FDA

Leucovorin Calcium

Approved 22 Feb 1993OralTablet

The FDA lists this product in 60 strengths and forms.

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Indications

Leucovorin is a folate analog indicated:

To reduce the toxicity of: o Methotrexate in adult patients with impaired methotrexate elimination, and o Folic acid antagonists or dihydrofolate reductase (DHFR) inhibitors following an overdose in adult patients. ( 1.1 )
For the treatment of cerebral folate transport deficiency in adult and pediatric patients who have a confirmed variant in the folate receptor 1 gene (FOLR1-CFTD). ( 1.2 ) Limitations of Use Leucovorin is not recommended for use in patients with a deficiency of methenyltetrahydrofolate synthetase (MTHFS) because MTHFS is a primary enzyme in the metabolism of leucovorin to 5-methenyltetrahydrofolate. ( 1.2 ) Limitations of Use Leucovorin is not indicated for the treatment of pernicious anemia or other megaloblastic anemias, due to the lack of vitamin B12, because of the risk of progression of neurologic manifestations despite hematologic remission. ( 1.3 )

1.1Reduction of Toxicity of Folic Acid Antagonists or Dihydrofolate Reductase Inhibitors

Leucovorin is indicated to reduce the toxicity of:

Methotrexate in adult patients with impaired methotrexate elimination, and
Folic acid antagonists or dihydrofolate reductase (DHFR) inhibitors following an overdose in adult patients.

1.2Cerebral Folate Transport Deficiency with Folate Receptor 1 Genetic Variant

Leucovorin is indicated for the treatment of cerebral folate transport deficiency in adult and pediatric patients who have a confirmed variant in the folate receptor 1 gene (FOLR1-CFTD). Limitations of Use Leucovorin is not recommended for use in patients with a deficiency of methenyltetrahydrofolate synthetase (MTHFS) because MTHFS is a primary enzyme in the metabolism of leucovorin to 5-methenyltetrahydrofolate (5-MTHF) [see Clinical Pharmacology ( 12.3 )] .

1.3Limitations of Use

Leucovorin is not indicated for the treatment of pernicious anemia or other megaloblastic anemias, due to the lack of vitamin B12, because of the risk of progression of neurologic manifestations despite hematologic remission.

Contraindications

Leucovorin is contraindicated in patients with a history of hypersensitivity reaction depending on indication as described below, to leucovorin (folinic acid), levoleucovorin, folic acid, or any component of leucovorin [see Description ( 11 )] :

At a glance

Brand name: Leucovorin Calcium
Route: Oral
Dosage form: Tablet
Applicant: Hikma
Status: Prescription
FDA approval: 22 Feb 1993
Application: ANDA072736-001

Indications

Leucovorin is a folate analog indicated:

To reduce the toxicity of: o Methotrexate in adult patients with impaired methotrexate elimination, and o Folic acid antagonists or dihydrofolate reductase (DHFR) inhibitors following an overdose in adult patients. ( 1.1 )
For the treatment of cerebral folate transport deficiency in adult and pediatric patients who have a confirmed variant in the folate receptor 1 gene (FOLR1-CFTD). ( 1.2 ) Limitations of Use Leucovorin is not recommended for use in patients with a deficiency of methenyltetrahydrofolate synthetase (MTHFS) because MTHFS is a primary enzyme in the metabolism of leucovorin to 5-methenyltetrahydrofolate. ( 1.2 ) Limitations of Use Leucovorin is not indicated for the treatment of pernicious anemia or other megaloblastic anemias, due to the lack of vitamin B12, because of the risk of progression of neurologic manifestations despite hematologic remission. ( 1.3 )

1.1Reduction of Toxicity of Folic Acid Antagonists or Dihydrofolate Reductase Inhibitors

Leucovorin is indicated to reduce the toxicity of:

Methotrexate in adult patients with impaired methotrexate elimination, and
Folic acid antagonists or dihydrofolate reductase (DHFR) inhibitors following an overdose in adult patients.

1.2Cerebral Folate Transport Deficiency with Folate Receptor 1 Genetic Variant

1.3Limitations of Use

Interactions

Certain Antiepileptic Drugs : Increase monitoring for seizure activity in leucovorin-treated patients taking certain concomitant antiepileptic drugs. Certain antiepileptic drugs may reduce the effectiveness of leucovorin. ( 7.1 , 7.2 )
Trimethoprim-Sulfamethoxazole : Avoid concomitant use of leucovorin with trimethoprim-sulfamethoxazole. ( 7.1 )
Fluorouracil : Leucovorin may enhance the toxicity of fluorouracil. Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients. ( 7.1 )

7.1Effects of Leucovorin on Other Drugs Certain Antiepileptic Drugs

Increase monitoring for seizure activity in leucovorin-treated patients taking certain concomitant antiepileptic drugs. Folic acid in high doses may reduce the effectiveness of certain antiepileptic drugs (e.g., phenobarbital, phenytoin, and primidone) and thereby increase the frequency of seizures in susceptible patients, including pediatric patients. It is not known whether folinic acid, including leucovorin, has the same effects; however, both folic and folinic acids, including leucovorin, share some common metabolic pathways.

Trimethoprim-Sulfamethoxazole Avoid concomitant use of leucovorin with trimethoprim-sulfamethoxazole. The effectiveness of trimethoprim-sulfamethoxazole can be decreased if used concomitantly with leucovorin, which was associated with increased rates of treatment failure and mortality in patients with HIV infection who receive trimethoprim-sulfamethoxazole for the acute treatment of Pneumocystis jirovecii pneumonia. Fluorouracil 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.

7.2Effect of Other Drugs on Leucovorin

Certain antiepileptic drugs may reduce folate absorption and metabolism leading to folate deficiency. As folic acid and folinic acid share common metabolic pathways, certain antiepileptic drugs may reduce the effectiveness of leucovorin.

Leucovorin Calcium

Indications

1.1Reduction of Toxicity of Folic Acid Antagonists or Dihydrofolate Reductase Inhibitors

1.2Cerebral Folate Transport Deficiency with Folate Receptor 1 Genetic Variant

1.3Limitations of Use

Contraindications

At a glance

Two medicines in one question?

Leucovorin Calcium

Indications

1.1Reduction of Toxicity of Folic Acid Antagonists or Dihydrofolate Reductase Inhibitors

1.2Cerebral Folate Transport Deficiency with Folate Receptor 1 Genetic Variant

1.3Limitations of Use

Contraindications

At a glance

Two medicines in one question?

Warnings and precautions

5.1Hypersensitivity Reactions

Interactions

7.1Effects of Leucovorin on Other Drugs Certain Antiepileptic Drugs

7.2Effect of Other Drugs on Leucovorin

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

Composition

Strengths and forms

Official product information