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HomeHealth articlesmethotrexateMethotrexate - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

Methotrexate - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

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Methotrexate - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

7 min read


Methotrexate is used in cancer treatment and autoimmune conditions. Learn about its uses, dosage, warnings, side effects, precautions, interactions, and more.

Medically reviewed by

Dr. Anshul Varshney

Published At February 22, 2022
Reviewed AtDecember 12, 2022


Methotrexate is a chemotherapeutic and immunosuppressant agent. It prevents the growth of certain cells in the body that reproduce quickly. These cells include cancer cells, skin cells, and cells in the bone marrow. Because of this property, this drug is used in the treatment of certain types of cancer, for example, cancer of the breast, lung, skin, head, or neck. It also prevents the immune cells in the body from attacking healthy cells in the body (autoimmune reaction). This autoimmune reaction can result in inflammation seen in conditions like psoriasis and rheumatoid arthritis.

Methotrexate is a prescription drug and is commonly prescribed only after all other treatment options have failed. It is available as an oral tablet, oral solution, self-injectable solution, and IV solution. You will be trained by your healthcare provider for the self-injectable solution. This drug is often used in combination with other drugs.

Drug Group:

Methotrexate belongs to the class of drugs called antimetabolites. Antimetabolites interfere with the enzymes necessary for DNA synthesis. These drugs act as a substitute for the metabolites that are used during metabolism for DNA synthesis. Antimetabolites are used in chemotherapy. As cancer cells multiply and grow more rapidly than normal cells, antimetabolites affect the replication of cancer cells more than they affect normal cells.

The other antimetabolites drugs are 5-Fluorouracil, 6-Mercaptopurine (6-MP), Floxuridine, Fludarabine, Hydroxycarbamide, and Phototrexate.

What Is Methotrexate Used For?

Methotrexate is used in the treatment of:

  1. Some types of cancer - This drug was originally developed and is still being used as a chemotherapeutic agent. It is used in the treatment of breast cancer, cancer of the head and neck, lymphoma, osteosarcoma, leukemia, cancer of the bladder, and trophoblastic neoplasms.

  2. Autoimmune conditions - Methotrexate is also used as a disease-modifying agent in the treatment of certain autoimmune diseases, such as rheumatoid arthritis, psoriasis, psoriatic arthritis, juvenile dermatomyositis, lupus, Crohn's disease, sarcoidosis, vasculitis, and eczema. It is also used in polyarticular juvenile idiopathic arthritis (JIA), which is the most common type of arthritis in children.

  3. Medical abortion - Methotrexate is also used to induce an abortion. It is used along with Misoprostol to terminate early pregnancies. It can also be used to terminate an ectopic pregnancy and molar pregnancy.

  4. Other autoimmune conditions - Sometimes, Methotrexate is also used to treat Crohn's disease, which is a condition caused by the immune system attacking the lining of the digestive tract. And also multiple sclerosis, which is a condition where the immune system attacks the nerves.

Never take Methotrexate or any other medicine without consulting your doctor first.

How Does Methotrexate Work?

Methotrexate works by inhibiting enzymes that are responsible for nucleotide synthesis, which includes thymidylate synthase, dihydrofolate reductase, amidophosphoribosyltransferase, and aminoimidazole carboxamide ribonucleotide transformylase (AICART). This action prevents cell division and reduces inflammation. The duration of action is quite long for this drug, which is why it is generally given only once weekly.

Methotrexate gets converted to methotrexate polyglutamate when it enters tissues. In patients with rheumatoid arthritis, Methotrexate polyglutamate inhibits AICART more efficiently than Methotrexate. As a result of this inhibition, AICART ribonucleotide accumulates, which ultimately results in the anti-inflammatory action.

Onset Of Action:

The drug starts working in about 1 to 2 hours after an oral dose, and an intramuscular injection takes about 30 to 60 minutes to start working. If given a low dose, the effect lasts anywhere between 9 and 30 hours, and between 24 and 45 hours if given a high dose. It might take around 3 to 6 weeks for you to see any improvement in your symptoms.


