Methotrexate Overview

Methotrexate is a medication commonly used in the treatment of various diseases, including certain types of cancer, rheumatoid arthritis, and psoriasis. It functions as a chemotherapy agent and immune system suppressant.

Mechanism of Action

Methotrexate inhibits the enzyme dihydrofolate reductase, which is involved in the synthesis of nucleotides. This inhibition reduces the production of DNA, RNA, and proteins, impeding cell proliferation. The suppression of rapidly dividing cells is particularly effective against cancer cells and overactive immune cells.

Administration Methods

Methotrexate can be administered orally, intramuscularly, intravenously, or subcutaneously depending on the condition being treated. The form of administration affects the bioavailability and distribution of the drug within the body. Oral administration is common for chronic conditions such as rheumatoid arthritis, while intravenous routes are typically used in oncology.

Dosing Information

Doses of methotrexate vary widely depending on the condition being treated. For cancer, dosages might be significantly higher compared to those used for autoimmune diseases. Dosing schedules can range from daily to weekly administration, and proper dosing requires careful consideration of patient-specific factors, including kidney function and overall health status.

Drug Interactions

Methotrexate has numerous potential drug interactions. Medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), penicillins, and proton pump inhibitors can enhance the toxicity of methotrexate. Concurrent administration of folic acid supplements may be recommended to mitigate side effects without diminishing efficacy.

Pharmacokinetics

After administration, methotrexate is absorbed and distributed throughout the body, reaching high concentrations in tissues such as the liver, kidneys, and bone marrow. It undergoes hepatic and intracellular metabolism. Methotrexate and its metabolites are primarily excreted by the kidneys, and renal function plays a critical role in the drug’s clearance.

Monitoring Parameters

Regular monitoring of liver function tests, renal function, and complete blood counts is essential in patients receiving methotrexate. Baseline tests should be conducted before starting therapy and periodically during treatment to detect potential toxicity and ensure continued safety and efficacy.

Storage Instructions

Methotrexate tablets should be stored at room temperature, away from moisture and direct sunlight. Injectable forms should be stored in a refrigerator and allowed to reach room temperature before administration. Proper storage ensures the medication maintains its stability and effectiveness.

Side Effects

Methotrexate may cause a range of side effects including nausea, stomatitis, hematologic alterations, hepatotoxicity, and pulmonary toxicity. The severity and type of side effects often depend on the dose and duration of treatment.

Contraindications

Methotrexate is contraindicated in patients with severe renal impairment, liver disease, or in those who are pregnant. Due to its teratogenic effects, it is crucial to ensure that patients who are of childbearing potential use effective contraception during treatment.

Formulations Available

Methotrexate is available in various formulations, including tablets, injectable solutions, and prefilled syringes. The choice of formulation is dependent on the indication and the patient’s ability to adhere to the treatment regime.

Therapeutic Uses

Methotrexate is used in treating cancers such as acute lymphoblastic leukemia, non-Hodgkin’s lymphoma, and osteosarcoma. It is also effective in managing autoimmune conditions such as rheumatoid arthritis, systemic lupus erythematosus, and severe psoriasis. Its immunosuppressive properties make it a versatile treatment option.

Drug Mechanisms

Methotrexate blocks folate pathways, essential for nucleotide synthesis, leading to inhibition of cellular reproduction. It predominantly affects high-turnover cells, making it effective in conditions with rapid cell proliferation.

Adverse Drug Reactions

Adverse reactions can range from mild to severe and may include mucosal ulcerations, bone marrow suppression, hepatotoxicity, interstitial pneumonitis, and gastrointestinal disorders. Long-term use requires vigilance for chronic toxicities.

Patient Counseling

Patients should be informed about the importance of adhering to the prescribed dosing schedule and monitoring appointments. Discuss potential side effects and ensure understanding of the need to promptly report any signs of toxicity.

Handling Precautions

Healthcare professionals should use protective gloves when handling methotrexate, particularly the injectable forms. Proper disposal of waste materials and contaminated sharps is necessary to avoid exposure and environmental contamination.

Special Populations

Methotrexate dosing may require adjustment in elderly patients due to altered pharmacokinetics and increased susceptibility to toxicity. Pediatric use also needs careful consideration of weight-based dosing and monitoring for long-term impacts on growth and development.

Laboratory Tests

Before initiating methotrexate, baseline tests including CBC, liver function tests, and renal function tests are mandatory. Periodic monitoring helps in early detection of potential adverse effects and adjustments in therapy.

Dose Adjustment

Dose adjustments may be required based on clinical response, tolerance, and changes in renal or hepatic function. Lower doses may be necessary in cases of renal impairment to prevent accumulation and toxicity.