Methotrexate

Say it: meth-oh-TREX-ate · Brand names: Trexall, Xatmep, Jylamvo, Otrexup, Rasuvo

Methotrexate is a chemotherapy medicine that blocks folate, a vitamin cancer cells need to make DNA.

What it is

Methotrexate blocks an enzyme that cells need to use folate, a B vitamin. Without it, cells cannot make DNA. Fast-growing cancer cells stop growing and die.

Often used for

• acute lymphoblastic leukemia (ALL)
• some lymphomas, including lymphoma in the brain
• osteosarcoma, a bone cancer
• breast cancer
• head and neck cancer
• a type of skin lymphoma called mycosis fungoides
• and some other conditions

How you get it

Methotrexate can be given through a vein (IV), into the spinal fluid, as a shot, or as a pill or liquid at home. High doses are given in the hospital over several hours, followed by a rescue medicine called leucovorin. Your schedule may be different.

Common side effects and what helps

• Mouth sores. Rinse often with a mild salt and baking soda rinse.
• Nausea and vomiting. Take your anti-nausea medicine as your team tells you.
• Low blood counts, which raise your risk of infection and bleeding. Wash your hands often.
• Feeling tired. Rest and short walks can help.
• Diarrhea. Drink fluids and tell your team if it is frequent.
• Changes in liver blood tests. Avoid alcohol.
• Skin that burns easily in the sun. Use sunscreen and cover up.

Call your care team right away if you have

• A fever of 100.4 degrees Fahrenheit (38 degrees Celsius) or higher, or chills
• Passing much less urine than usual
• A new cough, shortness of breath, or chest pain
• Mouth sores that keep you from eating or drinking
• Diarrhea that does not stop, or vomiting
• A rash that blisters or peels
• Bleeding or bruising that will not stop, black or bloody stools, or blood in your urine

Before you start, tell your team

• If you are pregnant, may become pregnant, or are breastfeeding
• If you have kidney or liver problems
• If you have fluid around your lungs or in your belly
• If you take NSAID pain relievers, acid reducers, or antibiotics like trimethoprim and sulfamethoxazole
• If you drink alcohol
• All the medicines, vitamins, and herbal products you take

Good to know

• With high doses, you get lots of IV fluids, blood tests to measure the medicine, and leucovorin rescue on a strict schedule.
• Many common medicines can raise methotrexate levels. Check with your team before starting any new medicine.
• You will have blood tests to check your blood counts, liver, and kidneys.
• It can cause serious harm to an unborn baby. Use birth control during and after treatment as your team advises.

At home

• If you take pills or liquid, take them exactly on the days your team tells you. Some plans are only once a week, and taking it daily by mistake can be very dangerous.
• If you miss a dose, ask your team what to do. Do not double up.
• Store at room temperature, away from children and pets.
• Caregivers should wear gloves if they touch the medicine and wash hands after.

Questions to ask

• Which days do I take this medicine?
• Which of my other medicines could interact with it?
• When do I take leucovorin, and what if I miss it?
• How often will I need blood tests?

Part of these treatment plans

• C10403 (CALGB 10403)
• Dose-dense MVAC
• Hyper-CVAD
• POMP

Side effect guides

• Fatigue (tiredness)
• Nausea and vomiting
• Diarrhea
• Mouth sores
• Low white blood cells and infection risk
• Low platelets and bleeding

Last updated: 2026-10-27. Medically reviewed by Veli Bakalov, MD, medical oncologist (October 2026). General education from Step by Step, the patient portal of HemeOncBuddy.