Methotrexate

Methotrexate (Methotrexate) is a drug that is used in medicine as an anticancer (antitumor) agent for the treatment of various types of cancer, and as an immunomodulatory and anti-inflammatory agent in rheumatologic diseases.

Here are a few of the main uses of methotrexate:

1. Oncology: Methotrexate is widely used in chemotherapy to treat various types of cancer such as leukemia, lymphoma, bladder cancer, breast cancer, cervical cancer and others. It is usually administered into the body in the form of injections or oral tablets.
2. Rheumatology: Methotrexate is used to treat rheumatoid arthritis, psoriasis, psoriatic arthritis and other inflammatory diseases of the joints and skin. In these cases, it is usually taken as tablets or injections.
3. Extrapulmonary sarcoidosis: Methotrexate may be used to treat sarcoidosis when it causes symptoms and requires therapy.

The mechanism of action of methotrexate is that it blocks folic acid, resulting in impaired nucleic acid synthesis and inhibition of cell division. This is especially important for rapidly dividing tumor cells, making methotrexate effective against cancer cells.

It is important to note that methotrexate is a powerful medication with serious side effects and should only be used when prescribed by and under the supervision of a doctor.

Indications Methotrexate

1. Oncology:

   • Leukemia (including acute lymphoblastic and acute myeloblastic leukemia).
   • Lymphomas (e.g., Hodgkin's lymphoma and non-Hodgkin's lymphoma).
   • Bladder Cancer.
   • Breast Cancer.
   • Cervical Cancer.
   • Head and neck cancer.
   • Other cancers.

2. Rheumatology:

   • Rheumatoid arthritis.
   • Psoriasis (including psoriatic arthritis).
   • Polyarthritis.
   • Ankylosing spondylitis.
   • Other inflammatory diseases of the joints and skin.

3. Sarcoidosis:

   • Extrapulmonary sarcoidosis, when it causes symptoms and requires therapy.
4. Psoriatic erythroderma: This is a condition in which most of the skin on the body is covered with psoriatic plaques.
5. Psoriatic pustulosis of fingers: This is a form of psoriasis characterized by the formation of blisters on the skin of the fingers.
6. Multiple Sclerosis: In some cases, methotrexate may be used to treat multiple sclerosis, especially when it is active.

Release form

1. Oral tablets: This is the most common form for treating autoimmune diseases such as rheumatoid arthritis and psoriasis. Methotrexate tablets are convenient to use but require a precise dosing schedule.
2. Solution for subcutaneous administration: Methotrexate in the form of solution for injection may be preferable for some patients, especially when a rapid onset of effect is needed or when the patient cannot take tablets. Injections also allow precise control of the dosage.
3. Solution for intramuscular and intravenous administration: These forms are more commonly used in oncology for chemotherapy. These forms are more commonly used in oncology for chemotherapy.
4. Solution for intrathecal administration: In some cases, such as in the treatment of certain cancers of the central nervous system, methotrexate may be administered directly into the cerebrospinal fluid.

Pharmacodynamics

1. Inhibition of dihydrofolate reductase (DHFR): Methotrexate inhibits the activity of the enzyme DHFR, which is involved in the conversion of dihydrofolic acid to tetrahydrofolic acid. Thus, it inhibits the synthesis of tetrahydrofolic acid, which is necessary for the formation of thymidine monophosphate and purine nucleotides, thus slowing down cell growth and division.
2. Anti-inflammatory effect: Methotrexate has an anti-inflammatory effect by inhibiting the synthesis of cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). This leads to reduced inflammation and decreased immune system activity.
3. Immunosuppressive effects: Methotrexate suppresses the immune system, particularly cellular immunity, which may be useful in treating autoimmune diseases and preventing transplant rejection.
4. Anti-cancer effects: Methotrexate is one of the main anti-tumor drugs and is used to treat various types of cancer including leukemia, lymphoma, breast cancer, lung cancer and others. It exerts its anti-tumor effects by inhibiting cell division and tumor growth.
5. Disease remission: In some cases, methotrexate can help achieve long-term remission in patients with cancer or autoimmune diseases.
6. Antiproliferative effect: Methotrexate may have antiproliferative effect by inhibiting cell division and cell growth.

