. 2008 May;4(5):337–347.

Table 5.

Methotrexate (MTX) Drug Interactions

Drug	Drug-Drug Interaction	Renal Impairment	Hepatic Impairment
MTX	Acitretin: may enhance hepatotoxic effects Cholestytamine: decreases levels of MTX Cotticostetoids: decrease MTX uptake into leukemic cells Cyclospotine: concomitant administration may increase toxicity of both Hepatotoxic agents: may increase the risk of hepatotoxic reactions (retinoids, sulfasalazine) Metcaptoputine: concomitant administration may increase levels NSAIDs: BM suppression, aplastic anemia, gastrointestinal toxicity with concomitant therapy Penicillins: increase MTX concentrations (due to ↓renal tubular secretion) Ptobenecid: increases MTX concentrations (due to ↓in renal tubular secretion) Salicylates: may increase serum concentration of MTX Sulfonamides: may increase MTX concentrations (due to ↓in renal tubular secretion); may ↓folate levels increasing the risk/severity of BM suppression Tettacyclines: may increase MTX toxicity Theophylline: MTX may increase theophylline levels	Elimination ↓with renal impairment; may require dose reduction/discontinuation CrCl 61–80 mL/minute: reduce dose to 75% CrCl 51–60 mL/minute: reduce dose to 70% CrCl 10–50 mL/minute: reduce dose to 30–50% CrCl <10 mL/minute: avoid use Hemodialysis: Not dialyzable (0–5%)	Use caution with preexisting liver impairment Bilirubin 3.1–5 mg/dL or AST >180 units: administer 75% of dose Bilirubin >5 mg/dL: Do not use