On an Immunotherapy Drug? Acetaminophen Makes It Less Effective, Research Says

If you or a loved one has cancer, you know by now that anti-cancer drugs are hard on the body. They can cause all kinds of painful symptoms, from gastrointestinal issues to pounding headaches, that make you want to reach for a bottle of Tylenol. In fact, many doctors often prescribe Tylenol along with a weak opioid, like codeine, to treat mild to moderate pain in patients with advanced cancer. Unfortunately, Tylenol may not be the best idea.

Recent research has found strong evidence that acetaminophen (Tylenol) reduces the effectiveness of certain anti-cancer drugs, leading to poor outcomes in some cancer patients. More specifically, acetaminophen may inhibit immunotherapy drugs called immune checkpoint inhibitors.

What are immune checkpoint inhibitors?

To understand immune checkpoint inhibitors (ICIs), you must first understand immune checkpoints. Immune checkpoints are receptors on the surface of T cells (T cells are a special kind of immune cell). When certain proteins bind to these checkpoint receptors, they inhibit T cell activity. This type of feature on a T cell sounds counter-productive, but checkpoints are important; they prevent an immune system overreaction.

Why does all of this matter? A cancer cell can trick a T cell by binding to the immune checkpoint. This “turns off” the T cell so it can’t destroy the cancer. And that’s where immune checkpoint inhibitors (ICIs) come in. ICIs are drugs that block cancer cells from binding to immune checkpoints. As a result, T cells can do their job and work to destroy cancer cells.

Of course, ICIs are not without their side effects. While they don’t necessarily suppress the immune system (and are generally more tolerable than chemotherapies), they can cause gastrointestinal issues such as nausea, vomiting, dysphagia, abdominal pain, and diarrhea. And, as research is discovering, ICIs may not work as well when taken with certain medications, such as acetaminophen.

What was the research?

In one study that involved 392 cancer patients — all of whom took an ICI drug called nivolumab (Opdivo) — patients that had detectable levels of acetaminophen in their bodies were 33 percent less likely to survive than the other patients.

In another study published in the Annals of Oncology, which involved 297 cancer patients, those who took acetaminophen at the beginning of the ICI treatment tended to have significantly worse health outcomes. Furthermore, the Annals of Oncology study also tested the efficacy of ICI drugs in animals with colon cancer. The study authors gave some of the animals acetaminophen before the ICI treatment, and those animals produced a weaker immune response as their bodies tried to fight the cancer.

What does this mean for patients on immunotherapy drugs?

These findings create a lot of questions. First, acetaminophen is an antipyretic, or a substance that reduces a fever by halting certain immune responses. Does this mean that patients on immunotherapy drugs should avoid all antipyretics? (Other antipyretics include aspirin and ibuprofen.) Second, the findings suggest that taking acetaminophen at the beginning of ICI treatment may be the worst time to take it. So, can cancer patients start taking acetaminophen one or two months into their treatment?

“Our results confirm that more research should be performed to understand the impact of [acetaminophen] on immunity and present a compelling case for caution in using this drug in cancer patients treated with [ICIs],” the study authors wrote. “Whether this rule applies at immunotherapy onset or all over the treatment duration, to all antipyretics, all regimens … and to other immunooncology agents … requires further investigations.”

In effect, we don’t yet have all the answers. But this research does shed light on an important issue, and may help improve the outcome of patients on immunotherapy drugs. If you or your loved one is on an ICI, talk to your doctor about your options for pain management, and don’t assume that your OTC drugs are benign.

This content is not a substitute for professional medical advice or diagnosis. Always consult your physician before pursuing any treatment plan.