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9 Things Parents Should Know About Methotrexate

Methotrexate is one of the most commonly used DMARDs for kids with arthritis. What should you know?

By Mary Anne Dunkin

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Since its introduction for juvenile arthritis over a quarter-century ago, methotrexate has significantly improved the lives for countless kids with the disease. But it isn't without risks and it doesn’t work for every child. If your child is taking methotrexate or her doctor has recommended it, here are nine things you need to know about this treatment mainstay. 

1. It’s not a quick fix. If your child is just starting methotrexate, don’t expect to see relief with the first dose or two – or three. Methotrexate is a disease-modifying antirheumatic drug (DMARD), often referred to as a slow-acting antirheumatic drug (SAARD) for a reason.  While methotrexate usually begins to show effects after a few weeks, it could be six to 12 weeks before you notice any significant benefit, says Thomas J.A. Lehman, MD, chief of pediatric rheumatology at the Hospital for Special Surgery in New York City.

In the meantime, your child’s doctor will likely prescribe other medications – including a non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Motrin) or naproxen (Naprosyn), or possibly a corticosteroid such as prednisone – to ease inflammation while the drug is taking effect. Once methotrexate takes effects, your child’s doctor will likely wean her off corticosteroids, but NSAIDs may be continued.

2. Regular monitoring is crucial. Despite its benefits, methotrexate carries rare but real risks of potentially serious side effects including liver problems and, less commonly, low blood cell counts or lung problems. Regular blood tests can help your child’s doctor monitor the effects of methotrexate and adjust the dose or discontinue the drug if necessary.

3. It must be taken with folic acid. If you aren’t already giving your child folic acid supplements, reconsider. Folic acid is the synthetic form of folate, a B vitamin your child needs. Methotrexate interferes with the body’s ability to use folate and, over time, can lead to depletion of folate stores. This can cause symptoms similar to folate deficiency including diarrhea, loss of appetite, mouth sores, or mild hair shedding. Folic acid supplements are your child’s best defense against these side effects and there aren’t risks with taking a supplemental amount. Dr. Lehman recommends 1 milligram (mg) daily.

4. Taking with food doesn’t help the nausea. Many children find nausea to be the most troubling side effect of methotrexate, says Dr. Lehman. Unfortunately, taking the drug with food or milk – as advised for some other arthritis medications – doesn’t help. That’s because methotrexate-related nausea is due not to stomach irritation but to the stimulation of a receptor in the brain that causes nausea, he says. If methotrexate makes your child sick, ask your doctor about prescribing ondansetron (Zofran), a drug that blocks the signal in the brain that causes nausea and vomiting.

5. Shots have benefits over pills. While both forms of methotrexate provide similar results, the injection has some benefits – mainly consistency. “You always know with an injection what becomes available to the body, while the amount of an oral dose that becomes available depends on what is in the stomach and other factors,” says Dr. Lehman. At high doses, methotrexate by injection may also be safer for the liver because it is absorbed and distributed through the circulation before it reaches the liver, whereas pills are digested, enter the circulation through blood vessels draining the stomach and intestines and then go directly to the liver.

 

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9 Things Parents Should Know About Methotrexate

Methotrexate is one of the most commonly used DMARDs for kids with arthritis. What should you know?

By Mary Anne Dunkin


Since its introduction for juvenile arthritis over a quarter-century ago, methotrexate has significantly improved the lives for countless kids with the disease. But it isn't without risks and it doesn’t work for every child. If your child is taking methotrexate or her doctor has recommended it, here are nine things you need to know about this treatment mainstay. 

1. It’s not a quick fix. If your child is just starting methotrexate, don’t expect to see relief with the first dose or two – or three. Methotrexate is a disease-modifying antirheumatic drug (DMARD), often referred to as a slow-acting antirheumatic drug (SAARD) for a reason.  While methotrexate usually begins to show effects after a few weeks, it could be six to 12 weeks before you notice any significant benefit, says Thomas J.A. Lehman, MD, chief of pediatric rheumatology at the Hospital for Special Surgery in New York City.

