Drug Facts
Composition & Profile
Identifiers & Packaging
How Supplied/Storage and Handling Leucovorin Calcium Tablets USP 5 mg tablets are supplied as a white to off-white, round, biconvex tablet; debossed with “ING” above “181” on one side and scoreline on other side. NDC 50742-181-30: Bottle of 30 Tablets NDC 50742-181-01: Bottle of 100 Tablets 10 mg tablets are supplied as a white to off-white, round, biconvex tablet; debossed with “ING” above “182” on one side and scoreline on other side . NDC 50742-182-12: Bottle of 12 Tablets NDC 50742-182-24: Bottle of 24 Tablets 15 mg tablets are supplied as a peach colored, round, biconvex tablet; debossed with “ING” above “183” on one side and scoreline on other side. NDC 50742-183-24: Bottle of 24 Tablets 25 mg tablets are supplied as a peach colored, round, biconvex tablet; debossed with “ING” above “184” on one side and scoreline on other side. NDC 50742-184-25: Bottle of 25 Tablets Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect From Light and Moisture. References Grem JL, Shoemaker DD, Petrelli NJ, Douglas HO. Severe and fatal toxic effects observed in treatment with high- and low-dose leucovorin plus 5-fluorouracil for colorectal carcinoma. Cancer Treat Rep 1987;71:1122. Link MP, Goorin AM, Miser AW et al. The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med 1986;314:1600-1606. Manufactured for: Ingenus Pharmaceuticals, LLC Orlando, FL 32811 Rx Only 554301 Revised: 01/2023 logo; Package Label - Principal Display Panel – 5 mg, 30's Label ingenus NDC 50742-181-30 Leucovorin Calcium Tablets, USP 5 mg* Rx Only 30 Tablets 5 mg 30's Label; Package Label - Principal Display Panel – 5 mg, 100's Label ingenus NDC 50742-181-01 Leucovorin Calcium Tablets, USP 5 mg* Rx Only 100 Tablets 5 mg 100's Label; Package Label - Principal Display Panel – 10 mg, 12's Label ingenus NDC 50742-182-12 Leucovorin Calcium Tablets, USP 10 mg* Rx Only 12 Tablets 10 mg 12's Label; Package Label - Principal Display Panel – 10 mg, 24's Label ingenus NDC 50742-182-24 Leucovorin Calcium Tablets, USP 10 mg* Rx Only 24 Tablets 10 mg 24's Label; Package Label - Principal Display Panel – 15 mg, 24's Label ingenus NDC 50742-183-24 Leucovorin Calcium Tablets, USP 15 mg* Rx Only 24 Tablets 15 mg 24's Label; Package Label - Principal Display Panel – 25 mg, 25's Label ingenus NDC 50742-184-25 Leucovorin Calcium Tablets, USP 25 mg* Rx Only 25 Tablets 25 mg 25's Label
- How Supplied/Storage and Handling Leucovorin Calcium Tablets USP 5 mg tablets are supplied as a white to off-white, round, biconvex tablet; debossed with “ING” above “181” on one side and scoreline on other side. NDC 50742-181-30: Bottle of 30 Tablets NDC 50742-181-01: Bottle of 100 Tablets 10 mg tablets are supplied as a white to off-white, round, biconvex tablet; debossed with “ING” above “182” on one side and scoreline on other side . NDC 50742-182-12: Bottle of 12 Tablets NDC 50742-182-24: Bottle of 24 Tablets 15 mg tablets are supplied as a peach colored, round, biconvex tablet; debossed with “ING” above “183” on one side and scoreline on other side. NDC 50742-183-24: Bottle of 24 Tablets 25 mg tablets are supplied as a peach colored, round, biconvex tablet; debossed with “ING” above “184” on one side and scoreline on other side. NDC 50742-184-25: Bottle of 25 Tablets Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect From Light and Moisture. References Grem JL, Shoemaker DD, Petrelli NJ, Douglas HO. Severe and fatal toxic effects observed in treatment with high- and low-dose leucovorin plus 5-fluorouracil for colorectal carcinoma. Cancer Treat Rep 1987;71:1122. Link MP, Goorin AM, Miser AW et al. The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med 1986;314:1600-1606. Manufactured for: Ingenus Pharmaceuticals, LLC Orlando, FL 32811 Rx Only 554301 Revised: 01/2023 logo
- Package Label - Principal Display Panel – 5 mg, 30's Label ingenus NDC 50742-181-30 Leucovorin Calcium Tablets, USP 5 mg* Rx Only 30 Tablets 5 mg 30's Label
- Package Label - Principal Display Panel – 5 mg, 100's Label ingenus NDC 50742-181-01 Leucovorin Calcium Tablets, USP 5 mg* Rx Only 100 Tablets 5 mg 100's Label
- Package Label - Principal Display Panel – 10 mg, 12's Label ingenus NDC 50742-182-12 Leucovorin Calcium Tablets, USP 10 mg* Rx Only 12 Tablets 10 mg 12's Label
- Package Label - Principal Display Panel – 10 mg, 24's Label ingenus NDC 50742-182-24 Leucovorin Calcium Tablets, USP 10 mg* Rx Only 24 Tablets 10 mg 24's Label
- Package Label - Principal Display Panel – 15 mg, 24's Label ingenus NDC 50742-183-24 Leucovorin Calcium Tablets, USP 15 mg* Rx Only 24 Tablets 15 mg 24's Label
- Package Label - Principal Display Panel – 25 mg, 25's Label ingenus NDC 50742-184-25 Leucovorin Calcium Tablets, USP 25 mg* Rx Only 25 Tablets 25 mg 25's Label
Overview
Leucovorin calcium tablets USP contain either 5 mg, 10 mg, 15 mg or 25 mg leucovorin as the calcium salt of N -[4-[[(2-amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl] amino]benzoyl]- L -glutamic acid. This is equivalent to either 5.4 mg, 10.8 mg, 16.21 mg or 27.01 mg of anhydrous leucovorin calcium USP, respectively. In addition, each tablet contains the following inactive ingredients: lactose monohydrate, anhydrous lactose, microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate and FD&C yellow #6 (15 mg and 25 mg). Leucovorin is a water soluble form of reduced folate in the folate group; it is useful as an antidote to drugs which act as folic acid antagonists. These tablets are intended for oral administration only. The structural formula of leucovorin calcium is: Structural Formula
Indications & Usage
Leucovorin is indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists.
