Check any message board in a rheumatoid arthritis (RA) group on social media and there’s one topic that pops up in posts constantly. It usually reads like this: “My doctor prescribed me methotrexate (MTX) and I’m terrified. Should I take it?” Then a stream of about 200 comments follows, about mouth sores and hair falling out and diarrhea, and it scares the beejesus out of you even more.

Taking any new medicine can be intimidating, especially one you might have to take for the rest of your life. Often, our doctors prescribe pills, injections, or infusions we’ve never heard of, and we’re either too shy or shocked to ask important questions about what the heck they are and what they might do to our bodies.

For anyone with RA, initiation into the MTX club seems particularly harrowing. I admit that I waited weeks to start taking it when I first got diagnosed with RA. But the truth is, it really wasn’t necessary to freak myself out. I wish I had known that but I, too, did not ask for or look for good information to ease my anxiety.

I admit that I waited weeks to start taking it when I first got diagnosed with RA. But the truth is, it really wasn’t necessary to freak myself out.

I interviewed my RA doctor, rheumatologist Gary Feldman, MD, medical director of Pacific Arthritis Care Center in Los Angeles, about methotrexate. “We’ve been using it since the late 1960s and we have a phenomenal amount of clinical data on tens of millions of patients,” he tells CreakyJoints. Here, he answers 11 of our most common questions and addresses our biggest concerns about methotrexate.

1. How does methotrexate work? Is it a pain pill?

“Methotrexate works on inflammation, it doesn’t work on pain,” Dr. Feldman explains. “But your inflammation causes pain. It’s not like someone poking you with a stick or having a headache. Methotrexate goes to the source of the problem, the inflammation. By reducing that inflammatory process, you help reduce the pain in a more directed way at the source and also in a more effective and long-lasting way. Methotrexate slows down the progression [of inflammation] so it reduces the destruction of the joints.”

2. Is methotrexate a cancer drug? Why am I taking a pill for cancer?

The distinction between using methotrexate to treat cancer and to treat rheumatoid arthritis is important. Technically speaking, methotrexate is a “cancer drug” — and it’s used to treat different kinds of cancer, including breast cancer. That’s because methotrexate attacks fast-dividing cells, which include cancer cells.

“But cancer patients take much higher doses of methotrexate for shorter amounts of time than RA patients,” says Dr. Feldman. “The doses for cancer therapy are actually almost 50 times higher. For RA patients, methotrexate is used in a completely different way.”

At these extremely lower doses, methotrexate has a completely different effect on the body. It is a disease-modifying agent that reduces inflammation. “I like to say it’s the difference between swimming in a pool and drinking a glass of water. Both use water but have a different effect,” says Dr. Feldman.

3. What’s the difference between taking methotrexate pills and getting shots?

Methotrexate is available in pill form or as a shot you inject. (Your rheumatologist will likely try the pills first because most people don’t want shots.) Oral methotrexate is available in 2.5 mg tablets. For adults with RA, the starting dose of methotrexate is usually around 7.5 to 15 mg a week (three to six tablets), depending on your disease activity or presence of co-occurring diseases, with the dose increasing as needed to control RA symptoms. The maximum dose is usually 25 mg/week.

“However, once you go over 15 mg per week, the methotrexate can become more difficult to absorb,” says Dr. Feldman. If taking more than 15 mg of MTX orally once a week isn’t working well for you, your doctor might recommend you try methotrexate injections or with splitting the oral dose into two doses over a 12-hour period. The potential side effects would be the same regardless of which form of methotrexate you take.

4. How long will methotrexate take to start working?

It’s not immediate. Many RA patients will start to experience an improvement in symptoms after six to eight weeks on methotrexate, but it can take up to six months before you would reach the full benefits of taking the drug. If you’re having a lot of debilitating RA symptoms, your doctor may prescribe corticosteroids as a short-term treatment to tamp down your RA flares while the methotrexate starts kicking in.

5. Why do I have to take folic acid? Should I take it on the same day as MTX or not?

Folic acid is a type of B vitamin. It’s currently recommended that all patients on low-dose methotrexate take folic acid (1 mg a day) to help offset potential side effects that come with taking methotrexate. The most concerning side effect would be any suppression of bone marrow cells, which produce new blood cells.

Some doctors advise that patients skip folic acid the same day or days you take methotrexate, believing it lessens the effects of methotrexate. Other doctors, including Dr. Feldman, think it doesn’t matter. “I personally don’t have a problem with my patients taking folic acid every day,” he says. “I haven’t seen any good studies to show that it negates the effects of methotrexate. Though I find that some patients find it hard to remember to exclude it on certain days.”

6. What are the worst side effects of methotrexate? Is my hair going to fall out?

Message boards are flooded with questions and comments about all sorts of gnarly side effects. Dr. Feldman admits that everyone reacts differently to methotrexate, but he insists that most side effects are mild and controllable.

