BlueCross BlueShield of Tennessee Medical Policy Manual

Levoleucovorin  (Fusilev™, Khapzory®)

NDC CODE(S)

00143-9558-XX LEVOLEUCOVORIN CALCIUM 50MG Solution Reconstituted (WEST-WARD)

00781-3201-XX LEVOLEUCOVORIN CALCIUM 10MG/ML Solution (SANDOZ) 

16714-0890-XX LEVOLEUCOVORIN CALCIUM 10MG/ML Solution (NORTHSTAR RX)

16714-0915-XX LEVOLEUCOVORIN CALCIUM 10MG/ML Solution (NORTHSTAR RX)

43598-0771-XX LEVOLEUCOVORIN CALCIUM 175MG/17.5ML Solution (DR.REDDY'S LABORATORIES)

43598-0773-XXLEVOLEUCOVORIN CALCIUM 10MG/ML Solution (DR.REDDY'S LABORATORIES)

50742-0494-XX LEVOLEUCOVORIN CALCIUM 10MG/ML Solution (INGENUS PHARMACEUTICALS)

50742-0495-XX LEVOLEUCOVORIN CALCIUM 10MG/ML Solution (INGENUS PHARMACEUTICALS)

68152-0101-XX FUSILEV 50MG Solution Reconstituted (ACROTECH BIOPHARMA)

70121-1099-XX LEVOLEUCOVORIN CALCIUM 50MG Solution Reconstituted (AMNEAL BIOSCIENCES) 

70121-1572-XX LEVOLEUCOVORIN CALCIUM 175MG/17.5ML Solution (AMNEAL BIOSCIEN) 

72266-0120-XX LEVOLEUCOVORIN CALCIUM 175MG/17.5ML Solution (FOSUN PHARMA US)

72266-0121-XX LEVOLEUCOVORIN CALCIUM 10MG/ML Solution (FOSUN PHARMA US)

68152-0112-XX KHAPZORY 175MG Solution Reconstituted (ACROTECH BIOPHARMA)

68152-0114-XX KHAPZORY 300MG Solution Reconstituted (ACROTECH BIOPHARMA)

71288-0104-XX LEVOLEUCOVORIN CALCIUM 50MG Solution Reconstituted (MEITHEAL PHARMACEUTICALS)

71288-0105-XX LEVOLEUCOVORIN CALCIUM 10MGML Solution (MEITHEAL PHARMACEUTICALS)

DESCRIPTION

Levoleucovorin is a folate analog and the pharmacologically active levo-isomer of d, l-leucovorin (racemic leucovorin). 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.

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL CRITERIA

Universal Criteria

Bone Cancer (Osteosarcoma), Dedifferentiated Chondrosarcoma, High-Grade Undifferentiated Pleomorphic Sarcoma (UPS)

Reduction of toxicity due to impaired elimination or inadvertent overdose with folic acid antagonists

Colorectal cancer

Gestational Trophoblastic Neoplasia

Used in combination with high-dose methotrexate for the following:

Used in combination with fluorouracil-based regimens for the following:

RENEWAL CRITERIA

DOSAGE/ADMINISTRATION

Levoleucovorin is dosed at one-half the usual dose of racemic d,l-leucovorin

INDICATION

DOSE

In combination with methotrexate (MTX)

·         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 treatment until methotrexate levels are less than 5 x 10-8 M (0.05 micromolar)

 

Reduction of toxicity due to impaired elimination or inadvertent overdose with folic acid antagonists

·         7.5 mg (approximately 5 mg/m2) IV every 6 hours until methotrexate levels are less than 5 x 10-8 M (0.05 micromolar).

·         Monitor serum creatinine and methotrexate levels at least every 24 hours. Increase the dose of levoleucovorin to 50 mg/m2 intravenously every 3 hours until the methotrexate level is less than 5 x 10-8 M for the following:

  • if the 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

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

Coverage will be provided for ninety days and may be renewed.

DOSING LIMITS

Max Units (per dose and over time) [HCPCS Unit]:

In combination with methotrexate or for inadvertent overdosage

In combination with fluorouracil

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).

SOURCES

1.     Fusilev [package insert]. Irvine, CA; Spectrum Pharmaceuticals, Inc; November 2020. Accessed April January 2021.

2.     Khapzory [package insert]. Irvine, CA; Spectrum Pharmaceuticals, Inc; March 2020. Accessed January 2021.

3.     Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) levoleucovorin. National Comprehensive Cancer Network, 2021. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

4.     Goorin A, Strother D, Poplack D, et al. Safety and efficacy of l-leucovorin rescue following high-dose methotrexate for osteosarcoma. Med Pediatr Oncol. 1995 Jun; 24(6):362-7.

5.     Lexicomp Online. (2021). AHFS DI. Levoleucovorin. Retrieved March 4, 2021 from Lexicomp Online with AHFS.

6.     MICROMEDEX Healthcare Series. Drugdex Evaluations. (2021, January). Levoleucovorin. Retrieved March 4, 2021 from MICROMEDEX Healthcare Series.

ORIGINAL EFFECTIVE DATE:  12/1/2016

MOST RECENT REVIEW DATE:    6/30/2021

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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.

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