ntahydrate equivalent to 10 mg levoleucovorin and 8.3 mg sodium chloride.
Contraindications
Fusilev is contraindicated for patients who have had previous allergic reactions attributed to folic acid or folinic acid.
Warnings and Precautions
Rate of Administration
Because of the Ca++ content of the levoleucovorin solution, no more than 16 mL (160 mg of levoleucovorin) should be injected intravenously per minute.
Potential for Enhanced Toxicity with 5-Fluorouracil
Fusilev enhances the toxicity of 5-fluorouracil. Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly d,l-leucovorin and 5-fluorouracil. When these drugs are administered concurrently in the palliative treatment of advanced colorectal cancer, the dosage of 5-FU must be lower than usually administered. Although the toxicities observed in patients treated with the combination of Fusilev and 5-FU are qualitatively similar to those observed with 5-FU alone, gastrointestinal toxicities (particularly stomatitis and diarrhea) are observed more commonly and may be of greater severity and of prolonged duration in patients treated with the combination.
In the first Mayo/NCCTG controlled trial, toxicity, primarily gastrointestinal, resulted in 7% of patients requiring hospitalization when treated with 5-FU alone or 5-FU in combination with 200 mg/m2 of d,l-leucovorin and 20% when treated with 5-FU in combination with 20 mg/m2 of d,l-leucovorin. In the second Mayo/NCCTG trial, hospitalizations related to treatment toxicity also appeared to occur more often in patients treated with the low dose d,l-leucovorin/5-FU combination than in patients treated with the high dose combination – 11% versus 3%. Therapy with Fusilev and 5-FU must not be initiated or continued in patients who have symptoms of gastrointestinal toxicity of any severity, until those symptoms have completely resolved. Patients with diarrhea must be monitored with particular care until the diarrhea has resolved, as rapid clinical deterioration leading to death can occur. In an additional study utilizing higher weekly doses of 5-FU and d,l-leucovorin, elderly and/or debilitated patients were found to be at greater risk for severe gastrointestinal toxicity.
Seizures and/or syncope have been reported rarely in cancer patients receiving d,l-leucovorin, usually in association with fluoropyrimidine administration, and most commonly in those with CNS metastases or other predisposing factors. However, a causal relationship has not been established.
Potential for interaction with trimethoprim-sulfamethoxazole
The concomitant use of d,l-leucovorin with trimethoprim-sulfamethoxazole for the acute treatment of Pneumocystis carinii pneumonia in patients with HIV infection was associated with increased rates of treatment failure and morbidity in a placebo-controlled study.
Adverse Reactions
Clinical Studies in High-Dose Methotrexate Therapy
Since clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The following table presents the frequency of adverse reactions which occurred during the administration of 58 courses of high-dose methotrexate 12 grams/m2 followed by Fusilev rescue for osteosarcoma in 16 patients age 6- |
