Could Common OTC Drugs Sabotage Cancer Immunotherapy?

Cancer patients and oncologists are working hard to get the best possible results from immune checkpoint blockade—one of the most promising advances in cancer care. But a new warning from Duke researchers suggests that some medications might influence cancer immunotherapy responses. We are not talking about other prescription drugs for conditions such as diabetes or hypertension. The authors of this article in the Journal of Clinical Oncology, (January 7, 2026), suggest that some of the interacting meds might include over-the-counter products people pick up at the pharmacy, supermarket or convenience store.

That doesn’t mean patients should panic or abruptly stop medications. It does mean that “everyday” pills for pain, heartburn, allergies, inflammation, or treatment side effects deserve a closer look during immunotherapy. The commentary published in the Journal of Clinical Oncology reviewed more than 50 studies and found evidence that certain widely used medications may be associated with weaker responses to immunotherapy. On the other hand, some drugs might actually improve the odds that immune checkpoint inhibitors will work.

Tracking ALL Medications is Essential

There is a catch with this commentary. The science is still evolving. Much of what researchers have so far comes from observational studies. That means they identify patterns, but can’t always prove cause and effect. Still, the signals are strong enough that both patients and clinicians may want to treat OTC meds as part of the cancer-treatment conversation, not as an afterthought.

Most cancer centers rely upon electronic health records. That means nurses or technicians ask patients what medications they are taking. This information is entered into a sophisticated online system that allows medical personnel to review the data. But if someone uses an OTC pain reliever intermittently or a nonprescription heartburn medicine when indigestion occurs, it might not be entered into the system. Such drugs are at the center of the new commentary.

How Medications Might Influence Cancer Immunotherapy

Immunotherapy is designed to help the immune system recognize and attack cancer cells. That’s very different from chemotherapy, which generally targets rapidly dividing cells more broadly.

Because immune checkpoint inhibitors depend on immune activity, medications that change inflammation levels, alter immune signaling, or affect the gut microbiome could potentially influence results. Some drugs may dampen immune activity. Others might shift the immune system in a way that makes checkpoint therapy more effective.

This is why the Duke team is urging better tracking of both prescription and over-the-counter medication use in cancer clinical trials. If researchers don’t record what patients are taking, it becomes much harder to interpret why treatment worked well for one person—but not for another.

Acetaminophen and Cancer Immunotherapy

Acetaminophen (Tylenol) is one of the most commonly used pain relievers in the world. Many people choose it because it seems gentle, and because it doesn’t cause stomach irritation the way aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) can.

But the Duke researchers found evidence suggesting acetaminophen (also known as APAP) use may be linked to reduced effectiveness of immune checkpoint blockade in certain situations.

In the authors’ own words:

“APAP acts by upregulating IL-10 and regulatory T cells (Tregs), providing an anti-inflammatory response that may resolve a fever or a headache, but is also likely more immunosuppressive than previously assumed. APAP has been linked with diminished responses to vaccines, unlike ibuprofen or other nonsteroidal anti-inflammatory drugs, and both mouse and human studies comport with the fact that APAP impairs immunotherapy responses by bolstering Tregs via IL-10.”

The Duke scientists go on to state that one team of researchers found that immunotherapy plus acetaminophen might produce reduced benefit in a test-tube model. They then note:

“These authors also evaluated this impact in 297 patients with advanced renal [kidney] cell carcinoma, where they observed that patients with detectable levels of APAP or APAP glucuronide [a metabolite of acetaminophen] had significantly worse OS [overall survival] than those without detectable levels. Furthermore, these authors evaluated 34 patients with advanced disease and observed that those with detectable APAP levels had significantly lower objective response rates to ICB [immune checkpoint blockade].”

Why would a pain reliever affect cancer therapy? Researchers are still sorting that out. It may relate to how acetaminophen affects inflammation and immune signaling. It may also reflect the fact that sicker patients are more likely to need symptom-relief medications, which can confuse the data.

What matters most is the practical takeaway: cancer patients on immunotherapy should not assume Tylenol is automatically safe for them.

A good question to ask the oncology team:

“If I need something for pain or fever during immunotherapy, what do you recommend?”

Other Medications That May Influence Cancer Immunotherapy:

Heartburn isn’t just uncomfortable—it can be miserable. And cancer treatment may make digestive symptoms worse. That is why so many people rely on proton pump inhibitors (PPIs) such as omeprazole (Prilosec), esomeprazole (Nexium) or pantoprazole (Protonix).

