Trimetrexate glucuronate

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Trimetrexate glucuronate
Trimetrexate glucuronate (NeuTrexin)
Trimetrexate glucuronate
( try-meh- TREX-ayt gloo- KYOU-roh-nayt)
Pregnancy Category: D NeuTrexin (Rx)

Classification: Miscellaneous anti-infective

See Also: See also Anti-Infectives .

Action/Kinetics: Inhibits the enzyme dihydrofolate reductase resulting in interference with thymidylate biosynthesis and inhibition of folate-dependent formyltransferases. This leads to inhibition of purine synthesis and disruption of DNA, RNA, and protein synthesis and ultimately cell death. Must be given with leucovorin to prevent serious or life-threatening complications, including bone marrow suppression, oral and GI mucosal ulceration, and renal and hepatic dysfunction. t 1/2: 11 hr. Highly bound to plasma protein and metabolized by the liver. Metabolites also appear to have an inhibitory effect on dihydrofolate reductase.

Uses: As alternative therapy with concurrent leucovorin for the treatment of moderate to severe Pneumocystis carinii pneumonia in immunocompromised clients. Treatment is indicated in clients with AIDS who are intolerant of or refractory to trimethoprim-sulfamethoxazole (TMP/SMZ) therapy or in whom this combination is contraindicated. Investigational: Treatment of non-small-cell lung, prostate, or colorectal cancer.

Contraindications: Hypersensitivity to trimetrexate, leucovorin, or methotrexate. Lactation.

Special Concerns: Use with caution in clients with impaired hematologic, renal, or hepatic function. Safety and efficacy have not been determined for clients less than 18 years of age for use in treating histologically confirmed PCP.

Side Effects: GI: N&V. Hematologic: Neutropenia, thrombocytopenia, anemia. Hepatic: Hepatic toxicity manifested by increased ALT, AST, alkaline phosphatase, and bilirubin. Renal: Increased serum creatinine. Electrolytes: Hyponatremia, hypocalcemia.

Overdose Management: Symptoms: Primarily hematologic. Treatment: Discontinue trimetrexate and administer leucovorin at a dose of 40 mg/m 2 q 6 hr for 3 days.

Drug Interactions: Since trimetrexate is metabolized by the P-450 enzyme system in the liver, drugs that stimulate or inhibit this enzyme system may cause drug interactions that may alter plasma levels of trimetrexate (e.g., erythromycin, rifabutin, rifampin). Acetaminophen / May alter trimetrexate metabolite levels Cimetidine / May trimetrexate metabolism Clotrimazole / Trimetrexate metabolism Ketoconazole / Trimetrexate metabolism Miconazole / Trimetrexate metabolism

How Supplied: Powder for injection: 25 mg

?IV Infusion
Pneumocystis carinii pneumonia.
Adults: 45 mg/m 2 once daily by IV infusion over 60-90 min. Leucovorin is given IV at a dose of 20 mg/m 2 over 5-10 min q 6 hr for a total daily dose of 80 mg/m 2. Leucovorin may also be given orally in four doses of 20 mg/m 2 spaced equally throughout the day (round the oral dose up to the next higher 25-mg increment). Doses of trimetrexate and leucovorin are modified depending on hematologic toxicity. If neutrophils are between 750 and 1,000/mm 3 and platelets between 50,000 and 75,000/mm 3, the dose of trimetrexate remains at 45 mg/m 2 once daily but the dose of leucovorin is increased to 40 mg/m 2 q 6 hr. If neutrophils are between 500 and 749/mm 3 and platelets between 25,000 and 49,999, the dose of trimetrexate is reduced to 22 mg/m 2 once daily and the dose of leucovorin is 40 mg/m 2 q 6 hr. If neutrophils are less than 500/mm 3 and platelets are less than 25,000/mm 3, trimetrexate is discontinued for 9 days with leucovorin still given at a dose of 40 mg/m 2 q 6 hr; from days 10 to 21, interrupt trimetrexate for up to 96 hr.

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