Side effects of methotrexate


Methotrexate is necessary for a number of diseases. Methotrexate therapy may be indicated, especially if NSAIDs (non-steroidal anti-inflammatory drugs) are not addressed. But active rheumatoid arthritis or severe forms of psoriasis - psoriasis - can be treated with methotrexate. Methotrexate belongs to the group of active substances called specific anti-inflammatory drugs and is administered in the form of a syringe. The application takes place either in the muscle, under the skin, or in a vessel, i.e. an artery or a vein. However, oral application, i.e. ingestion by mouth, is also possible. However, like all other drugs, methotrexate causes side effects if the appropriate framework conditions or contraindications are not observed.

Mechanism of action

Methotrexate (often short: MTX) is a Cell poison and works cytostatic. This means that it slows the reproduction of cells by inhibiting the production of tetrahydrofolic acid. Tetrahydrofolic acid is needed to Purines and Thymidines to build. Anyone who has paid close attention to biology lessons knows their way around by now at the latest: The nucleic bases guanine and adenine are called purines, thymidine is part of the nucleic base thymine. Together with cytosine, these three form the basic structure of DNA. But if methotrexate now inhibits the formation of three of the four nucleobases of DNA, then no functioning DNA can be produced. So the result is that cell division is stopped. Because if the genetic code from which a cell is built cannot be passed on, no cell can be produced either.

Methotrexate is mainly used in cancer therapy, in the therapy of Autoimmune diseases, and at Ectopic pregnancies used. Autoimmune diseases include, for example Rheumatoid arthritis, of the systemic lupus erythematosus, Crohn's disease, and Bechterew's disease. But also psoriasis, Multiple sclerosis, and Boeck's disease can be treated with methotrexate. Since methotrexate intervenes very deeply in the cellular circulation, there are unfortunately a number of side effects.

Side effects

  • "Very rare" side effects occur in less than 1 in 10,000 patients tested.
  • Every thousandth to ten thousandth patient has "rare" side effects.
  • "Occasional" side effects refer to an occurrence in one in every thousand to one hundredth patient tested.
  • "Common" side effects occur in every tenth to one hundredth patient.
  • "Very common" side effects are those that can occur in every tenth patient, ie in 10% of methotrexate intake.

To illustrate: Methotrexate leads to in "rare" cases Mood swings.
It means that at least one in ten thousand, but maximum every thousandth Patient had to suffer from this side effect after taking in test series.

In case of Methotrexate there are many different side effects that both Skin, eyes, lungs, as well as the Hairiness, the psyche, and Pregnancies can affect.

Side effects on the eyes

In rare cases, severe impairment of vision occurs in the eye. In very rare cases it can even lead to retinopathy, i.e. death of the retina, and conjunctivitis. Pneumonia often occurs in the lungs in combination with fever, chest pain, shortness of breath or shortness of breath, and dry cough. Pulmonary fibrosis can occasionally occur. Pulmonary fibrosis is an increase in the connective tissue in the lungs, which makes it difficult for oxygen to diffuse into the blood. This permanently decreases the oxygen content in the blood.

More information can be found here: The pulmonary fibrosis

Side effect on the lungs

In extremely rare cases, the use of methotrexate can cause serious side effects in the lungs. Taking the drug can cause a special type of pneumonia, which is also known as Mtx pneuomonitis.

The first signs of pneumonia caused by methotrexate may be a dry, tickly cough, which becomes more pronounced when taking the drug. Complaints such as shortness of breath and painful breathing can also occur. In such a case, the doctor who prescribed the methotrexate should be consulted as soon as possible. If necessary, he or she will have an X-ray of the lungs (chest X-ray) made. This is usually a good way to tell whether the lungs are inflamed or not. If there are changes in the x-ray that suggests Mtx pneumonitis, the drug must usually be discontinued.

Side effect on the skin

Methotrexate has a wide range of side effects that change the skin. In rare cases, acne and pigment changes in the nails occur. Occasionally, i.e. in 1% to 0.1% of cases, there is an increased sensitivity to light, herpes reactions, not only on the lip, and hair loss. Hair loss is particularly stressful for the patient as scalp hair forms part of the patient's appearance and personality.

In surveys, hair loss, along with nausea, was cited as one of the subjectively most serious side effects of methotrexate therapy. Many patients suffer from it so much that they discontinue therapy. In the case of hair loss, it is therefore particularly important to accompany the patient on his way and to show him treatment options. These can be the use of wigs, for example. Human hair wigs and toupees can hide hair loss well. But a bald head can also look appealing. Psychological support is therefore important.

