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Methotrexate dosage, forms, and strengths

Medically reviewed by Anne Jacobson, MD, MPH
Board-Certified Family Physician
Written by Georgia C. Yalanis, MD
Medical Doctor
Updated Feb 4, 2022  •  Published Feb 4, 2022
Fact Checked

Methotrexate is a medication that is used for chemotherapy and as an immunosuppressive agent. It is used alone or in combination with other anticancer agents to treat breast cancer, epidermoid cancers of the head and neck, advanced mycosis fungoides (cutaneous T cell lymphoma), lung cancer, osteosarcoma, and certain blood cell cancers including leukemia and non-Hodgkin’s lymphoma. 

As an immunosuppressive agent, methotrexate is used to treat psoriasis, rheumatoid arthritis, polyarticular juvenile rheumatoid arthritis, ulcerative colitis, and Crohn’s disease. Methotrexate is also used to treat some complications of pregnancy such as gestational choriocarcinoma, chorioadenoma destruens, hydatidiform mole, and ectopic pregnancy.

The Food and Drug Administration (FDA) has approved methotrexate for use in adults and children as young as infants. Typical doses of methotrexate vary widely according to indication.

RELATED: Methotrexate coupons | Methotrexate details

Methotrexate forms and strengths

Methotrexate is available in several preparations and sold under several brand names. 

  • Injection (Rasuvo, RediTrex, and generic equivalent): 7.5 mg, 10 mg, 12.5 mg, 15 mg, 17.5 mg, 20 mg, 22.5 mg, 25 mg

  • Tablet (Trexall and generic equivalent): 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg

  • Oral pediatric solution (Xatmep): 2.5 mg per 1 mL

Methotrexate dosage for adults

Methotrexate is used to treat certain cancers, immune-mediated inflammatory conditions, and some complications of pregnancy. Methotrexate has been used for decades and its side effects and toxicities are well understood. Certain individuals should not take methotrexate, as the adverse effects would outweigh any potential benefit of methotrexate treatment. It is important to discuss your complete health history, baseline health status, and goals of treatment with your healthcare provider before starting this medication.

Methotrexate dosage chart
Indication Therapy type Starting dosage Standard dosage Maximum dosage
Acute lymphoblastic leukemia  IV: 10-5000 mg/m^2/dose IV on specific day(s) of cycle  Variable based on therapy regimen, disease state, patient condition, and response to treatment  5000 mg/m^2/dose IV per cycle 
Meningeal leukemia  INJ: 12-15 mg intrathecally, every 2-5 days 12-15 mg intrathecally, every 2-5 days 15 mg intrathecally twice per week 
Mycosis fungoides  Monotherapy TAB: 25 mg by mouth per week  25-75 mg by mouth per week 75 mg by mouth per week
Combination therapy  10 mg/m^2/dose by mouth, 2 times per week 10 mg/m^2/dose by mouth, 2 times per week 10 mg/m^2/dose by mouth, 2 times per week
Non-Hodgkin lymphoma  Induction therapy IV: 1000 mg/m^2/dose IV on specific day of cycle  IV: 1000 mg/m^2/dose IV on specific day of cycle IV: 1000 mg/m^2/dose IV on specific day of cycle
Relapsed/refractory disease TAB: 2.5 mg by mouth, 2-4 times per week 2.5 mg by mouth, 2-4 times per week 10 mg by mouth per week
CNS lymphoma  Monotherapy IV: 8000 mg/m^2/dose IV on specific day of cycle  IV: 8000 mg/m^2/dose IV on specific day of cycle  IV: 8000 mg/m^2/dose IV on specific day of cycle 
Combination therapy 3000 mg/m^2/dose IV on specific day of cycle  3000, 3500, OR 8000 mg/m^2/dose IV on specific day of cycle 8000 mg/m^2/dose IV on specific day of cycle 
Osteosarcoma  INJ: 12 mg/m^2/dose IV on postoperative weeks 4, 5, 6, 7, 11, 12, 15, 16, 29, 30, 44, 45  12-15 mg/m^2/dose IV on postoperative weeks 4, 5, 6, 7, 11, 12, 15, 16, 29, 30, 44, 45  20 gm/dose 
Breast cancer INJ: 40 mg/m^2/dose IV on days 1, 8 of 28-day cycle x6 cycles 40 mg/m^2/dose IV on days 1, 8 of 28-day cycle x6 cycles 40 mg/m^2/dose IV on days 1, 8 of 28-day cycle x6 cycles
Squamous cell head or neck cancer INJ: 40-60 mg/m^2/dose IV per week 40-60 mg/m^2/dose IV per week 60 mg/m^2/dose IV per week
Rheumatoid arthritis TAB/INJ: 7.5 mg by mouth/SQ/IM per week  7.5-25 mg by mouth/SQ/IM per week 25 mg by mouth/SQ/IM per week
Psoriasis (severe) TAB/INJ: 7.5 mg by mouth/SQ/IM/IV per week 7.5-25 mg by mouth/SQ/IM/IV per week  30 mg by mouth/SQ/IM/IV per week
Gestational trophoblastic neoplasia  INJ: 30-200 mg/m^2/dose IM/IV on specific day(s) of cycle 30-200 mg/m^2/dose IM/IV on specific day(s) of cycle 300 mg/m^2/dose IM/IV on specific day(s) of cycle for high risk disease 
Ectopic pregnancy* INJ: 50 mg/m^2/dose IM/IV for a single dose only; Dose may be repeated in 7 days if bHCG levels not reduced by at least 15% 50 mg/m^2/dose IM/IV for a single dose only 50 mg/m^2/dose IM/IV for a single dose only

