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Leucovorin with high dose methotrexate (HDMTX)


What is high-dose methotrexate?

High-dose methotrexate (HDMTX) is an anticancer medicine. It is a clear yellow liquid given by vein (IV).

Leucovorin is sometimes called a “rescue” medicine. It is taken in an effort to “rescue” the normal cells in the body from the side effects of methotrexate. Leucovorin is available in several forms:

  • 5-mg, 15-mg, and 25-mg white tablets taken by mouth
  • A clear liquid taken by mouth
  • A clear to pale yellow liquid given by vein

Usually, leucovorin does not cause any side effects.

Possible side effects of high dose methotrexate


  • Nausea and vomiting
  • Diarrhea
  • Rash
  • Decreased kidney function

Later (usually more than a day after treatment starts)

  • Low blood counts 7 to 14 days after receiving HDMTX, with a higher risk of infection, bleeding, and anemia
  • Mouth and lip sores; sores around the anus
  • Decreased appetite
  • Rash
  • Hair loss 2 to 3 weeks after treatment
  • Skin more sensitive to the sun or sunlamps
  • Decreased kidney or liver function
  • Irritated eyes
  • Chest soreness

These are the most common side effects, but there may be others. Please report all side effects to the doctor or nurse.

In case of a severe side effect or reaction, call the doctor, nurse, or pharmacist at 595-3300. If you are outside the Memphis area, dial toll-free 1-866-2STJUDE (1-866-278-5833), and press 0 once the call is connected.

HDMTX can pose a health hazard to caregivers. All caregivers should take safety precautions while giving this drug. For 48 hours after this drug is given, the patient’s body fluids can contain the drug. During that 48-hour period, caregivers should follow safety guidelines when handling the patient’s vomit, blood, urine, and bowel movements, including diapers. These guidelines include wearing gloves when cleaning up body fluids. For a complete list of safety precautions, see “Do you know… Protecting caregivers from drug hazards.”

Special instructions for leucovorin with high-dose methotrexate

  • Leucovorin should always be taken after you receive HDMTX. Leucovorin works best when the amount of medicine remains constant in the body. To keep the amount constant, take this medicine at the planned times. Do not miss any leucovorin doses.
  • Store the oral liquid and IV forms of leucovorin in the refrigerator.
  • Store the oral tablet form of leucovorin at room temperature in a dry place.
  • You should drink plenty of liquid for 3 days after you receive HDMTX. The doctor or nurse will tell you how much liquid you should drink.
  • If you are urinating less often than usual after receiving HDMTX, be sure to tell the pharmacist or doctor.
  • At least one (1) week before receiving HDMTX, you should stop taking any multivitamin by mouth unless your doctor or pharmacist tells you otherwise. The folic acid in multivitamins may keep the methotrexate from working well. Do not start taking the vitamin again until your doctor or pharmacist tells you to do so.
  • Methotrexate makes the skin extra sensitive to sunlight. You should wear protective clothing and a sunscreen when you are outside during daylight hours.
  • Some medicines may affect the way your body processes methotrexate. Do not take these medicines the day you receive HDMTX. Do not take them for 48 hours after you receive HDMTX unless your doctor or pharmacist tells you to do so. These medicines include:
    • Omeprazole
    • Penicillin antibiotics (such as amoxicillin and Augmentin®)
    • Acyclovir
    • Amphotericin B
    • Some over-the-counter drugs, such as aspirin, ibuprofen, naproxen, and Pepto-Bismol®.
  • Refer to the “Do you know… After high dose methotrexate” handout for these details:
    • Dates and times for your methotrexate blood level tests
    • Dates and times for your doses of leucovorin
    • Your daily fluid intake goal for the 3 days after HDMTX
    • Guidelines about when to call St. Jude after receiving HDMTX


This document is not intended to take the place of the care and attention of your personal physician or other professional medical services. Our aim is to promote active participation in your care and treatment by providing information and education. Questions about individual health concerns or specific treatment options should be discussed with your physician.

St. Jude complies with health care-related federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex.

ATTENTION: If you speak another language, assistance services, free of charge, are available to you. Call 1-866-278-5833 (TTY: 1-901-595-1040).

ATENCIÓN: si habla español, tiene a su disposición servicios gratuitos de asistencia lingüística. Llame al 1-866-278-5833 (TTY: 1-901-595-1040).

تنبيه: إذا كنت تتحدث باللغة العربية فيمكنك الاستعانة بخدمات المساعدة اللغوية المتوفرة لك مجانا. .يرجى الاتصال بالرقم. 5833-278-866-1  (الهاتف النصي: 1040-595-901-1).