Is Oral or Injectable Methotrexate Better for Me?

Medications often come in different forms. These different versions of the same medications can raise questions about which one is the best. Sometimes, the choice may depend on the type of condition being treated. In other cases, it may depend on cost or insurance coverage. 

Methotrexate is a medication used to treat multiple chronic conditions, and it comes in different forms. The two available versions of this medication are the oral form and the injectable form. But when would a healthcare provider choose one over the other?

Let’s explore more about methotrexate, what conditions it treats, and which form may be the better choice for you.

What is methotrexate?

Methotrexate belongs to a group of medications called antifolate antimetabolites. These medications work by blocking the creation and repair of DNA — our body’s genetic building blocks — which halts the creation of new cells in our body. 

Because of how methotrexate works, it can be used in many different cancers, such as:

• Acute lymphocytic leukemia (ALL): cancer that affects certain white blood cells (lymphocytes)

• Non-Hodgkin lymphoma: cancer that affects lymphocytes and lymph nodes (small glands in the body that contain white blood cells)

• Osteosarcoma: cancer of the bones

• Certain types of breast cancer

Promotion disclosure

Methotrexate

Avg retail price

$30.18(Save 59.05%)

GoodRx discount

$12.36

See all discounts

How it works

Use GoodRx to find medications, pharmacies, and discounts.

GoodRx discounts can help you pay less for your prescription.

Bring your free coupon or savings card to the pharmacy.

Methotrexate also has anti-inflammatory properties, which makes it useful in autoimmune diseases, such as rheumatoid arthritis (RA) and psoriasis. Methotrexate has also been found to have benefits in treating certain conditions it’s not FDA-approved for, so it’s sometimes prescribed “off-label” for other purposes.

As mentioned above, methotrexate is available in oral and injectable forms. However, there are several differences between them. This includes their doses, side effects, and absorption in the body.

Using methotrexate as a cancer treatment is often individualized. Doses and length of treatment can change depending on different factors. If you’re taking methotrexate as part of chemotherapy, talk with your healthcare provider about the specifics of your treatment.

For the purposes of this discussion, we’ll mainly focus on using methotrexate for psoriasis and RA. 

What are the benefits of injectable methotrexate?

Methotrexate is a first-choice treatment for both psoriasis and RA. It’s not uncommon for people with these conditions to ask if one form is better than the other.

Injectable methotrexate has a few advantages over the oral form:

• Injectable methotrexate is more bioavailable than the oral form. This means more medication is active in the body, most likely because the injectable form doesn’t have to be absorbed in the digestive tract like the oral form.

• Injectable methotrexate may be more effective for RA than oral methotrexate. In a study comparing injectable to oral methotrexate, more people experienced an improvement of RA symptoms when methotrexate was injected under the skin.

• Injectable methotrexate may cause less stomach-related side effects. In a small study, people who switched from oral to injectable methotrexate experienced less vomiting and diarrhea. This could be because injectable methotrexate doesn’t need to be absorbed in the digestive tract.

Where does injectable methotrexate get injected?

Injectable methotrexate can be given in a few ways:

• Intravenous (IV) infusion — delivered directly into a vein

• Intrathecal injection — injected in the lower spine

• Subcutaneous (SC) injection — injected just beneath the skin

• Intramuscular (IM) injection — injected into a muscle

IV and intrathecal forms of methotrexate are most often used when treating cancer. The SC and IM forms are typically used when treating autoimmune diseases.

IM injections can be given in the middle of the thigh muscle, on the outside of the upper arm, or on the buttocks. SC injections can be given on the outside or back of the upper arm, on the outside of the upper thigh, or on the stomach at least 2 inches away from the belly button.

Injectable methotrexate comes in a vial that can be drawn up with a syringe or as an auto-injector pen, similar in style to an EpiPen. The vials are available as a generic, but the auto-injector pens are only available as the brand names Otrexup and Rasuvo.

Can injectable methotrexate be taken by mouth?

Injectable methotrexate isn’t designed to be taken by mouth. 

In 1999, researchers at the University of Minnesota conducted a small study with six people to see how an oral solution made from injectable methotrexate would compare to the pill form. The study concluded the solution could be an alternative to taking tablets.

However, this method is not an FDA-approved use for injectable methotrexate. It shouldn’t be tried without instructions from your healthcare provider. Attempting this on your own could affect how the medication works.

