What the FDA labels say about taking them together
Leucovorin and methotrexate
Leucovorin's FDA label of March 19, 2025 names methotrexate in its drug interactions section, and methotrexate's label names leucovorin too. The leucovorin label: “… 5-methyltetrahydrofolate and, in humans, remain 1-3 orders of magnitude lower than the usual methotrexate concentrations following intrathecal administration.”
Check it at the source: the leucovorin FDA label on DailyMed (effective March 19, 2025, Meitheal Pharmaceuticals Inc.); the methotrexate FDA label on DailyMed (effective May 27, 2026, Accord Healthcare Inc.).
What does the leucovorin label say about methotrexate?
Leucovorin label, drug interactionsPreliminary animal and human studies have shown that small quantities of systemically administered leucovorin calcium enter the CSF primarily as 5-methyltetrahydrofolate and, in humans, remain 1-3 orders of magnitude lower than the usual methotrexate concentrations following intrathecal administration.
Leucovorin label, warningsAs the time interval between antifolate administration (e.g., methotrexate) and leucovorin rescue increases, leucovorin calcium's effectiveness in counteracting toxicity decreases.
Source: FDA drug label (leucovorin calcium), Meitheal Pharmaceuticals Inc., effective March 19, 2025 (SPL set 9df20901-6980-4d4e-89ec-40f3c1f91852), via openFDA; the full label on DailyMed
What does the methotrexate label say about leucovorin?
Rasuvo label (Medexus Pharma Inc., December 15, 2025), drug interactionsPreliminary animal and human studies have shown that small quantities of intravenously administered leucovorin enter the CSF primarily as 5-methyltetrahydrofolate and, in humans, remain 1 to 3 orders of magnitude lower than the usual methotrexate concentrations following intrathecal administration.
Rasuvo label (Medexus Pharma Inc., December 15, 2025), warnings and precautionsIf necessary, this could include the use of leucovorin calcium and/or acute, intermittent hemodialysis with a high-flux dialyzer [see Overdosage (10) ].
Source: FDA drug label (Rasuvo, NDA205776), Medexus Pharma Inc., effective December 15, 2025 (SPL set d0075461-0e7e-4967-9c9b-d6440e912c0e), via openFDA
Source: FDA drug label (Methotrexate), Accord Healthcare Inc., effective May 27, 2026 (SPL set 874c7f43-a3be-4236-89cc-24c44e3c5813), via openFDA; the full label on DailyMed
These are the labels' own sentences. PlainMeds does not grade interactions; a pharmacist or prescriber can say what they mean for one person's medicines.
Both medicines on the record
| Leucovorin | Methotrexate | |
|---|---|---|
| Labeled for | Colorectal cancer | Rheumatoid arthritis, Psoriasis, Leukemia, lymphoma and myeloma, Breast cancer |
| Boxed warning | No | Yes |
| Pharmacy cost (NADAC) | $0.330 per tablet 5 mg tablet | $0.158 per tablet 2.5 mg tablet |
| Shortage now | No current entry | In shortage |
Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)
What next?
- Check more medicines together
- up to five at once