BlueCross BlueShield of Tennessee Medical Policy Manual

Levoleucovorin

NDC CODE(S)

Fusilev 50 mg powder for injection - 68152-0101-00 (Spectrum)

DESCRIPTION

Levoleucovorin is the levo isomeric form of racemic d,l-leucovorin, present as the calcium salt.  It is the pharmacologically active isomer of 5-formyl tetrahydrofolic acid.  Administration of levoleucovorin can counteract the therapeutic and toxic effects of folic acid antagonists such as methotrexate which act by inhibiting dihydrofolate reductase.  It can enhance the therapeutic and toxic effects of fluoropyrimidines used in cancer therapy such as 5-fluorouracil or 5-FU.

REFER TO DECISION SUPPORT TREE

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL

RENEWAL CRITERIA
INDICATION(S) DOSAGE & ADMINISTRATION
Advanced metastatic colorectal cancer (in combination with 5-FU)

100 mg/m2 administered by slow intravenous injection over a minimum of 3 minutes, followed by 5-FU at 370 mg/m2 by intravenous injection.

OR

10 mg/m2 administered 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.

Alternate Dosing Regimen

200 mg/m2 administered by intravenous injection DAY 1 followed by 5-FU 400 mg/m2 bolus on DAY 1, then 5-FU 1200 mg/m2 /day x 2 days IV continuous infusion; repeat every 14 days, Length of authorization for 90 days
Reduction of toxicity due to impaired elimination or inadvertent overdose with folic acid antagonists

Methotrexate overdosage: 7.5 mg (approximately 5 mg/m2) IV every 6 hours until methotrexate levels are less than 108 M (0.01 micromolar), length of authorization for 90 days

Osteosarcoma (In combination with high dose methotrexate)

 7.5 mg (approximately 5 mg/m2) IV every 6 hours for 10 doses starting 24 hours after beginning of methotrexate infusion. Dosing is based on a methotrexate dose of 12 grams/m2 administered by intravenous infusion over 4 hours. Continue until methotrexate levels are less than 5 x 108 M (0.05 micromolar), length of authorization  for 90 days

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.

ADDITIONAL INFORMATION 

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

No controlled studies were found in the published literature that validate the use of levoleucovorin for the treatment or prevention of other conditions or diseases.

SOURCES

Lexicomp Online. (2016). AHFS DI. Levoleucovorin calcium. Retrieved August 19, 2016 from Lexicomp Online with AHFS.

MICROMEDEX Healthcare Series. Drugdex Evaluations. (2016, August). Levoleucovorin. Retrieved August 19, 2016 from MICROMEDEX Healthcare Series.

National Comprehensive Cancer Network. (2016). NCCN Drugs & Biologics Compendium®. Levoleucovorin. Retrieved August 19, 2016 from the National Comprehensive Cancer Network.

U. S. Food and Drug Administration. (2011, April). Center for Drug Evaluation and Research. Fusilev® (levoleucovorin) for injection, powder, lyophilized, for solution for intravenous use. Retrieved August 19, 2016 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020140s002lbl.pdf.

ORIGINAL EFFECTIVE DATE:  12/1/2016

MOST RECENT REVIEW DATE:  12/1/2016

ID_MRx

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

Pharmaceutical Decision Support Tree

Levoleucovorin (Fusilev®)

  1. Is the unavailability of racemic d,l-leucovorin in any dosage strength, confirmed by the FDA Drug Shortage website: http://www.fda.gov/Drugs/drugsafety/DrugShortages/default.htm?

If yes, go to question #2

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is this the initial request for this agent?

If yes go to question #3

If no, go to question #12

  1. Is the individual 6 years of age or older?

If yes, go to question #4

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the agent used for the treatment of colorectal cancer that is ANY ONE of the following?

If yes, go to question #7

If no, go to question #5

  1. Is the agent used for methotrexate (folic acid antagonist) rescue to reduce toxicity and counteract the effects of impaired elimination or inadvertent overdosage of folic acid antagonist if undergoing treatment with a folic acid antagonist such as methotrexate?

If yes, go to question #8

If no, go to question #6

  1. Is the agent used for the treatment of osteosarcoma as a component of high-dose methotrexate regimen if used as rescue therapy for high-dose methotrexate?

If yes, go to question #8

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the request for 2500 billable units or less (0.5 mg = 1 billable unit) every 28 days in a 90 day period?

If yes, go to question #9

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the request for 1200 billable units or less (0.5 mg = 1 billable unit) every 28 days in a 90 day period?

If yes, go to question #10

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the dosage regimen requested ANY ONE of the following?

If yes, this meets medical necessity and appropriateness criteria

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the agent requested for methotrexate (folic acid antagonist) rescue to reduce toxicity or inadvertent overdose with folic acid antagonist with a dosage of 7.5 mg (approximately 5 mg/m2) IV every 6 hours until methotrexate levels are less than 108 M (0.01 micromolar)?

If yes, this meets medical necessity and appropriateness criteria

If no, go to question #11

  1. Is the agent requested for the treatment of osteosarcoma with 5-FU with dosage as follows?

If yes, this meets medical necessity and appropriateness criteria

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the individual continuing treatment as approved in initial criteria for use in colorectal cancer (palliative or adjuvant treatment with 5-FU), methotrexate (folic acid antagonist) rescue - impaired methotrexate elimination or inadvertent overdosage of folic acid antagonists or osteosarcoma (questions 4 - 11)?

If yes, go to question #13

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Was there absence of unacceptable toxicity from the agent, e.g., hypersensitivity reactions, seizures, and severe gastrointestinal disorders such as stomatitis, severe diarrhea, and severe nausea and vomiting?

If yes, this meets medical necessity and appropriateness criteria

If no, this does not meet medical necessity and/or medical appropriateness criteria

This document has been classified as public information.