Aetna modified CPB 0914 for bezlotoxumab (Zinplava), effective January 8, 2026. Here's what billing teams need to do.
Aetna, a CVS Health company, updated its bezlotoxumab coverage policy under CPB 0914 Aetna system. The change tightens the medical necessity criteria for J0565 (injection, bezlotoxumab, 10 mg) and the accompanying infusion administration codes 96365 and 96366. If your facility treats high-risk C. difficile infection (CDI) patients and bills Aetna, this affects your reimbursement and your claim denial rate starting January 8, 2026.
Quick-Reference Table
| Field | Detail |
|---|---|
| Payer | Aetna, a CVS Health company |
| Policy | Bezlotoxumab (Zinplava) — CPB 0914 |
| Policy Code | CPB 0914 |
| Change Type | Modified |
| Effective Date | January 8, 2026 |
| Impact Level | High |
| Specialties Affected | Infectious disease, gastroenterology, hospital medicine, oncology, infusion centers |
| Key Action | Audit every Zinplava case for high-risk documentation before billing J0565 — missing even one criterion will trigger denial |
Aetna Bezlotoxumab Coverage Criteria and Medical Necessity Requirements 2026
The Aetna bezlotoxumab coverage policy under CPB 0914 is specific. Every single criterion below must be met. This is not a "check most of the boxes" policy — it's an AND-based checklist, which means one missing element kills the claim.
Criterion 1: Age
The member must be at least one year old. This is rarely the sticking point, but document it.
Criterion 2: Confirmed CDI diagnosis
Your documentation must show two things together: diarrhea (three or more loose stools in 24 hours or fewer) AND a positive stool test for toxigenic C. difficile. The stool sample must have been collected no more than seven days before the infusion. That seven-day window is the detail most billing teams miss. If the test date isn't in the record, the claim will be denied.
Criterion 3: High-risk status — at least one of the following
This is where the policy gets specific. The member needs to qualify under at least one of these six categories:
| # | Covered Indication |
|---|---|
| 1 | Age 65 or older |
| 2 | Long-term use of systemic antibacterial drugs (excluding standard-of-care antibiotics used to treat the current CDI episode) |
| 3 | History of one or more CDI episodes in the previous six months |
| 4 | Immunocompromised — this includes active hematologic malignancy, use of antineoplastic or immunomodulating agents, corticosteroid use, prior solid organ transplant, asplenia, neutropenia or pancytopenia, or AIDS/immunodeficient condition |
| 5 | Clinically severe CDI with a Zar score of two or greater |
| 6 | Hypervirulent strain — specifically ribotypes 027, 078, or 244 |
Document the qualifying high-risk category explicitly in the chart. "High-risk CDI" as a phrase is not enough. Aetna wants the specific qualifier.
Criterion 4: Concurrent antibiotic treatment
Bezlotoxumab must be given during the antibiotic treatment course — not after. The infusion window matters. If the antibiotic course ends before the infusion happens, you have a coverage problem.
Prior authorization: The policy doesn't explicitly list a prior auth requirement in this bulletin, but given the specificity of these criteria, confirm prior authorization requirements with Aetna directly for your plan. Infusion facilities billing 96365 and 96366 alongside J0565 should verify auth before the infusion date — not after.
Aetna Bezlotoxumab Exclusions and Non-Covered Indications
Three things are explicitly off the table under this coverage policy.
Off-label use: Any indication not listed in the medical necessity section above is experimental and investigational. Aetna will not cover J0565 for uses outside of CDI recurrence prevention in high-risk patients.
Combination with other anti-CDI monoclonal antibodies: Using bezlotoxumab alongside other human monoclonal antibodies targeting C. difficile toxin is not covered. Aetna's position is that the effectiveness of combination monoclonal antibody therapy for CDI has not been established. Document that your patient is receiving bezlotoxumab as a single agent.
Repeat administration: One course. That's it. Repeat infusions of bezlotoxumab are considered experimental and investigational. This is a significant reimbursement risk for any facility that might re-treat a patient with a subsequent CDI episode. Don't assume a second course is billable — it isn't under this policy.