* Methotrexate is contraindicated for use as treatment for ectopic pregnancy in individuals with renal insufficiency.

Note: All dosing information provided for this medication is generalized or based on current chemotherapy protocols. Chemotherapy regimens may be variable based upon registration status in a clinical trial, institutional protocols, augmented dosing based on patient characteristics and tolerance, or provider experience and success rates with a specific dosing schedule or chemotherapy cycle regimen. Speak with your healthcare provider about the specific doses that are appropriate for your treatment needs. 

Methotrexate dosage for malignancy

Methotrexate is used alone or in combination chemotherapy to treat the following cancers of the blood, bone, breast, head, and neck:

  • Acute lymphoblastic leukemia (ALL)

  • Meningeal leukemia 

  • Mycosis fungoides (cutaneous T cell lymphoma)

  • Non-Hodgkin’s lymphoma 

  • Central nervous system (CNS) lymphoma 

  • Osteosarcoma 

  • Breast cancer

  • Squamous cell cancer of the head or neck

Cancer occurs when cells in the body grow and divide too rapidly or incorrectly. Cells need folate, or folic acid, to divide and grow. Methotrexate binds an enzyme in the body that normally binds folate. In doing this, folate is unavailable for cancer cells to divide and grow. 

Chemotherapy is dosed based on a variety of factors. Protocols vary with the type of cancer, the health condition of the person receiving the chemotherapy, and the physicians and institution where the cancer is being treated. Generally, the goal of treatment is to give doses that are aggressive enough to kill cancer cells while minimizing side effects. 

Methotrexate dosage for rheumatoid arthritis 

Methotrexate is used as a first-line medication in the treatment of inflammatory arthritis. It can be used alone, or to enhance the effects of other medications such as sulfasalazine or Humira. Methotrexate inhibits the function of cells that are overactive in rheumatoid arthritis such as T-cells, macrophages, endothelial cells, and fibroblasts. In doing this, methotrexate reduces inflammation.

For the treatment of rheumatoid arthritis, 7.5-25 mg of methotrexate is given once a week by mouth or as an injection under the skin or in a muscle. 

Methotrexate dosage for severe psoriasis 

Psoriasis is an inflammatory condition of the skin that causes itchy, scaly plaques. Methotrexate blocks the activity of a substance in the body called TNF-alpha, which is made by certain cells in the immune system and leads to inflammation. Methotrexate helps to decrease symptoms and flare-ups in people who have psoriasis. 

For the treatment of psoriasis, a weekly dose of 7.5-25 mg of methotrexate is given once a week by mouth, as an injection under the skin or in a muscle, or in an intravenous infusion. 

