Indications of Methotrax 15 mg

Neoplastic Diseases: Treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole In acute lymphoblastic leukemia Used in combination with other chemotherapeutic agents in the treatment of advanced stage non-Hodgkin’s lymphomas ... Read moreNeoplastic Diseases: Treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole In acute lymphoblastic leukemia Used in combination with other chemotherapeutic agents in the treatment of advanced stage non-Hodgkin’s lymphomas Treatment of breast cancer, epidermoid cancers of the head and neck, advanced mycosis fungoides (cutaneous T-cell lymphoma) and lung cancer, particularly squamous cell and small cell types. Rheumatoid Arthritis including Polyarticular-Course Juvenile Rheumatoid Arthritis: Indicated in the management of selected adults with severe, active rheumatoid arthritis, or children with active polyarticular-course juvenile rheumatoid arthritis, who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full dose non-steroidal anti-inflammatory agents (NSAIDs)Psoriasis: Indicated in the symptomatic control of severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy.

Theropeutic Class

Antidote preparations, Immunosuppressant

Pharmacology

Methotrax 15 mg inhibits dihydrofolic acid reductase. Dihydrofolates must be reduced to tetrahydrofolates by this enzyme before they can be utilized as carriers of one-carbon groups in the synthesis of p.r.n. nucleotides and thymidylate. Therefore, Methotrax 15 mg interferes with DNA synthesis, repair, and cellular replication. Actively proliferating tissues such as malignant cells, bone marrow, fetal cells, buccal and intestinal mucosa, and cells of the urinary bladder are in general more sensitive to this effect of Methotrax 15 mg. When cellular proliferation in malignant tissues is greater than in most normal tissues, Methotrax 15 mg may impair malignant growth without irreversible damage to normal tissues

Dosage of Methotrax 15 mg

Neoplastic Diseases-Choriocarcinoma and similar trophoblastic diseases: Orally or intramuscularly in doses of 15 to 30 mg daily for a five-day course. The courses are usually repeated for 3 to 5 times as required, with rest periods of one or more weeks interposed between courses, until any manifesting toxic symptoms subside. Since hydatidiform mole may precede choriocarcinoma, prophylactic chemotherapy with Methotrax 15 mg has been recommended. Chorioadenoma destruens is considered to be an invasive form of hydatidiform mole. Methotrax 15 mg is administered in these disease states in doses similar to those recommended for choriocarcinomaAcute Lymphoblastic Leukemia Induction dose: 3.3 mg/m2 in combination with prednisone 60 mg/m2 daily for 4 to 6 weeks Maintenance dose: Orally or IM administration 2 times a week in total weekly doses of 30 mg/m2 Alternate maintenance dose: 2.5 mg/kg IV every 14 days. If and when relapse does occur, reinduction of remission can again usually be obtained by repeating the initial induction regimen Lymphoma Burkitt's tumor Stages I to II: 10 to 25 mg once a day for 4 to 8 days Burkitt's tumor Stage III: Methotrax 15 mg is commonly given concomitantly with other antitumor agents Duration of therapy: All stages usually require several courses of therapy interposed with 7 to 10 day rest periods Lymphosarcoma Stage III: 0.625 to 2.5 mg/kg daily as a part of combination chemotherapy Mycosis Fungoides: Early stage dosing: 5 to 50 mg once a week; alternatively, 15 to 37.5 mg 2 times a week may be used in patients who have responded poorly to weekly therapyBreast Cancer: 40 mg/m 2 intravenously on the 1 st and 8 th day every 4 weeks in combination with cyclophosphamide and fluoracil for 6-12 cyclesHead and Neck Cancer: 40 mg/m2 IV weekly until disease progression or unacceptable toxicity (3 weeks equals one cycle; goal is to complete at least six cycles).Adult Rheumatoid Arthritis: Single doses of 7.5 mg once per week, Maximum dose: 20 mg/week in adults Polyarticular-Course Juvenile Rheumatoid Arthritis: 10 mg/m2 once weeklyPsoriasis: Single dose: 10 to 25 mg once per week, maximum dose: 30 mg/week

Administration of Methotrax 15 mg

Should be taken on an empty stomach. Best taken on an empty stomach. May be taken with meals to reduce GI discomfort. Avoid taking with milk-rich products.

