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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 Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 6/15/2016

Neutrexin (trimetrexate glucuronate) for Injection is an inhibitor of the enzyme dihydrofolate reductase (DHFR) used along with leucovorin as an alternative therapy for the treatment of moderate-to-severe Pneumocystis carinii pneumonia (PCP) in immunocompromised patients, including patients with the acquired immune deficiency syndrome (AIDS), who are intolerant of, or are refractory to, trimethoprim-sulfamethoxazole therapy or for whom trimethoprim-sulfamethoxazole is contraindicated. The brand name Neutrexin is discontinued, but generic versions may be available. Common side effects of Neutrexin (trimetrexate glucuronate) include:

Neutrexin is administered at a dose of 45 mg/m2 once daily by intravenous infusion over 60 minutes. Leucovorin must be administered daily during treatment with Neutrexin and for 72 hours past the last dose of Neutrexin. Neutrexin may interact with erythromycin, rifampin, rifabutin, azole antifungals, and acetaminophen. Tell your doctor all medications and supplements you use. Neutrexin is not recommended for use during pregnancy. It may harm a fetus. It is unknown if this drug passes into breast milk. Because of the potential for serious adverse reactions in nursing infants, breastfeeding while using this drug is not recommended.

Our Neutrexin (trimetrexate glucuronate) for Injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is Patient Information Overview?

A concise overview of the drug for the patient or caregiver from First DataBank.

Neutrexin Overview - Patient Information: Side Effects

SIDE EFFECTS: Consult your pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the entire patient information overview for Neutrexin (Trimetrexate Glucuronate Inj)

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Neutrexin FDA Prescribing Information: Side Effects
(Adverse Reactions)


Because many patients who participated in clinical trials of Neutrexin (trimetrexate glucuronate for injection) had complications of advanced HIV disease, it is difficult to distinguish adverse events caused by Neutrexin (trimetrexate glucuronate inj) from those resulting from underlying medical conditions.

Table 3 lists the adverse events that occurred in ≥ 1% of the patients who participated in the Comparative Study of Neutrexin (trimetrexate glucuronate inj) plus leucovorin versus TMP/SMX.

TABLE 3: NEUTREXIN (trimetrexate glucuronate inj) COMPARATIVE TRIAL Comparison of Adverse Events Reported for ≥ 1% of Patients

Adverse Events Number and Percent (%) of Patients with Adverse Events
(n = 109)
(n = 111)
Non-Laboratory Adverse Events:
  Fever 9 (8.3) 14 (12.6)
  Rash/Pruritus 6 (5.5) 14 (12.6)
  Nausea/Vomiting 5 (4.6)a 15 (13.5)a
  Confusion 3 (2.8) 3 (2.7)
  Fatigue 2 (1.8) 0 (0.0)
Hematologic Toxicity:
  Neutropenia ( ≤ 1000/mm3) 33 (30.3) 37 (33.3)
  Thrombocytopenia ( ≤ 75,000/mm3) 11 (10.1) 17 (15.3)
  Anemia (Hgb < 8 g/dL) 8 (7.3) 10 (9.0)
  Increased AST ( > 5 x ULNb) 15 (13.8) 10 (9.0)
  Increased ALT ( > 5 x ULN) 12 (11.0) 13 (11.7)
  Increased Alkaline Phosphatase ( > 5 x ULN) 5 (4.6) 3 (2.7)
  Increased Bilirubin (2.5 x ULN) 2 (1.8) 1 (0.9)
  Increased Serum Creatinine ( > 3 x ULN) 1 (0.9) 2 (1.8)
Electrolyte Imbalance:
  Hyponatremia 5 (4.6) 10 (9.0)
  Hypocalcemia 2 (1.8) 0 (0.0)
  No. of Patients With at Least one Adverse Eventc 58 (53.2) 60 (54.1)
a Statistically significant difference between treatment groups (Chi-square: p=0.022)
b ULN = Upper limit of normal range
c Patients could have reported more than one adverse event; therefore, the sum of adverse events exceeds the number of patients

Laboratory toxicities were generally manageable with dose modification of trimetrexate/leucovorin (see DOSAGE AND ADMINISTRATION).

Table 4 lists the adverse events resulting in discontinuation of study therapy in the Neutrexin (trimetrexate glucuronate inj) Comparative Study with TMP/SMX. Twenty-nine percent of the patients on the TMP/SMX arm discontinued therapy due to adverse events compared to 10% of the patients treated with TMTX/LV (p < 0.001).

TABLE 4: NEUTREXIN (trimetrexate glucuronate inj) COMPARATIVE TRIAL Adverse Events Resulting in Discontinuation of Therapy

Adverse Events Number and Percent (%) of Patients Discontinued for Adverse Eventsb
(n = 109)
(n = 111)
Non-Laboratory Adverse Events:
  Rash/Pruritus 3 (2.8) 5 (4.5)
  Fever 2 (1.8) 4 (3.6)
  Nausea/Vomiting 1 (0.9) 8 (7.2)
  Neurologic Toxicity 1 (0.9)c 2 (1.8)
Hematologic Toxicity:
  Neutropenia ( ≤ 1000/mm3) 4 (3.7) 6 (5.4)
  Thrombocytopenia ( ≤ 75,000/mm3) 0 (0.0) 4 (3.6)
  Anemia (Hgb < 8 g/dL) 0 (0.0) 4 (3.6)
  Increased AST ( > 5 x ULNa) 3 (2.8) 9 (8.1)
  Increased ALT ( > 5 x ULN) 1 (0.9) 4 (3.6)
  Increased Alkaline Phosphatase ( > 5 x ULN) 0 (0.0) 1 (0.9)
Electrolyte Imbalance:
  Hyponatremia 0 (0.0) 3 (2.7)
No. of Patients Discontinuing Therapy Due to an Adverse Eventb 11 (10.1)d 32 (28.8)d
a ULN = Upper limit of normal range
b Patients could discontinue therapy due to more than one toxicity; therefore the sum exceeds number of patients who discontinued due to toxicity
c Patient discontinued TMTX/LV due to seizure, though causal relationship could not be established.
d Statistically significant difference between treatment groups (Chi-square: p < 0.001)

Hematologic toxicity was the principal dose-limiting side effect.

Read the entire FDA prescribing information for Neutrexin (Trimetrexate Glucuronate Inj)

Report Problems to the Food and Drug Administration


You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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