Methotrexate can cause tinnitus. The FDA lists tinnitus as a known adverse reaction, and the Mayo Clinic includes “continuing ringing, buzzing, or other unexplained noise in the ears” among its less common side effects. While not one of the drug’s most frequent problems, tinnitus shows up often enough in patient reports to be a real concern for people taking it.
How Common Tinnitus Is on Methotrexate
Tinnitus falls into the “less common” category of methotrexate side effects, meaning it doesn’t affect most people but isn’t rare either. In a large study comparing side effects across patients with psoriatic arthritis and rheumatoid arthritis, roughly 22 to 28 percent of patients starting methotrexate reported tinnitus. Those numbers are higher than many people expect for a side effect labeled “less common,” though it’s worth noting that tinnitus is also common in the general population, especially among older adults who are the typical users of this drug. Not every case of tinnitus during treatment is necessarily caused by the medication itself.
Patients with psoriatic arthritis appeared more likely to report tinnitus (27.6%) than those with rheumatoid arthritis (22.1%). The reason for this difference isn’t fully understood, but it may relate to differences in underlying inflammation or the other medications these groups tend to use alongside methotrexate.
How Methotrexate May Damage Hearing
The inner ear has a protective barrier, similar to the blood-brain barrier, that shields its delicate structures from harmful substances in the bloodstream. Research in mice has shown that methotrexate can cross this barrier and directly damage two critical components of hearing: the outer hair cells in the cochlea (the tiny cells that amplify sound) and the neurons that carry sound signals to the brain. When these structures are damaged, the result can be ringing, buzzing, or hearing loss.
Methotrexate works by blocking an enzyme involved in processing folic acid, which is essential for cell growth and repair. This same mechanism that makes it effective against overactive immune cells and cancer also makes it capable of harming healthy cells in sensitive areas like the inner ear. Researchers have found that antioxidant compounds can protect inner ear structures from methotrexate damage in animal studies, which supports the idea that oxidative stress plays a role in how the drug injures hearing.
Tinnitus, Hearing Loss, and Dizziness Together
Tinnitus from methotrexate doesn’t always appear in isolation. The Mayo Clinic lists dizziness and hearing loss alongside tinnitus as less common side effects. In clinical case reports of patients experiencing inner ear toxicity from methotrexate, some had hearing loss alone, some had hearing loss with tinnitus, and a smaller number had tinnitus without measurable hearing loss. Vertigo has also been documented, though it appears to be rarer.
If you notice ringing in your ears while taking methotrexate, pay attention to whether sounds seem muffled or whether you’re having trouble following conversations. These additional symptoms can help your doctor determine whether the drug is affecting your inner ear more broadly.
Who Faces Higher Risk
Methotrexate toxicity of all kinds is significantly more likely in certain groups. Age is the biggest factor: in one study of severe methotrexate toxicity, every case occurred in patients over 70. Not a single severe case was found in younger patients. Impaired kidney function compounds the risk because the kidneys are responsible for clearing methotrexate from the body. When they work less efficiently, the drug accumulates to higher levels.
Several common medications can also raise methotrexate levels in your blood by interfering with how your kidneys process it. NSAIDs like ibuprofen and naproxen reduce the kidneys’ ability to clear methotrexate through multiple pathways. Aspirin does the same by displacing methotrexate from proteins in the blood. Since NSAIDs are themselves known to cause tinnitus at high doses, combining them with methotrexate could increase auditory side effects through two separate mechanisms. Diuretics (water pills) and proton pump inhibitors (heartburn medications like omeprazole) have also been identified as risk factors for methotrexate toxicity in older patients.
Does It Go Away After Stopping Treatment?
The evidence on reversibility is mixed and limited. A systematic review of immunosuppressant drugs and hearing found that cochleovestibular toxicity specifically tied to methotrexate is “extremely rare” in published reports, with only a handful of documented cases. Among patients on various immunosuppressants who developed hearing problems, stopping or adjusting the drug led to full hearing recovery in some and significant improvement in others, while a portion saw no change. For methotrexate specifically, one reported case of vertigo resolved after the drug was stopped, but outcomes for tinnitus and hearing loss cases were not consistently tracked.
The general pattern with drug-induced inner ear damage is that earlier detection improves the chances of recovery. Damage to outer hair cells can be permanent if it progresses too far, while changes driven by inflammation or fluid imbalance in the inner ear are more likely to reverse. This is why paying attention to early symptoms matters. Persistent ringing that starts after beginning methotrexate or after a dose increase is worth reporting promptly rather than waiting to see if it resolves on its own.
Low Dose vs. High Dose
Most people searching this question are taking low-dose methotrexate for conditions like rheumatoid arthritis, psoriatic arthritis, or psoriasis, typically 7.5 to 25 milligrams per week. The tinnitus rates of 22 to 28 percent mentioned earlier come from patients on these low-dose regimens, so the risk isn’t limited to the much higher doses used in cancer treatment. That said, higher doses increase exposure and therefore increase the potential for inner ear damage. The mouse study that demonstrated direct cochlear damage used high-dose methotrexate, and cancer patients receiving high-dose protocols face greater ototoxic risk overall.
Even at low doses, individual variation in kidney function, age, and concurrent medications can effectively raise the amount of active methotrexate in your system well beyond what the prescribed dose would suggest. This is one reason why blood monitoring and kidney function tests are standard parts of methotrexate treatment.