Interaction of Methotrax 15 mg

NSAIDs: Should not be administered prior to or concomitantly with high doses of Methotrax 15 mg, such as used in the treatment of osteosarcoma Salicylates, Phenylbutazone, Phenytoin and Sulfonamides: Toxicity may be increased Penicillin, Theophylline, Probenecid, Azathioprine, Retinoids, Sulfasalazine: Should be closely monitored for possible increased risk of hepatotoxicity Cisplatin: Caution must be exercised if high-dose Methotrax 15 mg is administered in combination Mercaptopurine: Methotrax 15 mg increases the plasma levels of mercaptopurine Tetracycline, Chloramphenicol and Nonabsorbable Broad Spectrum Antibiotics: May decrease intestinal absorption of Methotrax 15 mg Vitamin preparations containing folic acid or its derivatives: Decreases responses to systemically administered Methotrax 15 mg Trimethoprim/Sulfamethoxazole: Rarely increases bone marrow suppression

Contraindications

Alcoholism, alcoholic liver disease or other chronic liver disease Immunodeficiency syndromes Pre-existing blood dyscrasias, such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia Hypersensitivity to Methotrax 15 mg Pregnant women with psoriasis or rheumatoid arthritis Women of childbearing potential Nursing mothers Pregnancy should be avoided if either partner is receiving Methotrax 15 mg; during and for a minimum of three months after therapy for male patients, and during and for at least one ovulatory cycle after therapy for female patients

Side Effects of Methotrax 15 mg

The most frequently reported adverse reactions include ulcerative stomatitis, leukopenia, nausea and abdominal distress Other frequently reported adverse effects are malaise, undue fatigue, chills and fever, dizziness and decreased resistance to infection Methotrax 15 mg has been reported to cause impairment of fertility, oligospermia and menstrual dysfunction in humans, during and for a short period after cessation of therapy

Pregnancy and Lactation

Pregnancy category X. Studies in animals or human beings have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

Precautions and Warnings

Methotrax 15 mg formulations and diluents containing preservatives must not be used for intrathecal or high dose Methotrax 15 mg therapy It is necessary to follow patients on Methotrax 15 mg closely for toxic effects If adverse reactions occur, the drug should be reduced in dosage or discontinued and appropriate corrective measures should be taken. If necessary, this could include the use of leucovorin calcium If Methotrax 15 mg therapy is reinstituted, it should be carried out with caution, with adequate consideration of further need for the drug and increased alertness as to possible recurrence of toxicity Persistent liver function test abnormalities, and/or depression of serum albumin may be indicators of serious liver toxicity and require evaluation Folate deficiency: May increase Methotrax 15 mg toxicity

Overdose Effects of Methotrax 15 mg

Leucovorin is indicated to diminish the toxicity and counteract the effect of inadvertently administered overdosages of Methotrax 15 mg and its administration should begin as promptly as possible.

Storage Conditions

Store at a temperature not exceeding 30°C in a dry place. Protect from light and moisture.

Reconstitution

Intramuscular: Dilute powder with D5W or normal saline to a concentration ≤25 mg/ml (20 mg and 50 mg vials) and 50 mg/ml (1 g vial).Intrathecal: Reconstitute to 2.5-5 mg/ml with normal saline, D5W, lactated Ringer's, or Elliott's B solution. Use preservative-free preparations.Intravenous: Dilute powder with D5W or normal saline to a concentration ≤25 mg/ml (20 mg and 50 mg vials) and 50 mg/ml (1 g vial).Parenteral: Dilute powder with D5W or normal saline to a concentration ≤25 mg/ml (20 mg and 50 mg vials) and 50 mg/ml (1 g vial).

Drug Classes

Antidote preparations, Immunosuppressant

Mode Of Action

Methotrax 15 mg inhibits dihydrofolic acid reductase. Dihydrofolates must be reduced to tetrahydrofolates by thisenzyme before they can be utilized as carriers of one-carbon groups in the synthesis of purine nucleotides and thymidylate. Therefore, Methotrax 15 mg interferes with DNA synthesis, repair, and cellular replication. Actively proliferating tissues such as malignant cells, bone marrow, fetal cells, buccal and intestinal mucosa, and cells of the urinary bladder are in general more sensitive to this effect of Methotrax 15 mg. When cellular proliferation in malignant tissues is greater than in most normal tissues, Methotrax 15 mg may impair malignant growth without irreversible damage to normal tissues. In psoriasis, the rate of production of epithelial cells in the skin is greatly increased over normal skin. This difference in proliferation rates is the basis for the use of Methotrax 15 mg to control the psoriatic process.

Pregnancy

US FDA Pregnancy Category X. Methotrax 15 mg should be used in the treatment of neoplastic diseases only when the potential benefit outweighs the risk to the fetus. It is contraindicated in nursing mothers.

Pediatric Uses

Pediatric patients: Benefits should be weighed against the potential risk before using Methotrax 15 mg alone or in combination with other drugs, especially in pediatric patients or young adults.Geriatric patients: Elderly patients should be closely monitored for early signs of hepatic, bone marrow and renal toxicity.

Disclaimer

The information provided is accurate to our best practices, but it does not replace professional medical advice. We cannot guarantee its completeness or accuracy. The absence of specific information about a drug should not be seen as an endorsement. We are not responsible for any consequences resulting from this information, so consult a healthcare professional for any concerns or questions.