Antifolate Toxicities and Supportive Agents
| DRUG | TOXICITIES | SUPPORTIVE CARE and RESCUE |
|---|
| Methotrexate (MTX) | - Mucositis, nausea/vomiting, hepatotoxicity, impaired fertility, diarrhea, modest cytopenias
- Bactrim (trimethoprim/sulfamethoxazole) increases MTX-related myelosuppression, mucositis, nephrotoxicity
- MTX can accumulate in third spaces, which can slow renal elimination rates and increase exposure, thereby increasing toxicity. Special attention must be made for pleural or pericardial effusion, ascites, or severe leg edema
| |
| High-dose methotrexate | Acute kidney injury (AKI), neurotoxicity | - Urine alkalization prevents AKI
- Glucarpidase rescues from severe AKI
- Leucovorin prevents other life-threatening toxicities
|
| Pemetrexed (PMX) | Rash, diarrhea, cytopenias | - Dexamethasone to prevent rash
- Low doses of folic acid and intramuscular vitamin B12 are recommended to attenuate PMX and PDX-related cytopenias but does not reduce the anticancer efficacy of these agents
|
| Pralatrexate (PDX) | Mucositis, nausea, cytopenias, constipation, diarrhea | - Folic acid and vitamin B12 to prevent cytopenias
|