Neutrexin Disease Interactions

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

The use of trimetrexate is associated with severe and potentially life-threatening bone marrow suppression. Concomitant use with leucovorin significantly diminishes but does not eliminate this risk. Therapy with trimetrexate should be administered cautiously in patients with preexisting blood dyscrasias and in patients receiving other myelotoxic drugs. Close clinical monitoring of hematopoietic function is recommended during therapy, and patients should be instructed to immediately report any signs or symptoms suggestive of hematologic toxicity such as fever, sore throat, local infection, bleeding, pallor, dizziness, or jaundice. The dosages of trimetrexate and leucovorin should be adjusted for hematologic toxicity in accordance with the product package labeling.

Trimetrexate undergoes both renal and hepatic elimination. Therapy with trimetrexate should be administered cautiously in patients with renal and/or hepatic impairment, since they may be at increased risk for potentially life-threatening hematologic and gastrointestinal toxicities associated with the drug. In addition, trimetrexate may be nephro- and hepatotoxic. Elevations in serum creatinine and liver function tests occur in approximately 1% and up to 14%, respectively, of patients treated with trimetrexate and leucovorin. The manufacturer recommends blood tests at least twice a week during therapy to assess hematologic, renal, and hepatic function. Interruption of therapy is advised if serum creatinine level exceeds 2.5 mg/dL or if serum transaminase or alkaline phosphatase levels increase to > 5 times the upper limits of normal and these elevations are thought to be secondary to trimetrexate.