There have been no reports of habit-forming tendency in people taking Methotrexate.

Expiry Date:

Avoid taking this medicine after it expires. The expiry date will be printed on the back of the pack.

What Is the Dosage of Methotrexate?

The dosage of Methotrexate will be decided by your doctor based on your age, weight, and other medical conditions. You will be first started on a low dosage, and depending on how your body reacts, the dosage will be modified. Methotrexate is available in 2.5 mg, 1 g, 20 mg, 50 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 25 mg/mL, 10 mg/0.4 mL, 15 mg/0.4 mL, and many more strengths.

Methotrexate dosage for adults:

Methotrexate dosage for adults

Methotrexate is not approved to be used for psoriasis and rheumatoid arthritis in children between the ages of 0 and 17 years. For patients above 65 years, the doctor will check your kidney and liver function before prescribing this drug.

Methotrexate dosage for children:

Methotrexate dosage for children

This drug should not be used in children younger than 2 years of age.

Consult a doctor to know the exact dosage for other conditions.

How to Use Methotrexate?

The doctor will prescribe the dosage and the duration of Methotrexate depending on your condition and how your body reacts to the medicine. You might have to take this drug on a rotating schedule, meaning you will have to take it for several days, followed by several days or weeks where you do not have to take it. It is important to follow your doctor’s direction carefully.

For psoriasis or rheumatoid arthritis, this drug is usually prescribed once a week. Do not take it daily if only prescribed once a week, as it can lead to severe side effects and can also be fatal.

Make sure you understand when and how long to take Methotrexate before you leave the doctor’s office. Never take it more or less than prescribed. For anti-inflammatory action, it might take 3 to 12 weeks for the drug to show any effect. So, even if you feel well or do not feel any difference, continue to take Methotrexate, and never stop taking this drug without consulting your doctor first.

The self-injectable or intramuscular solution can be given by a doctor, or the doctor will train you or your caregiver to administer the drug carefully at home. Make sure you follow the doctor’s instructions carefully.

Missed Dose:

Set the alarm or a reminder to take this drug on time. Do not miss a dose of Methotrexate. If in case you miss a dose, you can take it as soon as you remember about missing the tablet. But if it is already time for the next dose, then do not take two tablets together, as it might result in severe adverse reactions. Just skip the missed dose and take the next dosage.

What Are the Drug Warnings and Precautions?

There are a few things that need to be considered before taking this tablet, and tell your doctor if you have any of the following conditions:

  1. Pregnancy - Methotrexate is known to end early pregnancy or can seriously harm the fetus. If you get pregnant while taking this medicine, stop the medicine and consult your doctor immediately. Methotrexate can also affect sperm. So both men and women who are getting treated with this drug should use birth control.

  2. Breastfeeding - Methotrexate is not recommended in breastfeeding women.

  3. Liver Damage - If you have a pre-existing liver condition, this medicine is not recommended for you. In patients with liver disease or injury, the concentration of this drug increases, which increases the risk of side effects. The doctor will check your liver function before prescribing this drug.

  4. Kidney Damage - If you have a pre-existing kidney condition, this medicine is not recommended for you. Methotrexate can damage the kidneys at higher doses. The doctor will constantly monitor your creatine levels while on this drug, and your dose will be adjusted accordingly.

  5. Lung Disease - This drug can result in serious lung conditions, such as pulmonary fibrosis and pulmonary interstitial infiltrates. In case you develop breathing difficulty and other breathing or respiratory symptoms while on this drug, consult your doctor immediately.

  6. Lowers White Blood Cell and Platelets Count - As this medicine can lower the neutrophils (a type of white blood cell) and platelet count, the doctor will closely monitor your blood cell count.

  7. Skin Reactions - Methotrexate can result in fatal skin reactions. It can cause Stevens-Johnson syndrome, skin ulcerations, and skin necrosis. If you notice any skin lesion or rash while taking this drug, consult your doctor immediately.