“The most common side effects are fatigue a day or two after you take methotrexate, which is why I suggest taking it at night,” he says. “Also gastrointestinal issues. Your stool may be loose, or you may feel queasy or nauseated for a day or two after. Hair thinning and loss does happen, but I don’t see it that often and folic acid does tend to minimize that. Mouth ulcers can occur later and methotrexate does make you sensitive to sunlight, so be careful sunbathing. But the most common side effects are fatigue and GI issues.”

7. Can I get pregnant or breastfeed while taking methotrexate?

Absolutely not. “Methotrexate is toxic to a fetus and can cause congenital mutations,” warns Dr. Feldman. Women should wait 90 days after stopping methotrexate to get pregnant. Men, too, should wait 90 days before trying to conceive because methotrexate may affect sperm (the sperm production cycle is 90 days). Do not breastfeed until the drug is completely out of your system. For more information about managing pregnancy with rheumatoid arthritis, check out our family planning patient guidelines.

8. Can I drink alcohol while taking methotrexate?

Methotrexate can affect liver function, which is why doctors will monitor your liver health closely while you take it. Methotrexate isn’t recommended for people who already have chronic liver disease or who are heavy drinkers and have alcohol-related liver damage. Because there is potential for liver damage in people taking MTX, they shouldn’t consume alcohol excessively.

For occasional drinkers, Dr. Feldman says the rules about how much alcohol is safe to drink while taking methotrexate depends on the rheumatologist. “Some doctors insist on no alcohol at all,” he explains. He tends to be a little looser with his patients. “I tell my patients you can have a few drinks per week, just not all at once.”

And don’t have the alcohol two days before you get your blood drawn at the office, he adds, because the alcohol can mess up the liver function test and confuse your doctor. But he thinks a drink here and there is not dangerous for patients without any liver issues.

9. Will methotrexate mess up my immune system?

Methotrexate tinkers with the immune system, but it doesn’t suppress it in the same way that some other RA drugs do. So taking methotrexate is rarely associated with increased infection risk unless you’re also taking other medications at the same time, such as glucocorticoids, immunosuppressive disease-modifying antirheumatic drugs (DMARDs), or biologics. There may be slight increase in infection, Dr. Feldman notes, “but we’re talking about a half a cold per year per person.”

Doctors may recommend patients with severe infections (say, being hospitalized for pneumonia) take a break from methotrexate while they recover, but you can still take it while you have minor infections like an upper respiratory virus or urinary tract infection. However, you should let your rheumatologist know if you have an infection that doesn’t get better after a few days, to make sure it doesn’t develop into something more serious.

10. What about getting vaccines while on methotrexate?

Methotrexate may slightly depress your body’s response to vaccinations, which means they might not be as effective as they would if you weren’t taking MTX. It’s generally advised that you be up to date on your vaccines before starting methotrexate, so ask your doctor about this.

Some doctors might suggest that you take a two-week “methotrexate holiday” following your annual flu vaccine because research shows this can improve your body’s response the vaccine. You can read more about getting the flu vaccine when you have arthritis here.

11. Will I ever need to take biologics?

Doctors may start you on methotrexate alone, which is known as methotrexate monotherapy, or combine methotrexate with other non-biologic DMARDs or with biologic DMARDs.

“For patients who have a more aggressive disease or what we call moderate to severe activity, methotrexate alone might not be adequate,” Dr. Feldman says.

If you aren’t responding to methotrexate after a two-month period, your rheumatologist may try some kind of combination therapy, such as adding sulfasalazine and hydroxychloroquine (called triple therapy) or adding a biologic drug such as etanercept (Enbrel), adalimumab (Humira), or infliximab (Remicade).

It would be unlikely that you would skip methotrexate altogether and go straight to a biologic. Also, many insurance companies will not even allow you to start a biologic until you’ve “failed” with methotrexate. Many patients, “if you catch their RA early,” do well on just methotrexate, Dr. Feldman says.

Here’s a final word about methotrexate from Dr. Feldman: “We have a lot of experience using this medication for the last 35 years. There are nuisance side effects for 10 to 15 percent of patients. But we are monitoring you very closely, and if we look at the control studies, it appears to be very effective for a significant portion of RA patients. It may be all you need. In my personal experience, it’s very safe. And it’s the right place to start for most patients. The sooner you get on it, the sooner you’ll know if it works.”

Watch: Starting Methotrexate for Rheumatoid Arthritis

This video is part of an educational project from researchers at Yale University, Berkshire Medical Center, Carnegie Mellon University, Hospital for Special Surgery, CreakyJoints and the Global Healthy Living Foundation, and ArthritisPower. It was made possible with support from the Rheumatology Research Foundation. Watch more videos from this series here.

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