Levoleucovorin - Fusilev™
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|Reconstitution and Infusion Instructions
Prior to intravenous injection, the 50 mg vial of Fusilev for Injection is reconstituted with 5.3 mL of 0.9% Sodium Chloride Injection, USP to yield a levoleucovorin concentration of 10 mg per mL. Reconstitution with Sodium Chloride solutions with preservatives (e.g. benzyl alcohol) has not been studied. The use of solutions other than 0.9% Sodium Chloride Injection, USP is not recommended. The reconstituted 10 mg per mL levoleucovorin contains no preservative. Observe strict aseptic technique during reconstitution of the drug product. Saline reconstituted levoleucovorin solutions may be further diluted, immediately, to concentrations of 0.5 mg/mL to 5 mg/mL in 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Initial reconstitution or further dilution using 0.9% Sodium Chloride Injection, USP may be held at room temperature for not more than a total of 12 hours. Dilutions in 5% Dextrose Injection, USP may be held at room temperature for not more than 4 hours. Visually inspect the reconstituted solution for particulate matter and discoloration, prior to administration. CAUTION: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if cloudiness or precipitate is observed. No more than 16 mL of reconstituted solutions (160 mg of levoleucovorin ) should be injected intravenously per minute, because of the calcium content of the levoleucovorin solution
Store at 25° C (77 °F) in carton until contents are used. Excursions permitted from 15-30° C (59-86 °F). Protect from light.
|Stability / Miscellaneous|
Fusilev for injection contains levoleucovorin calcium, which is one of several active, chemically reduced derivatives of folic acid. It is useful as antidote to the inhibition of dihydrofolate reductase by methotrexate.
1. INDICATIONS AND USAGE Fusilev™ is a folate analog. Fusilev rescue is indicated after high-dose methotrexate therapy in osteosarcoma. Fusilev is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosage of folic acid antagonists Limitations of Use Fusilev is not approved for pernicious anemia and megaloblastic anemias secondary to the lack of vitamin B12. Improper use may cause a hematologic remission while neurologic manifestations continue to progress 2. DOSAGE AND ADMINISTRATION
2.1 Administration Guidelines
Fusilev is indicated for intravenous administration only. Do not administer intrathecally.
2.2 Co-administration of Fusilev with other agents
2.3 Fusilev Rescue After High-Dose Methotrexate Therapy
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). The Fusilev dose should be adjusted or rescue extended based on the following guidelines.
Patients who experience delayed early methotrexate elimination are likely to develop reversible renal failure. In addition to appropriate Fusilev therapy, these patients require continuing hydration and urinary alkalinization, and close monitoring of fluid and electrolyte status, until the serum methotrexate level has fallen to below 0.05 micromolar and the renal failure has resolved.
Some patients will have abnormalities in methotrexate elimination or renal function following methotrexate administration, which are significant but less severe than the abnormalities described in the table above. These abnormalities may or may not be associated with significant clinical toxicity. If significant clinical toxicity is observed, Fusilev rescue should be extended for an additional 24 hours (total of 14 doses over 84 hours) in subsequent courses of therapy. The possibility that the patient is taking other medications which interact with methotrexate (e.g., medications which may interfere with methotrexate elimination or binding to serum albumin) should always be reconsidered when laboratory abnormalities or clinical toxicities are observed.
Delayed methotrexate excretion may be caused by accumulation in a third space fluid collection (i.e., ascites, pleural effusion), renal insufficiency, or inadequate hydration. Under such circumstances, higher doses of Fusilev or prolonged administration may be indicated.
Although Fusilev may ameliorate the hematologic toxicity associated with high dose methotrexate, Fusilev has no effect on other established toxicities of methotrexate such as the nephrotoxicity resulting from drug and/or metabolite precipitation in the kidney.
2.4 Dosing Recommendations for Inadvertent Methotrexate Overdosage
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.
5. WARNINGS AND PRECAUTIONS
5.1 Rate of Administration
5.2 Potential for Enhanced Toxicity with 5-Fluorouracil
5.3 Potential for interaction with trimethoprim-sulfamethoxazole
HOW SUPPLIED/STORAGE AND HANDLING
50 mg vial of freeze-dried powder – NDC 68152-101-00.
Store at 25° C (77 °F) in carton until contents are used. Excursions permitted from 15-30° C (59-86 °F). [See USP Controlled Room Temperature]. Protect from light.
| 1) [PACKAGE INSERT DATA] : FUSILEV (levoleucovorin calcium) injection, powder, lyophilized, for solution. [Spectrum Pharmaceuticals, Inc.] Irvine, CA 92618. Revised: 09/2008.