Antimetabolite drug Inhibits dihydrofolate reductase Methotrexate Antimetabolite drug Inhibits dihydrofolate reductase www.ppttopics.com
Major Hepatic Pulmonary Bone Marrow Renal Neuro www.ppttopics.com
Hepatotoxicity Hepatitis/Cirrhosis – long term use Screen for Hep B & Hep C Periodic monitoring of AST, ALT & albumin (every 4- 8 weeks) Diabetes, obesity, renal disease, alcohol consumption increases risk www.ppttopics.com
Myelosuppresion Major dose limiting side effect Pancytopenia/ macrocytic red blood cells Use cautiously with other folate antagonist like Trimethoprim-sulfamethoxazole. Check blood counts before initiation monthly during first 3-4 months then every six-eight weeks www.ppttopics.com
Pulmonary Chronic pulmonary fibrosis Acute hypersensivity pneumonitis initial symptoms–non productive cough usually reversible not dose related www.ppttopics.com
Nephrotoxicity Usually with high dose Kidney damage due to MTX crystals and tubular injury Monitor serum creatinine periodically Reduce methotrexate dose in renal insufficiency. www.ppttopics.com
Neuro Usually occurs with Intrathecal/very high doses Arachnoiditis Demyelinating encephalopathy www.ppttopics.com
Minor side effects GI –Nausea, vomiting, diarrhea, ulcerative stomatitis, mucositis (dose limiting side effect) Rash- macular punctate rash on extremities and spares the trunk CNS – headache, fatigue, or impaired ability to concentrate Alopecia Fever www.ppttopics.com
Others: Lymphoproliferative malignancies may develop after long term therapy, usually B- Cell origin Nodulosis – exacerbate rheumatoid nodule formation despite effective suppression of synovial inflammation Pregnancy - abortifacient www.ppttopics.com