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Leucovorin Side Effects

Medically reviewed by Last updated on April 21, 2020.

For the Consumer

Applies to leucovorin: powder for solution, solution, tablet

Side effects requiring immediate medical attention

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:


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


- reported with use in treatment of cancer

For Healthcare Professionals

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


Adverse events attributed to use of leucovorin/folinic acid by itself include allergic sensitization, including anaphylactoid reactions and urticaria; gastrointestinal and hematologic adverse events were common when used with fluorouracil.[Ref]


Very common (10% or more): Stomatitis (75%, when used with fluorouracil), nausea (74%, when used with fluorouracil), diarrhea (66%, when used with fluorouracil), vomiting (46%, when used with fluorouracil), dehydration (when used with fluorouracil)

Common (1% to 10%): Constipation (when used with fluorouracil)

Rare (less than 0.1%): Gastrointestinal disorders (after high doses)

Frequency not reported: Mucositis (when used with fluorouracil), cheilitis (when used with fluorouracil)[Ref]

When used with fluorouracil, diarrhea and dehydration have resulted in hospital admission and death.[Ref]


Very common (10% or more): Leucopenia (69%, when used with fluorouracil)

Common (1% to 10%): Thrombocytopenia (when used with fluorouracil)[Ref]


Very rare (less than 0.01%): Allergic reactions (sensitization, including anaphylactoid reactions, shock, and urticaria)

Frequency not reported: Stevens Johnson Syndrome and Toxic Epidermal Necrolysis (in combination with other agents)[Ref]


Very common (10% or more): Alopecia (42%, when used with fluorouracil), dermatitis (21%, when used with fluorouracil)

Frequency not reported: Palmar-plantar erythrodysesthesia (when used with fluorouracil)[Ref]


Very common (10% or more): Lethargy/malaise/fatigue (13%, when used with fluorouracil)

Uncommon (0.1% to 1%): Pyrexial reactions (following parenteral administration)[Ref]


Very common (10% or more): Anorexia (14%, when used with fluorouracil)

Frequency not reported: Hyperammonemia (when used with fluorouracil)


Common (1% to 10%): Infection (when used with fluorouracil)[Ref]

Nervous system

Rare (less than 0.1%): Increase in the frequency of attacks in epileptics, seizures, syncope[Ref]


Rare (less than 0.1%): Insomnia, agitation, depression[Ref]


1. Cerner Multum, Inc. "Australian Product Information." O 0

2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

3. "Product Information. Leucovorin Calcium (leucovorin)." Epic Pharma LLC, Laurelton, NY.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.