Drug General Information (ID: DDISYDHLV7)
Drug Name			Methotrexate		Drug Info		Ticarcillin		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antimetabolites				Antibiotics
Structure

Mechanism of Methotrexate-Ticarcillin Interaction (Severity Level: Major)
Competitive inhibition of renal tubular secretion Click to Show/Hide Mechanism Graph
Drug Name		Methotrexate				Ticarcillin
Mechanism		Methotrexate				Competitive inhibition of renal tubular secretion of methotrexate
Key Mechanism Factor 1
		Factor Name		Renal tubular secretion
		Factor Description		Renal tubular secretion allows selective transfer of substances from the blood around the capillaries into the renal tubules via filtrate. Drug excretion may be reduced when two drugs compete for renal tubular secretion.
Mechanism Description		Decreased elimination of Methotrexate caused by Ticarcillin mediated competitive inhibition of renal tubular secretion

Recommended Action
Management		If a penicillin must be used concurrently, close monitoring of methotrexate serum concentrations and of the patient for evidence of serious methotrexate toxicity are recommended. Leucovorin rescue should be available. Methotrexate dose reductions may be necessary. If broad-spectrum antibiotic coverage is needed during high-dose methotrexate therapy, use of other antimicrobials may be preferable. Patients should be advised to promptly report symptoms including fever, chills, sore throat, bruising, bleeding, stomatitis, or malaise to their physician.

References
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2	Dean R, Nachman J, Lorenzana AN "Possible methotrexate-mezlocillin interaction." Am J Pediatr Hematol Oncol 14 (1992): 88-92. [PMID: 1550270]
3	Mayall B, Poggi G, Parkin JD "Neutropenia due to low-dose methotrexate therapy for psoriasis and rheumatoid arthritis may be fatal." Med J Aust 155 (1991): 480-4. [PMID: 1921820]
4	Nierenberg DW, Mamelok RD "Toxic reaction to methotrexate in a patient receiving penicillin and furosemide: a possible interaction." Arch Dermatol 119 (1983): 449-50. [PMID: 6859880]
5	Product Information. Methotrexate (methotrexate). Lederle Laboratories, Wayne, NJ.
6	Product Information. Methotrexate and Methotrexate LPF (methotrexate). Lederle Laboratories, Wayne, NJ.
7	Product Information. Zosyn (piperacillin-tazobactam). Lederle Laboratories, Wayne, NJ.
8	Ronchera CL, Hernandez T, Peris JE, Torres F, et al. "Pharmacokinetic interaction between high-dose methotrexate and amoxycillin." Ther Drug Monit 15 (1993): 375-9. [PMID: 8249043]
9	Titier K, Lagrange F, Pehourcq F, Moore N, Molimard M "Pharmacokinetic interaction between high-dose methotrexate and oxacillin." Ther Drug Monit 24 (2002): 570-2. [PMID: 12142645]
10	Yamamoto K, Sawada Y, Matsushita Y, Moriwaki K, Bessho F, Iga T "Delayed elimination of methotrexate associated with piperacillin administration." Ann Pharmacother 31 (1997): 1261-2. [PMID: 9337457]