" INDICATED AFTER HIGH-DOSE METHOTREXATE THERAPY IN OSTEOSARCOMA.
" INDICATED TO DIMINISH THE TOXICITY AND COUNTERACT THE EFFECTS OF IMPAIRED METHOTREXATE ELIMINATION AND OF INADVERTENT OVERDOSAGE OF FOLIC ACID ANTAGONISTS.
" INDICATED FOR USE IN COMBINATION CHEMOTHERAPY WITH 5-FLUOROURACIL IN THE PALLIATIVE TREATMENT OF PATIENTS WITH ADVANCED METASTATIC COLORECTAL CANCER.
1. LEVOLEUCOVORIN RESCUE AFTER HIGH-DOSE METHOTREXATE THERAPY:
RECOMMENDATIONS FOR RESCUE ARE BASED ON A METHOTREXATE DOSE OF 12 GRAMS/M² ADMINISTERED BY IV INFUSION OVER 4 HOURS. LEVOLEUCOVORIN RESCUE AT A DOSE OF 7.5 MG (APPROXIMATELY 5 MG/M²) EVERY 6 HOURS FOR 10 DOSES STARTS 24 HOURS AFTER THE BEGINNING OF THE METHOTREXATE INFUSION.
SERUM CREATININE AND METHOTREXATE LEVELS SHOULD BE DETERMINED AT LEAST ONCE DAILY. FUSILEV ADMINISTRATION, HYDRATION, AND URINARY ALKALINIZATION (PH OF 7.0 OR GREATER) SHOULD BE CONTINUED UNTIL THE METHOTREXATE LEVEL IS BELOW 5 X 10-8 M (0.05 MICROMOLAR).
DOSING RECOMMENDATIONS FOR INADVERTENT METHOTREXATE OVERDOSAGE:
RESCUE SHOULD BEGIN AS SOON AS POSSIBLE AFTER AN INADVERTENT OVERDOSAGE AND WITHIN 24 HOURS OF METHOTREXATE ADMINISTRATION. LEVOLEUCOVORIN 7.5 MG (APPROXIMATELY 5 MG/M² ) SHOULD BE ADMINISTERED IV EVERY 6 HOURS UNTIL THE SERUM METHOTREXATE LEVEL IS LESS THAN 10-8 M.
SERUM CREATININE AND METHOTREXATE LEVELS SHOULD BE DETERMINED AT 24 HOUR INTERVALS. IF THE 24 HOUR SERUM CREATININE HAS INCREASED 50% OVER BASELINE OR IF THE 24 HOUR METHOTREXATE LEVEL IS GREATER THAN 5 X 10-6 M OR THE 48 HOUR LEVEL IS GREATER THAN 9 X 10-7 M, THE DOSE OF FUSILEV SHOULD BE INCREASED TO 50 MG/M² IV EVERY 3 HOURS UNTIL THE METHOTREXATE LEVEL IS LESS THAN 10-8 M. HYDRATION (3 L/DAY) AND URINARY ALKALINIZATION WITH NAHCO3 SHOULD BE EMPLOYED CONCOMITANTLY. THE BICARBONATE DOSE SHOULD BE ADJUSTED TO MAINTAIN THE URINE PH AT 7.0 OR GREATER.
ADMINISTRATION IN COMBINATION WITH 5-FLUOROURACIL (5-FU)
THE FOLLOWING REGIMENS HAVE BEEN USED HISTORICALLY FOR THE TREATMENT OF COLORECTAL CANCER:
1. LEVOLEUCOVORIN IS ADMINISTERED AT 100 MG/M² BY SLOW INTRAVENOUS INJECTION OVER A MINIMUM OF 3 MINUTES, FOLLOWED BY 5-FU AT 370 MG/M² BY INTRAVENOUS INJECTION.
2. LEVOLEUCOVORIN IS ADMINISTERED AT 10 MG/M² BY INTRAVENOUS INJECTION FOLLOWED BY 5-FU AT 425 MG/M² BY INTRAVENOUS INJECTION.
TREATMENT IS REPEATED DAILY FOR FIVE DAYS. THIS FIVE-DAY TREATMENT COURSE MAY BE REPEATED AT 4 WEEK (28-DAY) INTERVALS, FOR 2 COURSES AND THEN REPEATED AT 4 TO 5 WEEK (28 TO 35 DAY) INTERVALS PROVIDED THAT THE PATIENT HAS COMPLETELY RECOVERED FROM THE TOXIC EFFECTS OF THE PRIOR TREATMENT COURSE.
IN SUBSEQUENT TREATMENT COURSES, THE DOSAGE OF 5-FU SHOULD BE ADJUSTED BASED ON PATIENT TOLERANCE OF THE PRIOR TREATMENT COURSE. THE DAILY DOSAGE OF 5-FU SHOULD BE REDUCED BY 20% FOR PATIENTS WHO EXPERIENCED MODERATE HEMATOLOGIC OR GASTROINTESTINAL TOXICITY IN THE PRIOR TREATMENT COURSE, AND BY 30% FOR PATIENTS WHO EXPERIENCED SEVERE TOXICITY. FOR PATIENTS WHO EXPERIENCED NO TOXICITY IN THE PRIOR TREATMENT COURSE, 5-FU DOSAGE MAY BE INCREASED BY 10%.