, teratogenic and carcinogenic when given at therapeutic levels to animals and humans to destroy malignant cells (Weinstein and Hagle [265]).
Patients receive cytotoxic drugs over a period of months whereas healthcare workers are exposed to low levels of the drugs over a period of years, and risks from exposure need to be minimized at every opportunity (Polovich et al. [194]). The potential benefits of treatment for the patient outweigh the risk to them; healthcare workers have no benefit but are at risk of harm through exposure.
The American National Institute for Occupational Safety and Health (NIOSH 2014) described six characteristics of hazardous drugs:
- Carcinogenicity.
- Teratogenicity/developmental toxicity.
- Reproductive toxicity.
- Organ toxicity at low doses.
- Genotoxicity.
New drugs with structural and toxicity profiles that mimic those of existing drugs are regarded as hazardous, based on these criteria (NIOSH 2014).
In 2015, the International Agency for Research on Cancer (IARC) and the World Health Organization (WHO) re‐evaluated over 1000 chemical drugs to examine their carcinogenic potential to humans which reconfirmed cytotoxic drugs as hazardous (BJN [21]).
Common routes of exposure for healthcare workers are:
- contact with skin or mucous membranes (e.g. through accidental spillage or splashing)
- inhalation: aerosol, vapours and particles
- ingestion: eating/drinking in clinical areas/contaminated residue on the hands reaching the mouth
- percutaneous injury: needlestick injury (less common).
The risk to health associated with exposure is measured by the time, dose and routes of exposure. Safe levels of exposure to hazardous agents cannot be determined because of the lack of a reliable monitoring method to measure risk, so personal protective equipment (PPE) is vital for the protection of healthcare workers (Polovich et al. [194]). Many studies have demonstrated that healthcare workers are exposed to cytotoxic drugs through drug residue on contaminated worksurfaces, vial surfaces and surfaces in drug administration areas (Polovich et al. [194]). Cytotoxic drugs can be absorbed through the skin (although with the majority of the compounds there is little or no absorption through intact skin; the exceptions are those which are lipid soluble) (Weinstein and Hagle [265]). Skin exposure can occur by contact with contaminated equipment used in preparing or administering the drugs or during the handling and disposal of waste. More than 60 studies have demonstrated the presence of cytotoxic drugs in the urine of nurses and pharmacy personnel who were routinely involved in the handling of cytotoxic drugs (Polovich et al. [194]). Some studies have reported measurable amounts of drugs in personnel who did not report handling them, which may suggest that exposure happened because of contaminated workplace surfaces (Friese et al. [79]).
It is imperative therefore that the risks of exposure are kept to a minimum and that the workplace has a Control of Substances Hazardous to Health (COSHH) risk assessment completed to assess the level of risk and ensure that control measures are in place (HSE [104]).
In 2016 the European Parliament released ‘Preventing occupational exposure to cytotoxic and other hazardous drugs’, which is a list of 11 recommendations relating to protecting healthcare personnel and reducing exposure to a minimum (European Policy Recommendations [73]). It also advises that actions should be taken in the hierarchical order of prevention as set out by the International Society of Oncology Pharmacy Practitioners (ISOPP) 2007 (BJN [21]):
- Engineering controls are related to biological safety cabinets, aseptic isolators and closed system transfer devices
- Administrative controls include education and training relating to all aspects of cytotoxic drug handling, disposal and management of spillage, competency assessment of the healthcare worker and PPE to be worn at all times when handling cytotoxics (BJN [21])
- Workplace controls include ensuring that all procedures and practices are organized in a manner such that exposure and environmental contamination are minimized at every stage of the work flow pathway including disposal of waste
- Risks to personnel involved in the reconstitution and administration of cytotoxic drugs fall into three categories: acute effects, chronic effects and reproductive risks and systemic effects.
Acute effects
These are usually caused by direct contact with the skin, eyes and mucous membranes, for example dermatitis, inflammation of mucous membranes, excessive lacrimation, pigmentation, nausea, headaches, blistering (associated with mustine) and other miscellaneous, allergic reactions (Dranitsaris et al. [66], European Policy Recommendations [73], Weinstein and Hagle [265]).
Chronic effects and reproductive risks
Chronic effects may last for years and include damage to the bone marrow and kidney as well as effects on reproduction (European Policy Recommendations [73]). There is an association between the risk of cancer and handling cytotoxic drugs although it is difficult to quantify (Polovich et al. [194]).
Reproductive risks include menstrual dysfunction and infertility following exposure to cytotoxic drugs (European Policy Recommendations [73], Polovich et al. [194]). Studies have suggested that serious long‐term effects may result from exposure to cytotoxic drugs during pregnancy. Effects include miscarriages and stillbirths (Valanis et al. [251]), chromosomal abnormalities (Polovich et al. [194]), low birthweight and congenital abnormalities. However, when analysing the data, consideration needs to be given to the fact that most of the studies were conducted in the 1980s or based on staff exposure data from that time. During that period, PPE and safe working practices were not well established and therefore these data do not reflect current working practices.
The issue is of high importance to staff, and organizational procedures should be in place to minimize the risk of exposure to all staff at all times. A literature review by Gilani and Giridharan ([85]) showed that the risk of handling cytotoxic drugs could be reduced if staff adhered to the standard safety precautions (BJN [21]). It has been suggested that nurses ‘avoid working in high risk areas during the first 84 days of their pregnancy’ and that standard safety precautions including PPE should be adhered to (Gilani and Giridharan [85]). The Health and Safety Executive has issued guidance for new and expectant mothers and states that because ‘a safe level of exposure cannot be determined for these drugs, one should avoid exposure or reduce it to as low a level as possible’ (HSE [104]).
Systemic effects
It has been shown that although alterations in cell structure have been detected, they appear to be transient and at a low level. Studies have shown that changes to the DNA can occur following occupational exposure to cytotoxic drugs. Researchers demonstrated that DNA strand breaks were higher in exposed nurses than in controls (Polovich et al. [194]). A comet assay was used by Yoshida et al. ([277]) and revealed that a greater DNA tail length, which was due to the unravelling of genetic material, was present in nurses who routinely handled cytotoxic drugs as opposed to those who did not (Yoshida et al. [277]). Furthermore, chromosomal abnormalities in peripheral blood lymphocytes were identified in nurses and pharmacists who were handling alkylating agents (McDiarmid et al. [152]).
There is no legal obligation for employers to screen healthcare workers exposed to cytotoxic drugs; however, the Health and Safety Executive provides advice relating to the ‘health surveillance cycle’ which advocates that the employer should apply surveillance according to need (HSE [104]). Since occupational hazards of cytotoxic drugs pose a health risk for healthcare personnel, minimizing the risk of exposure by strict adherence to organizational policies is vital and the emphasis should be on clear guidelines to reduce occupational exposure to all staff at all times (BJN [21], European Policy Recommendations [73], Polovich et al. [194]).
Cytotoxic drugs may also have harmful short‐ or long‐term systemic effects if inhaled or ingested during preparation or handling. These effects include light‐headedness, dizziness, nausea, headache, rashes and skin discolouration and are normally associated with accidental spillage of the drugs during handling or with surface contamination (Polovich et al. [194]).
