Drug Index

Methotrexate

 
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Mechanism :

Methotrexate is an antimetabolite used in the treatment of certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis. Methotrexate 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 nucleotides and thymidylate. Therefore, methotrexate interferes with DNA synthesis, repair, and cellular replication.


Indication :

• Solid tumours

• Non-Hodgkin’s lymphoma

• Brain tumours

• Leukemia

• Juvenile idiopathic arthritis

• Dermatomyositis

• Vasculitis

• Uveitis


Contraindications :

Contraindicated in patients with psoriasis or rheumatoid arthritis with alcoholism, alcoholic liver disease or other chronic liver disease, who have overt or laboratory evidence of immunodeficiency syndromes, who have pre-existing blood dyscrasias, such as bone marrow hypoplasia, leukopenia, thrombocytopenia or significant anemia, and in patients with a known hypersensitivity to methotrexate. Folinic acid should be given along with it to prevent megaloblastic anemia.


Dosing :

ALL:

Induction: 3.3 mg/sqm PO/IM/IV every day.

Maintenance: 15 mg/sqm PO/IM twice a week. Alternately can give 2.5 mg/kg IV on day 1 of 14-day cycle.

CNS leukemia:

<1 year: 6 mg intrathecally every 2-5 days.

1 year: 8 mg intrathecally every 2-5 days.

2 years: 10 mg intrathecally every 2-5 days.

3 years and older: 12 mg intrathecally every 2-5 days.

Juvenile idiopathic arthritis:

2-16 years: 10-15 mg/sqm PO/IM every week. Max: 25 mg/week. Give with folic acid 1 mg OD or leucovorin 5 mg every week.


Adverse Effect :

Nausea and abdominal distress, ulcerative stomatitis, leukopenia, arachnoiditis with intrathecal administration, glossitis, gingivitis, ulcerative stomatitis, anorexia, diarrhoea, thrombocytopenia, malaise and fatigue, chills and fever and decreasing resistance to infection, azotemia, nephropathy, hepatotoxicity, osteopenia.


Interaction :

NSAIDs: Reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal toxicity.
Salicylates, phenylbutazone, phenytoin, and sulfonamides: Toxicity may be increased because of displacement by certain drugs.
Tetracycline, chloramphenicol, and nonabsorbable broad spectrum antibiotics: May decrease intestinal absorption of methotrexate or interfere with the enterohepatic circulation.
Penicillins: May reduce the renal clearance of methotrexate; increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed.
Theophylline: Methotrexate may decrease the clearance of theophylline.
Folic acid or its derivatives: May decrease responses to systemically administered methotrexate.


07/19/2019 04:03:31 Methotrexate
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