Concomitant prescription of methotrexate and folic acid

Methotrexate, MTX, is a structural analog of folic acid, its main mode of action is the inhibition of the DHFR, see here.

MTX has two types of clinical uses,

• As antineoplastic, at very high dose, often  with folinic acid rescue
• As "anti-inflammatory drug" in rheumatology, dermatology, at low dose. In this type of clinical uses there is a tendency to add to MTX folic acid or folinic acid (which is more expensive) in order to reduce adverse effects of MTX (for example rise in hepatic enzymes) while preserving its efficacy. Indeed mechanisms of action of MTX other than the inhibition of DHFR were advanced, for example a decrease of adenosine release. The addition of folic acid could reduce the inhibition of DHFR and the addition of folinic acid suppress the consequences of the inhibition of DHFR while letting persist the other effects supposed to play a part in inflammation. This addition can however reduce the therapeutic effect of MTX which requires an increase in its dosage.

The optimization of the dosage of MTX when used alone is not easy; it is necessary to find a compromise between beneficial and adverse effects. It is not sure that the addition of a second drug to MTX facilitates the optimization. See this paper for review.