Trimetrexate

What is Trimetrexate

NOTE: This drug is discontinued in the US.

Trimetrexate is a parenteral, non-classical folate antagonist. It is structurally similar to methotrexate and trimethoprim. Trimetrexate was approved as an orphan drug for the treatment of Pneumocystis pneumonia (PCP) in patients with AIDS.

Other orphan drug designations include the treatment of metastatic colorectal carcinoma, head and neck carcinoma, pancreatic carcinoma, and advanced non-small cell carcinoma of the lung.

Trimetrexate was made available under a treatment IND in February 1988 and was approved by the FDA in December 1993.

Leucovorin should be administered concomitantly to offset potential hematologic toxicity. Neutrexin® was discontinued September 2006 by MedImmune for business reasons.

While some product with an expiration date of January 31, 2007 was available until time of expiration, there are currently no other suppliers of trimetrexate glucuronate.

Brand Name

Neutrexin

Indications

  1. colorectal cancer
  2. pancreatic cancer
  3. Pneumocystis jirovecii (formerly Pneumocystis carinii)
  4. Pneumocystis pneumonia (PCP)

Side Effects

  1. anaphylactoid reactions
  2. bone marrow suppression
  3. chills
  4. diaphoresis
  5. diarrhea
  6. dyspnea
  7. elevated hepatic enzymes
  8. esophagitis
  9. fever
  10. hepatotoxicity
  11. hypocalcemia
  12. hyponatremia
  13. hypotension
  14. nausea
  15. nephrotoxicity
  16. neutropenia
  17. rash
  18. seizures
  19. stomatitis
  20. syncope
  21. thrombocytopenia
  22. vomiting

Monitoring Parameters

  • CBC with differential
  • LFTs
  • serum calcium
  • serum creatinine/BUN
  • serum sodium

Contraindications

  • accidental exposure
  • bone marrow suppression
  • breast-feeding
  • chemotherapy
  • children
  • dental disease
  • dental work
  • hepatic disease
  • hepatotoxicity
  • hypocalcemia
  • hyponatremia
  • infants
  • intramuscular injections
  • leukopenia
  • neonates
  • nephrotoxicity
  • neutropenia
  • ocular exposure
  • pregnancy
  • radiation therapy
  • renal failure
  • renal impairment
  • stomatitis
  • thrombocytopenia

Interactions

  • Acetaminophen
  • Acetaminophen; Aspirin, ASA; Caffeine
  • Acetaminophen; Butalbital
  • Acetaminophen; Butalbital; Caffeine
  • Acetaminophen; Butalbital; Caffeine; Codeine
  • Acetaminophen; Caffeine
  • Acetaminophen; Caffeine; Dihydrocodeine
  • Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
  • Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
  • Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
  • Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine
  • Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine
  • Acetaminophen; Codeine
  • Acetaminophen; Dextromethorphan
  • Acetaminophen; Dextromethorphan; Doxylamine
  • Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine
  • Acetaminophen; Dextromethorphan; Phenylephrine
  • Acetaminophen; Dextromethorphan; Pseudoephedrine
  • Acetaminophen; Dichloralphenazone; Isometheptene
  • Acetaminophen; Diphenhydramine
  • Acetaminophen; Guaifenesin; Phenylephrine
  • Acetaminophen; Hydrocodone
  • Acetaminophen; Oxycodone
  • Acetaminophen; Pentazocine
  • Acetaminophen; Propoxyphene
  • Acetaminophen; Pseudoephedrine
  • Acetaminophen; Tramadol
  • Amprenavir
  • Atazanavir
  • Atazanavir; Cobicistat
  • Barbiturates
  • Benzhydrocodone; Acetaminophen
  • Bosentan
  • Carbamazepine
  • Cimetidine
  • Conivaptan
  • Dapsone
  • Darunavir
  • Darunavir; Cobicistat
  • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
  • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
  • Delavirdine
  • Efavirenz
  • Efavirenz; Emtricitabine; Tenofovir
  • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
  • Erythromycin
  • Erythromycin; Sulfisoxazole
  • Fluconazole
  • Fluorouracil, 5-FU
  • Fosamprenavir
  • Fosphenytoin
  • Imatinib
  • Indinavir
  • Itraconazole
  • Ketoconazole
  • Leucovorin
  • Levoleucovorin
  • Lopinavir; Ritonavir
  • Nelfinavir
  • Nevirapine
  • Ombitasvir; Paritaprevir; Ritonavir
  • Phenytoin
  • Protease inhibitors
  • Pyrimethamine
  • Pyrimethamine; Sulfadoxine
  • Rifamycins
  • Ritonavir
  • Rufinamide
  • Saquinavir
  • Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole
  • Telithromycin
  • Tipranavir
  • Trimethoprim
  • Voriconazole
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