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Leevarin 15 Tablets

Generic Name- Leucovorin calcium

Drug Class- Folate Analog

Description- Leucovorin, also known as folinic acid, is a naturally occurring, reduced form of folic acid. It is usually indicated as an antidote to reduce toxic effects of methotrexate and for use in combination with 5-fluorouracil in various cancers. It is converted into tetrahydrofolate , without requiring metabolism by dihydrofolate reductase. Tetrahydrofolate is an essential enzyme for synthesis of purines and pyrimidine. It allows for some purine/pyrimidine synthesis, diminishing the toxic effects of folic acid antagonist-type chemotherapeutic drugs while still permitting the antitumor activity of the folic acid antagonist through dihydrofolate reductase inhibition.


Product Description

Leevarin 15 (Leucovorin calcium) tablets are intended for oral administration.

Indications and Usage

  • Leucovorin calcium is indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists

Limitations of Use

  • Leucovorin calcium in tablet form is not intended for use in combination with 5-FU in various cancers such as colorectal cancer because higher plasma levels of drugs are not attained through oral administration

Dosage and Administration

Leucovorin Rescue after High-Dose Methotrexate Therapy:

  • Recommended dose of leucovorin, when serum methotrexate levels are approximately 10 micromolar at 24 hours after administration, 1 micromolar at 48 hours, and less than 0.2 micromolar at 72 hours: 15 mg PO every 6 hours for 60 hours (10 doses starting at 24 hours after start of methotrexate infusion)
  • Recommended dose of leucovorin when serum methotrexate level remaining above 0.2 micromolar at 72 hours, and more than 0.05 micromolar at 96 hours after administration: Continue 15 mg PO every 6 hours, until methotrexate level is less than 0.05 micromolar

Leucovorin rescue after impaired methotrexate elimination or inadvertent over dosage:

  • Recommended dose of leucovorin after an inadvertent overdosage and within 24 hours of methotrexate administration when there is delayed excretion: 10 mg/m2 PO every 6 hours until serum methotrexate level is less than 10-8 M3,5

Dosage Form and Strengths

  • Supplied as tablets for oral use
  • Available as 15mg

Clinical Efficacy

  • Effective in preventing myelosuppression, gastrointestinal toxicity, nephrotoxicity and neurotoxicity that can result secondary to high dosages of methotrexate and other folic acid antagonists1
  • Reduces the incidence of transaminitis (hepatic damage), gastrointestinal complications, and stomatitis (oral ulcers) when administered after weekly doses of methotrexate1

Adverse Reactions

  • The most commonly reported adverse events following administration of leucovorin calcium include GI upset (nausea, vomiting diarrhea), leukopenia, alopecia, stomatitis, erythema, pruritus, skin rash, and urticaria


  • It is contraindicated in patients with a known hypersensitivity to leucovorin calcium

Special Precautions

  • Neurological manifestations and hematological remission may progress in patients receiving leucovorin therapy for the treatment of megaloblastic anemia, particularly in the presence of concurrent vitamin B12 deficiency or pernicious anemia, so caution is necessary in these patients
  • It is essential to monitor serum methotrexate concentration for determining the optimal dose and duration of treatment with leucovorin
  • Higher doses of leucovorin or prolonged administration may be indicated in patients with delayed methotrexate excretion caused by a third space fluid accumulation (i.e., ascites, pleural effusion), renal insufficiency, or inadequate hydration
  • Concomitant use of leucovorin with trimethoprim-sulfamethoxazole for the acute treatment of Pneumocystis carinii pneumonia in patients with HIV infection can cause increased rates of treatment failure and mortality 
  • Leucovorin may enhance the toxicity of fluorouracil, leading to severe gastrointestinal effects, diarrhea and dehydration, so caution should be used
  • Leucovorin calcium can counteract the antiepileptic effect of phenobarbital, phenytoin and primidone, and increase the frequency of seizures in susceptible children
  • Pregnant women and breast feeding mothers should receive leucovorin calcium only when needed and caution should be exercised as there is a lack of studies to determine the effects of leucovorin on fetus
Chemotherapy Tablet Leucovorin Calcium 15mg Manufacturer