Leucovorin Calcium Information
Leucovorin calcium (Leucovorin calcium)
Leucovorin calcium (Leucovorin calcium) Description
Leucovorin calcium (Leucovorin calcium) Tablets contain either 5 mg or 25 mg leucovorin as the calcium salt of -[4-[[(2-amino-5-formyl-1, 4, 5, 6, 7, 8-hexahydro-4-oxo-6-pteridinyl)-methyl]amino]benzoyl]--glutamic acid. This is equivalent to 5.40 mg or 27.01 mg of anhydrous Leucovorin calcium (Leucovorin calcium) . In addition each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. The 25mg tablet also contains D&C yellow no. 10 and FD&C blue no. 1.
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 (Leucovorin calcium) is:
CHCaNO Molecular Weight: 511.51
Leucovorin calcium (Leucovorin calcium) Clinical Pharmacology
Leucovorin is a racemic mixture of the diastereoisomers of the 5-formyl derivative of tetrahydrofolic acid. The biologically active compound of the mixture is the (-)--isomer, known as , or (-)-folinic acid. Leucovorin does not require reduction by the enzyme dihydrofolate reductase in order to participate in reactions utilizing folates as a source of “one-carbon” moieties. Following oral administration, leucovorin is rapidly absorbed and enters the general body pool of reduced folates. The increase in plasma and serum folate activity (determined microbiologically with ) seen after oral administration of leucovorin is predominantly due to 5-methyltetrahydrofolate.
Twenty normal men were given a single, oral 15 mg dose (7.5 mg/m) of Leucovorin calcium (Leucovorin calcium) and serum folate concentrations were assayed with . Mean values observed ( one standard error) were:
Oral tablets yielded areas under serum folate concentration-time curves (AUCs) that were 12% greater than equal amounts of leucovorin given intramuscularly and equal to the same amounts given intravenously.
Oral absorption of leucovorin is saturable at doses above 25 mg. The apparent bioavailability of leucovorin was 97% for 25 mg, 75% for 50 mg and 37% for 100 mg.
Leucovorin calcium (Leucovorin calcium) Indications And Usage
Leucovorin calcium (Leucovorin calcium) tablets are indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists.
Leucovorin calcium (Leucovorin calcium) Contraindications
Leucovorin is improper therapy for pernicious anemia and other megaloblastic anemias secondary to the lack of vitamin B. A hematologic remission may occur while neurological manifestations continue to progress.
Leucovorin calcium (Leucovorin calcium) 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. 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 pneumonia in patients with HIV infection was associated with increased rates of treatment failure and mortality in a placebo controlled study.
Leucovorin calcium (Leucovorin calcium) Precautions
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 CSF primarily as 5-methyltetrahydrofolate and, in humans, remain 1 to 3 orders of magnitude lower than 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).
Leucovorin calcium (Leucovorin calcium) Adverse Reactions
Allergic sensitization, including anaphylactoid reactions and urticaria, has been reported following the administration of both oral and parenteral leucovorin.
Leucovorin calcium (Leucovorin calcium) Overdosage
Excessive amounts of leucovorin may nullify the chemotherapeutic effect of folic acid antagonists.
Leucovorin calcium (Leucovorin calcium) Dosage And Administration
Leucovorin calcium (Leucovorin calcium) tablets are intended for oral administration. Because absorption is saturable, oral administration of doses greater than 25 mg is not recommended.
Leucovorin calcium (Leucovorin calcium) How Supplied:
Leucovorin calcium (Leucovorin calcium) Tablets, USP are available as:
5 mg: White, round, unscored, biconvex tablets. Debossed with on one side and 484 on the other side.
NDC 51079-581-06 - Unit dose blister packages of 50 (5 cards of 10 tablets each).
25 mg: Pale green, round, unscored, biconvex tablets. Debossed with on one side and 485 on the other side.
NDC 51079-582-05 - Unit dose blister packages of 20 (2 cards of 10 tablets each).
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]Protect from light and moisture.
Leucovorin calcium (Leucovorin calcium)
Leucovorin calcium (Leucovorin calcium)
Leucovorin calcium (Leucovorin calcium)
