Trimetrexate Glucuronate

A to Z Drug Facts

 Action Inhibits dihydrofolate reductase necessary for DNA, RNA and protein synthesis, leading to cell death.

 Indications As alternative therapy, with concurrent leucovorin administration, for treatment of moderate-to-severe Pneumocystis carinii neumonia in immunocompromised patients in whom trimethoprim-sulfamethoxazole cannot be used. Unlabeled use(s): Treatment of non-small cell lung, prostate and colorectal cancer.

 Contraindications Clinically significant sensitivity to trimetrexate, leucovorin or methotrexate.

 Route/Dosage

ADULTS: IV 45 mg/m² q/day by IV infusion over 60–90 min for 21 days. Leucovorin may be administered IV at dose of 20 mg/m² over 5–10 min q 6 hrs for total daily dose of 80 mg/m² or PO t dose of 20 mg/m² q 6 hr for 24 days. Adjust dose of trimetrexate and leucovorin according to hematologic toxicity. Interruption of therapy may be necessary for hematologic, hepatic, renal or mucosal toxicity or for uncontrolled fever.

 Interactions

Acetaminophen, cimetidine, clotrimazole, erythromycin, fluconazole, ketoconazole, miconazole, rifabutin, rifampin: May alter trimetrexate levels. Zidovudine: Zidovudine should be discontinued during trimetrexate therapy to allow for full therapeutic doses of trimetrexate. INCOMPATIBILITIES: Do not mix with solutions containing either chloride ion (eg, sodium chloride) or leucovorin, because precipitation occurs instantly.

 Lab Test Interferences None well documented.

 Adverse Reactions

CNS: Confusion; fatigue. DERM: Rash; pruritus. GI: Nausea; vomiting; increased serum transaminases; increased alkaline phosphatase; ncreased bilirubin. GU: Increased serum creatinine. HEMA: Neutropenia; thrombocytopenia; anemia. META: xyponatremia; hyocalcemia. OTHER: Fever.

 Precautions

Pregnancy: Category D. Lactation: Undetermined. Children: Safety and efficacy not established in children < 18 yr. Under Compassionate Use Protocol, younger children have been treated. Special risk patients: Use drug with caution in patients with impaired hematologic, renal or hepatic function and in patients who require concomitant therapy with nephrotoxic, myelosuppressive or hepatotoxic drugs. Concurrent leucovorin: Trimetrexate must be used with concurrent leucovorin to avoid potentially serious or life-threatening complications including bone marrow suppression, oral and GI mucosal ulceration and renal and hepatic dysfunction.

 Administration/Storage

• Administer IV trimetrexate and leucovorin solutions separately. Leucovorin solution may be administered prior to or after trimetrexate. In either case flush IV line thoroughly with at least 10 ml of 5% Dextrose Injection between infusions.
• Avoid contact with skin or mucosa. If trimetrexate contacts skin or mucosa. If trimetrexate contacts skin or mucosa, immediately and thoroughly wash with soap and water.
• Reconstitute with 2 ml of 5% Dextrose for Injection or Sterile Water to yield concentration of 12.5 mg/ml. Do not reconstitute with solutions containing either chloride ion or leucovorin, because precipitation will occur instantly.
• Observe solution, which should dissolve product completely approximately 30 sec after dilution. Reconstituted solution will appear as pale greenish-yellow solution. Do not use if cloudiness or particulate matter is observed.
• Filter solution (0.22 mcm) prior to dilution.
• Further dilute reconstituted solution with 5% Dextrose Injection to yield final concentration of 0.25–2 mg/ml.
• Administer diluted solution by IV infusion over 60–90 min.
• Flush IV line with at least 10 ml of 5% Dextrose Injection before and after administering trimetrexate.
• Store vials at controlled room temperature and protect from exposure to light.
• After reconstitution, retain solution at room temperature or under refrigeration for no longer than 24 hours. Do not freeze reconstituted solution.
• Use cytotoxic drug precautions for proper disposal.

 Assessment/Interventions

• Obtain patient history, including drug history and any known allergies.
• Assess integrity of IV site prior to infusion.
• Assess for signs and symptoms of oral and GI mucosal ulceration, changes in mental status, fatigue and signs and symptoms of infection.
• Implement safety precautions until individual response is determined.
• Implement measures to prevent infection.
• Monitor for side effects, including bone marrow suppression and renal and hepatic dysfunction throughout therapy.
• Monitor vital signs, renal and hepatic function, hematologic studies, I&O, body weight and stools for occult blood.
• Consider termination of treatment if fever (oral temperature ³ 105°F) cannot be controlled by antipyretics.
• Consider discontinuation of therapy if serum creatinine is > 2.5 mg/dl or if transaminase or alkaline phosphatase levels become > 5 times normal.

 Patient/Family Education

• Explain that continued, frequent monitoring by physician is necessary.
• Inform patient that blood test must be performed at least twice weekly.
• Explain that leucovorin therapy must be continued for 72 hr after last dose of trimetrexate.
• Describe potential side effects, and what should be reported to physician: fever, mucosal toxicity, etc.
• Explain measures to prevent infection.
• Advise patient to use caution while driving or performing other tasks requiring mental alertness.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts