Methotrexate

[Drug name] Methotrexate injection

[Common name] Methotrexate injection

[Trade name] Midu

[English name] Methotrexate Injection

[Ingredients] Methotrexate

[Characteristics]

Methotrexate is a clear yellow liquid.

[Indications]

It is effective in acute leukemia, especially acute lymphoblastic leukemia, choriocarcinoma and malignant mole. It has certain effects on head and neck tumors, breast cancer, glossopharyngeal cancer, bladder cancer, testicular tumors, lung cancer and pelvic tumors.

[Packaging specifications]

1000mg/10ml

[Usage and dosage]

1. For the treatment of leukemia, adults usually take 2.5mg to 10mg/day orally, with a total dose of about 50mg to 150mg. Children: 1.5mg~5mg/day.

2. For the treatment of chorioepithelial carcinoma, 10mg~20mg/day, intramuscular injection or oral administration, or intravenous infusion, for 5 to 10 days, the course of treatment is 80mg~100mg.

3. For the treatment of head and neck cancer or gynecological cancer, 10 mg to 20 mg/time is administered through arterial intubation, once a day or every other day, and 7 to 10 times is a course of treatment.

4. For the treatment of general solid tumors and normal liver and kidney function, 30mg to 50mg/time, intravenous injection, once every 5 to 10 days, 5 to 10 times is a course of treatment; it can also be 0.4mg/kg each time, intravenous injection, twice a week.

5. In rescue therapy, vincristine 1mg~2mg/time is injected intravenously. Half an hour later, methotrexate 1g~5g/m2 is administered intravenously for 6 hours. Start intramuscular injection of calcium leucovorin 4 to 6 hours later, 6mg to 12mg (~15mg)/time, and then intramuscularly inject once every 6 hours until 72 hours. Depending on the situation, the medication can be administered once a month.

[Adverse reactions]

1. The main gastrointestinal reactions are stomatitis, lip ulcers, pharyngitis, nausea, vomiting, gastritis and diarrhea.

2. Myelosuppression is mainly manifested by a decrease in white blood cells, which also has a certain impact on platelets. In severe cases, a decrease in whole blood and bleeding in the skin or internal organs may occur.

3. A single application of a large amount can cause an increase in serum alanine aminotransferase (ALT) or drug-induced hepatitis. A small amount of sustained application can cause cirrhosis of the liver.

4. Kidney damage is common at high doses, with hematuria, proteinuria, oliguria, azotemia, uremia, etc.

5. There are also alopecia, dermatitis, pigmentation and drug-induced pneumonia. When the intrathecal or head and neck artery injection dose is too large, symptoms such as headache, back pain, vomiting, fever and convulsions may occur.

6. Use in early pregnancy can cause teratogenesis, and a few patients have delayed menstruation and decreased reproductive function.

[Contraindications]

1. Those who are allergic to a certain component of this drug

2. Severe liver and kidney damage (when serum creatinine is >2 mg%, it is a contraindication. When it is 1.5-2 mg%, the dose is reduced to 25% of the usual amount)

3. Alcoholics

4. Hematopoietic system diseases (bone marrow aplasia, leukemia, etc.) Cytopenia, thrombocytopenia, anemia)

5. Infection

6. Oral and gastrointestinal ulcers

7. Recent surgical wounds

[Notes]

Methotrexate can only be used by doctors with experience in antimetabolite chemotherapy. If it is a non-tumor condition, it must be used by a specialist. Because of the possibility of fatal or serious toxic reactions, patients must be fully informed of the risks and should be administered the medication under their supervision. Possible complications should be managed by appropriate facilities. In cases of large doses or impaired drug excretion (renal impairment, pleural effusion, ascites), drug toxicity must be closely monitored. Deaths have been reported following the use of methotrexate to treat malignancy and psoriasis.

[Pharmacological effects]

Pharmacology

The main mechanism of action of methotrexate is to competitively inhibit folate reductase. During DNA synthesis and cell replication, folic acid must be reduced to tetrahydrofolate by this enzyme. Methotrexate inhibits the reduction of folate and interferes with tissue cell replication. Methotrexate is a cell cycle-specific drug that mainly acts on cells during the DNA synthesis phase. Actively proliferating tissues such as malignant tumor cells, bone marrow, embryonic cells, skin epithelial cells, oral and intestinal mucosa, and bladder cells are generally more sensitive to the effects of methotrexate. Cells in malignant tumor tissue proliferate faster than in most normal tissues, so methotrexate can weaken the growth of malignant tumors without causing irreversible damage to normal tissue. The proliferation ability of skin epithelial cells in psoriasis is much stronger than that in normal skin. This difference in proliferation rates is the basis for the use of methotrexate to control the progression of psoriasis.

Toxicology

In vitro, methotrexate caused chromosomal aberrations in Chinese hamster A(T1)C1-3 cells, induced morphological changes in mouse C3H/10T1/2 clone 8 cells, and was associated with an increase in the tk gene mutation rate of mouse lymphoma cells L5178Y/tk±. In vivo, it causes an increase in the ratio of polychromatic red blood cells in mice and a transient, reversible increase in the number of chromosomal aberrations in human bone marrow cells. The clinical significance of these findings has not yet been established.

Carcinogenicity and Mutagenicity

There are no human data on the tumorigenic risk of methotrexate. Some animal studies evaluating the carcinogenic potential of methotrexate are currently inconclusive. There is evidence that methotrexate causes chromosomal damage in animal somatic cells and human bone marrow cells. Before using methotrexate alone or in combination with other drugs, especially in children and young adults, the benefits should be analyzed against the potential risks. Methotrexate can cause embryotoxicity, miscarriage, and fetal malformations in humans. It has also been reported that methotrexate can cause damage to human fertility, oligospermia, and menstrual irregularities during medication and within a short period of time after discontinuation of medication.