Leucovorin (Leucovorin Calcium) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

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 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).

OVERDOSAGE

Excessive amounts of leucovorin may nullify the chemotherapeutic effect of folic acid antagonists.

CONTRAINDICATIONS

Leucovorin is improper therapy for pernicious anemia and other megaloblastic anemias secondary to the lack of vitamin B₁₂. A hematologic remission may occur while neurological manifestations continue to progress.

REFERENCES

1. Grem JL, Shoemaker DD, Petrelli NJ, Douglas HO Jr: 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.
2. 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 BY
BARR LABORATORIES, INC.
POMONA, NY 10970

OCTOBER 2002
BR-484, 485