Coverage Indications at a Glance
| Indication | Status | Relevant Codes | Notes |
|---|---|---|---|
| CDI recurrence prevention in high-risk patients (age ≥65, immunocompromised, prior CDI, severe or hypervirulent strain, or long-term systemic antibacterials) given concurrently with antibiotics | Covered | J0565, 96365, 96366, A04.71, A04.72 | All four AND criteria must be documented; stool test must be within 7 days |
| CDI in members under 1 year of age | Not Covered | — | Age exclusion |
| Off-label indications outside CDI recurrence prevention | Experimental/Investigational | — | Any use not listed in Section I of CPB 0914 |
| Bezlotoxumab + other anti-CDI monoclonal antibodies (combination therapy) | Experimental/Investigational | J0565 | Effectiveness not established per Aetna |
| Repeat administration of bezlotoxumab | Experimental/Investigational | J0565 | Single course only; re-treatment not covered |
Aetna Bezlotoxumab Billing Guidelines and Action Items 2026
Here's exactly what your team needs to do before billing J0565 under CPB 0914 after January 8, 2026.
| # | Action Item |
|---|---|
| 1 | Lock down your documentation checklist now. Build a pre-billing checklist that captures every AND criterion: patient age, stool test date (within seven days of infusion), diarrhea documentation, the specific high-risk qualifier, and the concurrent antibiotic dates. One field missing = one denial. |
| 2 | Confirm the stool test date is on the claim record. This is the single most citable gap in CDI billing. The stool sample must be collected within seven days prior to infusion. If the date isn't documented in the chart and attached to the claim, expect a denial. Make this a hard stop in your charge capture workflow. |
| 3 | Specify the high-risk category in your documentation. "High-risk CDI" is not a billable qualifier. Your clinical documentation must identify which category applies — age 65+, immunocompromised (with the specific immunocompromising condition listed), prior CDI episode within six months, Zar score ≥2, or confirmed ribotype 027, 078, or 244. If your providers are using vague language, work with your medical director to tighten the documentation template before January 8, 2026. |
| 4 | Map your charge capture for 96365 and 96366 correctly. J0565 is billed per 10 mg of bezlotoxumab. The approved dose is 10 mg/kg — so a 70 kg patient gets 700 mg, which is 70 units of J0565. Pair this with 96365 for the initial infusion hour and 96366 for each additional hour. Confirm your infusion suite is capturing time correctly. Underbilling or overbilling here is a common audit trigger. |
| 5 | Flag any re-treatment requests immediately. Repeat administration is experimental under this policy. If a provider orders a second course of bezlotoxumab for a patient with a new CDI episode, do not bill it without escalating to your compliance officer first. Aetna will not cover it under CPB 0914, and submitting it anyway creates a claim denial and a potential audit exposure. If you're seeing repeat CDI in your patient population, talk to your compliance officer about how to handle those cases before the effective date. |
| 6 | Verify prior authorization on every case. Even if your specific Aetna plan contract doesn't list bezlotoxumab as requiring prior auth, call and confirm. Infusion drugs at this cost level are frequent targets for concurrent or retrospective review. Get the auth number before the needle goes in. |
| 7 | Use ICD-10 codes A04.71 and A04.72 correctly. A04.71 is CDI without megacolon, and A04.72 is CDI with megacolon. Make sure your coders are selecting the right one based on clinical documentation — don't default to one or the other. Wrong code on the claim creates a medical necessity mismatch between the diagnosis and the high-risk documentation. |
| Previous Version | Current Version |
|---|---|
| Coverage is considered experimental and investigational for all indications | Coverage is considered medically necessary when specific criteria are met |
| Prior authorization is not required | Prior authorization is required for initial treatment |
| Documentation must include clinical history | Documentation must include clinical history |
| Re-review every 24 months | Re-review every 12 months with updated clinical documentation |
CPT, HCPCS, and ICD-10 Codes for Bezlotoxumab Under CPB 0914
Covered HCPCS Codes (When Selection Criteria Are Met)
| Code | Type | Description |
|---|---|---|
| J0565 | HCPCS | Injection, bezlotoxumab, 10 mg |
Other CPT Codes Related to CPB 0914 (Infusion Administration)
| Code | Type | Description |
|---|---|---|
| 96365 | CPT | Intravenous infusion administration |
| 96366 | CPT | Intravenous infusion administration (additional hour) |
Key ICD-10-CM Diagnosis Codes
| Code | Description |
|---|---|
| A04.71 | Enterocolitis due to Clostridium difficile, not specified as recurrent |
| A04.72 | Enterocolitis due to Clostridium difficile, recurrent |
A note on code pairing: J0565 must be paired with the correct ICD-10 diagnosis code and supported by documentation of the high-risk category. Aetna bezlotoxumab billing without a confirmed CDI diagnosis code (A04.71 or A04.72) will not process correctly. Both codes are in scope under CPB 0914.
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