Methotrexate dosage for conditions of pregnancy 

Methotrexate is used to treat the following complications of pregnancy:

  • Ectopic pregnancy 

  • Gestational trophoblastic disease including molar pregnancy

  • Malignancy associated with pregnancy including choriocarcinoma and chorioadenoma destruens (a type of cancer that grows into the muscular wall of the uterus after conception)

Methotrexate is a competitive inhibitor of folate, which is necessary for important steps in the synthesis of DNA. As conception-related tissues are often rapidly dividing, methotrexate is an effective therapy for treating these conditions. 

Ectopic pregnancy happens when a fertilized egg implants outside of the uterus. If this happens in a fallopian tube, the tube may rupture as the pregnancy grows. Methotrexate is an effective treatment for ectopic pregnancy because it stops these cells from dividing.

Gestational trophoblastic disease is a spectrum of diseases where abnormal trophoblast cells (cells that would normally provide nutrition to the embryo) grow after conception. These cells do not form as they should and instead invade the uterus and surrounding tissues. These cells may also metastasize to other parts of the body. Methotrexate interrupts the DNA synthesis in these tissues, stopping their growth and proliferation. 

For ectopic pregnancy, methotrexate is administered as a single 50 mg injection. It may be repeated in seven days if the hormone markers of pregnancy have not decreased.

For gestational trophoblastic disease, treatment protocols will vary based upon disease state. 

Methotrexate dosage for children

In pediatric patients, methotrexate is given as a tablet or solution taken by mouth, administered intravenously or intrathecally (in the tissues around the brain and spinal cord) for chemotherapy, or intramuscularly as an injection. This medication has been approved for use in children as young as infants for the treatment of pediatric arthritis and cancers of the blood and bone.

Methotrexate dosage by age
Indication Age Therapy type Recommended dosage 
Acute lymphoblastic lymphoma  All ages  Treatment 10-5000 mg/m^2/dose IV on specific day of cycle; OR 20-30 mg/m^2/dose IM once per week 
Maintenance Variable based on therapy regimen, disease state, patient condition, and response to treatment 
Meningeal leukemia  < 1 year of age  Treatment 6 mg intrathecally, every 2-5 days
Prophylaxis 6 mg intrathecally, once per week 
1 year of age  Treatment 8 mg intrathecally, every 2-5 days
Prophylaxis 8 mg intrathecally, once per week
2 years of age Treatment 10 mg intrathecally, every 2-5 days 
Prophylaxis 10 mg intrathecally, once per week
3-8 years of age Treatment 12 mg intrathecally, every 2-5 days 
Prophylaxis 12 mg intrathecally, once per week
9 years of age and older  Treatment 12-15 mg intrathecally, every 2-5 days 
Prophylaxis 12-15 mg intrathecally, once per week
Non-Hodgkin’s lymphoma  All ages  1000 OR 3000 mg/m^2/dose IV on specific day of cycle
CNS lymphoma  All ages Monotherapy 8000 mg/m^2/dose IV on specific day of cycle 
Combination therapy 3000 OR 3500 OR 8000 mg/m^2/dose IV on specific day of cycle 
Osteosarcoma All ages 12 g/m^2/dose IV on postoperative weeks 4, 5, 6, 7, 11, 12, 15, 16, 29, 30, 44, 45 
Juvenile idiopathic arthritis 2 years of age and older  10-15 mg/m^2/dose by mouth, SC, or IM, once per week; OR 10 mg/m^2/dose by mouth twice per day, over three days per week 

Note: Listed pediatric dosing for this medication is generalized and based on current manufacturer recommendations. Pediatric dosing for this medication may be variable based upon institutional protocols, formulation adjustments for neonates and low birth weight infants, and possible need for a high-dose regimen to treat a specific condition. Speak with your healthcare provider about the specific doses of this medication in a treatment setting. 

Methotrexate dosage restrictions

Methotrexate should not be used or should be used with dose adjustments in certain individuals. 