  8. Gastrointestinal Tract Injury - This medicine can cause severe diarrhea and ulcerative stomatitis (infection of the mouth). The symptoms of ulcerative stomatitis are swollen and bleeding gums, oral ulcers, and loose teeth.

  9. Infections - As this drug suppresses the immune system, the chances of infections are more. In case you develop an infection, the doctor will stop chemotherapy and give you broad-spectrum antibiotics.

  10. Tumor Lysis Syndrome - If Methotrexate is used for a rapidly growing tumor, it can lead to a condition called tumor lysis syndrome. The common symptoms of this syndrome are problems passing urine, vomiting, diarrhea, muscle weakness, and upset stomach. Inform your doctor if you experience any of these symptoms.

  11. Malignant Lymphoma - This medicine might increase the risk of malignant lymphoma (a type of blood cancer).

Apart from these precautions and drug warnings, some medications can increase the risk of side effects. This includes the use of NSAIDs along with Methotrexate. Radiation therapy, along with this drug, may increase the risk of muscle or bone damage.

What Are the Side Effects of Methotrexate?

The common side effects seen with Methotrexate include:

  • Stomach upset.

  • Nausea.

  • Vomiting.

  • Diarrhea.

  • Tiredness.

  • Dizziness.

  • Hair fall.

  • Fever.

  • Headache.

  • Chills.

  • Oral sores.

  • Easy bruising.

  • Blisters in the lungs.

  • Skin ulcers.

  • Sun sensitivity.

  • Bronchitis.

  • Increased susceptibility to infections.

  • Skin rash.

  • Runny nose.

These symptoms are usually mild and most usually go away in a few days. If it does not, consult a doctor immediately.

The serious side effects seen with Methotrexate include:

  • Liver injury -

    • Jaundice.

    • Severe itching.

    • Vomiting.

    • Pale stools.

    • Dark urine.

  • Kidney injury -

    • Inability to pass urine.

    • Decreased urination.

    • Bloody urine.

  • Abnormal bleeding -

    • Blood in vomit (ground coffee appearance).

    • Blood in stools.

    • Gum bleeding.

    • Easy bruising.

    • Vaginal bleeding (apart from menstruation).

  • Pancreas injury -

    • Severe abdominal pain.

    • Stomach upset.

    • Back pain.

  • Lymphoma -

    • Fatigue.

    • Chills.

    • Fever.

    • Unexplained weight loss.

  • Bone pain.

  • Lung sores -

    • Dry cough.

    • Dyspnea - (shortness of breath).

    • Fever.

  • Damage to the bone marrow -

    • Reduced white blood cell count.

    • Reduced red blood cell count.

    • Reduced platelet count.

  • Skin reactions -

    • Skin redness, swelling, or blisters.

In case you notice any of these symptoms, call your doctor immediately. This drug can also cause other side effects that are not listed here.

What Are the Interactions of Methotrexate?

It is natural for all drugs to interact with other drugs, food, and supplements. This interaction can result in certain unwanted side effects. The common interactions of Methotrexate are:

  • With Medicine -

    • Nonsteroidal anti-inflammatory drugs (NSAIDs) - Ibuprofen, Naproxen, Ketoprofen, Aspirin, and Diclofenac.

    • Asthma drugs - Theophylline.

    • Antiepileptic drugs - Phenytoin.

    • Proton pump inhibitors - Omeprazole, Pantoprazole, and Esomeprazole.

    • Gout drugs - Probenecid.

    • Antibiotics - Amoxicillin, Ampicillin, and Nafcillin.

    • Retinoids.

    • Immunosuppressants - Azathioprine.

    • Nitrous oxide.

    • Azole antifungal drugs.

    • Atorvastatin.

  • With vaccines -

    • Avoid getting a live vaccine while on Methotrexate, as this drug can lower your body's immune response, and the vaccine may result in infection.

  • With alcohol -

    • Do not drink alcohol while taking this medicine, as it can increase the liver side effects of Methotrexate. It can also worsen any pre-existing liver condition. If your skin or eyes turn yellow, consult a doctor immediately.

