Rheumatoid arthritis (RA) is an autoimmune condition in which the body’s immune system attacks the synovium — the tissue that lines your joints. Because RA can cause joint damage that worsens over time, many people living with the condition take at least one disease-modifying antirheumatic drug (DMARD) to slow its progression. Some people take multiple DMARDs and other medications to manage RA and its symptoms.

Treating rheumatoid arthritis and managing its symptoms might require several medications. It’s no surprise that many people with RA are concerned about medication-related problems such as drug interactions, which can occur when two or more medications are combined (drug-drug interactions). In some cases, these interactions can be lethal.

Following a few rules of thumb can help reduce your risk of dangerous drug interactions. This article also discusses potential interactions between specific medications used for RA.

Other RA medications could also interact with other drugs, so reach out to your rheumatology team for information specific to your regimen.

General Tips To Prevent Drug Interactions

Here are some general tips for preventing drug interactions:

• Use the same pharmacy to fill all your medications, if possible.
• Know the purpose of each medication.
• Be open with your health care provider about your use of alcohol, tobacco, and any recreational drugs.
• Maintain a list of all your medications, and share it with your pharmacist and all other health care providers. Make sure to include both prescribed and over-the-counter (OTC) medications, as well as dietary supplements, herbs, and natural remedies. Also include the names of the health care providers who prescribed the medications and any special directions on how to take your medications.

Making all your health care providers aware of everything you take to treat your RA or any comorbidities (other health conditions that occur at the same time), as well as to manage symptoms, is vital to prevent dangerous drug interactions.

Risk Factors for Drug Interactions

Certain factors increase the risk of drug interactions. You may be at higher risk of interactions if you:

• Have multiple comorbidities
• Are an older adult
• See several health care providers
• Take a lot of medications
• Self-medicate using OTC drugs or dietary supplements

Read more about common comorbidities in people with RA.

Traditional DMARD Drug Interactions

Traditional DMARDs are often the first treatments doctors recommend for people diagnosed with RA. Examples of conventional DMARDs and their potential drug interactions include methotrexate, hydroxychloroquine (sold as Plaquenil), sulfasalazine (Azulfidine), and leflunomide (Arava).

Methotrexate

Especially at higher doses, methotrexate may interact with medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), which include:

• Ibuprofen (sold under brand names such as Motrin and Advil)
• Naproxen (Aleve)
• Diclofenac (Cataflam)

Many people with RA take both methotrexate and NSAIDs, which could result in high methotrexate levels and more side effects. Similar issues can occur when combining methotrexate with a proton pump inhibitor (PPI) such as omeprazole (Prilosec), which is used to treat heartburn.

In most cases, your physician will review your NSAID use and methotrexate dosing and determine if it is safe to take these together.

Hydroxychloroquine

The following drugs can interact with hydroxychloroquine:

• The NSAID diclofenac might increase your chances of liver problems.
• Acetaminophen (Tylenol) may have a higher risk of side effects.
• Oxycodone may lead to high levels of methotrexate and more side effects.
• Tramadol may not work as well.
• Corticosteroids may increase some of hydroxychloroquine’s potentially toxic effects, such as heart damage. This is very rare, and many people can use hydroxychloroquine and corticosteroids safely.
• PPIs might decrease hydroxychloroquine’s effectiveness.

Sulfasalazine

Taking NSAIDs and sulfasalazine together might increase your risk of a stomach bleed. The combination could also be toxic to your blood and harm bone marrow, which produces blood cells.

Leflunomide

Leflunomide might cause a buildup of NSAIDs in your body, leading to additional NSAID-related side effects. This condition is not common, however, and many people take both types of medications under the guidance of their rheumatologist.

Biologic DMARD Drug Interactions

Biologic DMARDs are made from cells and proteins. Different types of biologic DMARDs for RA vary in their potential interactions with other drugs.

TNF-Alpha Inhibitors

Tumor necrosis factor (TNF)-alpha inhibitors generally pose few problems when used with other medications. However, some researchers have suggested that TNF-alpha could boost the effects of drugs that suppress the immune system, raising the risk of infection.

TNF-alpha inhibitors for RA include:

• Adalimumab (Humira)
• Certolizumab pegol (Cimzia)
• Etanercept (Enbrel)
• Infliximab (Remicade)
• Golimumab (Simponi)

Interleukin Antagonists

Interleukin antagonists for RA include drugs such as tocilizumab (Actemra) and sarilumab (Kevzara). Interleukin antagonists may affect the way the liver breaks down other medications to be cleared from the body, making these drugs less effective. If you’re taking warfarin (sold as Coumadin), for example, your health care provider may need to closely monitor the results of your blood tests and adjust your warfarin dose as necessary.

Using multiple biologic DMARDs at the same time could severely suppress your immune system and put you at an increased risk of serious infections.

Abatacept

Taking abatacept (Orencia) with other biologic DMARDs isn’t recommended, and it also should be avoided if you’re taking Janus kinase (JAK) inhibitors. Combining these medications may seriously suppress your immune system and raise your chances of developing life-threatening infections.

Notify your health care provider if you are experiencing symptoms of an infection or taking antibiotics for an infection. If you developed a serious infection while on abatacept, your health care provider may have you stop using this medication.

JAK Inhibitor Interactions

A new category of DMARDs, JAK inhibitors, also should not be combined with biologic DMARDs. JAK inhibitors include:

• Baricitinib (Olumiant)
• Tofacitinib (Xeljanz)
• Upadacitinib (Rinvoq)

Additionally, tofacitinib may cause dangerous interactions when used with CYP3A4 inhibitors. This category of drugs includes the antifungal drug fluconazole.

Symptom-Management Drug Interactions

To manage joint pain and swelling, people with RA often use other types of drugs besides DMARDs, including:

• NSAIDs, including cyclooxygenase-2 (COX-2) inhibitors
• Opioids
• Corticosteroids (like prednisone)

Taking these drugs in some combinations may result in drug interactions. Combining an NSAID and a steroid, for example, may increase your chances of getting ulcers that are hard to heal. Using a COX-2 inhibitor such as celecoxib (Celebrex) or meloxicam (Mobic) with the opioid oxycodone might raise the risk of adverse effects. Taking a COX-2 inhibitor with tramadol could reduce the amount of pain relief provided.

Some people with RA wonder whether it is OK to take corticosteroids such as prednisone and acetaminophen at the same time. According to researchers, there are no known interactions between these two drugs. However, like many pharmaceuticals, both drugs can interact with other medications. Whenever you start a new drug, even one that can be found OTC, talk to a health care professional if you have concerns or questions about drug interaction.

If You Suspect a Drug Interaction

If you think you may be experiencing a drug interaction, write a description of your symptoms and side effects so you can accurately share the details with your health care provider. If you are taking several medications for the treatment of rheumatoid arthritis and have concerns that they may interact, discuss this with your health care provider too. Your doctor can help you better understand your risk of interactions.

If there are potential interactions between medications you’re taking, your doctor may advise taking steps such as:

• Monitoring for serious side effects
• Adjusting doses
• Changing your medication schedule
• Switching to a different drug

Always check in with your health care provider before making any changes to your medications or the way you take them. Some drugs can cause even more problems if you stop taking them abruptly.

Talk With Others Who Understand

Living with RA can be challenging, but you don’t have to go through it alone. When you join myRAteam, you’ll gain a community of more than 200,000 people who understand what it’s like to live with RA.

Do you still have questions about interactions with your RA medications? Do you plan to discuss these concerns with your doctor? Share your thoughts in the comments below or by posting on your Activities page.