Trimetrexate

Trimetrexate is an antimicrobial drug that has been approved for the treatment of moderate to severe Pneumocystis pneumonia (PCP) in people who are intolerant of or do not respond to cotrimoxazole (Septrin).1 It is also active against Toxoplasma gondii in the test tube.

Trimetrexate is administered intravenously. It must always be given with folinic acid (also known as leucovorin), an approved drug that is used to protect against the side-effects of folate antagonist drugs such as trimetrexate. Cells that absorb folinic acid are protected against trimetrexate, while those that do not absorb folinic acid can be seriously damaged by trimetrexate. Since folinic acid is taken up by human cells but not by Pneumocystis jiroveci organisms, the combination of folinic acid with trimetrexate allows the effects of the trimetrexate to be targeted against Pneumocystis. Without folinic acid, trimetrexate could cause serious or even fatal side-effects including bone marrow suppression and kidney or liver damage. Folinic acid treatment must be continued for 72 hours after the last dose of trimetrexate.

Even taken with folinic acid, trimetrexate can cause liver, kidney, gastrointestinal and blood toxicities. AZT (zidovudine, Retrovir) should be discontinued during trimetrexate treatment as both drugs can damage the bone marrow.

The combination of trimetrexate plus dapsone also seems to effective against PCP and is being studied further in trials.

Trimetrexate is also known as trimetrexate glucoronate. It is manufactured by US Bioscience Inc under the trade name Neutrexin.

References

  1. Allegra CJ et al. Trimetrexate for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. J Infect Dis 170: 165-172, 1994

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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.