Levoleucovorin Calcium (levoleucovorin calcium)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Levoleucovorin calcium, the levorotatory (l) isomer of racemic d,l-leucovorin, is one of several active, chemically reduced derivatives of folic acid.
Levoleucovorin is the levorotatory (l) isomer of racemic d,l-leucovorin. Levoleucovorin is the pharmacologically active isomer and constitutes approximately 50% of racemic leucovorin; therefore, the effects of levoleucovorin are observed at half the dose of racemic leucovorin. Because levoleucovorin is a reduced derivative of folic acid and does not require reduction by dihydrofolate reductase to participate in reactions utilizing folates, the drug counteracts the therapeutic and toxic effects of folic acid antagonists (e.g., methotrexate).
The drug also enhances the efficacy and toxicity of fluoropyrimidines (e.g., fluorouracil) by stabilizing binding of the fluorouracil metabolite 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) to thymidylate synthase (an enzyme responsible for DNA repair and replication), thus enhancing inhibition of this enzyme.
Levoleucovorin is actively and passively transported across cell membranes. In vivo, levoleucovorin is converted to 5-methyltetrahydrofolic acid (5-methyl-THF), the primary circulating form of active reduced folate. Levoleucovorin and 5-methyl-THF are polyglutamated intracellularly by the enzyme folylpolyglutamate synthetase.
Folylpolyglutamates are active and participate in numerous biochemical pathways that require reduced folate.
Following IV administration of a single 15-mg dose of levoleucovorin in healthy male volunteers, peak serum concentrations of (6S)-5-methyl-5,6,7,8-tetrahydrofolate (the l-isomer of 5-methyl-THF) were reached within 0.9 hours. The mean terminal half-life of total tetrahydrofolate and (6S)-5-methyl-5,6,7,8-tetrahydrofolate were 5.1 and 6.8 hours, respectively. Levoleucovorin and its metabolites are excreted in urine.
Data from several crossover studies in healthy individuals and patients with colorectal cancer have shown no substantial differences in exposure to the l-isomer of leucovorin or to 5-methyltetrahydrofolate regardless of whether IV racemic leucovorin or an equipotent dose of IV levoleucovorin is administered.
USES: This medication is used to treat or prevent serious blood cell disorders (such as thrombocytopenia, neutropenia, anemia) caused by certain drugs (folic acid antagonists such as methotrexate, trimethoprim, pyrimethamine). Some brands may also be used with a certain cancer drug (5-fluorouracil) to treat patients with colon cancer.
Generic name: levoleucovorin calcium
Pronunciation: (LEE-voe-LOO-koe-VOR-in)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Levoleucovorin Calcium
Indications
The following indications are listed for Levoleucovorin Calcium:
- Adjunct To Fluorouracil Treatment Of Colorectal Cancer
- Bone Marrow Suppression Due To Folic Acid Antagonism
- Methotrexate Toxicity
- Pyrimethamine Toxicity
- Sulfadiazine Toxicity
- Trimethoprim Toxicity
- Trimetrexate Toxicity
Also known as: Adjunct To Fluorouracil Treatment Of Adenocarcinoma Of Colon And Rectum, Adjuvant Therapy With 5-Fu For Colorectal Cancer, Bone Marrow Depression Due To Folic Acid Antagonism, Bone Marrow Hypoplasia Due To Folic Acid Antagonism, Hypoplasia Of Bone Marrow Due To Folic Acid Antagonism, Mtx Toxicity, Myelosuppression Due To Folic Acid Antagonism, Tmp Toxicity.
Dosing
Levoleucovorin is commercially available as the calcium pentahydrate; dosage of the drug is expressed in terms of levoleucovorin (i.e., 64 mg of levoleucovorin calcium pentahydrate is equivalent to 50 mg of levoleucovorin).
Levoleucovorin is dosed at one-half the usual dosage of racemic leucovorin. (See Description.) The manufacturer makes no specific recommendations regarding dosage in pediatric patients; however, safety and efficacy of levoleucovorin have been evaluated in 16 patients 6-21 years of age. (See Uses: Toxicity Associated with Folic Acid Antagonists.)
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Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Pernicious anemia or other megaloblastic anemias secondary to lack of vitamin B12; such use may obscure the diagnosis of pernicious anemia by alleviating hematologic manifestations while allowing neurologic complications to progress.
Hypersensitivity to folic acid or folinic acid.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in more than 15% of patients receiving levoleucovorin rescue following high-dose methotrexate therapy include vomiting, stomatitis, and nausea. Less frequently reported adverse effects, occurring in less than 10% of patients, include diarrhea, dyspepsia, typhlitis, dyspnea, dermatitis, confusion, neuropathy, abnormal renal function, and taste perversion.
Adverse effects reported in more than 50% of patients with advanced-stage colorectal cancer receiving levoleucovorin in combination with fluorouracil include diarrhea, nausea, and stomatitis. Other frequently reported adverse effects, occurring in 20-40% of patients, include vomiting, asthenia/fatigue/malaise, anorexia/decreased appetite, dermatitis, and alopecia. The incidence of adverse effects is similar to that reported in patients receiving an equipotent dosage of racemic leucovorin in combination with fluorouracil.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of levoleucovorin have been evaluated in 16 patients 6-21 years of age. (See Uses: Toxicity Associated with Folic Acid Antagonists.) The manufacturer makes no specific recommendations regarding use in pediatric patients.
Category C. (See Users Guide.)
It is not known whether levoleucovorin is distributed into milk; because of the potential for serious adverse reactions to levoleucovorin in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
Clinical studies of levoleucovorin in the treatment of osteosarcoma did not include patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients.
In a clinical trial evaluating levoleucovorin in combination with fluorouracil for the treatment of advanced-stage colorectal cancer, adverse reactions were consistent with known toxicities of fluorouracil; no overall differences in adverse effects were observed between geriatric patients (65 years of age or older) and younger adults. However, deaths from severe enterocolitis, diarrhea, and dehydration have been reported in geriatric patients receiving weekly racemic leucovorin concomitantly with fluorouracil. (See Cautions: Precautions and Contraindications, in Leucovorin Calcium 92:12.)
ICD codes
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Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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