How methotrexate works
Methotrexate (MTX) is a drug that is used in high doses for numerous cancers and in low doses for rheumatic diseases, among others. Depending on the dose used, it has an inhibitory effect on cell division (cytostatic) or a dampening effect on the immune system (immunosuppressive) and an anti-inflammatory (antiphlogistic) effect.
In psoriasis, rheumatoid arthritis and inflammatory bowel diseases (Crohn’s disease and ulcerative colitis), the immune system is overactivated and attacks the body’s own cells. This results in a constant inflammatory reaction in the body, which can leave great damage in its wake. Therefore, the immune system must be “modulated” – for example with methotrexate as a representative of the so-called immune modulators:
In low concentrations, it inhibits the activation of folic acid, which the cells of the immune system urgently need for cell division. This suppresses the acute inflammatory reaction. However, the effect of the treatment does not appear until one to two months after the start of treatment.
MTX is also suitable for the treatment of cancer. However, the dosage of the active ingredient must be significantly higher than for psoriasis, for example.
Regardless of its dosage, methotrexate also inhibits folic acid activation and thus cell division in healthy body cells. To mitigate this side effect, folinic acid is additionally given in a time-released manner.
Uptake, degradation and excretion
Absorption from the intestine when the active ingredient is taken in tablet form varies widely (20 to 100 percent). Excretion is relatively slow via the kidneys.
In the event of side effects in the gastrointestinal tract or swallowing problems, MTX can be injected under the skin (subcutaneously). In this way, the active ingredient enters the bloodstream rapidly and completely. However, breakdown and excretion remain identical.
When is methotrexate used?
The indications for use (indications) of methotrexate include:
- Cancers (including acute lymphoblastic leukemia, non-Hodgkin’s lymphoma, breast cancer, and lung cancer)
- rheumatoid arthritis (inflammation of the joints caused by rheumatism)
- severe juvenile idiopathic arthritis (rheumatoid joint inflammation in childhood and adolescence)
- severe psoriasis (psoriasis)
- mild to moderate Crohn’s disease (alone or in combination with corticosteroids)
How methotrexate is used
In cancer treatment, the dosage is significantly higher. It depends on the type of tumor and the treatment regimen. Doses of between 40 and 80 milligrams of methotrexate per square meter of body surface area, which can be injected or swallowed, are common. The duration of treatment here is between seven and 14 days.
Also possible are so-called “high-dosage regimens” in which between one and 20 grams of MTX are administered once.
Since the active substance is excreted via the kidneys, the dose must be reduced in patients with kidney dysfunction.
What are the side effects of methotrexate?
Often (that is, in one to ten percent of those treated) methotrexate causes side effects such as inflammation of the mucous membranes of the mouth and intestines, damage to the mucous membranes in the gastrointestinal tract, and bone marrow inhibition (bone marrow depression). The latter means that the formation of blood cells, which normally occurs in the bone marrow, is disrupted.
Occasionally (in less than one percent of those treated), headaches, increased susceptibility to infections (e.g., pneumonia), allergic skin rashes, and osteoporosis occur. Even more rarely, men may experience decreased fertility.
Side effects understandably occur much more frequently with “high-dose therapy” than with low-dose MTX.
Contraindications
Pregnant women, breastfeeding women, patients with a weakened immune system, and those with severe renal or hepatic impairment should not receive medications containing methotrexate.
Drug interactions
Other drugs for the treatment of rheumatoid arthritis or psoriasis (so-called basic therapeutics such as hydroxychloroquine) must not be combined with methotrexate.
During MTX treatment, patients should not be vaccinated with a live vaccine, as severe vaccination complications may otherwise occur due to the suppressed immune system.
Blood clotting must be checked regularly if blood thinning agents are used at the same time.
Drugs that, like methotraxate, have an influence on folic acid metabolism (e.g., sulfonamide antibiotics, trimethoprim) may increase the side effects of MTX when used concomitantly.
Other drugs such as phenylbutazone (analgesic), phenytoin (antiepileptic), and sulfonylureas (diabetes drugs) are also capable of enhancing the effects of MTX.
Oral antibiotics and cholestyramine (medication for high cholesterol), on the other hand, may weaken the effect of MTX.
Traffic ability and operation of machines
Reactivity is not permanently affected by taking methotrexate.
Age Limitation
MTX is approved for use from the age of three years.
The active substance methotrexate harms both the unborn child and the infant and must therefore not be given during pregnancy or breastfeeding.
Pregnancy must be ruled out by a doctor before starting treatment. Effective contraception must be ensured during treatment.
If a woman being treated with methotrexate for rheumatoid arthritis or inflammatory bowel disease wishes to become pregnant, she should switch from MTX to a better-tested drug such as prednisone/prednisolone, sulfasalazine, hydroxychloroquine, or azathioprine.
MTX should be discontinued three months before a planned pregnancy. After discontinuation, increased folic acid intake is recommended to restore folic acid metabolism to normal.
How to obtain medication with methotrexate
All medications containing methotrexate require a prescription in Germany, Austria, and Switzerland. You can therefore only obtain MTX from a pharmacy with a prescription from your doctor.
How long has methotrexate been known?
The active substance methotrexate was developed in the USA as early as 1955. At that time, its effect was only assumed to be as a cancer treatment.
Other interesting facts about methotrexate
In the event of poisoning with methotrexate, for example if the dosage is too high in patients with renal dysfunction, the so-called carboxypeptidase G2 is given as an antidote. This breaks down methotrexate so that its concentration in the blood rapidly falls to non-toxic levels.
Another way of rapidly reversing the effect of MTX is the so-called “leucovorin rescue”, i.e. the high-dose administration of leucovorin.
