Methotrexate. Pharm D student: Noha Alaa El Dine Alexandria University Hospitals Supervised by: Prof. Nashaat Lotfy Professor of Oncology Faculty of Medicine. Mechanism of action. MTX is an antifolate belonging to the antimetabolite class of antineoplastic agents.
Pharm D student: Noha Alaa El Dine
Alexandria University Hospitals
Supervised by: Prof. Nashaat Lotfy
Professor of Oncology Faculty of Medicine
MTX is an antifolate belonging to the antimetabolite class of antineoplastic agents.
MTX is a cell cycle specific chemotherapeutic agents that acts on S-phase &
thus inhibit DNA synthesis
THF included at two stages in the biosynthesis of purines (adenine and guanine) and at one stage in the synthesis of pyrimidines (thymine, cytosine, and uracil)
Acute Lymphoid Leukemia
Diffuse Large B-Cell Lymphoma
Gestational Trophoblastic Neoplasm
Juvenile Rheumatoid Arthritis
Locally Advanced Breast Carcinoma
Malignant Tumor of Head and Neck
Metastatic Breast Carcinoma
Small Cell Lung Carcinoma
Acute Myeloid Leukemia
Acute Promyelocytic Leukemia
Malignant Tumor of Cervix
Malignant Tumor of Urinary Bladder
Metastatic Colorectal Cancer
Systemic Lupus Erythematosus
WBCs > 1500/mm3
Platelets > 75,000/mm3
Neutrophils > 200/mm3
SGPT (ALT)<450 U
Normal s. Cr.
Previous mucositis should be healed
& pleural effusions should be drained prior to MTX administration
Reconstitution. Reconstitute lyophilized powder for injection immediately before use with a sterile, preservative-free solution (e.g., 5% dextrose injection, 0.9% sodium chloride injection)
Reconstitute 20 mg vial to a concentration ≤25 mg/mL Reconstitute 1 g vial with 19.4 mL of appropriate solution to yield a concentration of 50 mg/mL.
Dilution. When high doses are administered by IV infusion, dilute total dose of reconstituted solution in 5% dextrose injection.
May further dilute commercially available solution for IV injection containing preservatives with a compatible solution (e.g., 0.9% sodium chloride injection).
Preservative-free solutions may be diluted immediately prior to use with an appropriate sterile, preservative-free solution (e.g., 5% dextrose injection, 0.9% sodium chloride injection)
Dermatologic and Sensitivity Reactions.
Severe, occasionally fatal cutaneous or sensitivity reactions e.g.,
reported in pediatric and adult patients within days of receiving drug at various dosages, by various routes, and for various conditions.
Perform CBCs, including differential and platelet counts, at least weekly in patients with neoplastic disease
If profound leukopenia and fever occur, observe patient closely and initiate broad-spectrum antibiotic therapy if there are signs of infection.
Blood or platelet transfusions may be necessary in patients with severe myelosuppression.
Possible hepatotoxicity; may be acute (increased serum aminotransferase concentrations) or chronic (fibrosis and cirrhosis).
Additive Adverse Drug effect:
Close monitoring of
LFTs & renal function
MTX cause damage of GIT
Reduce absorption of Verapamil & Phenytoin by 20-35% and so loss of therapeutic effect.
MTX may decrease clearance of theophylline
Salicylates & NSAIDs can cause severe, possibly fatal MTX toxicity including hematologic and GI toxicity( HD-MTX) either by competition with MTX for active tubular secretion & delay of elimination or by decreasing renal perfusion (due to inhibition of PG synthesis (PD interaction).
Concomitant use of penicillins (e.g., amoxicillin, carbenicillin) may decrease renal clearance of methotrexate, presumably by inhibiting renal tubular secretion of the drug & thus increase serum concentrations of methotrexate, resulting in GI or hematologic toxicity
NSAIDs should be avoided in patients receiving HD -MTX
However, the precise mechanism of this resistance development has not been established.