Renal dose adjustments

Methotrexate therapy is contraindicated for:

  • Adults on peritoneal dialysis 

  • Use as a treatment for ectopic pregnancy in women with significant kidney impairment 

  • Adults with a creatinine clearance (CrCl) less than 10 who are not on hemodialysis

  • Adults and children with CrCl 10-50: decrease dose by 50%

Doses should be modified for the following:

  • Children with CrCl <10: decrease dose by 70%

  • Adults on hemodialysis: decrease dose by 50% and give after dialysis

  • Children on hemodialysis: decrease dose by 70% and give after dialysis

  • Children on peritoneal dialysis: decrease dose by 70%

Hepatic dose adjustments

Use of methotrexate is contraindicated for: 

  • Individuals with rheumatoid arthritis or psoriasis and chronic liver disease 

  • Use as a treatment for ectopic pregnancy in women with significant liver impairment

  • Children with juvenile idiopathic arthritis and chronic liver disease 

Pregnancy 

Methotrexate is toxic to the growing cells of an embryo or fetus. Pregnant women should not take methotrexate. Women of childbearing age should have pregnancy status verified before starting methotrexate. Use reliable contraception during treatment and for six months after the final dose of methotrexate is given. Methotrexate can also cause chromosomal damage to sperm cells. Males with female partners of reproductive age should use reliable contraception during treatment and for the six months after the final dose of methotrexate is given. 

Breastfeeding 

Methotrexate is present in human milk. Due to the potential for serious adverse events, including bone marrow suppression, women should not breastfeed while taking methotrexate and for one week after the final dose has been given. 

Methotrexate dosage for pets

As an immunosuppressive and anticancer agent, methotrexate is used to treat the following conditions in cats and dogs:

  • Immune system diseases, including lupus, hemolytic anemia, pemphigus, thrombocytopenia, rheumatoid arthritis, and proliferative urethritis 

  • Blood system cancers including lymphoma 

  • Solid tumors 

This medication is typically given to pets in food, in tablet form. Caregivers must wear gloves when handling this medication as well any animal urine or feces while animals are taking this medication.

Nursing and pregnant animals should not be given methotrexate.

This medication can negatively interact with several medications including nonsteroidal anti-inflammatory drugs (NSAIDs), cyclosporine, and folic acid. It is important to notify your veterinarian about any medications or supplements your pet may be taking prior to starting therapy with methotrexate. 

Typical veterinary doses of methotrexate are different for dogs and cats:

  • Dogs: Low-dose methotrexate may be given at 2.5 mg, and higher doses may reach up to 12.5 mg by oral tablet or subcutaneous or intramuscular injection. 

  • Cats: Standard doses are 2.5-5.0 mg/m^2 by mouth, two to three times per week, or 0.3-0.8 mg/m^2 given by injection once per week.

How to take methotrexate

Methotrexate is taken by mouth in tablet or solution form, or administered intravenously, intramuscularly, intrathecally, or subcutaneously by a healthcare provider. 

  • Take this medication as directed. The dose of this medication may need to be adjusted to find what works best for you. 

  • Read and follow the patient instructions that come with this medication. Talk to your healthcare provider if you have questions. 

  • Take all doses how and when they are prescribed. If you are taking the medication yourself and miss your weekly dose, take your missed dose as soon as you remember. If it is almost time for your next dose, wait until then and take a regular dose. Do not take extra medicine to make up for a missed dose. If you forget to take this medicine for several weeks in a row, talk to your doctor before you start taking it again.

  • If needed, it is ok to crush the tablet and mix it with soft food such as applesauce or jelly. 

  • Do not take this medication with caffeine. 

  • If you are administering this medication to children in solution form, do not mix this medication with milk, hot beverages, or hot food. It is okay to give this medication to children with a small meal or snack. 

  • Avoid administering this medication with alcohol or alcohol-containing medications such as cough syrup.

  • If you are helping anyone else or pets take this medication, wear gloves while administering it. 

  • Some individuals may need to take a folate supplement while taking this medication. 

  • Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light.

Methotrexate dosage FAQs

How long does it take methotrexate to work?

Methotrexate plasma serum levels peak within one to two hours of administration. Depending on the condition methotrexate is being used to treat, it usually takes upwards of six to 12 weeks before a reduction in symptoms is noticed. When used as chemotherapy, the tumor burden may be significantly reduced without notable symptom reduction. 

How long does methotrexate stay in your system?

Methotrexate has a half-life (the time it takes for a drug to lose half of its biological activity) of approximately three to 10 hours with low doses (<15 mg/m^2) and eight to 15 hours with higher doses. Most drugs are completely eliminated from the body in four to five half-lives, so traces of methotrexate may continue to circulate for up to three days. 

How long can you take methotrexate?

