Methotrexate Dosage: Uses, Reminders, Side Effects

Methotrexate is a common prescription medication for rheumatoid arthritis, other inflammatory types of arthritis and autoimmune disease, several types of cancer, and more. Methotrexate dosage is different from that of other medications in that you only take it once a week.

That can be confusing, especially if your healthcare provider or pharmacist haven't explained it. It's not uncommon for someone to overdose on methotrexate because they take it every day. Too much methotrexate can cause severe toxic effects, especially liver toxicity. Never take more than is prescribed or change the dosing schedule on your own.

This article goes through the uses of methotrexate and the doses for them, plus the side effects and warnings you need to be aware of with this drug.

Methotrexate Dosage for Autoimmune Disease

Methotrexate is approved by the Food and Drug Administration (FDA) for some types of autoimmune arthritis and other autoimmune diseases. It's used off-label (without FDA approval) for several other diseases in this category.

In autoimmune diseases, your immune system mistakenly attacks healthy cells in your body as if they were a virus or bacterium. Methotrexate calms the immune system and lessens the attack.

Rheumatoid Arthritis

Rheumatoid arthritis (RA) involves autoimmune activity against the lining of your joints (the synovium). It commonly strikes the hands, wrists, and knees but can target any joint.

Some people with RA develop systemic disease, meaning the immune system targets organs or systems throughout the body. Common targets are the eyes, heart, and lungs.

The oral (tablet) form of methotrexate is typically prescribed for RA. The injectable form may be used if you have trouble swallowing the pills.

The suggested weekly adult dose of methotrexate for rheumatoid arthritis is:

• A starting dose of 7.5 milligrams (mg) taken all at once, in pill or injectable forms
• OR three doses of 2.5 mg taken every 12 hours over a 36-hour period

If the starting dose doesn't give you enough symptom relief, your healthcare provider may gradually increase it, usually to a weekly dosage of 20 mg.

Some studies have suggested that the optimal dosage is between 25 mg and 30 mg, but that increases the risk of bone marrow suppression and other serious side effects.

Psoriatic Disease

Psoriatic disease includes plaque psoriasis and psoriatic arthritis. Methotrexate is used for both of these conditions.

Plaque Psoriasis

Plaque psoriasis, also called just psoriasis, is an autoimmune disease that speeds up the growth of new skin cells. New cells form before the old ones have sloughed off, so they "pile up" on the surface. The result is thick, scaly patches that may itch or be quite painful.

The once-a-week adult methotrexate dosage for psoriasis is:

• Between 10 mg and 25 mg (pill or injectable forms)
• A maximum of 25 mg or 30 mg, depending on the specific brand

Psoriatic Arthritis

Psoriatic arthritis (PsA) involves both psoriasis and joint pain. Methotrexate is given off-label for PsA.

The weekly adult dose of pill or injectable methotrexate for PsA is:

• A starting dose of 7.5 mg
• A typical maintenance dose of 15 mg
• A maximum dose of 25 mg, if needed
  

Polyarticular Juvenile Idiopathic Arthritis

Polyarticular juvenile idiopathic arthritis (PJIA) is a type of childhood arthritis involving five or more joints. ("Polyarticular" means "many joints.")

Healthcare providers calculate the pediatric methotrexate dosage based on the child's body weight. The formula for the weekly dose (pills or injections) is:

• A starting dose of 10 mg per meter squared (m²)
• A standard dose of 15 mg per m²

Higher doses haven't been shown to work better, so pediatric doses are usually kept in this range.

Systemic Lupus Erythematosus

In systemic lupus erythematosus (SLE or lupus), the immune system not only attacks various tissues around the body, but the inflammatory response is also out of control. Common targets include:

• Skin
• Joints
• Kidneys
• Heart

Methotrexate is prescribed off-label for SLE. The weekly dosage depends on whether it's given as a pill or injection.

For pills, the dosage guidelines say:

• A starting dose of 7.5 mg
• Monthly increases of 2.5 mg
• Maximum dosage of 20 mg

For methotrexate injections, it's:

• A starting dose of either 5 mg or 10 mg
• Increases of either 5 mg or 10 mg
• Maximum dosage of 50 mg

Most people with lupus respond well to injected dosages between 7.5 mg and 20 mg.

