Leucovorin Side Effects

It is possible that some side effects of leucovorin may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

For the Consumer

Applies to leucovorin: injectable, powder for solution, solution, tablet

Along with its needed effects, leucovorin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking leucovorin:

  • Skin rash, hives, or itching
  • wheezing

Check with your doctor as soon as possible if any of the following side effects occur while taking leucovorin:

Rare - reported with use in treatment of cancer
  • Convulsions (seizures)

For Healthcare Professionals

Applies to leucovorin: compounding powder, injectable powder for injection, injectable solution, oral tablet


Hypersensitivity side effects, including hives, pruritus, urticaria, anaphylactoid reaction, and anaphylaxis have rarely been associated with both oral and parenteral administration of leucovorin.


Gastrointestinal side effects associated with orally administered leucovorin include transient diarrhea. Diarrhea is usually observed when leucovorin is given with 5-fluorouracil. It typically resolves spontaneously.


Limited data suggest the importance of folic acid antagonism as the basis for methotrexate activity in rheumatoid arthritis. More data are needed.

Musculoskeletal side effects have included increased musculoskeletal complaints and arthralgias, which have been associated with the use of low-dose orally administered leucovorin used to ameliorate side effects from methotrexate in patients with rheumatoid arthritis.


Hematologic side effects have included rare cases of thrombocytosis.


Respiratory side effects have included rare complaints of wheezing.

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