Levoleucovorin (Fusilev and Khapzory) — CPB 0889 | AETNA Coverage Update

Aetna modified CPB 0889 covering levoleucovorin (Khapzory) for commercial medical plans, effective December 6, 2025. Here's what billing teams need to know.

Aetna, a CVS Health company, updated this coverage policy to clarify medical necessity criteria for J0641 and J0642 — the two HCPCS codes for levoleucovorin injection. The policy governs when Khapzory qualifies as medically necessary over its cheaper alternative, leucovorin (J0640), and the documentation requirements that come with that distinction. If your team bills infusion codes 96365–96368 alongside J0641 or J0642 for oncology patients, this update directly affects your prior authorization workflow.

Quick-Reference Table

Aetna Levoleucovorin Coverage Criteria and Medical Necessity Requirements 2025

The core issue with the Aetna levoleucovorin coverage policy is simple but easy to miss: levoleucovorin is only covered when leucovorin is not an appropriate or available option. That condition isn't a formality. Aetna requires documented proof.

Specifically, the leucovorin shortage must appear on the FDA's Drug Shortages Index (accessdata.fda.gov/scripts/drugshortages/default.cfm) at the time of prescribing. If you can't point to an active FDA shortage listing, Aetna will not consider J0641 or J0642 medically necessary — regardless of the clinical rationale in your notes. This is the step most billing teams miss.

When that shortage condition is satisfied, CPB 0889 Aetna covers levoleucovorin for three indications. Rescue treatment after high-dose methotrexate therapy is the most common. The policy also covers treatment of a folate antagonist overdose or impaired methotrexate elimination. The third covered indication is combination therapy with fluorouracil-based chemotherapy regimens — relevant for colorectal and GI oncology practices billing J9190 (fluorouracil) alongside J0641 or J0642.

Precertification is required for all Aetna participating providers and members in applicable plan designs. Call (866) 752-7021 or fax (888) 267-3277 to start the prior authorization process. Statement of Medical Necessity forms are available through Aetna's Specialty Pharmacy Precertification portal.

Reimbursement for levoleucovorin billing depends on meeting all three layers: the FDA shortage documentation, one of the three covered indications, and an approved prior auth. Skip any one of these and you're looking at a claim denial.

Aetna Levoleucovorin Exclusions and Non-Covered Indications

Aetna is direct here: all indications not listed in the three covered categories are considered experimental, investigational, or unproven.

There's no gray list. If your provider is using levoleucovorin for an off-label indication not covered by rescue after high-dose methotrexate, folate antagonist overdose, or fluorouracil combination therapy — don't expect coverage under this policy. Aetna will classify it as unproven and deny it.

This also means the coverage policy doesn't extend to situations where leucovorin is available but the prescriber prefers levoleucovorin. Preference isn't a covered indication. The shortage must be active and documented.

Coverage Indications at a Glance

Aetna Levoleucovorin Billing Guidelines and Action Items 2025

The effective date for this modified coverage policy is December 6, 2025. If your team hasn't updated its workflows yet, do it now. Here's what needs to happen.

CPT, HCPCS, and ICD-10 Codes for Levoleucovorin Under CPB 0889

Covered HCPCS Codes (When Selection Criteria Are Met)

Key ICD-10-CM Diagnosis Codes

The policy lists 259 ICD-10-CM codes. The table below covers the primary categories. Make sure your ICD-10 codes align with the clinical indication on file — especially for GI and hematologic malignancies where fluorouracil regimens are common.

The full code list of 259 ICD-10-CM codes is available in the full policy at app.payerpolicy.org/p/aetna/0889.