Calcium folinate, also known as folinic acid, is a reduced form of folic acid used to prevent or treat folate deficiency and to “rescue” normal cells from the toxic effects of high-dose Methotrexate. It is also combined with 5-Fluorouracil to enhance cancer treatment and used in treating megaloblastic anemia. First synthesized in the 1940s during studies on folate metabolism, calcium folinate became widely used in the 1950s and 1960s for anemia and as a methotrexate antidote, with the calcium salt favored for its stability and ease of administration.
BRAND NAMES
Some common brand names for Calcium folinate include:
Leucovorin
Wellcovorin
Elosar
Fusilev
MECHANISM OF ACTION
Calcium folinate works by bypassing the enzyme blocked by folic acid antagonists, restoring essential folate in cells needed for DNA and protein synthesis. This protects normal cells from drugs like methotrexate and, when combined with 5-fluorouracil, enhances its anticancer effects.
PHARMACOKINETICS
Absorption
Calcium folinate is well absorbed orally, with peak blood levels usually reached within 1–2 hours after administration. Its absorption is efficient, allowing both oral and intravenous forms to be used effectively, depending on the clinical need.
Distribution
Calcium folinate is widely distributed in body tissues, including the liver, kidney, and bone marrow. Its volume of distribution (Vd) is approximately 0.4–0.8 L/kg in adults. It crosses the placenta but only minimally penetrates the blood-brain barrier.
Metabolism
Calcium folinate is partially metabolized in the liver to active and inactive folate derivatives, including 5-methyltetrahydrofolate. It does not require activation by dihydrofolate reductase, allowing it to bypass the metabolic block caused by folate antagonists like methotrexate.
Excretion
Calcium folinate is primarily excreted by the kidneys through urine, mostly as unchanged drug and its metabolites. Renal clearance is rapid, with a half-life of approximately 6–12 hours, depending on dose and kidney function.
PHARMACODYNAMICS
Calcium folinate restores active folate in cells, supporting DNA and protein synthesis. It protects healthy cells from methotrexate toxicity and boosts the anticancer effect of 5-fluorouracil by enhancing its action on thymidylate synthase.
DOSAGE AND ADMINISTRATION
Calcium folinate can be given orally or intravenously. For methotrexate rescue, it is usually started 24 hours after methotrexate at doses of 10–100 mg/m² every 6–12 hours. For use with 5-fluorouracil, typical doses are 20–25 mg/m² before chemotherapy, adjusted as needed for kidney function or treatment protocol.
CONTRAINDICATIONS
Calcium folinate is contraindicated in patients with known hypersensitivity to folinic acid or any of its components. Caution is advised in patients with undiagnosed anemia or vitamin B12 deficiency, as it may mask hematologic signs and delay diagnosis. It should also be used carefully in patients with renal impairment, where accumulation may occur.
DRUG INTERACTIONS
Methotrexate: Calcium folinate reduces toxicity but may decrease the efficacy of methotrexate in cancer therapy if used too early.
5-Fluorouracil (5-FU): Calcium folinate enhances its anticancer effect.
Anticonvulsants (e.g., phenytoin, phenobarbital): May reduce folate activity.
Trimethoprim or pyrimethamine: Can interfere with folate metabolism, altering effectiveness.
FOOD INTERACTIONS
Calcium folinate has no significant food interactions, and its absorption is not affected by meals, so it can be taken with or without food. However, a well-balanced diet with adequate folate may support its therapeutic effects.
SIDE EFFECTS
Allergic reactions: Rash, itching, or hives
Gastrointestinal: Nausea, vomiting, diarrhea, or abdominal discomfort
Fever or malaise in some patients
Rarely, hypersensitivity reactions like bronchospasm or anaphylaxis may occur
OVER DOSE
Calcium folinate overdose is rare and usually well tolerated because it is a naturally occurring form of folate. Symptoms may include nausea, vomiting, or abdominal discomfort. Severe toxicity is uncommon, but in case of overdose, supportive care is recommended, and monitoring of renal function may be necessary.
TOXICITY
Calcium folinate has low toxicity even at high doses because it is a reduced form of folic acid. It is generallywell tolerated, and serious adverse effects are rare. Excessive doses may cause gastrointestinalsymptoms such as nausea, vomiting, or diarrhea, and very rarely allergic reactions. There is no significant organ toxicity reported at therapeutic or moderately high doses.
