Trimetrexate


Generic Medicine Info
Indications and Dosage
Intravenous
Neoplastic disease
Adult: > 18 yr: Usually in combination with folinic acid rescue, 8 mg/m2 daily as infusion over 60-90 min for 5 days at 3 wk intervals or 150-220 mg/m2 as infusion over 60-90 min, every 28 days.

Intravenous
Pneumocystis (carinii) jirovecii pneumonia
Adult: >18yr: 45 mg/m2 infusion over 60-90 min once daily for 21 days, in association with folinic acid rescue for 24 days; folinic acid may be given as IV (over 5-10 minutes) or orally at 20 mg/m2 every 6 hr (total daily dose of 80 mg/m2). Alternatively, trimetrexate dose may be given based on patient's weight. < 50 kg: trimetrexate 1.5 mg/kg daily with folinic acid 0.6 mg/kg 4 times daily; 50-80 kg: trimetrexate 1.2 mg/kg daily with folinic acid 0.5 mg/kg 4 times daily; > 80 kg: trimetrexate 1 mg/kg daily with folinic acid 0.5 mg/kg 4 times daily; trimetrexate and folinic acid to be given for 21 days and 24 days respectively. See lit for dosage adjustment of trimetrexate and folinic acid based on neutrophil and platelet counts.
Renal Impairment
Interrupt therapy if serum creatinine concentration > 2.5 mg/dl and elevation is due to trimetrexate.
Hepatic Impairment
Interrupt therapy if transaminase or alkaline phosphatase concentrations > 5 times the upper limit of normal.
Reconstitution
Vials containing 25 or 200 mg of trimetrexate powder to be reconstituted with 2 or 16 ml of 5% dextrose or sterile water for inj resulting in a solution containing 12.5 mg/ml of trimetrexate. Reconstituted product should appear as a pale greenish-yellow solution. Do not use if cloudiness or precipitate is observed. Reconstituted solution to be further diluted with 5% dextrose to provide a final trimetrexate concentration of 0.25-2 mg/ml before admin as IV infusion. IV lines should be flushed with at least 10 ml of 5% dextrose between trimetrexate and folinic acid infusions to prevent precipitation.
Incompatibility
Incompatible with foscarnet. Mixing with folinic acid or chloride ions results in precipitation.
Contraindications
Severe blood disorders. Hypersensitivity to trimetrexate, methotrexate or folinic acid. Pregnancy, lactation.
Special Precautions
Blood disorders; renal or hepatic impairment. Monitor hepatic, renal function and blood counts at least twice a week and adjust trimetrexate and folinic acid dose according to neutrophil and platelet counts. Treatment with zidovudine and other myelosuppressive drugs to be interrupted to allow full doses of trimetrexate to be given. Folinic acid must be used concurrently with trimetrexate therapy and continued for 72 hr after the last dose of trimetrexate to avoid life-threatening toxicity.
Adverse Reactions
Nausea, vomiting, stomatitis, hypersensitivity reactions, increase in LFT, oral and GI mucosal ulceration, renal and hepatic dysfunction.
Potentially Fatal: Anaphylactic reactions, blood dyscrasias such as neutropenia and thrombocytopenia.
IV/Parenteral: D
Overdosage
Symptoms: haematological toxicity. Management: trimetrexate to be stopped and folinic acid to be admin at a dose of 40 mg/m2 every 6 hr for 3 days.
Drug Interactions
Possible interactions with drugs that affect hepatic cytochrome P450 systems. Monitor closely.
Action
Description: Trimetrexate inhibits the enzyme dihydrofolate reductase and this disrupts the production of DNA and RNA precursors, leading to cell death. At therapeutic doses of trimetrexate, the selective transport of trimetrexate, but not folinic acid, into the Pneumocystis carinii organism allows the folinic acid to protect normal host cells from the cytotoxicity of trimetrexate. It is used as an alternative therapy for treatment of moderate-to-severe Pneumocystis carinii pneumonia (PCP) in immunocompromised patients, who are are unable to tolerate trimethoprim-sulfamethoxazole therapy.
Pharmacokinetics:
Distribution: Protein binding: extensive. Saturable binding with free fraction increasing at plasma concentration >1mcg/ml.
Metabolism: Oxidative O-demethylation followed by conjugation to the sulfate or glucuronide.
Excretion: Mainly via urine, as unchanged drug and metabolites (Some are active metabolites). Terminal elimination half-life: 16-18 hr.
Storage
Unconstituted vial: store at 20-25°C (68-77°F); protect from light. Reconstituted vial: store at room temperature (20-25°C) up to 6 hr or under refrigeration at 2-8°C up to 24 hr. Reconstituted solution that is further diluted with 5% dextrose or sterile water: store at 2-8°C under refrigeration or at room temperature (20-25°C) for up to 24 hr; do not freeze.
Disclaimer: This information is independently developed by MIMS based on Trimetrexate from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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