Methotrexate is an organic chemical compound belonging to folic acid antagonists, which has been used as a cytostatic drug, in other words an anti-cancer drug. It is also used to treat psoriasis and autoimmune diseases.

Methotrexate , by inhibiting metabolic pathways, prevents the synthesis of purine bases - these are essential elements for the construction of DNA. The consequence of this is a disruption of DNA, RNA and protein synthesis, which leads to inhibition of cell division and apoptotic cell death.

Apoptosis is a natural process, necessary for the proper functioning of a living organism, in order to maintain the balance, cells cannot live for too short or too long.

The action of methotrexate particularly affects rapidly dividing cells, such as cancer cells.

When is methotrexate used?

Methotrexate is used most often in the treatment of cancer diseases, but also in the treatment of other diseases such as psoriasis or some autoimmune diseases that are based on too rapid, uncontrolled cell division.

Methotrexate is most commonly used in neoplastic diseases such as:

  • chorionic epithelioma
  • non-Hodgkin's lymphoma
  • acute myeloid leukemia
  • acute lymphocytic leukemia
  • solid tumors of the head and neck
  • ovarian cancer
  • nipple cancer
  • bladder cancer
  • testicular cancer
  • lung cancer

In much lower doses, methotrexate is also used as an immunosuppressive drug in the treatment of severe forms of psoriasis and, among others, in rheumatoid arthritis and ankylosing spondylitis.

As an immunosuppressive drug, it is classified as DMARDs, ie drugs modifying the course of the disease. All drugs in this group have anti-inflammatory and immunosuppressive effects, interfering with the natural, usually progressive course of the disease. In other words, they inhibit disease progression, prolonging remission time.

However, all those who count on an immediate effect of treatment unfortunately have to be patient - methotrexate starts working after more than 2 months of use, and the full effect is usually achieved after 3 months.

How can be servedmethotrexate?

Oral administration of the drug is not always possible, and sometimes even inadvisable, especially in patients with digestive system diseases. Therefore, in addition to the tablet form, methotrexate can be administered:

  • subcutaneously
  • intramuscularly
  • intraarterial
  • intrathecal (into the spinal-spinal fluid)
  • intraventricularly through the Ommaya reservoir (it is a rubber bulb connected by a catheter to the intrathecal space of the brain; usually the Ommaya reservoir is implanted below the border of the scalp)

Can I take other medications with methotrexate?

Before starting treatment with methotrexate, tell your doctor about all medications you are taking or have recently taken, including over-the-counter medications, herbal remedies, or other naturally derived medications.

It is especially important to inform your doctor that you are taking the following medications:

  • salicylates
  • sulfonamides
  • antibiotics (such as tetracycline, chloramphenicol, ciprofloxacin, penicillin)
  • barbiturates
  • kidney and liver toxic drugs
  • drugs excreted via the kidneys and live vaccines
  • medications containing folic acid and vitamin preparations and oral iron preparations containing folic acid
  • disease-modifying drugs (such as gold s alts, penicillamine, hydroxychloroquine, sulfasalazine, azathioprine, cyclosporine)
  • proton pump inhibitors (e.g. omeprazole, pantoprazole)
  • levetiracetam
  • non-steroidal anti-inflammatory drugs
  • sedatives
  • oral contraceptives

These drugs may cause the malabsorption of methotrexate or increase its concentration in the body. This can lead to either the drug being ineffective or, on the contrary, the concentration being too high, increasing the likelihood of side effects.

When not to use methotrexate?

This drug may not always be used (despite medical indications). The main contraindications include:

  • allergy to the active substance or any of the other ingredients of the drug
  • liver and kidney problems
  • disorders of the hematopoietic system (e.g. after prior radiotherapy or chemotherapy)
  • alcohol abuse
  • immune system disorders
  • stomatitis and active gastric or duodenal ulcer disease
  • pregnancy or breastfeeding

When to be careful with methotrexate treatment?

Before starting the applicationmethotrexate, tell your doctor about any other illnesses and conditions, even if they seem insignificant to you. Caution should be exercised, e.g. in the case of:

  • the patient has diabetes and is treated with insulin
  • the patient has e.g. tuberculosis, hepatitis B or C, shingles
  • Patient has or has had kidney or liver disease
  • patient has lung dysfunction or trouble breathing
  • the patient is significantly overweight
  • the patient is dehydrated or has a disorder that may lead to dehydration (vomiting, diarrhea, stomatitis)

All these cases can significantly affect the effectiveness of the therapy, and it should be remembered that sometimes the patient's life depends on its success.