In the meantime, your child’s doctor will likely prescribe other medications – including a non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Motrin) or naproxen (Naprosyn), or possibly a corticosteroid such as prednisone – to ease inflammation while the drug is taking effect. Once methotrexate takes effects, your child’s doctor will likely wean her off corticosteroids, but NSAIDs may be continued.

2. Regular monitoring is crucial. Despite its benefits, methotrexate carries rare but real risks of potentially serious side effects including liver problems and, less commonly, low blood cell counts or lung problems. Regular blood tests can help your child’s doctor monitor the effects of methotrexate and adjust the dose or discontinue the drug if necessary.

3. It must be taken with folic acid. If you aren’t already giving your child folic acid supplements, reconsider. Folic acid is the synthetic form of folate, a B vitamin your child needs. Methotrexate interferes with the body’s ability to use folate and, over time, can lead to depletion of folate stores. This can cause symptoms similar to folate deficiency including diarrhea, loss of appetite, mouth sores, or mild hair shedding. Folic acid supplements are your child’s best defense against these side effects and there aren’t risks with taking a supplemental amount. Dr. Lehman recommends 1 milligram (mg) daily.

4. Taking with food doesn’t help the nausea. Many children find nausea to be the most troubling side effect of methotrexate, says Dr. Lehman. Unfortunately, taking the drug with food or milk – as advised for some other arthritis medications – doesn’t help. That’s because methotrexate-related nausea is due not to stomach irritation but to the stimulation of a receptor in the brain that causes nausea, he says. If methotrexate makes your child sick, ask your doctor about prescribing ondansetron (Zofran), a drug that blocks the signal in the brain that causes nausea and vomiting.

5. Shots have benefits over pills. While both forms of methotrexate provide similar results, the injection has some benefits – mainly consistency. “You always know with an injection what becomes available to the body, while the amount of an oral dose that becomes available depends on what is in the stomach and other factors,” says Dr. Lehman. At high doses, methotrexate by injection may also be safer for the liver because it is absorbed and distributed through the circulation before it reaches the liver, whereas pills are digested, enter the circulation through blood vessels draining the stomach and intestines and then go directly to the liver.


 

6. Methotrexate is used with other drugs. When methotrexate doesn’t work as well as expected, doctors sometimes add another DMARD such as sulfasalazine (Azulfidine), hydroxychloroquine (Plaquenil), leflunomide (Arava), azathioprine (Imuran), cyclosporine (Neoral) as well as the newer biologic response modifiers (biologics) a subset of DMARDs. While there is less research to support methotrexate combos in children, recent studies have shown benefits of methotrexate in combination with one of several other drugs including etanercept (Enbrel), infliximab (Remicade) and adalimumab (Humira) for JA.

7. The injection is “drinkable.” If your child’s doctor has prescribed oral methotrexate and she has trouble swallowing pills, ask the doctor about prescribing the injectable liquid, which can also be taken orally. While the medication has to be measured into a syringe (slightly more work for parents), it goes down easier than a pill – and it costs less.

8. Alcohol is off limits. Taking methotrexate with alcohol increases the risk of liver damage. Although you may not consider this an issue for children, studies show that alcohol use among teens – and even preteens – is prevalent. “Children and teenagers must be warned about the risks,” says Dr. Lehman. “And even then, parents of all children must realize they may be under significant peer pressure to drink.” If you have any reason to suspect your child is drinking, speak to her doctor about a change of medication. 

9. It doesn’t work for all kids. “Probably two-thirds of children with JIA get a significant benefit from methotrexate,” says Dr. Lehman. How do you know if your child will be among those two-thirds – or the approximately one-third that doesn’t get significant benefit? That’s a question researchers are trying to answer, and a recent study offers some clues. 

In a study of 563 children with polyarticular JIA who had been newly treated with methotrexate for six months, researchers compared variables recorded when kids started methotrexate with response to the drug at six months. They found that children who were sick longer before they began methotrexate benefited less from it once they started it. If your child has been on methotrexate for 12 weeks and you haven’t noticed improvement – or if you find the side effects of methotrexate unacceptable – Dr. Lehman advises speaking to your child’s doctor about other treatment options.