What does leucovorin do with methotrexate?

This drug is also sometimes called folinic acid or calcium folinate.

Leucovorin is not a chemotherapy drug. However, it is often given as part of chemotherapy. Leucovorin is administered to make the treatment more effective or to reduce side effects.

This information deals with leucovorin when administered alongside drugs such as fluorouracil (5-FU) or methotrexate.

Leucovorin is common given with 5-FU to treat cancers of the colon, rectum, and other parts of the digestive system. It has been proven that adding leucovorin increases the effectiveness of 5-FU. Leucovorin can also be given with the chemotherapy drug tegaful-uracil, which is similar to 5-FU.

Leucovorin is commonly given with methotrexate, which is used to treat many different types of cancer. It is mostly given with high doses of methotrexate and can help reduce side effects. This is sometimes referred to as "folinic acid rescue" or "leucovorin rescue."

HOW IS LEUCOVORIN ADMINISTERED?

Leucovorin is given in the chemotherapy day unit or during a hospital stay. A chemotherapy nurse will give it to you. You will also be able to see a doctor or nurse before having chemotherapy. Chemotherapy drugs may be given in the following ways:

  • Through a thin tube (line) inserted into a vein in the arm or hand by a nurse
  • Through a tube that goes below the skin of your chest to a nearby vein (central line)
  • Through a thin tube that is placed in a vein of the arm and goes up through a vein toward the chest (PICC)

Leucovorin can also be given in tablet form. Before you leave the hospital, your nurse or pharmacist will give you the tablets to take home with you. It is important to take the tablets exactly as explained to you.

OTHER INFORMATION ON LEUCOVORIN

OTHER DRUGS

Some medicines can interact with leucovorin or be harmful if they are taken alongside leucovorin. This includes medications that can be purchased in a store or pharmacy. Tell your doctor if you are taking any medicines, including over-the-counter drugs, complementary therapies, and herbal remedies.


As promised, I wanted to follow up my last couple of posts (oxaliplatin and 5-fluorouracil [5-FU]) with a quick discussion on leucovorin calcium, the "FOL" in the FOLFOX regimen that is so commonly given in the outpatient setting. Although leucovorin is not a chemotherapy agent or generally used as a stand-alone drug, it certainly is important. Leucovorin has a specific function, and you should be able to explain its purpose.

Leucovorin is a reduced folinic acid that is used in combination with two chemotherapy drugs in particular, high-dose methotrexate and 5-FU. When leucovorin is given with high-dose methotrexate (typically for treatment of leukemias, lymphomas, and osteosarcoma), it is being used as a chemoprotectant. Methotrexate works by depleting folic acid in cells, which causes cell death. Unfortunately, it does not just target cancer cells. Healthy cells can sustain significant side effects, including myelosuppression (WBC, RBC, Plt), hair loss, mouth sores, diarrhea, and liver, lung, nerve, and kidney damage.

Cue our superhero sidekick. Leucovorin is added to methotrexate treatment as a rescue agent because these regimens would otherwise deliver lethal doses of chemotherapy. Often called "leucovorin rescue," it essentially saves the body from toxicity by providing another source of folic acid to those healthy cells in need over a required two- to three-day period of multiple doses. By starting leucovorin 24 hours after methotrexate is given, the chemotherapy has time to work against the cancer cells causing cell death. Methotrexate levels (lab) will be drawn on a regular basis until they decrease to a specified level considered to be safe to discontinue leucovorin administration. Successful rescue requires rapid elimination of methotrexate through the kidneys, which also depends on an adequate pre- and post-hydration protocol. Doses of leucovorin rescue will be ordered at evenly spaced intervals, and it is critical to administer those on time. Severe immunosuppression and toxicity can occur if doses are missed or not given on time.

On the flip side of a chemoprotectant, this drug can also enhance certain chemotherapy drugs such as 5-FU when treating colorectal and head and neck cancers. If given alone, 5-FU only stays in the body for a short period of time; however, adding leucovorin improves the binding of 5-FU to an enzyme in cancer cells. (Cue superhero music: doo, doo, doo-doo! It's Super 5-FU!) This allows the chemotherapy to stay inside the body longer and have a better opportunity to kill more cancer cells.

This unique complementary drug is available as a pill or can be given as an injection (IV or IM). The dose and route of delivery will vary based on the diagnosis you are treating. When administered with 5-FU, it is given via IV typically over two hours. If giving it as part of the FOLFOX, FOLFIRI, or FOLFIRINOX regimen (FOL stands for folinic acid), it can be administered concurrently with oxaliplatin or irinotecan over two hours to save the patient infusion time.

Although side effects from the drug specifically are rare and extremely mild, remember that it enhances 5-FU and can thereby increase the side effects from that drug, particularly the gastrointestinal symptoms of nausea, mouth sores, and diarrhea. Very rarely, leucovorin can cause allergic reactions such as rash, itching, fever, chills, flushing, hypotension, chest pain, shortness of breath, back pain, and swelling of the face, tongue, and throat. Be sure to instruct your patients to notify you immediately if they experience any of these symptoms during infusion. Functioning as a chemoprotectant when given with methotrexate actually decreases the severity of side effects from its chemo-partner.

Although leucovorin may not be the central star of any treatment, it is a pretty super sidekick with the impressive ability to enhance the effects of one chemotherapy (5-FU) and protect against the toxicity of another (high-dose methotrexate). Hopefully, when you find yourself providing patient education you'll be sure to explain the importance of this, at times, unsung hero.

How does leucovorin rescue methotrexate?

Successful rescue by leucovorin depends on rapid elimination of MTX by the kidneys, which requires aggressive pretreatment as well as posttreatment hydration and urinary alkalinization. The main toxicities of HDMTX are elevated serum transaminase levels and renal insufficiency, which can delay drug clearance.

Is leucovorin always given with methotrexate?

Leucovorin is also given with a chemotherapy agent called methotrexate, but in this case it is given to "rescue" normal, healthy cells from the damage caused by the methotrexate. In order to give the methotrexate time to kill the cancer cells, leucovorin is started 12-24 hours after the methotrexate is given.

Why is leucovorin 24 hours after methotrexate?

By starting leucovorin 24 hours after methotrexate is given, the chemotherapy has time to work against the cancer cells causing cell death. Methotrexate levels (lab) will be drawn on a regular basis until they decrease to a specified level considered to be safe to discontinue leucovorin administration.

Is leucovorin an antidote for methotrexate?

Leucovorin is used as an antidote to the harmful effects of methotrexate (a cancer medicine) that is given in high doses. It is used also to prevent or treat certain kinds of anemia. Leucovorin acts the same way in the body as folic acid, which may be low in these patients.