Pediatric Lupus Dosage

For children with lupus, the pill form may be given at weekly dosages of:

• Between 5 mg and 10 mg

Few studies have tested methotrexate for childhood lupus so the maximum safe dosage hasn't been established. In one study, 80% of kids responded to the 5 mg or 10 mg dosage.

Crohn's Disease

Methotrexate pills and injections are used off-label for treating Crohn's disease, which causes inflammation in your digestive tract. It's a condition that typically has flares (times of intense symptoms) and remissions (times of lesser or absent symptoms).

Crohn's disease most often causes pain and other symptoms in the small intestine and first portion of the large intestine. But it can affect any part of the digestive system.

For Crohn's, methotrexate is typically used in addition to other medications. For the pill form, the weekly dosage for Crohn's disease is:

• Between 12.5 mg and 15 mg
• Maximum dosage of 25 mg

For methotrexate injections, the weekly dosage varies depending on how active the disease is:

• For active Crohn's, it's 25 mg
• To help maintain remission, it's 15 mg

Injections are typically preferred for people whose Crohn's disease interferes with absorption in the small intestine.

Methotrexate Dosage for Other Uses

Methotrexate was a cancer drug before it was approved for rheumatoid arthritis. It's also used to treat ectopic pregnancies. Both these uses stem from methotrexate's ability to stop certain cells from growing.

The dosage used for rheumatoid arthritis and other inflammatory diseases is small compared to that used for cancer and ectopic pregnancy. Pills that you manage at home are less likely for these uses than injections or infusions that are given by medical personnel.

Acute Lymphocytic Leukemia

Acute lymphocytic leukemia (ALL) is a blood cancer. It causes rapid overgrowth of immature white blood cells called lymphocytes. After starting in the bone marrow, it quickly invades the bloodstream and possibly other organs and systems.

For ALL, the methotrexate dosage is weight-based. It's part of a chemotherapy regimen involving several drugs. It may be given in intramuscular injections, or, especially for higher doses, intravenously (IV).

The dosage of intramuscular injections is the same for children and adults:

• A starting dose of between 20 mg per m² and 30 mg per m²
• The dosage is then adjusted depending on the disease state and many other factors

IV methotrexate for ALL is given by a healthcare provider at a medical facility. The schedule and dosage depend on the disease state and many other factors. It may be given more or less frequently than once a week.

IV dosage may range from:

• Between 10 mg per m² and 5,000 mg per m²

Maintenance Treatment

Once cancer is in remission, methotrexate pills, injections, or IV infusions may be used as maintenance therapy to help prevent a recurrence.

Starting maintenance dosages are:

• Pills: 20 mg per m² one time per week
• Injections: Given twice a week for a total weekly dose of 30 mg per m²
• IV infusions: 2.5 mg per kilogram (kg) of weight every 14 days

The maintenance dosage may be adjusted based on lab test and other factors.

Ectopic Pregnancy

In an ectopic pregnancy, the fetus implants and develops outside of the uterus, usually in a fallopian tube. As the fetus grows, the fallopian tube generally ruptures. This can cause life-threatening internal bleeding and emergency surgery is required.

So far, doctors are unable to re-implant a fetus developing ectopically to a uterus or other location. The pregnancy is always lost.

Some ectopic pregnancies are removed surgically. Others are treated with methotrexate because it stops cells from growing. The body can then absorb the pregnancy over the next several weeks.

Methotrexate injections are used for ectopic pregnancies. Several dosing options are available:

• Single-dose regimen: A single injection of 50 mg per m² with a repeated injection a few days later if pregnancy hormones are still in the blood.
• Two-dose regimen: Two injections of 50 mg per m² three days apart, followed by a third and fourth injection if pregnancy hormones are still in the blood.
• Fixed multiple-dose regimen: Up to four injections of 1 mg per kg of weight, then surgery if pregnancy hormones are still elevated.
  

Testing During Methotrexate Use

While you're on methotrexate, you'll need to have periodic laboratory tests to monitor:

• Blood cell counts
• Liver enzymes
• Kidney function

If your test results worsen, your healthcare provider may switch you to a different drug.

