Employee health professionals should be aware that 34 hazardous drugs have been added to the list of those that pose a risk to healthcare workers who prepare and administer them to patients with cancer and other conditions.
The National Institute for Occupational Safety and Health (NIOSH) recently released the updated list of hazardous drugs, bringing the total to well over 100 that pose risk to healthcare workers.1 NIOSH estimates millions of healthcare workers are potentially exposed to hazardous drugs used in the workplace, including those used for cancer chemotherapy, antiviral drugs, hormones, and some bioengineered drugs.
This list categorizes drugs into the following three groups.
Antineoplastic drugs: These primarily chemotherapy drugs meet one or more of the NIOSH criteria for a hazardous drug. In addition to many of these drugs being cytotoxic (e.g., toxic to living cells), the majority are hazardous to males or females who are actively trying to conceive, women who are pregnant or may become pregnant, and women who are breast-feeding, NIOSH warns.
New antineoplastic drugs include afatinib, axitinib, belinostat, bosutinib, cabozantinib, carfilzomib, dabrafenib, enzalutamide, histrelin, xazomib, panobinostat, pertuzumab, pomalidomide, ponatinib, regorafenib, trametinib, trifluridine/tipiracil (combination only), vismodegib, and ziv-aflibercept.
Non-antineoplastic hazardous drugs: These drugs meet one or more of the NIOSH criteria for a hazardous drug, including those with the manufacturer’s safe-handling guidance. Some of these drugs may pose reproductive risks similar to those described for antineoplastic drugs. Newly listed drugs in this group include ospemifene, paliperidone, teriflunomide, and tofacitinib.
Non-antineoplastic drugs that primarily have adverse reproductive effects: The new drugs in this category include clomiphene, eslicarbazepine, lomitapide, macitentan, pamidronate, pasireotide, peginesatide, riociguat, and temazepam.
Depending on the activity in handling these drugs, NIOSH urges all or some combination of personal protective equipment including double chemotherapy gloves, protective gown, eye/face protection, respiratory protection, and a ventilated engineering control.
Hospital Employee Health talked to Thomas Connor, PhD, a research biologist in the NIOSH division of applied research and technology, about the new hazardous drugs and the ongoing process of reviewing and amending the list.
HEH: Can you provide a little background on this process with regard to how hazardous drugs in healthcare are determined and listed in NIOSH reports?
Connor: Originally in 2004, we published an alert on hazardous drugs. We did not have a list at that time, so we borrowed lists from different organizations — NIH, Johns Hopkins, and so forth. In 2010 we started updating the list every other year. We have done so in 2010, 2012, 2014, and now 2016. We are currently working on 2018 and, actually, 2020 already. We monitor the FDA website for new drug approvals and new warnings on existing drugs.
There have been a lot of new warnings recently because drug companies are trying to get their drugs to the market more quickly. We are seeing post-marketing adverse effects, and we have to look at all of those. So basically we have two triggers — one is the new drug approvals, and the other is the warnings for existing drugs. We look at all of those for a two-year period. I think the FDA approves 15 to 25 new drugs every year; it hovers around 20. About a third of the antineoplastic drugs are used for cancer treatment.
This all goes through a very rigorous review process. We have an expert panel that reviews these, and then we publish our proposed list in the Federal Register and we get public comment back. So it takes two years to do our review each time.We are also a little out of date — we lag behind the FDA.
HEH: Just to clarify, the post-marketing effects are reported when the drug has been approved and in public use?
Connor: Yes. When they do clinical trials they may have a few hundred to a couple thousand people, but then they give [the drugs] to a million people [after approval]. Then you start to see different effects of the drugs in different populations of people. There’s a new [emphasis on] developing more targeted therapies. A lot these are relatively nontoxic, but a lot of them have serious reproductive effects. It’s kind of 50-50, but they are starting to get away from the drugs that cause general toxicity — the hair loss and all of those other side effects we associate with cancer drugs. They are going to more targeted therapies, but those have some [hazardous risks] of their own.
HEH: You mention that antineoplastic drugs comprise a majority of the drugs, particularly some that are already on the market.
Connor: They have a lot of acute effects. A lot of the old chemotherapy drugs are still being used. In healthcare workers we see acute effects like nausea, skin, and mucous membrane irritations. We do see adverse reproductive effects. Probably close to 100% [of antineoplastic drugs] have adverse reproductive effects. Some of them also cause secondary cancer in patients and we know they cause genetic damage in healthcare workers. There is some indication of cancer in healthcare workers, but it hasn’t been studied that well.
HEH: Are healthcare workers not always using proper protective equipment for safe handling of the drugs? Is that a principal issue?
Connor: That is part of it. NIOSH has done surveys of healthcare workers [handling hazardous drugs]. Glove use is not 100% and use of protective gowns is relatively low — maybe 50% of the time. So certainly part of it is not using personal protective equipment.
HEH: Should employee health professionals look at this updated list and determine which hazardous drugs are being used in their facilities?
Connor: The main goal of this list is to make people aware of which drugs they need to use precautions with. So many institutions in the U.S. and around the world have taken this list and looked at the formulary in their hospital to do a comparison and see which drugs they are using are on the list. That would be their starting point, and then they would make recommendations within their healthcare facility regarding the engineering controls, what types of PPE, and so forth. Some of them are new drugs and some of them have been on the market for a number of years. It is a mix of both. The main purpose of this list is to raise awareness of which drugs precautions are needed for.
HEH: What about the non-antineoplastic drugs and the list of other drugs that may cause reproductive problems?
Connor: The non-antineoplastic drugs have other side effects — they may cause cancer in animals, immunosuppression, and things like that. Some of those in group 2 have adverse reproductive effects. All of those drugs in group 3 have adverse reproductive effects — that’s the only effect they have. If you are not at reproductive risk — post-menopausal or you are using effective contraception — the risk is extremely low.
HEH: Some these drugs pose reproductive risk to men as well?
Connor: Yes, some of these have adverse reproductive effects for men. The groups that we say are at risk are men and women who are actively trying to conceive, women who are pregnant, and women who are breast-feeding. In the document, we put together some potential exposure [scenarios] in healthcare. It is just some general guidance. For example, in dispensing a single intact pill to a patient, there is no risk to the healthcare worker. However, there is more oral chemotherapy being used in pediatric and geriatric populations, and the pills have to be ground up and put in some kind of liquid or applesauce to give to the patients. That poses a risk because you are producing dust and so forth. We try to cover most of the scenarios in there.
REFERENCE
- NIOSH. NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings, 2016. DHHS (NIOSH) Publication No. 2016-161. September 2016:
http://bit.ly/2i4gE2a.
