Blue Cross Blue Shield of Minnesota Medical Policy


Medical Policy:
Effective Date:
May 3, 2021
Issued Date:
May 3, 2021
Last Revision Date:
April 2021
Annual Review:
April 2021

This policy version was replaced May 30, 2022. To find the newest version, go to, read and accept the Blue Cross Medical Policy Statement, then select “Blue Cross and Blue Shield of Minnesota Medical Policies.” This will bring up the Medical Policy search screen. Enter the policy number without the version number (last 3 digits).

Bezlotoxumab is a human monoclonal antibody that binds to Clostridioides (formerly Clostridium) difficile toxin B and neutralizes its effects. Bezlotoxumab is administered by intravenous infusion.

The U.S. Food and Drug Administration has approved bezlotoxumab (Zinplava®) to reduce recurrence of Clostridioides (formerly Clostridium) difficile infection (CDI) in patients 18 years of age or older who are receiving antibacterial drug treatment of CDI and are at high risk for CDI recurrence. According to the prescribing information, bezlotoxumab is not indicated for treatment of CDI and is not an antibacterial drug. Bezlotoxumab should only be used in conjunction with antibacterial drug treatment of CDI.

Heart failure has occurred in bezlotoxumab-treated patients with a history of congestive heart failure. In patients with a history of congestive heart failure, bezlotoxumab should be reserved for use when the benefit outweighs the risk.

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Policy Position Coverage is subject to the specific terms of the member's benefit plan.

I.   Bezlotoxumab may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

  • Age 18 years or older; AND
  • Confirmed Clostridioides (formerly Clostridium) difficile infection (CDI), including BOTH of the following:
    • Passage of 3 or more loose stools within 24 hours or less; AND
    • Positive stool test for toxigenic Clostridioides (formerly Clostridium) difficile from a stool sample collected no more than 7 days prior to treatment with bezlotoxumab; AND
  • Currently receiving antibacterial therapy (e.g., metronidazole, vancomycin, fidaxomicin) for CDI; AND
  • Patient is at high risk of CDI recurrence, as defined by at least ONE of the following:
    • Age 65 years or older; OR
    • One or more episodes of CDI within 6 months prior to the episode under treatment; OR
    • Immunocompromised state; OR
    • Severe CDI at presentation (CDI with abdominal distension, hypoalbuminemia [serum albumin <3 g/dL], and white blood cell count ≥15,000 cells/mm³); OR
    • Clostridioides (formerly Clostridium) difficile ribotype 027; AND
  • No FDA labeled contraindications to bezlotoxumab (see table 1 below); AND
  • Bezlotoxumab will only be administered as a single dose per active CDI episode; AND
  • The dose is within the FDA labeled dose for the indication (see table 2 below).

II.  Bezlotoxumab is considered EXPERIMENTAL/INVESTIGATIVE for all other indications due to the lack of clinical evidence demonstrating an impact on improved health outcomes.


Table 1. FDA Labeled Contraindications


FDA Labeled Contraindications



 Table 2. Dosing

 FDA Labeled Indications


 Reduce recurrence of Clostridioides (formerly Clostridium) difficile infection (CDI)

 Single dose of 10 mg/kg



Denial Statements

No additional statements.


Blue Cross and Blue Shield of Minnesota medical policies apply generally to all Blue Cross and Blue Plus plans and products. Benefit plans vary in coverage and some plans may not provide coverage for certain services addressed in the medical policies. When determining coverage, reference the member’s specific benefit plan, including exclusions and limitations.

Medicaid products may provide different coverage for certain services, which may be addressed in different policies. For Minnesota Health Care Program (MHCP) policies, please consult the MHCP Provider Manual website.

Medicare products may provide different coverage for certain services, which may be addressed in different policies. For Medicare National Coverage Determinations (NCD), Local Coverage Determinations (LCD), and/or Local Coverage Articles, please consult CMS, National Government Services, or CGS websites. 

Note that services with specific coverage criteria may be reviewed retrospectively to determine if criteria are being met. Retrospective denial of claims may result if criteria are not met.

Blue Cross and Blue Shield of Minnesota reserves the right to revise, update and/or add to its medical policies at any time without notice. Codes listed on this policy are included for informational purposes only and are subject to change without notice. Inclusion or exclusion of a code does not constitute or imply member coverage or provider reimbursement. 

These guidelines are the proprietary information of Blue Cross and Blue Shield of Minnesota. Any sale, copying or dissemination of the medical policies is prohibited; however, limited copying of medical policies is permitted for individual use.


CPT® codes copyright American Medical Association® 2022. All rights reserved.

CDT codes copyright American Dental Association® 2022. All rights reserved.