FDA

Leucovorin Calcium Preservative Free

Approved 26 Oct 2017InjectionInjectable

The FDA lists this product in 18 strengths and forms.

Indications

Leucovorin calcium rescue is indicated after high-dose methotrexate therapy in osteosarcoma. Leucovorin Calcium for Injection is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists. Leucovorin Calcium for Injection is indicated in the treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible.

Leucovorin Calcium for Injection is also indicated for use in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. Leucovorin Calcium for Injection should not be mixed in the same infusion as 5-fluorouracil because a precipitate may form.

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.

Warnings and precautions

In the treatment of accidental overdosages of folic acid antagonists, intravenous leucovorin should be administered as promptly as possible. As the time interval between antifolate administration [e.g., methotrexate (MTX)] and leucovorin rescue increases, leucovorin's effectiveness in counteracting toxicity decreases. In the treatment of accidental overdosages of intrathecally administered folic acid antagonists, do not administer leucovorin intrathecally.

LEUCOVORIN MAY BE HARMFUL OR FATAL IF GIVEN INTRATHECALLY. Monitoring of the serum MTX concentration is essential in determining the optimal dose and duration of treatment with leucovorin. Delayed MTX 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. Because of the benzyl alcohol contained in certain diluents used for leucovorin, when doses greater than 10 mg/m 2 are administered, leucovorin should be reconstituted with Sterile Water for Injection, USP, and used immediately (see DOSAGE AND ADMINISTRATION ). Because of the calcium content of the leucovorin solution, no more than 160 mg of leucovorin should be injected intravenously per minute (16 mL of a 10 mg per mL, or 8 mL of a 20 mg per mL solution per minute).

Indications

Warnings and precautions

Adverse reactions

Allergic sensitization, including anaphylactoid reactions and urticaria, has been reported following administration of both oral and parenteral leucovorin. No other adverse reactions have been attributed to the use of leucovorin per se . Table 1 summarizes significant adverse events occurring in 316 patients treated with the leucovorin-5-fluorouracil combinations compared against 70 patients treated with 5-fluorouracil alone for advanced colorectal carcinoma.

These data are taken from the Mayo/NCCTG large multicenter prospective trial evaluating the efficacy and safety of the combination regimen. TABLE 1 PERCENTAGE OF PATIENTS TREATED WITH LEUCOVORIN/FLUOROURACIL FOR ADVANCED COLORECTAL CARCINOMA REPORTING ADVERSE EXPERIENCES OR HOSPITALIZED FOR TOXICITY High LV = Leucovorin 200 mg/m 2 , Low LV = Leucovorin 20 mg/m 2 Any = percentage of patients reporting toxicity of any severity Grade 3+ = percentage of patients reporting toxicity of grade 3 or higher (High LV)/5-FU (N=155) (Low LV)/5-FU (N=161) 5-FU Alone (N=70) Any (%) Grade 3+ (%) Any (%) Grade 3+ (%) Any (%) Grade 3+ (%) Leukopenia 69 14 83 23 93 48 Thrombocytopenia 8 2 8 1 18 3 Infection 8 1 3 1 7 2 Nausea 74 10 80 9 60 6 Vomiting 46 8 44 9 40 7 Diarrhea 66 18 67 14 43 11 Stomatitis 75 27 84 29 59 16 Constipation 3 0 4 0 1 - Lethargy/Malaise/Fatigue 13 3 12 2 6 3 Alopecia 42 5 43 6 37 7 Dermatitis 21 2 25 1 13 - Anorexia 14 1 22 4 14 - Hospitalization for Toxicity 5% 15% 7% TABLE 2 GUIDELINES FOR LEUCOVORIN CALCIUM DOSAGE AND ADMINISTRATION DO NOT ADMINISTER LEUCOVORIN CALCIUM INTRATHECALLY Clinical Situation Laboratory Findings Leucovorin Calcium Dosage and Duration Normal Methotrexate Elimination Serum methotrexate level 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, IM, or IV q 6 hours for 60 hours (10 doses starting at 24 hours after start of methotrexate infusion).

Delayed Late Methotrexate Elimination 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, IM, or IV q 6 hours, until methotrexate level is less than 0.05 micromolar. Delayed Early Methotrexate Elimination and/or Evidence of Acute Renal Injury Serum methotrexate level of 50 micromolar or more at 24 hours, or 5 micromolar or more at 48 hours after administration, OR; a 100% or greater increase in serum creatinine level at 24 hours after methotrexate administration (e.g., an increase from 0.5 mg/dL to a level of 1 mg/dL or more). 150 mg IV q 3 hours, until methotrexate level is less than 1 micromolar; then 15 mg IV q 3 hours until methotrexate level is less than 0.05 micromolar.

To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals, Inc. at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Leucovorin Calcium Preservative Free

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Leucovorin Calcium Preservative Free

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Interactions

Pregnancy and breastfeeding

Adverse reactions

Composition

Strengths and forms

Official product information

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