The Duke researchers highlight evidence that PPIs may be associated with poorer outcomes from immunotherapy in some studies. Again, that does not mean patients should forego such acid-suppressing medications. But patients may want to have the oncology team check out the article published in the Journal of Clinical Oncology, (January 7, 2026).

A question to ask:

“Do I need this heartburn medicine every day during immunotherapy—or are there safer options?”

Steroids Might Work Against Cancer Immunotherapy

Corticosteroids (like prednisone or dexamethasone) can be essential medications. They’re often used to reduce swelling, improve breathing, manage pain, ease brain metastasis symptoms, and treat serious inflammatory reactions.

Unfortunately, steroids can also suppress immune activity. That creates a difficult dilemma when the entire goal of immunotherapy is to activate the immune system against cancer.

Powerful immunotherapy may also trigger autoimmune responses that are hard to treat (arthritis, thyroiditis, colitis, etc.). Such conditions are typically treated with corticosteroids to reduce the inflammation.

The Duke team found evidence suggesting corticosteroids may also reduce the effectiveness of immune checkpoint inhibitors [ICBs] in some situations:

“Studies have observed that patients who are taking steroids while on ICB therapy have lower overall survival (OS) and higher progression rates. Additionally, there is evidence that steroid use within 1 month before initiation of ICB therapy leads to an increased risk of mortality within the first 6 months of treatment.”

If this sounds a bit like walking a tightrope, it really is. Sometimes steroids are absolutely essential for survival and cannot be avoided. That’s why it is so important to discuss such drug interactions with the oncology care team.

A question to ask:

“Is this the best steroid dose that will control my symptoms during immunotherapy without undermining the anti-cancer benefits?”

Some Drugs Might Help Cancer Immunotherapy:

There’s a surprising flip side to all this: some medications may actually improve response to immune checkpoint blockade. The Duke researchers highlight evidence that drugs such as antihistamines, statins, and certain antidepressants known as SSRIs might be associated with better immunotherapy outcomes in some studies.

They also raise interest in other medications that affect metabolism and inflammation. For example, some scientists are beginning to explore whether GLP-1 drugs used for diabetes and weight loss, such as liraglutide, could influence immune response in ways that might matter for cancer treatment.

That said, this is not an invitation for patients to add new medications in hopes of “boosting” immunotherapy. These signals are intriguing, but they still require careful research.

A good question to ask:

“Are there any medications I’m taking that might interact with my immune system, either positively or negatively, and affect treatment outcome?”

What Patients Can Do Now If on Cancer Immunotherapy:

The most important message from this Duke commentary is not “stop your medicines.” It’s “make sure your cancer team knows what you’re taking.”

Here are some practical steps that can help:

Bring a complete medication list to every oncology appointment.
That means prescriptions, OTC drugs, allergy pills, sleep aids, acid reducers, vitamins, supplements, and “as needed” products.

Don’t change your medication routine on your own.
Stopping steroids suddenly can be dangerous. Stopping reflux medicine abruptly can cause rebound symptoms. Uncontrolled pain can take a serious toll.

Ask directly about OTC drugs.
Many patients assume the oncologist only needs to know about chemotherapy-related prescriptions. This research suggests the “little things” like OTC drugs might not be so little.

Keep a simple medication log during immunotherapy.
If anything changes (new symptoms, new side effects, a new OTC drug) that record can help your care team troubleshoot quickly.

Bottom Line: Don’t Panic—Communicate

Immune checkpoint blockade has transformed cancer care. But it depends on a complex immune system that can be influenced by more than just the cancer drug itself.

According to Duke researchers, some common medications—possibly including acetaminophen, proton pump inhibitors, and corticosteroids—may reduce the effectiveness of immunotherapy. Other drugs, such as antihistamines, statins, or SSRIs, may be linked to better outcomes in some studies.

Better research is needed. Better tracking in clinical trials is needed. But right now, one step is immediately useful:

If you’re receiving cancer immunotherapy, tell your oncologist about every medication you take—even over-the-counter drugs—and ask whether any changes should be considered.

Final Words

Do you know someone undergoing cancer treatment? If so, please forward this article to them or their family. We hope it provides some new information that might have an important impact on their therapy.