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Neutrexin Side Effects

Generic name: trimetrexate

Note: This document contains side effect information about trimetrexate. Some dosage forms listed on this page may not apply to the brand name Neutrexin.

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 (the active ingredient contained in Neutrexin) 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 (the active ingredient contained in Neutrexin) and leucovorin.[Ref]


Gastrointestinal side effects associated with trimetrexate (the active ingredient contained in Neutrexin) 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 (the active ingredient contained in Neutrexin) 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]


Respiratory side effects have included dyspnea and rare cases of pneumonitis.[Ref]


Metabolic abnormalities have included hyponatremia (4.6%) and hypocalcemia (1.8%).[Ref]


Dermatologic side effects have included alopecia in a few patients treated with trimetrexate (the active ingredient contained in Neutrexin) [Ref]

Nervous system

Nervous system side effects have included confusion (2.8%) and fatigue (1.8%).[Ref]


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2. "Product Information. NeuTrexin (trimetrexate)." Apothecon Inc (2022):

3. Gesme DH, Jr Jett JR, Schreffler DD, Su JQ, Mailliard JA, Foley JF, Krook JE, Maksymiuk AW, Hatfield AK, Ebbert LP, et al. "A randomized phase II trial of amonafide or trimetrexate in patients with advanced non-small cell lung cancer. A trial of the North Central Cancer Treatment Group." Cancer 71 (1993): 2723-6

4. Weiss GR, Liu PY, O'Sullivan J, Alberts DS, Brown TD, Neefe JR, Hutchins LF "A randomized phase II trial of trimetrexate or didemnin B for the treatment of metastatic or recurrent squamous carcinoma of the uterine cervix: a Southwest Oncology Group trial." Gynecol Oncol 45 (1992): 303-6

5. Witte RS, Elson P, Bryan GT, Trump DL "Trimetrexate in advanced renal cell carcinoma. An ECOG phase II trial." Invest New Drugs 10 (1992): 51-4

6. 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

7. Conti JA, Kemeny N, Goker E, Tong W, Colofiore J, Andre M, Ragusa K, Bertino JR "A Phase I trial of sequential trimetrexate (TMTX), fluorouracil (FU) and high-dose leucovorin (LV) in previously treated patients (pts) with gastrointestinal (GI) carcinoma (Ca) (Meeting abstract)." Proc Annu Meet Am Soc Clin Oncol 12 (1993): a567

8. Hum M, Holcenberg JS, Tkaczewski I, Weaver JW, Wilson J, Kamen BA "High-dose trimetrexate and minimal-dose leucovorin: a case for selective protection?" Clin Cancer Res 4 (1998): 2981-4

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

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.