2 DOSAGE AND ADMINISTRATION For intravenous administration only. Do not administer intrathecally. 1 ) Rescue After High-Dose Methotrexate Therapy Rescue recommendations are based on methotrexate dose of 12 grams/m 2 administered by intravenous infusion over 4 hours.
5 mg (approximately 5 mg/m 2 ) every 6 hours, 24 hours after the beginning of methotrexate infusion. 05 micromolar). Adjust dose if necessary based on methotrexate elimination; refer to Full Prescribing Information. 3 ) Overdosage of Folic Acid Antagonists or Impaired Methotrexate Elimination Start as soon as possible after methotrexate overdosage or within 24 hours of delayed methotrexate elimination.
05 micromolar). 4 ) Metastatic Colorectal Cancer in Combination with Fluorouracil The following regimens have been used for the treatment of colorectal cancer: Levoleucovorin injection 100 mg/m 2 by intravenous injection over a minimum of 3 minutes, followed by fluorouracil 370 mg/m 2 once daily for 5 consecutive days.
5 ) Levoleucovorin injection 10 mg/m 2 by intravenous injection followed by fluorouracil 425 mg/m 2 once daily for 5 consecutive days. 5 ) Administer fluorouracil and levoleucovorin injection separately to avoid the formation of precipitate.
The above five-day courses may be repeated every 4 weeks for 2 courses, then every 4 to 5 weeks, if the patient has recovered from toxicity from the prior course. Do not adjust levoleucovorin injection dosage for toxicity. 1 Important Use Information Levoleucovorin injection is indicated for intravenous administration only .
Do not administer intrathecally . 2 Co-administration of Levoleucovorin Injection with Other Agents Due to the risk of precipitation, do not co-administer levoleucovorin injection with other agents in the same admixture. 3 Recommended Dosage for Rescue After High-Dose Methotrexate Therapy The recommended dosage for levoleucovorin injection is based on a methotrexate dose of 12 grams/m 2 administered by intravenous infusion over 4 hours.
5 mg (approximately 5 mg/m 2 ) as an intravenous infusion every 6 hours. Monitor serum creatinine and methotrexate levels at least once daily. 05 micromolar). Adjust the levoleucovorin injection dose or extend the duration as recommended in Table 1 .
Table 1 Recommended Dosage for Levoleucovorin Injection based on Serum Methotrexate and Creatinine Levels * These patients are likely to develop reversible renal failure. 05 micromolar and the renal failure has resolved. 2 micromolar at 72 hours.
5 mg by intravenous infusion every 6 hours for 60 hours (10 doses starting at 24 hours after start of methotrexate infusion). 05 micromolar at 96 hours after administration. 05 micromolar. 5 mg/dL to a level of 1 mg/dL or more). 05 micromolar.
Impaired Methotrexate Elimination or Renal Impairment Decreased methotrexate elimination or renal impairment which are clinically important but less severe than the abnormalities described in Table 1 can occur following methotrexate administration.
If toxicity associated with methotrexate is observed, in subsequent courses extend levoleucovorin injection rescue for an additional 24 hours (total of 14 doses over 84 hours). , ascites, pleural effusion), renal insufficiency, or inadequate hydration can delay methotrexate elimination.
Under such circumstances, higher doses of levoleucovorin injection or prolonged administration may be indicated. 4 Recommended Dosage for Overdosage of Folic Acid Antagonists or Impaired Methotrexate Elimination Start levoleucovorin injection as soon as possible after an overdosage of methotrexate or within 24 hours of methotrexate administration when methotrexate elimination is impaired.
As the time interval between methotrexate administration and levoleucovorin injection increases, the effectiveness of levoleucovorin injection to diminish methotrexate toxicity may decrease. 05 micromolar). Monitor serum creatinine and methotrexate levels at least every 24 hours.
Increase the dosage of levoleucovorin injection to 50 mg/m 2 intravenously every 3 hours and continue levoleucovorin injection at this dosage until the methotrexate level is less than 5 x 10 -8 M for the following: if serum creatinine at 24-hours increases 50% or more compared to baseline if the methotrexate level at 24-hours is greater than 5 x 10 -6 M if the methotrexate level at 48-hours is greater than 9 x 10 -7 M, Continue concomitant hydration (3 L per day) and urinary alkalinization with sodium bicarbonate.
Adjust the sodium bicarbonate dose to maintain urine pH at 7 or greater. 5 Dosage in Combination with Fluorouracil for Metastatic Colorectal Cancer The following regimens have been used for the treatment of colorectal cancer: Levoleucovorin injection 100 mg/m 2 by intravenous injection over a minimum of 3 minutes, followed by fluorouracil at 370 mg/m 2 by intravenous injection, once daily for 5 consecutive days.
Levoleucovorin injection 10 mg/m 2 by intravenous injection, followed by fluorouracil 425 mg/m 2 by intravenous injection, once daily for 5 consecutive days. Administer fluorouracil and levoleucovorin injection separately to avoid the formation of a precipitate.
This five-day course may be repeated every 4 weeks for 2 courses, then every 4 to 5 weeks, if the patient has recovered from the toxicity from the prior course. Do not adjust levoleucovorin injection dosage for toxicity. Refer to fluorouracil prescribing information for information on fluorouracil dosage and dosage modifications for adverse reactions.
6 Preparation for Administration Levoleucovorin Injection Levoleucovorin contains no preservative. Observe strict aseptic technique during reconstitution of the drug product. Discard unused portion. 9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP.
9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP for more than 4 hours at room temperature. Visually inspect the diluted solution for particulate matter and discoloration prior to administration. Do not use if cloudiness or precipitate is observed.
Inject no more than 16 mL of levoleucovorin injection (160 mg of levoleucovorin) intravenously per minute, because of the calcium content of the levoleucovorin solution.