Side effect on the nerve tracts

Taking methotrexate can damage the nerve tracts in the body. These side effects, known as polyneuropathy, can manifest themselves as pain, tingling and paresthesia (paresthesia), especially in the arms or legs. The symptoms of polyneuropathy often show up on the feet or hands for the first time and then increase over time towards the trunk.

If there is a polyneuropahtia while taking methotrexate, a causal connection is possible but not confirmed. Nerve damage can have many other causes. The most common causes of polyneuropathy are inadequately controlled diabetes and regular alcohol consumption. If the above-mentioned symptoms of polyneuropathy occur while taking methotrexate, the doctor must therefore assess whether the drug should continue to be taken or should be discontinued.

Read more about the topic here: Therapy of polyneuropathy

Side effect on the central nervous system (CNS)

Mild central nervous system (CNS) side effects of methotrexate are quite common and may affect up to 1 in 10 people. Typical symptoms are complaints such as tiredness, drowsiness or headache. Occasionally (in a maximum of 1 in 100 users) dizziness, confusion or even damage to organs of the brain (encephalopathy) and convulsions may occur as a result of the use of methotrexate. Very rare possible side effects are changes in taste, pain and abnormal sensations or tingling in the arms and legs, and muscle weakness.

Meningitis is also very rare. Typical symptoms are severe headaches, nausea, vomiting, neck stiffness and clouding of consciousness. When methotrexate is used in a tumor disease, side effects in the CNS can occur in rare cases, which lead to paralysis or speech disorders. If such serious side effects occur, the attending physician must be contacted immediately.

Side effect on the bladder

Methotrexate can occasionally cause bladder side effects. This can lead to an inflammation of the bladder, which can be manifested by pain when urinating and possibly bloody urine. An emptying disorder of the bladder can also be a symptom.
The attending physician should be consulted if symptoms occur. The doctor should assess whether the symptoms could be attributed to taking the medication or not. The dose may then need to be reduced or methotrexate discontinued altogether. Bladder infections are not uncommon, especially in women, so that a change in medication is often not indicated at all.

Side effect on the liver

Methotrexate quite often causes mild side effects on the liver. On the one hand, this is due to the fact that the drug is metabolized via the liver and can damage the tissue there, and on the other hand, it can lead to an inflammatory reaction in the liver. Often there are no symptoms or symptoms and the side effects of methotrexate on the liver are only noticeable in the laboratory blood tests when the liver values ​​are increased.

You can find out more about the topic here: Increase in liver values

Often such a slight increase is not a problem and the drug can still be taken. However, if, in the opinion of the doctor, the side effects on the liver are too pronounced or even symptoms arise, the drug must be discontinued. If the examination reveals side effects of the liver, there can be many other causes besides methotrexate.

Hair loss side effect

Hair loss is a rare but possible consequence of drug use. However, there are again a multitude of possible causes of hair loss, so it could be a coincidence if hair loss occurs while taking methotrexate.
In the event that a connection is likely, the following should be considered in consultation with the doctor: If the drug is important and there is no alternative to the treatment, the side effect of hair loss should be accepted. If necessary, however, methotrexate can also be discontinued and another medication taken.


Also depression is one of the known side effects of methotrexate therapy. It occurs with a frequency of 1 to 0.1%. That is, out of 1,000 people who take methotrexate, 1-10 people will develop depression.

Methotrexate and alcohol - are they compatible?

alcohol: One of the most feared side effects when taking methotrexate is a Increase in liver values. Since alcohol consumption also has a negative effect on the liver and thereby the Liver values If methotrexate is taken at the same time, there is a risk of additional stress on the body. Most of the methotrexate is metabolized the day after ingestion and can no longer be found in the body. However, the metabolism creates a building block - also called a metabolite - which is very similar to methotrexate. This is eliminated from the body on the second day after ingestion. In principle, it is then possible to consume alcohol again without hesitation. Of course, this should be done in moderation, regardless of the methotrexate intake. It therefore also makes sense Match methotrexate intake with weekly events: If the "regulars' table" always takes place on Saturday evening, at which one or the other beer is also drunk, it makes more sense to inject the methotrexate at the beginning of the week and not the day before. If in doubt, the liver values ​​can be determined very easily by taking a blood sample from the family doctor. The analysis takes no more than 3 days. A one-time derailment of the liver values ​​is not a big deal.Unlike other organs, the liver is amazing resilient, and can be very regenerate well. However, it can with persistently poor liver values to the Functional failure come what a Liver transplant would make necessary. Usually, however, the liver values ​​normalize when alcohol consumption is coordinated with methotrexate intake.

