Leucovorin Side Effects

Not all side effects for leucovorin may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

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

In addition to its needed effects, some unwanted effects may be caused by leucovorin. In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking leucovorin:

  • Skin rash, hives, or itching
  • wheezing

If any of the following side effects occur while taking leucovorin, check with your doctor or nurse as soon as possible:

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.[Ref]


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.[Ref]


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

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.[Ref]


Hematologic side effects have included rare cases of thrombocytosis.[Ref]


Respiratory side effects have included rare complaints of wheezing.[Ref]


1. "Product Information. Wellcovorin (leucovorin)." Glaxo Wellcome, Research Triangle Park, NC.

2. Strom CM, Brusca RM, Pizzi WJ "Double-blind, placebo-controlled crossover study of folinic acid (Leucovorin for the treatment of fragile X syndrome." Am J Med Genet 44 (1992): 676-82

3. Tishler M, Caspi D, Fishel B, Yaron M "The effects of leucovorin (folinic acid) on methotrexate therapy in rheumatoid arthritis patients." Arthritis Rheum 31 (1988): 906-8

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