Trimetrexate: Difference between revisions

Trimetrexate
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Latest revision as of 01:41, 20 February 2025

An antineoplastic and antimicrobial agent

Trimetrexate is a chemotherapeutic agent used primarily in the treatment of Pneumocystis pneumonia and certain types of cancer. It is a dihydrofolate reductase inhibitor, which means it interferes with the enzyme responsible for the reduction of dihydrofolate to tetrahydrofolate, a form of folic acid necessary for the synthesis of nucleic acids.

Mechanism of Action[edit]

Trimetrexate works by inhibiting the enzyme dihydrofolate reductase (DHFR). This inhibition prevents the conversion of dihydrofolate to tetrahydrofolate, thereby depleting the cellular pools of tetrahydrofolate. As a result, the synthesis of thymidylate and purine nucleotides is disrupted, leading to impaired DNA synthesis and cell death. This mechanism is particularly effective against rapidly dividing cells, such as cancer cells and certain types of pathogenic microorganisms.

Clinical Uses[edit]

Trimetrexate is primarily used in the treatment of:

Pneumocystis pneumonia (PCP) in patients who are intolerant to or have failed standard therapies such as trimethoprim-sulfamethoxazole.
Certain types of cancer, including colorectal cancer and non-small cell lung cancer.

Administration and Dosage[edit]

Trimetrexate is administered intravenously. The dosage and duration of treatment depend on the specific condition being treated, the patient's response to therapy, and the presence of any adverse effects. It is often used in combination with leucovorin to mitigate the toxic effects on normal cells.

Side Effects[edit]

Common side effects of trimetrexate include:

Myelosuppression, leading to neutropenia, thrombocytopenia, and anemia.
Gastrointestinal disturbances, such as nausea, vomiting, and diarrhea.
Hepatotoxicity, which may manifest as elevated liver enzymes.

Precautions[edit]

Due to its potential for severe myelosuppression, patients receiving trimetrexate should be closely monitored with regular blood tests to assess blood cell counts. The use of leucovorin is essential to protect normal cells from the toxic effects of trimetrexate.

Related pages[edit]

Trimetrexate

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-{{intro}}
+{{Short description|An antineoplastic and antimicrobial agent}}
-Trimetrexate is a parenterally administered folate antagonist that is used as a second line therapy for severe Pneumocystis jirovecii (previously carinii) pneumonia.
+{{Drugbox
+| verifiedfields = changed
+| verifiedrevid = 477002123
+| image = Trimetrexate.svg
+| image2 =
+}}
-{{livtox}}
+'''Trimetrexate''' is a [[chemotherapeutic agent]] used primarily in the treatment of [[Pneumocystis pneumonia]] and certain types of [[cancer]]. It is a [[dihydrofolate reductase inhibitor]], which means it interferes with the enzyme responsible for the reduction of dihydrofolate to tetrahydrofolate, a form of [[folic acid]] necessary for the synthesis of [[nucleic acids]].
-Trimetrexate therapy has been associated with transient, mild serum enzyme elevations during therapy, but has not been convincingly linked to instances of acute, clinically apparent [[liver injury]].
-{{moa}}
+==Mechanism of Action==
-Trimetrexate (trye" me trex' ate) is a folic acid analogue which acts as an antagonist inhibiting the enzymes involved in folate dependent synthetic pathways such as thymidine synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase.  Inhibition of these enzymes leads to decrease in intracellular thymidine and purine which interferes with [[RNA]] and [[DNA]] synthesis and leads to apoptotic cell death in rapidly dividing cells.  Trimetrexate is a nonclassical folate antagonist and, unlike methotrexate, is lipid soluble which leads to different pharmacokinetics and tissue distribution.  Trimetrexate was developed as an antineoplastic agent and showed some activity against breast, lung and head and neck cancer, but had difficult toxicities and never received approval for these uses in the United States.  Trimetrexate is also taken up by pathogens including Pneumocystis jirovecii where it blocks the folate dependent synthetic pathways and causes their death.  At the same time, folate being water soluble can partially block the systemic effects of trimetrexate, but is not taken up by the pathogens.  For this reason, high doses of trimetrexate combined with leucovorin “rescue” were evaluated as therapy of Pneumocystis jirovecii in patients who were resistant or intolerant of first line anti-Pneumocystis therapies.  Trimetrexate was approved for use as a second line therapy of moderate-to-severe Pneumocystis jirovecii pneumonia in immunodeficient patients in the United States in 1993.  It remains available as a second line drug for this indication, but has not been widely used.
+Trimetrexate works by inhibiting the enzyme [[dihydrofolate reductase]] (DHFR). This inhibition prevents the conversion of dihydrofolate to tetrahydrofolate, thereby depleting the cellular pools of tetrahydrofolate. As a result, the synthesis of [[thymidylate]] and [[purine nucleotides]] is disrupted, leading to impaired [[DNA synthesis]] and cell death. This mechanism is particularly effective against rapidly dividing cells, such as cancer cells and certain types of [[pathogenic microorganisms]].
-{{dose}}
+==Clinical Uses==
-Trimetrexate is available in single use vials of 25 or 200 mg as a powder for reconstitution under the brand name Neutrexin.  The recommended dose is 45 mg/m2 once daily for 21 days concurrent with leucovorin, orally or intravenously, four times daily for 24 days.
+Trimetrexate is primarily used in the treatment of:
-{{se}}
+* [[Pneumocystis pneumonia]] (PCP) in patients who are intolerant to or have failed standard therapies such as [[trimethoprim-sulfamethoxazole]].
-When given with leucovorin, trimetrexate is well tolerated, but can cause many of the ceommon [[side effects]] of other folate antagonists such as [[fatigue]], [[nausea]], [[vomiting]], [[anorexia]], [[diarrhea]], [[alopecia]], anemia, [[neutropenia]] and rash.  Uncommon, but potentially serious adverse events include febrile [[neutropenia]], [[infections]], [[dehydration]], [[renal failure]], [[arrhythmias]] and [[peripheral neuropathy]].
+* Certain types of [[cancer]], including [[colorectal cancer]] and [[non-small cell lung cancer]].
-{{cancer drugs}}
+==Administration and Dosage==
+Trimetrexate is administered intravenously. The dosage and duration of treatment depend on the specific condition being treated, the patient's response to therapy, and the presence of any adverse effects. It is often used in combination with [[leucovorin]] to mitigate the toxic effects on normal cells.
-{{coststubd}}
+==Side Effects==
+Common side effects of trimetrexate include:
+* [[Myelosuppression]], leading to [[neutropenia]], [[thrombocytopenia]], and [[anemia]].
+* [[Gastrointestinal disturbances]], such as [[nausea]], [[vomiting]], and [[diarrhea]].
+* [[Hepatotoxicity]], which may manifest as elevated [[liver enzymes]].
+==Precautions==
+Due to its potential for severe [[myelosuppression]], patients receiving trimetrexate should be closely monitored with regular [[blood tests]] to assess [[blood cell counts]]. The use of leucovorin is essential to protect normal cells from the toxic effects of trimetrexate.
+==Related pages==
+* [[Dihydrofolate reductase]]
+* [[Pneumocystis pneumonia]]
+* [[Chemotherapy]]
+* [[Antifolate]]
+[[Category:Antineoplastic and immunomodulating agents]]
+[[Category:Antimicrobial agents]]
+<gallery>
+File:Trimetrexate.svg|Trimetrexate
+</gallery>