In 2017, the FDA approved an oral methotrexate solution — Xatmep. This version would be a better option if an oral liquid is needed.

How long does it take for injectable methotrexate to work?

The answer to this question depends on what condition you’re treating.

When taken for RA, methotrexate can take several weeks to start working. Some people may start to see improvement after 3 months. However, it could take up to 6 months to get methotrexate’s full effects.

When being used for psoriasis, it’s possible to start seeing results in about 4 to 6 weeks. Full effects can be expected about 6 months after starting methotrexate.

As discussed earlier, methotrexate treatment for cancer varies from person to person. It’s best to contact your healthcare provider regarding your chemotherapy regimen or if you have general concerns about methotrexate’s effectiveness.

What are the side effects of injectable methotrexate?

Side effects of methotrexate are similar for the injectable and oral forms. The most common are stomach-related, such as nausea and vomiting. As mentioned above, this may happen less often with the injectable form, but it’s still a common side effect. 

Other possible side effects include headache, diarrhea, mouth sores, and fever. Methotrexate can also put stress on the liver. While taking this medication, your healthcare provider may regularly order a group of blood tests called liver function tests (LFTs) to check your liver health.

Kidney damage is another possible side effect of methotrexate, especially at high doses. If you have kidney problems, your risk of this side effect is higher. Depending on your dose and medical history, your healthcare provider may monitor your kidney health with blood tests called a renal panel.

Some people may experience hair loss with methotrexate. This happens more frequently for people with psoriasis. Hair loss shouldn’t be excessive, so speak with your healthcare provider if you notice severe hair loss or bald patches. Normal hair growth usually resumes once you stop the medication.

Methotrexate can also cause bone marrow suppression. This is a rare but life-threatening side effect that could lower several types of blood cells in your body. It’s usually only seen with higher doses used for cancer treatments.

What are the benefits of taking methotrexate pills?

One major benefit of taking methotrexate pills, rather than the injectable solution, is not having to deal with needles. Some people are uncomfortable using needles and would rather take something by mouth.

People with vision problems may find it hard to read the small numbers on a syringe or auto-injector pen. Taking pills may make it easier to know they’re taking the correct dose of methotrexate.

Other people may have trouble giving themselves shots due to the severity of their condition. RA can cause swelling and discomfort in the hands. This can make drawing medication into a small syringe difficult. The risk of giving an incorrect dose may be higher in this situation.

What are the side effects of methotrexate pills?

Side effects are similar across all forms of methotrexate. The biggest difference between the pill form and the injectable form is the likelihood of stomach-related side effects. Nausea, vomiting, and mouth sores are common with oral methotrexate and can lead some people to ask for an alternative.

Another important side effect with both injectable and oral methotrexate has to do with folic acid (vitamin B9). Methotrexate can lower folic acid levels in the body. This is thought to contribute to some side effects, such as nausea, vomiting, and liver problems.

Your healthcare provider may prescribe a folic acid supplement to take while using methotrexate. Studies have shown that adding folic acid can relieve nausea and vomiting as well as lower stress on the liver. But it’s important to only take folic acid if it’s prescribed to you. If you’re being treated for cancer, folic acid can lower methotrexate’s effectiveness. 

How to save on methotrexate

There are many ways to save on injectable and oral methotrexate. Both are available as brand-name medications. But you can also find them as lower-cost generics. GoodRx can help you navigate many ways to save on your prescription.

• Save with GoodRx. GoodRx can help you save over 50% off the average retail price of the generic version of methotrexate. Generic oral methotrexate’s price and generic injectable methotrexate’s price at certain pharmacies are both less than $12 with a free GoodRx discount.

• Save with patient assistance programs. If you’re uninsured or underinsured, you may be eligible for Otrexup injection’s patient assistance program, which offers the medication free of cost.

• Save with a copay savings card. If you have commercial insurance and meet eligibility requirements, Otrexup’s price is as little as $0 using a savings card from the manufacturer.

Why trust our experts?

Written by:

Clay M. Cooper, PharmD

Clay Cooper, PharmD, has over 10 years of pharmacy practice experience in a variety of healthcare settings, including in independent community pharmacy, retail pharmacy, and long-term care pharmacy. He is a licensed pharmacist in Tennessee, Mississippi, and Alabama.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Our editorial standards

Meet our experts