Therapy of an ectopic pregnancy with methotrexate

If the egg cells implant in the fallopian tube after fertilization, the fallopian tube may tear and the pregnancy terminated later.

At a Ectopic pregnancy there is an implantation of the fertilized egg in the Fallopian tubes. The fallopian tube provides the connection between uterus (also uterus), and Ovaries (Ovaries). After the male sperm have found their way through the uterus, they continue to travel via the fallopian tubes to the woman's ovaries. There you will find the fertilization the female Egg cell(n) instead. The fertilized egg then travels back the same way the sperm came and again passes through the fallopian tube. On its way to the uterus, however, it can "get stuck" in the fallopian tube for various reasons and implant itself there. Reasons for this implantation in the wrong place are, for example Scars in the fallopian tubethat the fertilized egg cannot get past. Has the Egg implanted in the fallopian tube, one speaks of an ectopic pregnancy.

This represents a considerable complication, as the fallopian tube does not have the properties of the uterus that enable the egg cell to mature into the embryo and fetus. For example, as the egg cell grows, there is no space in the fallopian tube. This can lead to a rupture of the fallopian tubes, i.e. one Rupture of the fallopian tube. The maturing egg cell then either goes off and it comes to Termination of pregnancy.

Or else, the egg cell nests in the Peritoneum one that is outside the torn fallopian tube. Such an implantation is then referred to as Abdominal pregnancy, or also Ectopic pregnancy.
In either case, there is a rupture of the fallopian tube severe pain connected, there are symptoms of a "acute abdomen“.

However, an ectopic pregnancy can be relatively easily achieved using the Ultrasound diagnose during a gynecological examination. Once the diagnosis has been made, the fertilized egg cell is removed by surgery or medicine.
The egg cell is definitely in the fallopian tube not viable, but can in the most favorable case, if treatment is not received Pain (see acute abdomen), in the worst case to death the mother lead.

Since surgical therapy for ectopic pregnancy is often not desired, as medicinal alternative Methotrexate can be used.
A operational Supply can to Scarring within the fallopian tube, which one new ectopic pregnancy favored.
This scarring does not occur with methotrexate therapy. However, strict requirements apply to the use of methotrexate in an ectopic pregnancy: On the one hand, the embryo, including the surrounding tissue, must not measure more than four centimeters. On the other hand, the mirror of the plays Pregnancy hormones HCG play a role.

HCG is usually greatly increased in pregnancies, only slightly increased in ectopic pregnancies, and low in the absence of pregnancy.
Incidentally, it is also used with commercially available Pregnancy tests used for determination. A very high HCG value would be unusual in an ectopic pregnancy, and would against methotrexate therapy speak.
However, if all criteria are met, methotrexate can be injected to bring about destruction of the embryonic tissue. However, the dose is much lower than with chemotherapy or treatment for psoriasis.

Therefore, the usual side effects associated with methotrexate therapy do not arise. As already described, the advantage of using methotrexate is the lack of scarring in the fallopian tube.
Only 7% of women treated with methotrexate develop another ectopic pregnancy after treatment.
However, should be up to another attempt at pregnancy Waited 6-12 months to give the fallopian tube enough time to regenerate.

Fertility and pregnancy on methotrexate

Methotrexate works teratogenic, that is, it damages the embryo, or the "ripening fruit" if you want to translate the term literally. Methotrexate therapy is therefore not possible during pregnancy. It can too Hereditary defects of the embryo, and in the worst case scenario, an abortion. Even after stopping methotrexate therapy, damage to the ova and Sperm enter. Appropriate contraception must therefore be guaranteed for this period. However, fertility itself is not affected by methotrexate therapy in women. In men it can become one Decrease in sperm count come. However, this returns to normal after the end of therapy. A reduced sperm count cannot be recognized externally - i.e. from the amount of ejaculate - since the sperm itself is only good 1% share in ejaculation to have. In addition, the amount of ejaculation is individually different anyway, and fluctuates between 2 and 6 milliliters.