General Toxicity Notes
Myelosuppressive and may aggravate uremic predisposition to hemorrhage and infection.
Excreted Unchanged %
80-90
Half-Life (Normalesrd) Hours
8-12/Increased
Plasma Protein Binding %
45-50
Volume Of Distribution L/Kg
0.76
Dose For Normal Renal Function
5-10 mg/wk (rheumatoid arthritis) 15 mg/d to 12 g/m2 (cancer)
Adjustment For Renal Failure Method
D
Adjustment For Renal Failure Gfr, Ml/Min >50 [Recommended Level]
100% [A]
Adjustment For Renal Failure Gfr, Ml/Min 10-50 [Recommended Level]
50% [A]
Adjustment For Renal Failure Gfr, Ml/Min <10 [Recommended Level]
Avoid [A]
Supplement For Dialysis [Recommendation Level]: Ihd
IHD: Give dose, [B]
Supplement For Dialysis [Recommendation Level]: Pd
PD: None, [D]
Supplement For Dialysis [Recommendation Level]: Crrt
CRRT: Dose for GFR 10-50, [A]
References
Jambou P, Levraut J, Favier C, Ichai C, Milano G, Grimaud D. Removal of methotrexate by continuous venovenous hemodiafiltration. Contrib Nephrol. 1995; 116: 48-52. [PMID: 8529381] / Jolivet J, Cowan KH, Curt GA, Clendeninn NJ, Chabner BA. The pharmacology and clinical use of methotrexate. N Engl J Med. 1983; 309: 1094-104. [PMID: 6353235] / Kepka L, De Lassence A, Ribrag V, Gachot B, Blot F, Theodore C, et al. Successful rescue in a patient with high dose methotrexate-induced nephrotoxicity and acute renal failure. Leuk Lymphoma. 1998; 29: 205-9. [PMID: 9638991] / Montagne N, Milano G, Caldani C, Bracco J, Ayela P, Cassuto E, et al. Removal of methotrexate by hemodiafiltration. Cancer Chemother Pharmacol. 1989; 24: 400-1. [PMID: 2791196] / Saland JM, Leavey PJ, Bash RO, Hansch E, Arbus GS, Quigley R. Effective removal of methotrexate by high-flux hemodialysis. Pediatr Nephrol. 2002; 17: 825-9. [PMID: 12376811] / Shen DD, Azarnoff DL. Clinical pharmacokinetics of methotrexate. Clin Pharmacokinet. 1978; 3: 1-13. [PMID: 346283] / Thomson AH, Daly M, Knepil J, Harden P, Symonds P. Methotrexate removal during haemodialysis in a patient with advanced laryngeal carcinoma. Cancer Chemother Pharmacol. 1996; 38: 566-70. [PMID: 8823500]
Toxicity Notes
Nephrotoxicity decreased by urinary alkalinization and forced diuresis.