Written by a parent, not a doctor. Nothing here is medical advice.

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Methotrexate — weekly pills

Updated September 2026.

Also known as: MTX, weekly methotrexate

The weekly maintenance-pill version of the same drug, at a small dose.

The weekly methotrexate pill is a small dose of a folate blocker. Folate, a B vitamin, is what a cell uses to make fresh DNA building blocks, and an enzyme called DHFR keeps folate in its usable form. Methotrexate is shaped like folate and jams that enzyme. Dividing cells run out of fresh parts and stop.

Once inside a cell, methotrexate gets a tail of glutamate units added that traps it there for days, so one weekly dose keeps working all week. Together with the nightly mercaptopurine it is the backbone of maintenance.

I made an everyday analogy and a more scientific visualization of weekly methotrexate.

Everyday analogy

Methotrexate is like a pencil jammed in a shared sharpener.

Methotrexate is like a pencil jammed in a shared sharpener. Two seated, yellow-skinned workers copy house drawings at a shared workbench. They read their original sheets, make copies and sharpen their ordinary pencils in turn; three successful sharpening visits establish the routine. The worker on the right puts an ordinary pencil into a pot, lifts the teal pencil and tries the same sharpener. Its tip stays lodged in the feed opening. The worker returns the remaining teal pencil to the pot and takes back the ordinary pencil. Both workers keep copying until their points wear down. Each tries the blocked sharpener separately, then returns to the paper without a renewed point. The final faint marks leave both copies unfinished. A close-up makes the blunt point visible. Teal identifies methotrexate. Copying represents copying DNA; the sharpener represents an enzyme that keeps folate usable, and sharp pencils represent usable folate needed to help make DNA building blocks. The jam is a simplified picture of inhibition, not a permanently broken enzyme. The shared sharpener Read the original. Make a copy. Keep the pencil sharp. COPYING ROOM ORIGINAL COPY COPY ORIGINAL JAMMED Teal pencil = methotrexate Worn-down point No clear line to copy with UNFINISHED UNFINISHED The workers read, copy and sharpen their pencils again and again. A teal pencil jams the sharpener, like methotrexate blocking a needed step. Their points wear down. Sharpening fails, and the copies are left unfinished.

1 / 3 Copy and sharpen

The workers read, copy and sharpen their pencils again and again.

  • The teal pencil blocking the sharpener represents methotrexate. The jam shows a blocked process, not a permanently broken enzyme.

  • Copying a sheet represents copying DNA, the instructions a cell copies before it divides.

  • The sharpener represents an enzyme that keeps folate usable. Sharp pencils represent usable folate, which helps cells make DNA building blocks.

  • Without that help, DNA copying can slow or stop. This is a simplified picture of one action of methotrexate.

Press play below for a more accurate visualization.

Interactive visual

How oral methotrexate stays inside cells and limits their DNA supply

Poster for How oral methotrexate stays inside cells and limits their DNA supply
Read transcript

## From the gut to blood In maintenance, methotrexate may be a weekly tablet. Because the gut absorbs it, the medicine enters the blood. ## A tail helps it stay Blood carries methotrexate to the cell. A folate transporter in the membrane lets the medicine pass inside. Inside, an enzyme adds glutamate units one at a time. This tail helps methotrexate remain in the cell. The tailed medicine stays inside longer, so it can keep interfering with the cell’s folate pathway. ## First, the normal supply Normally, DHFR restores active folate. Watch the green folate enter its pocket and leave in an active form. Active folate helps other enzymes make DNA building blocks. Those blocks supply the DNA copying machinery. ## The folate supply is blocked Methotrexate resembles folate, so it can enter the same enzyme pocket. Methotrexate occupies the pocket, so DHFR cannot restore active folate normally. With less active folate, the supply of DNA building blocks falls. The copying machinery slows and stalls. ## Taking the cell apart When DNA copying stalls, the stressed cell can activate its self-destruct program. Mitochondria release a signal, so caspases activate and dismantle the cell from inside. ## Sealed packets, then cleanup Because the dying cell breaks into small sealed packets, a cleanup cell can wrap and swallow them.

Side effects

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