Leucovorin is a medication also known as folinic acid, a specific and active form of the B vitamin folate. It serves as a supportive care drug, administered alongside primary medical treatments to either protect the body or enhance the effectiveness of another medication. Its purpose is not to treat the primary condition itself, but rather to manage the effects of other powerful drugs.
Leukovorin’s Role in Chemotherapy
In cancer treatment, leukovorin plays two distinct and seemingly contradictory roles depending on the chemotherapy agent it accompanies. One of its most common applications is in what is known as “leukovorin rescue.” This procedure is used following the administration of high-dose methotrexate, a chemotherapy drug. Methotrexate works by interfering with how cells use folate, a process that is especially active in rapidly dividing cells, which includes both cancer cells and certain healthy cells.
To prevent methotrexate from causing severe damage to healthy tissues, such as the lining of the digestive system and bone marrow, leukovorin is given to patients. The “rescue” typically begins 12 to 24 hours after the methotrexate treatment has concluded. This timing allows the methotrexate sufficient opportunity to attack the cancer cells. Leukovorin provides healthy cells with the active folate they need to function, shielding them from the chemotherapy’s lingering toxic effects.
Conversely, when paired with a different chemotherapy drug, 5-fluorouracil (5-FU), leukovorin’s function shifts from protection to potentiation. It enhances the cancer-killing ability of 5-FU, particularly in treatments for colorectal cancer. This dual capacity to either mitigate toxicity or increase potency showcases its versatility in oncological care.
The Biochemical Mechanism
Many cellular processes, including DNA synthesis and repair, depend on having access to an activated form of folic acid. The chemotherapy drug methotrexate works by blocking an enzyme called dihydrofolate reductase (DHFR), which is responsible for converting dietary folic acid into its usable, active form. This blockade starves both cancerous and healthy cells of the active folate they need to replicate.
Leukovorin is effective as a rescue agent because it is an already active form of folic acid. It does not require the DHFR enzyme to become useful to the cell. By administering leukovorin after methotrexate, doctors can supply healthy cells with the finished product they need, bypassing the enzymatic blockade created by the chemotherapy. This allows normal cellular functions to resume in healthy tissues while the cancer cells, having been exposed to the methotrexate for a longer period, are unable to recover.
When used with 5-fluorouracil (5-FU), leukovorin’s mechanism is one of stabilization. The 5-FU drug works by inhibiting a different enzyme, thymidylate synthase, which is necessary for creating one of the building blocks of DNA. Leukovorin helps the active form of 5-FU bind more tightly and for a longer duration to this target enzyme. This strengthened bond intensifies the inhibition of DNA synthesis within the cancer cells, leading to a more potent therapeutic effect.
Applications Beyond Chemotherapy
While its role in cancer care is well-known, leukovorin has other medical uses. It can be prescribed for the treatment of megaloblastic anemia, a condition characterized by abnormally large and immature red blood cells. This anemia is often caused by a deficiency in folic acid. Leukovorin is particularly useful for patients who cannot properly absorb standard folic acid supplements, providing a direct source of the active vitamin.
The medication also serves as an antidote for overdoses of certain drugs known as folic acid antagonists. These include medications like the antibiotic trimethoprim and the antimalarial drug pyrimethamine, which, like methotrexate, work by interfering with folate metabolism. In cases of overdose, leukovorin can counteract the toxic effects by replenishing the body’s supply of active folate.
Administration and Potential Side Effects
Leukovorin can be administered in several ways, depending on the specific medical need. It is available as an oral tablet or as a solution for injection. Injections may be given intravenously (into a vein) or intramuscularly (into a muscle). The dosage, timing, and method of administration are determined by the healthcare team based on the specific chemotherapy regimen or medical condition being treated.
Side effects from leukovorin itself are uncommon. More often, the side effects a patient experiences are related to the chemotherapy drug it is paired with. For instance, when used with 5-fluorouracil, leukovorin can sometimes intensify the side effects of that medication, such as diarrhea or mouth sores. In rare instances, an allergic reaction to leukovorin may occur, with symptoms like a rash, hives, or difficulty breathing that require immediate medical attention.
Patients should communicate with their healthcare providers about their medical history, including any allergies or other medications they are taking. Patients should never take supplemental folic acid unless directed, as it may interfere with treatment. All questions or concerns about treatment should be discussed with a qualified doctor or pharmacist.