Pharmacokinetics

1. Absorption: Methotrexate is usually well and rapidly absorbed from the gastrointestinal tract after oral administration. Food may affect the rate and extent of its absorption.
2. Distribution: Methotrexate has a large volume of distribution and can penetrate the blood-brain barrier. It also penetrates into breast milk.
3. Metabolism: Methotrexate is not metabolized in the liver and is excreted by the kidneys almost unchanged. However, hydroxylation and glucuronidation may occur in small amounts.
4. Excretion: The main route of excretion of methotrexate from the body is through the kidneys. It is excreted almost completely unchanged.
5. Half-life: The half-life of methotrexate may vary depending on dose and patient, but is usually about 3-10 hours in adults and about 2-5 hours in children.
6. Mechanism of action: Methotrexate inhibits dihydrofolate reductase, which leads to impaired synthesis of tetrahydrofolic acid, which is necessary for nucleic acid synthesis. This leads to impaired cell division and reduced cell growth, making it an effective antitumor agent.

Dosing and administration

Methotrexate in tablets

• Rheumatoid arthritis: The standard starting dose is 7.5 mg once weekly, which can be gradually increased depending on the response to treatment. The maximum recommended dose is 20-25 mg per week.
• Psoriasis: Initial dose is usually 10-25 mg once weekly, with possible subsequent dose adjustments.

Methotrexate in the form of injections

• The dosage and route of administration for injections can vary considerably depending on the therapeutic indication. Injections can be subcutaneous, intramuscular, intravenous or even intrathecal (into the cerebrospinal fluid) depending on the disease.
• Cancer: Dosage for cancer treatment is usually much higher than for autoimmune diseases and requires precise medical monitoring.

Important notes

• Methotrexate is taken strictly once a week to treat autoimmune diseases, which is important not to be confused with taking it daily to avoid overdose.
• During treatment with methotrexate, doctors recommend regular blood tests to monitor the function of the liver, kidneys, and hematopoietic system.
• It is important to discuss with your doctor the possible side effects and precautions for using methotrexate, including effects on fertility and potential risks to pregnant women.
• Avoid drinking alcohol during treatment with methotrexate as it may increase the risk of liver damage.

Use Methotrexate during pregnancy

The use of methotrexate during pregnancy may pose serious risks to fetal development.

Methotrexate can cause toxic effects on the fetus, such as congenital anomalies and premature birth, especially when used early in pregnancy. Therefore, methotrexate is considered Category X by the FDA (Food and Drug Administration) for use during pregnancy, which means that its use during pregnancy is strongly contraindicated.

Contraindications

1. Pregnancy and breastfeeding: Methotrexate may cause harm to the fetus and may lead to miscarriage, malformations and other dangerous effects on the fetus. It is therefore contraindicated during pregnancy and breastfeeding.
2. Active infection: In the presence of active infection, methotrexate may worsen the course of the infection due to its immunosuppressive effect.
3. Serious liverand kidneydisorders: In patients with serious liver or kidney disease, methotrexate may accumulate in the body, which may lead to toxic effects. Therefore, its use should be cautious or even contraindicated in such cases.
4. Alcoholism: In people with alcohol dependence, the use of methotrexate may increase the toxic effects on the liver.
5. Contraception: Patients using methotrexate should use effective contraceptive methods, as it can cause fetal harm if a woman becomes pregnant while taking the drug.
6. Hypersensitivity to methotrexate: People with known hypersensitivity to methotrexate or other components of the drug should also avoid its use.
7. Hematopoietic disorders: Methotrexate may decrease the number of platelets and white blood cells, which may lead to an increased risk of bleeding and infections.

