Generic Name

Trimetrexate Glucuronate

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Classification

FDA Approved Indications

• Treatment of severe pneumocystis pneumonia in patients with HIV who cannot tolerate or have failed other therapies

Mechanism of Action

Trimetrexate inhibits dihydrofolate reductase, leading to decreased synthesis of purines and pyrimidines, essential for DNA synthesis, thereby exerting antineoplastic and antimicrobial effects.

Dosage and Administration

Adult: Typically, 15 mg/m^2 IV every 8 hours for 21 days, then reassessed.

Pediatric: Data limited; dosing based on body surface area, under specialist guidance.

Geriatric: Dose adjustments may be necessary due to decreased clearance in the elderly; monitor closely.

Renal Impairment: Adjust dose based on renal function; consult specific guidelines.

Hepatic Impairment: Use cautiously; no specific adjustments established.

Pharmacokinetics

Absorption: Administered IV; bioavailability is 100% intravascular.

Distribution: Widely distributed; crosses blood-brain barrier.

Metabolism: Primarily hepatic glucuronidation.

Excretion: Renal excretion of unchanged drug and metabolites.

Half Life: Approximately 10-12 hours.

Contraindications

• Known hypersensitivity to trimetrexate or related compounds.

Precautions

• Monitor for myelosuppression.
• Use with caution in hepatic or renal impairment.
• Folate supplementation should be considered to reduce toxicity.

Adverse Reactions - Common

• Myelosuppression (neutropenia, thrombocytopenia, anemia) (Common)
• Gastrointestinal upset (nausea, vomiting) (Common)
• Elevated hepatic enzymes (Common)

Adverse Reactions - Serious

• Bone marrow suppression leading to infection risk (Serious)
• Hepatotoxicity (Serious)
• Mucositis/stomatitis (Serious)

Drug-Drug Interactions

• Other myelosuppressive agents
• Drugs that affect renal or hepatic function

Drug-Food Interactions

N/A

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Report fever, sore throat, or bleeding immediately.
• Use effective contraception during and for at least 3 months after therapy.
• Avoid alcohol and hepatotoxic drugs.

Special Considerations

Black Box Warnings:

• Myelosuppression can be severe and life-threatening.
• Fatal opportunistic infections and secondary malignancies may occur.

Genetic Factors: Limited data.

Lab Test Interference: May cause false elevations in liver function tests.

Overdose Management

Signs/Symptoms: Severe myelosuppression, hepatotoxicity, mucositis.

Treatment: Supportive care; possibly leucovorin rescue; symptomatic management; no specific antidote.

Storage and Handling

Storage: Store at room temperature, protected from light.

Stability: Stable under proper storage conditions for specified shelf life.