1. Antimetabolite drug Inhibits dihydrofolate reductase
Methotrexate
Antimetabolite drug
Inhibits dihydrofolate reductase

2. Major
Hepatic
Pulmonary
Bone Marrow
Renal
Neuro

3. 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

4. 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

5. Pulmonary Chronic pulmonary fibrosis
Acute hypersensivity pneumonitis initial symptoms–non productive cough usually reversible not dose related

6. Nephrotoxicity Usually with high dose
Kidney damage due to MTX crystals and tubular injury
Monitor serum creatinine periodically
Reduce methotrexate dose in renal insufficiency.

7. Neuro Usually occurs with Intrathecal/very high doses Arachnoiditis
Demyelinating encephalopathy

8. 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

9. 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