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Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)



Neutrexin (trimetrexate glucuronate for injection) must be used with concurrent leucovorin to avoid potentially serious or life-threatening complications including bone marrow suppression, oral and gastrointestinal mucosal ulceration, and renal and hepatic dysfunction. Leucovorin therapy must extend for 72 hours past the last dose of Neutrexin (trimetrexate glucuronate inj) . Patients should be informed that failure to take the recommended dose and duration of leucovorin can lead to fatal toxicity. Patients should be closely monitored for the development of serious hematologic adverse reactions (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).

Neutrexin (trimetrexate glucuronate inj) can cause fetal harm when administered to a pregnant woman. Trimetrexate has been shown to be fetotoxic and teratogenic in rats and rabbits. Rats administered 1.5 and 2.5 mg/kg/day intravenously on gestational days 6-15 showed substantial postimplantation loss and severe inhibition of maternal weight gain. Trimetrexate administered intravenously to rats at 0.5 and 1.0 mg/kg/day on gestational days 6-15 retarded normal fetal development and was teratogenic. Rabbits administered trimetrexate intravenously at daily doses of 2.5 and 5.0 mg/kg/day on gestational days 6-18 resulted in significant maternal and fetal toxicity. In rabbits, trimetrexate at 0.1 mg/kg/day was teratogenic in the absence of significant maternal toxicity. These effects were observed using doses 1/20 to 1/2 the equivalent human therapeutic dose based on a mg/m2 basis. Teratogenic effects included skeletal, visceral, ocular, and cardiovascular abnormalities. If Neutrexin (trimetrexate glucuronate inj) is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.



Patients receiving Neutrexin (trimetrexate glucuronate for injection) may experience severe hematologic, hepatic, renal, and gastrointestinal toxicities. Caution should be used in treating patients with impaired hematologic, renal, or hepatic function. Patients who require concomitant therapy with nephrotoxic, myelosuppressive, or hepatotoxic drugs should be treated with Neutrexin (trimetrexate glucuronate inj) at the discretion of the physician and monitored carefully. To allow for full therapeutic doses of Neutrexin (trimetrexate glucuronate inj) , treatment with zidovudine should be discontinued during Neutrexin (trimetrexate glucuronate inj) therapy.

Neutrexin (trimetrexate glucuronate inj) -associated myelosuppression, stomatitis, and gastrointestinal toxicities generally can be ameliorated by adjusting the dose of leucovorin. Mild elevations in transaminases and alkaline phosphatase have been observed with Neutrexin (trimetrexate glucuronate inj) administration and are usually not cause for modification of Neutrexin therapy (see DOSAGE AND ADMINISTRATION). Seizures have been reported rarely ( < 1%) in AIDS patients receiving Neutrexin (trimetrexate glucuronate inj) ; however, a causal relationship has not been established. Trimetrexate is a known inhibitor of histamine metabolism. Hypersensitivity/allergic type reactions including but not limited to rash, chills/rigors, fever, diaphoresis and dypsnea have occurred with trimetrexate primarily when it is administered as a bolus infusion or at doses higher than those recommended for PCP, and most frequently in combination with 5FU and leucovorin. In rare cases, anaphylactoid reactions, including acute hypotension and loss of consciousness have occurred. Neutrexin (trimetrexate glucuronate inj) infusion should be permanently discontinued in all patients with severe hypersensitivity reactions. Epinephrine should be available for treatment of acute allergic symptoms.

Neutrexin (trimetrexate glucuronate inj) has not been evaluated clinically for the treatment of concurrent pulmonary conditions such as bacterial, viral, or fungal pneumonia or mycobacterial diseases. In vitro activity has been observed against Toxoplasma gondii, Mycobacterium avium complex, gram positive cocci, and gram negative rods. If clinical deterioration is observed in patients, they should be carefully evaluated for other possible causes of pulmonary disease and treated with additional agents as appropriate.

Laboratory Tests

Patients receiving Neutrexin (trimetrexate glucuronate inj) with leucovorin protection should be seen frequently by a physician. Blood tests to assess the following parameters should be performed at least twice a week during therapy: hematology (absolute neutrophil counts [ANC], platelets), renal function (serum creatinine, BUN), and hepatic function (AST, ALT, alkaline phosphatase).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis: Long term studies in animals to evaluate the carcinogenic potential of trimetrexate have not been performed.

Mutagenesis: Trimetrexate was not mutagenic when tested using the standard Ames Salmonella mutagenicity assay with and without metabolic activation. Trimetrexate did not induce mutations in Chinese hamster lung cells or sister-chromatid exchange in Chinese hamster ovary cells. Trimetrexate did induce an increase in the chromosomal aberration frequency of cultured Chinese hamster lung cells; however, trimetrexate showed no clastogenic activity in a mouse micronucleus assay.

Impairment of fertility: No studies have been conducted to evaluate the potential of trimetrexate to impair fertility. However, during standard toxicity studies conducted in mice and rats, degeneration of the testes and spermatocytes including the arrest of spermatogenesis was observed.

Pregnancy, Teratogenic Effects


Pregnancy Category D

Nursing Mothers

It is not known if trimetrexate is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from trimetrexate, it is recommended that breast feeding be discontinued if the mother is treated with Neutrexin (trimetrexate glucuronate inj) .

Pediatric Use

The safety and effectiveness of Neutrexin (trimetrexate glucuronate inj) for the treatment of histologically confirmed PCP has not been established for patients under 18 years of age. Two children, ages 15 months and 9 months, were treated with trimetrexate and leucovorin using a dose of 45 mg/m2 of trimetrexate per day for 21 days and 20 mg/m2 of leucovorin every 6 hours for 24 days. There were no serious or unexpected adverse effects.

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 1/11/2017


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