  • With disease - Patients who are suffering from the following diseases should not take Methotrexate -

    • Liver disease.

    • A weakened immune system.

    • With low blood cell counts.

    • Kidney disease.

    • Ulcers or ulcerative colitis.

    • Lung disease.

    • Psoriasis.

What Are the Common Brand or Trade Names of Methotrexate?

The common brand or trade names of Methotrexate are:

  1. Injection Otrexup 25 mg/0.4 mL.

  2. Injection Rasuvo 20 mg/0.4 mL.

  3. Tablet Imutrex-10.

Frequently Asked Questions


What Are the Most Common Side Effects of Methotrexate?

Nausea, vomiting, diarrhea, dizziness, poor appetite, mouth sores, fever, easy bruising, and headaches are the most common side effects of Methotrexate.


What Should You Avoid While Taking Methotrexate?

Methotrexate can interact with prescription and non-prescription medicines, such as birth control pills, vitamin supplements, etc. Never take this medicine while taking Sulfamethoxazole and Trimethoprim antibiotics.


How Common Is Hair Loss With Methotrexate?

Hair loss is a possible side effect of Methotrexate. This drug stops cancer and immune cells from multiplying, and sometimes can also affect hair follicles. As hair follicles are responsible for hair growth, taking Methotrexate might cause hair loss.


How Does Methotrexate Make You Feel?

Most people who are on this drug feel tired and dizzy. Patients also suffer from painful ulcers in the mouth, abdominal pain, diarrhea, and nausea. Your doctor must have weighed the side effects against the benefits of this drug before prescribing it.


What Time of Day Is Best to Take Methotrexate?

Methotrexate can be taken at either 10 in the morning or 6 in the evening. As this drug can result in tiredness and dizziness, most doctors recommend taking it in the evening.


How Dangerous Is Methotrexate?

The dosage of Methotrexate used for psoriasis, and rheumatoid arthritis usually does not result in dangerous or life-threatening side effects. If used in higher doses, this drug can result in irreversible liver, kidneys, pancreas, and other organs, which can be fatal.


Is Methotrexate a Steroid?

No, it is not a steroid. Methotrexate belongs to the drug group, antimetabolites, as it works by preventing cancer cells from multiplying and by suppressing the immune system. As it is also used for rheumatoid arthritis, it is also called a disease-modifying anti-rheumatic drug.


How Long Can You Take Methotrexate?

Depending on the disease being treated, you might have to take this drug for a couple of months to several years. There are many rheumatoid arthritis patients who have taken this drug for as long as 20 years.


Is Weight Gain a Side Effect of Methotrexate?

This drug does not result in weight gain. Instead, some patients lose weight due to the side effects of the drug, such as nausea, vomiting, diarrhea, and loss of appetite.


How Does Methotrexate Lower Your Immunity?

In autoimmune diseases, the cells in the immune system get triggered and multiply even by healthy body cells, which results in inflammation. Methotrexate prevents these immune cells from multiplying and prevents inflammation. It not only relieves symptoms of the autoimmune condition but prevents the immune system from causing permanent damage.


Can You Lose Weight While on Methotrexate?

Most patients lose their appetite due to the side effects of this drug, which results in weight loss.


What Happens if You Do Not Take Folic Acid With Methotrexate?

Methotrexate is known to reduce the levels of folic acid in the body, resulting in symptoms like mouth ulcers, tiredness, and headaches. To prevent these side effects, your doctor might give you Folic acid supplements along with Methotrexate.


Is Methotrexate Used in Chemotherapy?

Yes, Methotrexate is a chemotherapeutic agent. It is used in the treatment of some types of cancer, for example, breast cancer, lung cancer, skin cancer, etc.


How Do I Know if Methotrexate Is Working?

This drug might start working gradually. It usually takes about 3 to 12 weeks for Methotrexate to start working. You will notice your symptoms improving gradually.
Dr. Anshul Varshney
Dr. Anshul Varshney

Internal Medicine


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