| Recommended Dose and Dosage Regimen | The recommended dose of methotrexate varies depending on the indication and individual patient factors. For the treatment of rheumatoid arthritis (RA) in adults, the initial dose typically ranges from 7.5 to 15 mg orally once weekly, with gradual dose escalation based on response and tolerability. For psoriasis, the initial dose may range from 10 to 25 mg orally once weekly. Higher doses of methotrexate may be used for certain malignancies or autoimmune conditions. Follow your healthcare provider’s instructions regarding dosing and administration. |
| Frequency of Administration | Methotrexate is usually administered once weekly for most indications, although dosing frequency may vary depending on the specific condition being treated and individual patient response. |
| Route of Administration | Methotrexate is available for oral or parenteral administration, including oral tablets, subcutaneous injections, or intramuscular injections. |
| Mechanism of Action (MOA) | Methotrexate is an antimetabolite and antifolate agent that inhibits dihydrofolate reductase (DHFR), leading to impaired folate metabolism and disruption of DNA synthesis, repair, and cellular replication. Methotrexate also exerts anti-inflammatory and immunosuppressive effects by inhibiting purine and pyrimidine synthesis, suppressing T-cell activation and proliferation, and modulating cytokine production. |
| Pharmacokinetics (PK) | Methotrexate is well absorbed after oral administration, with peak plasma concentrations reached within 1-2 hours. It undergoes hepatic metabolism and is excreted primarily in the urine, with a terminal elimination half-life of approximately 3-10 hours. Methotrexate exhibits dose-dependent pharmacokinetics, with higher doses resulting in nonlinear elimination kinetics. The pharmacokinetics of methotrexate may be altered in patients with hepatic impairment, renal impairment, or concomitant use of other medications that affect its metabolism or elimination. |
| Pharmacodynamics (PD) | Methotrexate exerts its pharmacodynamic effects by inhibiting folate metabolism, interfering with DNA synthesis and cellular proliferation, and modulating immune responses. In rheumatoid arthritis, methotrexate suppresses inflammation by reducing cytokine production, inhibiting leukocyte migration, and attenuating synovial hyperplasia and joint destruction. In psoriasis, methotrexate inhibits keratinocyte proliferation and suppresses cutaneous inflammation. In cancer chemotherapy, methotrexate targets rapidly dividing cancer cells and inhibits tumor growth. |
| Pathophysiology | Methotrexate is indicated for the treatment of various inflammatory and autoimmune conditions, including rheumatoid arthritis, psoriasis, psoriatic arthritis, juvenile idiopathic arthritis, and certain neoplastic diseases such as leukemia, lymphoma, and trophoblastic tumors. Methotrexate is also used as a disease-modifying antirheumatic drug (DMARD) in the management of rheumatoid arthritis to reduce disease activity, improve functional status, and prevent joint damage. |
| Primary Indications | Rheumatoid arthritis, psoriasis, psoriatic arthritis, juvenile idiopathic arthritis, certain neoplastic diseases (e.g., leukemia, lymphoma, trophoblastic tumors). |
| Contraindications | Contraindications to methotrexate use include hypersensitivity to methotrexate or any component of the formulation, severe liver disease, severe renal impairment, active infections, pregnancy, breastfeeding, and immunodeficiency. Methotrexate should not be used concomitantly with hepatotoxic drugs or in patients with preexisting hematologic or gastrointestinal disorders. Use caution in patients with hepatic, renal, pulmonary, hematologic, or metabolic disorders, as well as in patients with a history of alcoholism, peptic ulcer disease, or compromised immune function. |
| Purpose of Taking Medication | The purpose of methotrexate therapy is to suppress inflammation, modulate immune responses, and inhibit cellular proliferation in various inflammatory and autoimmune conditions, including rheumatoid arthritis, psoriasis, and certain neoplastic diseases. Methotrexate is used to reduce disease activity, alleviate symptoms, improve functional status, and prevent complications associated with chronic inflammatory disorders or malignancies. |
| Usage Instructions | Take methotrexate orally as directed by your healthcare provider, usually once weekly with or without food. Methotrexate tablets should be swallowed whole with a full glass of water; do not crush, chew, or split the tablets. For subcutaneous or intramuscular injections, follow proper injection techniques and rotate injection sites to minimize irritation or adverse effects. |
| Precautions and Care | Patients taking methotrexate should be closely monitored for signs of adverse effects, including hepatotoxicity, myelosuppression, gastrointestinal toxicity, pulmonary toxicity, and renal dysfunction. Regular monitoring of liver function tests, complete blood count, and renal function is recommended during methotrexate therapy to assess treatment response and detect potential complications. Use caution when prescribing methotrexate in elderly patients or those with comorbidities, and consider dose adjustments based on individual patient factors and tolerability. |
| Dietary Considerations | There are no specific dietary restrictions associated with methotrexate use, although alcohol consumption should be limited or avoided due to the risk of hepatotoxicity and potential drug interactions. Maintain a balanced diet and adequate hydration to support overall health and well-being during methotrexate therapy. |
| Missed Dose | If a dose of methotrexate is missed, take it as soon as remembered, unless it is almost time for the next scheduled dose. Do not double the dose to make up for a missed one. Resume the regular dosing schedule and consult your healthcare provider if unsure about missed doses or medication instructions. |
| Possible Side Effects | Common side effects of methotrexate may include nausea, vomiting, diarrhea, abdominal discomfort, stomatitis, fatigue, headache, dizziness, hair loss, and skin rash. Serious adverse effects may include hepatotoxicity, myelosuppression, interstitial lung disease, renal dysfunction, and increased risk of infections or malignancies. Contact your healthcare provider if you experience severe or persistent side effects while taking methotrexate. |
| Storage and Disposal | Store methotrexate tablets at room temperature away from moisture and heat. Keep the medication out of reach of children and pets. Unused or expired medication should be disposed of properly according to local regulations or guidelines for pharmaceutical waste disposal. |
| Overdose or Emergency | In case of methotrexate overdose or emergency, seek immediate medical attention or contact a poison control center. Overdose may lead to severe toxicity, including bone marrow suppression, hepatotoxicity, renal failure, and gastrointestinal toxicity. Treatment of methotrexate overdose may involve supportive care, activated charcoal, folinic acid rescue, and appropriate management of complications. Hemodialysis may be necessary to remove methotrexate from the bloodstream in severe cases of overdose or toxicity. |
| Monitoring and Laboratory Tests | Patients receiving methotrexate therapy require regular monitoring of liver function tests (alanine transaminase, aspartate transaminase), complete blood count (including platelet count), renal function tests (serum creatinine, blood urea nitrogen), and pulmonary function tests, particularly during the initial phase of treatment and dose adjustments. Additional monitoring parameters may include serum methotrexate levels, folate levels, and assessments of disease activity or treatment response, depending on the indication for methotrexate therapy. |
