Why Take Folic Acid with Methotrexate?

why take folic acid with methotrexate

Introduction

Today we ask the question – why take folic acid with methotrexate? As part of the NAPLEX exam, or any other pharmacy licensing exam, you are expected to know the detailed theory behind every clinical decision.

Methotrexate was first used in the 1950s as an anticancer agent. Formerly, the drug was known as a amethopterin. Since then, the drug has gone on to become an important medicine in the treatment of autoimmune inflammatory disorders such as rheumatoid arthritis, psoriasis, psoriatic arthritis, eczema and various forms of vasculitis.

  • Methotrexate is also used in ectopic pregnancy, a condition in which pregnancy occurs outside the womb. Methotrexate is, after all, an abortifacient.

Methotrexate use is not without consequence.

The drug is associated with a wide range of often serious side effects. Many of these adverse effects relate to how methotrexate impacts folic acid levels in the body. For this reason, folic acid supplementation is recommended for patients taking methotrexate.

Here, we outline why folic acid supplementation is recommended, when folic acid should be taken, and how folic acid improves the clinical effect of methotrexate.

What is Folate?

Folate is a form of vitamin B9.

As an essential vitamin, folate levels must be maintained to ensure adequate cell growth and repair. In the case of folate, then, the recommended daily intake by the FDA is currently set at 400 micrograms per day.

  • Folate is found in beans, chickpeas, yeast extract, green leafy vegetables, beetroot, red bell peppers, strawberries and some nuts – such as hazelnuts and walnuts.

Folate is essential for production of cellular DNA, RNA, amino acids and to facilitate the process of cell division.

How Methotrexate Works

Methotrexate works as an antimetabolite – inhibiting folate synthesis.

More specifically, methotrexate competitively inhibits the enzyme dihydrofolate reductase (DHFR); the enzyme needed to convert folate into the more active form, tetrahydrofolate (THF). As we have learned, folate is essential for purine and pyrimidine synthesis needed for RNA and DNA synthesis.

This makes methotrexate an effective tool against actively dividing cells, including cancer cells and other immune cells that may be stationed as “overactive” – hence its use in treating rheumatoid arthritis and other autoimmune conditions.

However, methotrexate is indiscriminate; it also targets healthy cells, too.

Folic Acid Supplementation

By inhibiting folate synthesis, methotrexate is responsible for both its mechanism of action and its adverse effect profile.

Methotrexate targets actively dividing cells. Of course, this includes healthy cells, too, which the body would do well to maintain. By interfering in folate synthesis, methotrexate leads to common adverse effects such as:

  • Ulcerative stomatitis – or mouth sores
  • Leucopenia- or low white blood cell count
  • Hair loss
  • Teratogenicity – increasing birth defect risk
  • Fatigue

Folic acid supplementation isgiven to minimize the probability of these adverse effects.

Folic acid supplementation must be given for two reasons:

  • To ensure that methotrexate works as optimally as possible
  • To ensure that long-term adverse effects of methotrexate are minimized

One way to ensure that both functions are achieved is for patients to take folic acid on a separate day – and not the same day – as methotrexate.

Dose and Frequency of Folic Acid

The precise dose and frequency of folic acid use depends on the patient, their doctor and the malady that the patient has.

Many doctors recommend folic acid use several times a week, sometimes 6-days per week. Other healthcare professionals recommend one large dose of folic acid taken once weekly on a day other than methotrexate use. Remember – methotrexate is always taken once weekly – never more.

However, the common denominator remains the same – namely, that folic acid is routinely recommended for patients taking methotrexate, but that folic acid supplementation should be taken on a day, or days, other than the day of methotrexate treatment.

This ensures that the patient’s body receives adequate folic acid replenishment to satisfy healthy cells of the body, whilst ensuring that on the day that methotrexate treatment is given, that the treatment is maximally effective.

That’s the answer to today’s question – why take folic acid with methotrexate. Check back to our NAPLEX blog soon for even more great clinical tips and knowledge to help you pass your pharmacy licensing exam.

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