Dosage & Administration
Leucovorin calcium tablets are intended for oral administration. Because absorption is saturable, oral administration of doses greater than 25 mg is not recommended. Impaired Methotrexate Elimination or Inadvertent Overdosage Leucovorin rescue should begin as soon as possible after an inadvertent overdosage and within 24 hours of methotrexate administration when there is delayed excretion (see WARNINGS ). Leucovorin 15 mg (10 mg/m 2 ) should be administered IM, IV, or PO every 6 hours until the serum methotrexate level is less than 10 -8 M. In the presence of gastrointestinal toxicity, nausea, or vomiting, leucovorin should be administered parenterally. Serum creatinine and methotrexate levels should be determined at 24-hour intervals. If the 24-hour serum creatinine has increased 50% over baseline or if the 24-hour methotrexate level is greater than 5 x 10 -6 M or the 48-hour level is greater than 9 x 10 -7 M, the dose of leucovorin should be increased to 150 mg (100 mg/m 2 ) IV every 3 hours until the methotrexate level is less than 10 -8 M. Doses greater than 25 mg should be given parenterally (see CLINICAL PHARMACOLOGY ). Hydration (3 L/d) and urinary alkalinization with sodium bicarbonate should be employed concomitantly. The bicarbonate dose should be adjusted to maintain the urine pH at 7.0 or greater. The recommended dose of leucovorin to counteract hematologic toxicity from folic acid antagonists with less affinity for mammalian dihydrofolate reductase than methotrexate (i.e., trimethoprim, pyrimethamine) is substantially less, and 5 to 15 mg of leucovorin per day has been recommended by some investigators. Patients who experience delayed early methotrexate elimination are likely to develop reversible nonoliguric renal failure. In addition to appropriate leucovorin therapy, these patients require continuing hydration and urinary alkalinization, and close monitoring of fluid and electrolyte status, until the serum methotrexate level has fallen below 0.05 micromolar and the renal failure has resolved. Some patients will have abnormalities in methotrexate elimination or renal function following methotrexate administration, which are significant but less severe. These abnormalities may or may not be associated with significant clinical toxicity. If significant clinical toxicity is observed, leucovorin rescue should be extended for an additional 24 hours (total 14 doses over 84 hours) in subsequent courses of therapy. The possibility that the patient is taking other medications which interact with methotrexate (e.g., medications which may interfere with methotrexate elimination or binding to serum albumin) should always be reconsidered when laboratory abnormalities or clinical toxicities are observed.
Warnings & Precautions
WARNINGS In the treatment of accidental overdosage of folic acid antagonists, leucovorin should be administered as promptly as possible. As the time interval between antifolate administration (e.g., methotrexate) and leucovorin rescue increases, leucovorin’s effectiveness in counteracting hematologic toxicity decreases. Monitoring of the serum methotrexate concentration is essential in determining the optimal dose and duration of treatment with leucovorin. Delayed methotrexate excretion may be caused by a third space fluid accumulation (i.e., ascites, pleural effusion), renal insufficiency, or inadequate hydration. Under such circumstances, higher doses of leucovorin or prolonged administration may be indicated. Doses higher than those recommended for oral use must be given intravenously. Leucovorin may enhance the toxicity of fluorouracil. Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly leucovorin and fluorouracil. 1 Concomitant granulocytopenia and fever were present in some but not all of the patients. The concomitant use of leucovorin with trimethoprim-sulfamethoxazole for the acute treatment of Pneumocystis carinii pneumonia in patients with HIV infection was associated with increased rates of treatment failure and mortality in a placebo-controlled study.
Contraindications
Leucovorin is improper therapy for pernicious anemia and other megaloblastic anemias secondary to the lack of vitamin B 12 . A hematologic remission may occur while neurologic manifestations continue to progress.
Adverse Reactions
Allergic sensitization, including anaphylactoid reactions and urticaria, has been reported following the administration of both oral and parenteral leucovorin. To report SUSPECTED ADVERSE REACTIONS, contact Ingenus Pharmaceuticals, LLC at 1-877-748-1970 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch .
Drug Interactions
Folic acid in large amounts may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone, and increase the frequency of seizures in susceptible children. Preliminary animal and human studies have shown that small quantities of systemically administered leucovorin enter the CSF primarily as 5-methyltetrahydrofolate and, in humans, remain 1 to 3 orders of magnitude lower than the usual methotrexate concentrations following intrathecal administration. However, high doses of leucovorin may reduce the efficacy of intrathecally administered methotrexate. Leucovorin may enhance the toxicity of fluorouracil (see WARNINGS ).
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