When used for chemotherapy, methotrexate is only administered over the course of the cycle(s) or time needed for prophylaxis. However, it is not uncommon for methotrexate to be used as a long-term medication in individuals with rheumatoid arthritis. Some people take it for many years. 

Can you overdose on methotrexate?

Methotrexate is potentially fatal in overdose. Overdose usually occurs when a weekly dose is inadvertently taken as a daily dose. Toxic doses for this medication are extremely variable, with medical textbooks citing up to 25% of individuals taking therapeutic doses experiencing bone marrow suppression. If you believe you have mistakenly taken too much of this medication, it is important to receive medical attention right away.

Individuals who are taking this medication should be closely monitored for bone marrow, liver, kidney, and lung toxicities. This monitoring may include blood tests, liver function tests, bone marrow biopsy, and chest X-rays. 

Symptoms of overdose are broad as this medication affects most organ systems, but especially those organs with rapidly dividing tissues. 

What are the side effects of methotrexate?

Adverse effects of methotrexate may include, but are not limited to the following: 

  • Pulmonary toxicity: damage to lungs resulting in dry cough and shortness of breath

  • Hepatotoxicity: including cirrhosis, fibrosis of the liver, and elevated transaminases 

  • Severe bone marrow suppression: causing anemia, thrombocytopenia, and risk for serious infections 

  • Gastrointestinal toxicity: damage results in intestinal hemorrhage, perforation, or severe diarrhea, nausea, and vomiting 

  • Skin toxicity: including skin necrosis and exfoliative dermatitis 

What interacts with methotrexate?

Methotrexate has several important drug interactions individuals and caregivers should be aware of. It is important to notify your healthcare provider about all medications and supplements you are taking or may take in the future.

Methotrexate is contraindicated for use with all live vaccines, which include:

  • Adenovirus vaccine

  • BCG intravesical vaccine

  • Cholera vaccine

  • Influenza nasal vaccine 

  • MMR vaccine

  • Rotavirus vaccine 

  • Smallpox vaccine 

  • Typhoid vaccine 

  • Varicella vaccine 

  • Yellow fever vaccine 

Note: The COVID-19 vaccines are not live vaccines. Discuss your COVID-19 vaccination status with your healthcare provider if you are currently taking or will be taking methotrexate. Informed decision-making should be used when considering any type of vaccine administration in immunocompromised individuals. 

Methotrexate is also contraindicated for use with the following medications: 

  • Acitretin, a vitamin A derivative used to treat severe psoriasis and other skin reactions 

  • Cidofovir, an antiviral medication used to treat cytomegalovirus 

  • Talimogene laherparepvec, a genetically modified oncolytic viral therapy used to treat unresectable cutaneous cancers including melanoma 

Other medications that should not be used with methotrexate include:

  • Theophylline: Decreases the effectiveness of methotrexate and increases theophylline levelsTrimethoprim preparations: Affects the bone marrow and increases the risk of infectionsNSAIDs including ibuprofen and some medications for cough, cold, or sore throat: Increases the risk of acute renal failure, ulcers and bleeding in the gastrointestinal tract, affects the bone marrow, and increases the risk of infections 

  • Phenytoin: May affect seizure control and affect the efficacy of both medications

  • Probenecid: Increases methotrexate levels and risk of renal failure, bone marrow suppression, and infections

  • Tetracyclines: Possibly decreases gastrointestinal absorption and interferes with enterohepatic circulation by inhibiting bowel flora 

Medically reviewed by Anne Jacobson, MD, MPH
Board-Certified Family Physician

Anne Jacobson, MD, MPH, is a board-certified family physician, writer, editor, teacher, and consultant. She is a graduate of University of Wisconsin School of Medicine and Public Health, and trained at West Suburban Family Medicine in Oak Park, Illinois. She later completed a fellowship in community medicine at PCC Community Wellness and a master's in Public Health at the University of Illinois-Chicago. She lives with her family near Chicago.

... 
Written by Georgia C. Yalanis, MD
Medical Doctor

Georgia C. Yalanis, MD, MSc, is a physician-scientist with expertise in “bench-to-bedside” medicine. She uses translational medicine applications to help clients and companies create products that are scientifically and technologically advanced while still being clinically useful. She has worked in the regulatory and biotech space and has a passion for individuals being empowered to make informed decisions about their medical and health care.

... 

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