Leucovorin Side Effects

Medically reviewed by Drugs.com. Last updated on Mar 20, 2025.

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

Serious side effects of leucovorin

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:

Rare side effects

• 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 side effects

- 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.

General adverse events

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]

Gastrointestinal

• 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]

Hematologic

• Very common (10% or more): Leucopenia (69%, when used with fluorouracil)
• Common (1% to 10%): Thrombocytopenia (when used with fluorouracil)^[Ref]

Hypersensitivity

• 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]

Dermatologic

• 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]

Other

• Very common (10% or more): Lethargy/malaise/fatigue (13%, when used with fluorouracil)
• Uncommon (0.1% to 1%): Pyrexial reactions (following parenteral administration)^[Ref]

Metabolic

• Very common (10% or more): Anorexia (14%, when used with fluorouracil)
• Frequency not reported: Hyperammonemia (when used with fluorouracil)

Immunologic

• 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]

Psychiatric

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

Further information

Leucovorin side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

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