Side effects Methotrexate

1. Gastrointestinal disorders: This may include nausea, vomiting, diarrhea, anorexia (loss of appetite), stomach pain, or mouth ulcers.
2. Decreased blood cell count: Methotrexate may decrease the number of whiteblood cells (leukopenia), red blood cells (anemia), and platelets (thrombocytopenia), which may increase the risk of infections, anemia, and bleeding.
3. Hypersensitivity to sunlight: Some patients may experience hypersensitivity to the sun or photosensitivity, which may cause sunburns or skin rashes upon exposure to sunlight.
4. Increased levels of liver enzymes: Methotrexate may cause an increase in AST and ALT levels indicating liver damage.
5. Mucositis: This is inflammation of the mucous membranes of the mouth, throat, or stomach that can lead to pain and difficulty swallowing.
6. Pneumonitis: A rare but serious side effect characterized by inflammation of the lungs and manifested by coughing, difficulty breathing, and chest pain.
7. Hair: Some patients may experience hair loss or changes in hair texture.
8. Decreased immune system function: This can increase the risk of infections.
9. Hepatotoxicity: Methotrexate may cause liver damage.
10. Nephrotoxicity: Rarely, methotrexate can cause kidney damage.

Overdose

1. Toxic effect on bone marrow: Methotrexate inhibits cell division and growth, including bone marrow cells, which may lead to hematological disorders such as severe aplastic anemia, leukopenia and thrombocytopenia.
2. Gastrointestinal symptoms: Include nausea, vomiting, diarrhea, anorexia, abdominal pain, and other gastrointestinal disorders.
3. Renal failure: In severe overdose of methotrexate, acute or chronic renal failure may develop due to toxic effects on the kidneys.
4. Hepatotoxic effects: Overdose may cause liver damage and dysfunction, which may manifest as elevated liver enzymes, jaundice, and other signs of liver failure.
5. Central Nervous System (CNS) Symptoms: Includes headache, drowsiness, insomnia, confusion, seizures, and other symptoms of neurological disorders.
6. Other organs and systems: The lungs, heart, blood vessels, and other organs may also be affected, which can lead to acute or chronic complications.

Interactions with other drugs

1. NSAIDs (non-steroidal anti-inflammatory drugs): The use of NSAIDs in combination with methotrexate may increase its toxicity, especially in relation to the liver and kidneys. In addition, NSAIDs may reduce renal tubular filtration, which may lead to accumulation of methotrexate in the body and increase its undesirable effects.
2. Drugsaffecting renal function: The use of drugs that reduce renal function (e.g. Some antibiotics, diuretics and anti-inflammatory drugs) may increase the blood concentration of methotrexate and increase its toxicity.
3. Anticancer drugs: Methotrexate may increase the toxicity of other anticancer drugs, especially when used concomitantly in high doses.
4. Antirheumatic drugs: The use of methotrexate in combination with other antirheumatic drugs (e.g., leflunomide, hydroxychloroquine, sulfasalazine) may enhance its therapeutic effect in the treatment of rheumatoid arthritis and other inflammatory diseases.
5. Bleeding-enhancing drugs: Use of methotrexate with bleeding-enhancing drugs (e.g., acetylsalicylic acid) may increase the risk of bleeding.
6. Antibiotics and antifungals: Some antibiotics and antifungals may increase the toxicity of methotrexate by decreasing its metabolism in the liver.

Storage conditions

1. Temperature: It is generally recommended to store methotrexate at controlled room temperature, which is 20 to 25 degrees Celsius. Temporary storage at 15 to 30 degrees Celsius (59 to 86 degrees Fahrenheit) is sometimes allowed.
2. Light: The drug should be stored in a dark place protected from direct sunlight. Light may degrade the active ingredients of the drug.
3. Packaging: Store methotrexate in its original container to protect it from moisture and light. Close the container tightly after use.
4. Children: Be sure to keep methotrexate out of the reach of children to prevent accidental use.
5. Special conditions: In some cases, there may be additional storage recommendations on the package or in the drug instructions. Please refer to these recommendations for more precise information.