Connect with others who understand.

sign up log in
Resources
About myRAteam

Connect with others who understand.

sign up log in
Resources
About myRAteam

How To Avoid Dangerous Interactions With RA Medications

Posted on July 20, 2022
Medically reviewed by
Diane M. Horowitz, M.D.
Article written by
Ross Phan, PharmD

Rheumatoid arthritis (RA) is an autoimmune condition in which the body’s immune system attacks the synovium — the tissue that lines your joints. Since 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 RA 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 will also discuss potential interactions between some 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), as well as to manage symptoms, is vital to preventing 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 (co-occurring health conditions)
  • 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 or conventional 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:

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.
  • Steroids may increase some of hydroxychloroquine’s potential toxic effects, such as heart damage. This is very rare, and many people are able to 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 is not common, 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-alpha (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:

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 (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 with 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:

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
  • Steroids

Taking these drugs in some combinations may result in drug interactions. Combining NSAIDs and steroids, 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.

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 RA medications and have concerns they may interact, discuss this with your health care provider too. Your doctor can help you better understand your risks 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 talk 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 193,000 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.

References
  1. Rheumatoid Arthritis: Causes, Symptoms, Treatments and More — Arthritis Foundation
  2. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis — American College of Rheumatology
  3. Drug Interactions in the Treatment of Rheumatoid Arthritis and Psoriatic Arthritis — Rheumatology International
  4. Real-World Questions and Concerns About Disease-Modifying Antirheumatic Drugs (DMARDs): A Retrospective Analysis of Questions to a Medicine Call Center — BMC Rheumatology
  5. COX Inhibitors — StatPearls
  6. Methotrexate — Methotrexate Tablet: Highlights of Prescribing Information — U.S. Food and Drug Administration
  7. Xatmep — Methotrexate Solution: Highlights of Prescribing Information — U.S Food and Drug Administration
  8. Methotrexate — Methotrexate Injection: Highlights of Prescribing Information — U.S. Food and Drug Administration
  9. Hydroxychloroquine — MedlinePlus
  10. What Are “Biologics” Questions and Answers — U.S. Food and Drug Administration
  11. Actemra — Tocilizumab Injection, Solution, Concentrate: Highlights of Prescribing Information — U.S. Food and Drug Administration
  12. Kevzara — Sarilumab Injection, Solution: Highlights of Prescribing Information — U.S. Food and Drug Administration
  13. Soft-Tissue Infections With Atypical Mycobacteria in Two Patients With Inflammatory Diseases Using TNF-Inhibitors and/or Leflunomide — Acta Clinica Belgica
  14. Cytochrome P450 — ScienceDirect
  15. Disease Modifying Anti-Rheumatic Drugs (DMARD) — StatPearls
  16. Orencia — Abatacept: Highlights of Prescribing Information — U.S. Food and Drug Administration
  17. Xeljanz — Tofacitinib Tablet, Film, Coated: Highlights of Prescribing Information — U.S. Food and Drug Administration
  18. Olumiant — Baricitinib Tablet, Film Coated: Highlights of Prescribing Information — U.S. Food and Drug Administration
  19. Rinvoq — Upadacitinib Tablet, Extended Release: Highlights of Prescribing Information — U.S. Food and Drug Administration
  20. CYP3A4 — ScienceDirect
  21. Understanding and Preventing Drug-Drug and Drug-Gene Interactions — Expert Review of Clinical Pharmacology
  22. Risk Factors for Potential Drug Interactions in General Practice — European Journal of General Practice
  23. Potential Drug Interactions in Patients With Rheumatoid Arthritis — Revista Brasileira de Reumatologia
  24. CDER Conversation: Evaluating the Risk of Drug-Drug Interactions — U.S. Food and Drug Administration
  25. Multiple Autoimmune Syndrome — Maedica
  26. The Key Comorbidities in Patients With Rheumatoid Arthritis: A Narrative Review — Journal of Clinical Medicine
  27. Safe Use of Medicines for Older Adults — National Institute on Aging
  28. Drug Interaction and Pharmacist — Journal of Young Pharmacists

All updates must be accompanied by text or a picture.
Diane M. Horowitz, M.D. is an internal medicine and rheumatology specialist. Review provided by VeriMed Healthcare Network. Learn more about her here.
Ross Phan, PharmD is a MyHealthTeam writer with a doctorate in Pharmacy. She is also a founder of Off Script, a pharmacy consulting business. Learn more about her here.

Related articles

Methotrexate is a commonly used disease-modifying antirheumatic drug (DMARD) for rheumatoid...

Can Methotrexate for RA Cause Body Odor?

Methotrexate is a commonly used disease-modifying antirheumatic drug (DMARD) for rheumatoid...
Getting a second opinion regarding your rheumatoid arthritis (RA) diagnosis can improve your...

Your Guide To Getting a Second Opinion

Getting a second opinion regarding your rheumatoid arthritis (RA) diagnosis can improve your...
When you have rheumatoid arthritis (RA), flare-ups can be tough to predict. You won’t always be...

Can Methotrexate Make RA Joint Pain Worse Instead of Better?

When you have rheumatoid arthritis (RA), flare-ups can be tough to predict. You won’t always be...
Tumor necrosis factor (TNF) inhibitors were the first biologics approved by the U.S. Food and...

TNF Inhibitors for RA: What To Know About This Drug Class

Tumor necrosis factor (TNF) inhibitors were the first biologics approved by the U.S. Food and...
Many people with rheumatoid arthritis (RA) try methotrexate (Trexall) as a treatment option. This...

Methotrexate Withdrawal and RA Flares

Many people with rheumatoid arthritis (RA) try methotrexate (Trexall) as a treatment option. This...
If you’re living with rheumatoid arthritis (RA), you may experience muscle spasms, cramps, and...

Muscle Relaxants and RA: What To Know

If you’re living with rheumatoid arthritis (RA), you may experience muscle spasms, cramps, and...

Recent articles

Like rheumatoid arthritis (RA), Sjögren’s syndrome (pronounced SHOW-grins, sometimes called SS)...

Rheumatoid Arthritis vs. Sjögren’s Syndrome: What’s the Difference?

Like rheumatoid arthritis (RA), Sjögren’s syndrome (pronounced SHOW-grins, sometimes called SS)...
Rheumatoid arthritis (RA) is an autoimmune disease that occurs when the immune system attacks the...

What Causes Rheumatoid Arthritis?

Rheumatoid arthritis (RA) is an autoimmune disease that occurs when the immune system attacks the...
Rheumatoid arthritis (RA) affects each person a little differently. Symptoms depend on the...

Symptoms of Rheumatoid Arthritis

Rheumatoid arthritis (RA) affects each person a little differently. Symptoms depend on the...
It’s beneficial to get a diagnosis of rheumatoid arthritis (RA) as soon as possible after you...

The Importance of an Early Diagnosis

It’s beneficial to get a diagnosis of rheumatoid arthritis (RA) as soon as possible after you...
Although rheumatoid arthritis (RA) is primarily a disease of the joints, it can have effects...

Conditions Related to Rheumatoid Arthritis

Although rheumatoid arthritis (RA) is primarily a disease of the joints, it can have effects...
If you’re living with rheumatoid arthritis (RA), you may occasionally experience muscle twitches...

Muscle Twitches and Rheumatoid Arthritis: Can RA Cause Muscle Spasms?

If you’re living with rheumatoid arthritis (RA), you may occasionally experience muscle twitches...
myRAteam My rheumatoid arthritis Team

Thank you for subscribing!

Become a member to get even more:

sign up for free

close