Methotrexate Side Effects

The most common side effects of methotrexate are:

• Nausea
• Headache
• Dizziness
• Fatigue
• Blurry vision

To avoid nausea, you may be advised to divide the dose throughout the day (but all pills are still taken on the same day). Your doctor may also switch you to a subcutaneous (under the skin) injection.

Methotrexate Warnings

Methotrexate comes with several important warnings. Paying attention to these can help you avoid problems or spot them early.

When you're taking methotrexate, you need to take a few safety precautions:

• Do not drink alcohol while taking methotrexate.
• Tell your healthcare provider if you develop an active infection. Ask whether it's safe to take antibiotics.
• Discuss vaccinations with your healthcare provider. If you're taking higher doses, you should avoid live vaccines.

Warnings about methotrexate include:

• Serious rash, which can lead to potentially fatal complications
• Increased risk of soft tissue and bone death when given with radiation therapy for cancer
• Anemia, bone marrow suppression, infection, and blood disorders
• Increased risk of dehydration, especially with kidney damage or use with kidney drugs
• Tumor lysis syndrome (parts of a tumor enter the bloodstream), which can cause organ damage
• New cancer, especially lymphomas or other lymphatic disease
• Brain toxicity, which may be proressive, irreversible, and fatal; seizures are possible in children

Overlapping Conditions

You need to be especially careful with methotrexate if you have a couple of health conditions.

• Diabetes: Methotrexate increases the risk of lung toxicity, which can be fatal.
• Alcoholism, liver disease, obesity: Methotrexate can cause severe and potentially irreversible liver toxicity.
  
• Kidney disease or impairment: Kidney drugs may increase the methotrexate levels in your blood, leading to kidney damage.
• Digestive disease: Those with conditions such as peptic ulcer disease or ulcerative colitis are at risk of gastrointestinal toxicity.

Methotrexate and Pregnancy

Methotrexate is dangerous during pregnancy and breastfeeding. It's only used during pregnancy as a cancer treatment, and the risks and benefits must be carefully weighed.

If you're taking this drug, take steps to avoid getting pregnant for at least six months after you stop taking it.

Methotrexate can cause:

• Birth defects, including facial deformities, nervous system or heart abnormalities, and intellectual impairment
• Restricted growth
• Miscarriage
• Stillbirth

Your healthcare provider should go over these risks with you before prescribing methotrexate. Be sure you also discuss birth control and follow safety measures:

• If you can get pregnant, you should have a pregnancy test before starting methotrexate.
• Use reliable contraception while taking methotrexate and until you've been off the drug for at least six months.
• Biological males who can impregnate someone should use reliable birth control during methotrexate use and for at least three months after the final dose.
• If you get pregnant while taking methotrexate, let your healthcare provider know right away.

During or after use, methotrexate may cause:

• Infertility in people of any sex
• Low sperm count
• Irregular menstruation

It's unknown whether methotrexate infertility is reversible.

Methotrexate Drug Interactions

The risk of methotrexate toxicity is higher if it's taken with certain other medications, such as:

• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Acid reflux medications
• Some antibiotics

These drug interactions can be deadly. Make sure your healthcare provider and pharmacist have a complete list of your medications, both prescription and over-the-counter.

Allergic Reaction to Methotrexate

If you have signs of an allergic reaction while taking methotrexate, get emergency medical attention. Signs to watch for include:

• Hives and other skin reactions
• Difficulty breathing
• Swelling of face, lips, tongue, or throat

Stop taking methotrexate and call your healthcare provider if you develop:

• A dry cough
• Shortness of breath
• Diarrhea
• Vomiting
• White patches or sores inside your mouth
• Blood in your urine or stool
• Rapid weight gain
• Decreased urine production
• Seizure
• Rash or blisters
• Peeling skin
• Fever
• Chills
• Flu symptoms
• Weakness
• Lightheadedness
• Any other unusual symptoms

Call your provider right away if you notice any of these symptoms. Don't wait to see if symptoms go away on their own.

A Word From Verywell

Always follow the exact dosing directions for methotrexate and watch for potential problems and side effects. Taken properly, methotrexate can be a safe and effective medication for autoimmune disease, cancer, and ectopic pregnancy.