Methotrexate
Brand Name: Trexall
Generic Available
Common Dosage Forms:
Tablets: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg
Injection: 25 mg/mL base (as sodium salt)
FDA Indications/Dosages:
Treatment of gestational choriocarcinoma, chorioadenoma, chorioadenoma destruens, and hydatidiform mole: 15-30 mg daily, either orally or intramuscularly, for a five-day course. Such courses are repeated for 3-5 times as required, with rest periods of 1 or more weeks interposed between courses.
Treatment of advanced stage non-Hodgkin's lymphomas: 10-25 mg/day orally for 4-8 days. Several courses are usually given with 7–10-day rest periods between each course.
Treatment of breast cancer, epidermoid cancers of the head and neck, advanced mycosis fungoides (cutaneous T-cell lymphomas), non-metastatic osteosarcoma, and lung cancer: Methotrexate can be used alone or in combination with other anticancer agents. Treatments are variable and depend on multiple factors, including the stage of the disease and whether a combination treatment is being used.
Treatment and prophylaxis of meningeal leukemia: Doses are based on age and must be given intrathecally using preservative-free forms of the drug. Doses are given at intervals of 2-5 days. For children <1 year, give 6 mg. For children 1 year old, give 8 mg. For children 2 years old, give 10 mg. For children 3 years and older, give 12 mg.
Symptomatic control of severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy:
Weekly Schedule: 10-25 mg per week until adequate response is achieved.
Divided Oral Dose Schedule: 2.5 mg at 12-hour intervals for three doses.
For the management of severe, acute rheumatoid arthritis in adults: 7.5 mg weekly as one dose or in three 2.5 mg doses given at 12-hour intervals. Maximum weekly dose is 20 mg.
For the management of active polyarticular-course juvenile rheumatoid arthritis in children who have had an insufficient therapeutic response to first-line therapy: Start with 10 mg/m^2 given once weekly with a maximum weekly dose of 30 mg/m^2. Doses over 20 mg/m^2 should be given either intramuscularly or subcutaneously.
Monitor: CBC, SCr, LFT, chest radiograph
Pharmacology/Pharmacokinetics: Methotrexate inhibits dihydrofolic acid reductase, an enzyme which reduces dihydrofolate tetrahydrofolate. Tetrahydrofolate are important in the synthesis of purine nucleotides and thymidylate. Therefore, methotrexate interferes with DNA synthesis, repair, and cellular replication. Actively proliferating tissues are more sensitive to this effect. Its mechanism of action in the treatment of rheumatoid arthritis is unknown. Doses in the therapeutic range are well absorbed orally with peak plasma levels reached in 1-2 hours. Food delays absorption and reduces peak concentrations. Its terminal half-life is 3-10 hours for lower doses and 15 hours for higher doses. Excretion occurs via renal glomerular filtration and active tubular secretion.
Drug Interactions: NSAIDs may increase methotrexate serum levels and should not be used during high-dose therapy. Phenytoin and sulfonamides may displace protein-bound methotrexate. May increase the plasma levels of mercaptopurine. Oral antibiotics may decrease absorption of oral methotrexate. Penicillin may reduce the renal clearance of methotrexate. May decrease the clearance of theophylline.
Contraindications/Precautions: BECAUSE OF THE POSSIBILITY OF SERIOUS TOXICITY REACTIONS (WHICH CAN BE FATAL), METHOTREXATE SHOULD ONLY BE USED IN LIFE-THREATENING NEOPLASTIC DISEASES, OR IN PATIENTS WITH PSORIASIS OR RHEUMATOID ARTHRITIS WITH SEVERE, RECALCITRANT, DISABLING DISEASES WHICH IS NOT ADEQUATELY RESPONSIVE TO OTHER FORMS OF THERAPY. Use is contraindicated in pregnant women except in neoplastic cases where the potential benefit to the patient outweighs the risk to the fetus. Pregnancy should be avoided if either partner is receiving methotrexate and for three months after discontinuing the drug for male patients and for one ovulatory cycle for female patients. Do not use in nursing mothers. Do not use in psoriasis or rheumatoid arthritis patients with alcoholism, alcoholic liver disease, other chronic liver diseases, immunodeficiency syndromes, or preexisting blood dyscrasias. Patients undergoing methotrexate therapy should be closely monitored on a monthly basis including a baseline assessment of complete blood count, hepatic enzymes, renal function tests, and a chest X-ray. For chronic use indications (psoriasis, arthritis), a liver biopsy should be performed pretreatment, at 4-8 weeks, and when cumulative dose reaches 1.5 gram. Use with caution during infections and in immunocompromised patients. Pregnancy Category X.
Adverse Effects: The most frequent adverse effects are ulcerative stomatitis, leukopenia, nausea, and abdominal distress. Other frequent adverse effects are malaise, fatigue, chills and fever, dizziness, sun sensitivity, and decreased resistance to infection. Potentially serious effects include rash, nephrotoxicity, hepatotoxicity, cough, and anemia.
Patient Consultation:
Preferably taken on an empty stomach.
It is important to keep well-hydrated while taking this medication.
Avoid alcohol and salicylates while taking this medication.
Avoid prolonged exposure to natural or artificial sunlight.
It is important to follow appropriate contraceptive measures during therapy and for 3 months (males) and one ovulatory cycle (females) after completing therapy.
If a dose is missed, and you are on a weekly dosing schedule, take the dose as soon as possible and restart your weekly schedule from that date.
If a dose is missed and you are on a daily schedule, contact your physician.
It is important to have periodic blood work completed during therapy.
Contact your physician if any of the frequent adverse effects (listed above) are persistent or troublesome.
Contact your physician if you experience any of the following: diarrhea, vomiting, abdominal pain, black stools, jaundice, unexplained muscle pain, any type of infection, sore throat, cough, dyspnea, hypoxemia, or any type of unknown skin reaction.
