Trimetrexate Side Effects
Applies to trimetrexate: intravenous powder for injection
Because many patients in clinical trials had advanced HIV disease, it was difficult to distinguish between trimetrexate-associated side effects and underlying medical conditions. In a clinical trial, 10% of patients in the trimetrexate-leucovorin group discontinued treatment due to side effects, as compared to 29% in the sulfamethoxazole-trimethoprim group.[Ref]
Hematologic toxicity has been the primary dose-limiting adverse effect. In a clinical trial (n=109) trimetrexate commonly caused myelosuppression, resulting in neutropenia (<= 1000/mm3) in 30%, thrombocytopenia (<=75,000/mm3) in 10%, and anemia (Hgb<8 g/dL) in 7% of patients also treated with leucovorin. Therapy was discontinued in 3.7% of patients due to hematologic toxicity.[Ref]
Renal toxicity consisting of elevations in serum creatinine greater than 3 times upper normal limits has occurred in 0.9% of clinical trial patients treated with trimetrexate and leucovorin.[Ref]
Gastrointestinal side effects associated with trimetrexate have included nausea and vomiting in 5% or more of patients also treated with leucovorin. Mucositis and diarrhea also occur relatively often.[Ref]
Hepatic side effects have included transient elevations in liver function tests in up to 14% (n=109) of trial patients who also received leucovorin with increases greater than 5 times upper normal limits in AST (13.8%), ALT (11%), alkaline phosphatase (4.6%), and 2.5 times upper normal limit increases in bilirubin (1.8%). Discontinuation of therapy was necessary in approximately 3% of cases.[Ref]
Hypersensitivity reactions to trimetrexate have occurred and are generally limited to skin rash and pruritus. However, severe reactions consisting of bronchospasm, hypotension, rigors, and fever have occurred rarely.[Ref]
Nervous system side effects have included confusion (2.8%) and fatigue (1.8%).[Ref]
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8. Fossella FV, Winn RJ, Holoye PY, Hallinan B, Raber MN, Hoelzer K, Young JA, Readling J, Bowers B, Hong WK "Phase II trial of trimetrexate for unresectable or metastatic non- small cell bronchogenic carcinoma." Invest New Drugs 10 (1992): 331-5
9. Allegra CJ, Chabner BA, Tuazon CU, et al. "Trimetrexate for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome." N Engl J Med 317 (1987): 978-85
10. Grem JL, King SA, Costanza ME, Brown TD "Hypersensitivity reactions to trimetrexate." Invest New Drugs 8 (1990): 211-4
11. King SA, Grem JL "Acute allergic reactions to trimetrexate (TMTX) (meeting abstract)." Proc Annu Meet Am Soc Clin Oncol 7 (1988): a284
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Some side effects may not be reported. You may report them to the FDA.