Driving and using machines and methotrexate

Side effects from the central nervous system may occur with the use of methotrexate, such as:

  • feeling tired
  • dizziness
  • sometimes even fainting

In some cases they may impair the ability to drive or use machines. If you feel tired or dizzy, do not drive, for example, until you feel better.

Methotrexate and pregnancy and fertility

Methotrexate is not recommended for pregnant women. However, if methotrexate is used during pregnancy due to cancer, or if the patient becomes pregnant during treatment, there may be a risk to the normal development of the fetus. Unfortunately, methotrexate has an embryotoxic effect and causes fetal defects and may cause miscarriage or premature birth. In this case, the benefits of such treatment should be assessed.

Methotrexate also temporarily affects sperm and egg production. Fortunately, this effect disappears after discontinuing the therapy.

To avoid potential harm to the fetus, patients should avoid conceiving a child (fertilization) while taking methotrexate and for at least 6 months afterwards.

Side effects of methotrexate

Contrary to appearances, methotrexate causes few side effects. Usually, at the beginning of treatment, some patients develop nausea and sometimes vomiting. They usually disappear spontaneously after a few weeks or after increasing the dose of folic acid.

However, if the gastrointestinal symptoms persist, which may lead to dehydration that may endanger the patient's he alth, it is necessary to change the oral preparation to, e.g.administered subcutaneously, and if the symptoms persist, which is relatively rare, then methotrexate is changed to sulfasalazine.

The most common side effects are changes in the blood. Usually, it is a decrease in the level of leukocytes or lymphocytes, which weakens the body and promotes the occurrence of infection. That is why regular checks are so important.

Contact your doctor immediately if you experience any of the following symptoms:

  • dry, irritating cough, shortness of breath, exercise-independent dyspnoea
  • fever
  • chest pain
  • unexplained bleeding (including vomiting blood) or bruising
  • severe peeling or blistering of the skin
  • mouth ulcers
  • black or tarry stools
  • hard-to-control diarrhea
  • pain or difficulty urinating
  • blood in urine or blood in stool
  • yellowing of the skin

Preparation for methotrexate therapy

Before starting treatment, your doctor may recommend that you take a chest X-ray to check the condition of your lungs. He should also order blood tests and check the patient's kidney and liver function.

During the therapy, all these parameters should also be checked regularly, and if necessary, the doctor may change the dose of the drug or change it to a different one. The patient should under no circumstances do it "on his own".

Methotrexate with food, drink and alcohol

The tablets with methotrexate should be taken on an empty stomach, washed down with water.

During treatment, you should avoid drinking alcohol, as well as excessive amounts of coffee, caffeinated drinks and excessive amounts of black tea - as this may lead to serious liver damage.

Drink plenty of fluids as dehydration (i.e. reducing the amount of water in your body) may increase the toxic effects of the drug. This should be remembered especially on hot days.

Methotrexate overdose

During treatment with methotrexate, use the dose recommended by the attending physician - most often it is an oncologist. You should never change it yourself.

In the event that the patient has taken a larger dose of the drug than it should, contact a physician immediately. Take the medicine pack with you so that you know what medicine you have taken and in what dose.

An overdose of methotrexate can cause severe toxic reactions due to the severity of the side effects. Symptoms of overdose include:

  • easy bruising orbleeding
  • weakness
  • wounds in the mouth
  • nausea
  • vomiting
  • black or bloody stools
  • coughing up blood or vomiting with content that looks like coffee grounds
  • passing less urine

The antidote used in the case of methotrexate poisoning is calcium folinate.

Remember!

In order to achieve the greatest possible effectiveness of treatment, and at the same time not to harm the patient, the doctor-patient cooperation is necessary. Even the most effective drugs will not work if the patient does not take them or takes them differently than agreed with the treating physician.

The patient must not hide from the doctor information about coexisting diseases and about other medications taken, even if they are of plant origin.

On the other hand, if the doctor does not order tests and does not monitor the patient's general he alth, it will expose the patient to the risk of side effects of the drug.

About the authorKarolina NowakA pharmaceutical technician by education. Currently, he is professionally fulfilled working in a pharmacy. Empathetic, sensitive and fond of contact with other people. Privately, a lover of a good book.

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