Methotrexate is one of the oldest and most cost-effective medicines available for rheumatoid arthritis (RA). It’s also one of the most commonly used RA therapies. Here’s what to know about this drug if you have RA.
Methotrexate Is a First-Line Treatment for RA
Methotrexate falls into the category of disease-modifying antirheumatic drugs, or DMARDs. These drugs do more than deal with symptoms; they actually slow down progression of the disease.
About 60 percent of people with RA are currently on or have been on methotrexate, according to Johns Hopkins Arthritis Center.
In addition to being an effective treatment, methotrexate works relatively quickly and has a milder side-effect profile than other medicines used for RA, says Andrew Tenpas, PharmD, a clinical assistant professor of pharmacy practice at Texas A&M University in Kingsville, Texas.
“We have so much experience with methotrexate, and we know it’s effective and safe,” says Bahar Moghaddam, MD, a rheumatologist at Mount Sinai Hospital in New York City.
Methotrexate Fights Inflammation
RA is an inflammatory form of arthritis. Methotrexate is thought to work by causing cells to release a molecule called adenosine that blocks chemicals that promote inflammation. Reducing inflammation helps prevent pain and joint damage otherwise experienced by people with the disease.
Scientists realized early on that the drug, initially used to treat cancer, could be useful for RA. By the 1980s, well-designed gold-standard studies began to confirm its value for this condition.
Your Doctor Will Determine Your Dose
Most people with RA begin with a 7.5 milligram (mg) dose of methotrexate tablets taken once a week. Over time, if that is not enough to help, your doctor will increase your dosage, perhaps up to 20 mg. The pills are 2.5 mg each, and the usual dose is 3 to 10 pills. According to the Arthritis Foundation, most people take a weekly dose between 10 and 25 mg for inflammatory arthritis.
“It is extremely important to understand that the drug is taken once weekly, not once each day,” Dr. Tenpas says, noting that mistaking this dosage has led to toxicity in some patients.
Methotrexate can also be given by weekly injection. People can give the methotrexate shot to themselves using an auto-injector. Taking the drug this way allows more of it to get into your system without increasing unwanted side effects.
Dosages for the injected drug are generally similar as for the oral version. The injection is available in 25 mg/ml or 50 mg/2ml vials. The usual dose is 7.5 mg to 25 mg per week.
Methotrexate Doesn’t Provide Immediate Relief
Because methotrexate doesn’t simply suppress pain symptoms, it may take a while for people to see whether the drug is effective.
You may see improvement in symptoms three to six weeks after starting the drug, but full benefits can take even longer — up to 12 weeks, according to the American College of Rheumatology.
For many people, methotrexate alone, once it starts workin, is enough to manage RA symptoms. B
ut if you continue to have symptoms after 12 weeks, speak to your doctor about other treatment options, such as combining methotrexate with other disease-modifying drugs.
Methotrexate Has Some Side Effects
As with many drugs, people can experience unpleasant, and in rare cases dangerous, side effects from methotrexate. If you experience anything that concerns you, be sure to speak with your healthcare provider.
Side effects may include:
- Gastrointestinal Upset This is the most common side effect for people with RA.
- Mouth Sores Up to a third of people taking methotrexate for RA develop mouth ulcers.
- Headache and Fatigue Sometimes referred to as “methotrexate fog,” this might occur a day after taking a methotrexate dose.
- Hair Loss Hair loss or thinning while on methotrexate is slow and is reversed once you stop taking the medication; taking folic acid can also help counteract this effect.
- Rash
- Dizziness
Methotrexate may also lower the ability of the immune system to fight infections.
People taking methotrexate should call their physician immediately if they experience more serious side effects. These include seizures, confusion, weakness on one or both sides of the body, blurred vision or sudden loss of sight, and loss of consciousness.
You May Be Able to Minimize Those Side Effects
Some side effects from methotrexate result from a drop in folic acid levels in the body. To reduce these effects, doctors generally prescribe folic acid supplements along with the drug.
Many people find taking the oral medicine with food can prevent stomach upset, Tenpas says.
Some experts recommend splitting the dose by taking half in the morning and the other half 12 hours later to ease these gastrointestinal side effects. If that doesn’t help, talk to your doctor about switching from the oral to the injectable version of the drug.
To deal with mouth sores, the Arthritis Foundation suggests using a saltwater rinse or special mouthwash containing a lidocaine pain reliever. If nausea is an issue, you can request a prescription for anti-nausea medicine.
Methotrexate Isn’t for Everyone
Methotrexate is contraindicated for those with certain conditions and diseases, including:
- Liver disease or cirrhosis
- Alcohol use disorder
- Kidney disease
- Blood disorders
- HIV/AIDS
- People undergoing radiation therapy
Pregnancy Concerns
Don’t take methotrexate if you’re pregnant, trying to become pregnant, or if you’re breastfeeding. It can interfere with fetal development, and it can pass into breast milk. The Arthritis Foundation recommends using at least two methods of contraception while you’re on methotrexate and for at least three months after you discontinue using it. For men, many experts recommend waiting at least three months after stopping the drug before trying to conceive.
Methotrexate Can Impact Vaccine Effectiveness
Because methotrexate affects the immune system, researchers have found that it can blunt the effectiveness of certain vaccines.
The American College of Rheumatology conditionally recommends delaying the dosing of methotrexate for two weeks after flu and COVID-19 vaccines, if disease activity allows.
Anyone who takes methotrexate should work with their physician to discuss their specific drug regimen at the time of any vaccines.
Interactions With Other Medications
It’s vital that you let your doctor know what other medications you’re taking, including any vitamins or supplements. Don’t take methotrexate while taking antibiotics containing trimethoprim sulfamethoxazole (Bactrim, Sulfatrim).
Methotrexate Can Raise the Risk of Liver Disease
The release of adenosine, which is believed to fight inflammation, also causes the buildup of scar tissue in the liver. Because methotrexate has been associated with liver damage, people with RA frequently worry about how taking the drug will affect this crucial organ.
Fortunately, people who take this drug for RA appear to have a lower risk for this than people who take it for some other conditions.
Still, because of the potential for liver problems, regular alcohol use with methotrexate is not considered safe. “People are encouraged to minimize — if not avoid — alcohol consumption,” Tenpas says.
Regular Blood Tests Are Needed for Monitoring
When you’re on methotrexate, routine blood tests will be performed every 4 to 12 weeks to check your liver function and your complete blood count (CBC) because methotrexate can also cause a decrease in blood counts.
Not all of the negative effects of the drug cause noticeable symptoms, which is why routine blood tests are helpful for people taking this medication. Your rheumatologist can make changes to your dose of methotrexate if there is ever a problem.
The Takeaway
- Methotrexate is a mainstay treatment for rheumatoid arthritis, recognized for its ability to slow disease progression and offer symptom relief when used regularly.
- Although methotrexate can take a few weeks to show benefits, many people with RA find it helps manage symptoms effectively over time, often in combination with other therapies if needed.
- Side effects like gastrointestinal issues, mouth sores, and fatigue are common, but these can often be managed by adjustments like taking folic acid, splitting doses, or switching to an injectable form.
- It is crucial to discuss potential drug interactions and vaccine scheduling with your doctor because methotrexate affects the immune system and can interact with other medications, including some antibiotics.
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