Methotrexate is a medication used to treat various conditions, including certain cancers and autoimmune diseases like rheumatoid arthritis, psoriasis, and some types of leukemia. This drug interacts closely with folate, a B vitamin essential for cellular processes. Understanding this interaction is key to how methotrexate works and why folate is often prescribed alongside it.
Understanding Methotrexate’s Action
Methotrexate functions as a chemotherapy agent and an immune system modulator, depending on the dosage. It primarily works by interfering with the body’s use of folate, acting as a folate antagonist.
The drug inhibits dihydrofolate reductase (DHFR), an enzyme that converts dihydrofolate into tetrahydrofolate. This folate is necessary for DNA and RNA synthesis. By blocking DHFR, methotrexate reduces tetrahydrofolate availability, disrupting DNA synthesis and cell division. This disproportionately affects rapidly dividing cells, such as cancer cells or immune cells involved in autoimmune responses.
Role of Folate in Treatment
Folate, often supplemented as folic acid or folinic acid, is commonly prescribed alongside methotrexate to mitigate its side effects. Methotrexate’s interference with folate metabolism can lead to a deficiency in healthy cells. This deficiency can cause side effects such as nausea, vomiting, mouth sores (stomatitis), fatigue, liver toxicity, and bone marrow suppression.
Folate supplementation helps protect healthy cells from methotrexate’s anti-folate effects without significantly compromising its therapeutic action on diseased cells. Folic acid is a synthetic form of vitamin B9, while folinic acid (leucovorin) is a more readily active form of folate. Folinic acid can bypass the DHFR enzyme inhibition, allowing healthy cells to produce necessary nucleic acids and amino acids.
Folate supplementation can reduce the incidence of gastrointestinal side effects, including nausea and vomiting, and lower the risk of elevated liver enzymes. It also helps reduce patient withdrawal from methotrexate treatment due to adverse effects. Folic acid is typically given weekly, while folinic acid is used for more severe toxicities or in specific situations, sometimes given daily or shortly after a high dose of methotrexate.
Important Considerations for Patients
Adhering to the prescribed folate regimen is important for individuals taking methotrexate. Folic acid is typically taken once a week, often 24 hours after the methotrexate dose, to prevent interference with its effectiveness. It should not be taken on the same day as methotrexate.
A common dose of folic acid is 5 mg once weekly, though some patients may take 1 mg daily, excluding the methotrexate day. If side effects persist, a healthcare provider may increase the folic acid dose, up to 10 mg weekly or even 6 times a week, omitting the methotrexate day. Regular blood tests are necessary to check for side effects such as bone marrow suppression or liver issues.
While dietary folate is present in foods like leafy green vegetables, supplementation is necessary to effectively counteract methotrexate’s effects. Patients should communicate any side effects or concerns with their healthcare provider, as adjustments to the folate regimen or methotrexate dosage may be necessary to optimize treatment and minimize adverse effects.