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After High-Dose Methotrexate

Methotrexate is a type of chemotherapy. When your child is given a high dose of methotrexate (HDMTX), they will also take leucovorin. Leucovorin helps relieve some of the side effects of methotrexate.

Follow your care team’s about how to take these medications.

IV hydration

Your child must stay well hydrated after getting high-dose methotrexate. They will get IV fluids by a portable pump for at least 3 days afterward. The amount of fluid given is based on your child’s size and how well their body tolerates each course of methotrexate. The amount of fluid given may change with future courses of methotrexate.

When to contact your care team

Call your provider or clinical pharmacist if your child has:

  • Repeated vomiting or diarrhea
  • Fever while away from the hospital during the 72 hours after high-dose methotrexate

Your child may need extra IV fluids to replace fluids lost from diarrhea or vomiting.

Mercaptopurine after high dose methotrexate for leukemia

Leukemia patients will begin mercaptopurine the same day that high-dose methotrexate is given. Mercaptopurine is often called 6-MP. Mercaptopurine is a type of chemotherapy. It works by slowing or stopping cells from growing. It is used along with other medicines.

Mercaptopurine is taken by mouth every day for 14 days.

Read more about side effects and tips for taking and storing mercaptopurine.

Methotrexate levels in the blood

After your child gets high-dose methotrexate, lab staff will check their methotrexate blood levels once every 24 hours for 3 days. Your care team will tell you when to return for these tests.

After each blood test, you must remain at the hospital until your child is seen by a clinical pharmacist. This staff member will tell you:

  • If your child’s methotrexate blood level is high
  • If your child needs to keep getting IV fluids
  • If the leucovorin dose and schedule has changed
  • If your child needs to have more methotrexate blood tests


Leucovorin is a medicine that helps reduce the side effects of high-dose methotrexate. Your child will always take leucovorin after high-dose methotrexate.

Leucovorin works best when a constant amount is in the body. So, your child must take this medicine at scheduled times. Do not miss any leucovorin doses. If your child does miss a dose, call the clinical pharmacist or doctor right away to find out how to make up the dose.

Your child may get leucovorin by mouth or by IV. Store the IV form of leucovorin in the refrigerator, out of the reach of children.

Leucovorin dosing

Your child should have 1 dose of leucovorin by IV or by mouth every 6 hours for a total of 6 doses. Your care team will tell you when to take each dose.

The dose, scheduled times, and length of leucovorin treatment are based on your child’s methotrexate blood level. If the blood level is high, your care team may change the leucovorin therapy. They will also tell you when your child should have another methotrexate blood test.

  • Your child should take the leucovorin at the scheduled time. They do this even if their methotrexate blood level sample is not taken at the scheduled time.
  • If your child vomits within 1 hour of taking leucovorin by mouth, give them another dose of leucovorin.
  • If your child vomits within 1 hour of taking the repeated dose, call your care team right away. Your care team can arrange for your child to get leucovorin by IV.

If you have questions about your child’s medicines or methotrexate blood levels, talk to your child’s doctor, clinical pharmacist, or nurse. Always follow the instructions given by your care team.

Key Points

  • After taking high-dose methotrexate, your child needs extra care, such as IV hydration and leucovorin.
  • It is important to return for blood tests as scheduled by your care team.
  • Be sure your child takes leucovorin at the times your care team has told you. This helps manage side effects of methotrexate.
  • Your child may also take mercaptopurine. Be sure to follow all the instructions your care team gives you. It is important that your child goes to all appointments and gets blood tests to monitor the amount of mercaptopurine in their body.

Reviewed: August 2022