Clinical Policy: Enzalutamide (Xtandi)
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Defines medical necessity and authorization criteria for enzalutamide (Xtandi) for members with castration-resistant or metastatic castration-sensitive prostate cancer and governs prior authorization and continuation for Ambetter Georgia lines of business.
No material clinical or coverage changes in this revision.
Coverage Criteria for Enzalutamide (Xtandi)
inv-01: Initial Therapy — Initial Approval — Prostate Cancer
Initial Approval — Prostate Cancer: covered when ALL of the following are met
See Appendix D for CRPC definition.
Dosing limits (must meet one)
- a: If prescribed concomitantly with a strong CYP2C8 inhibitor (e.g., gemfibrozil): dose does not exceed 80 mg per day.
- b: Dose does not exceed 160 mg per day (standard dose).
- c: If prescribed concomitantly with a strong CYP3A4 inducer (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital): dose does not exceed 240 mg per day.
- d: Dose is supported by practice guidelines or peer-reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence).
inv-02: Continuation Therapy — Continued Therapy — Prostate Cancer
Continued Therapy — Prostate Cancer: covered when ALL of the following are met
Providers must submit supporting documentation (e.g., chart notes, labs).
Dose increase limits (must meet one)
- a: If prescribed concomitantly with a strong CYP2C8 inhibitor (e.g., gemfibrozil): new dose does not exceed 80 mg per day.
- b: New dose does not exceed 160 mg per day.
- c: If prescribed concomitantly with a strong CYP3A4 inducer (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital): new dose does not exceed 240 mg per day.
- d: New dose is supported by practice guidelines or peer-reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence).
inv-03: Other Indications / Off-label
Other diagnoses/indications
Approval duration generally 6 months or as specified by the off‑label policy or the request.
Non-FDA approved indications that are not specifically addressed in this policy are not authorized unless the provider submits sufficient documentation demonstrating efficacy and safety in accordance with the applicable off‑label use policies (HIM.PA.154 for Marketplace and CP.PMN.53 for Medicaid) or other applicable evidence of coverage documents.
Coverage is not authorized for non‑FDA approved indications unless the criteria of the referenced off‑label use policies are met and supporting clinical evidence is provided to justify use for the requested indication.
Initial Therapy Requirements
inv-14: Initial Therapy (Prostate Cancer) — Initial therapy dosing and prescriber requirements
Initial therapy dosing and prescriber requirements
Dose limits (must meet one)
- a: If prescribed with a strong CYP2C8 inhibitor (e.g., gemfibrozil): dose ≤ 80 mg/day.≤ 80 mg/day
- b: Standard dose ≤ 160 mg/day.≤ 160 mg/day
- c: If prescribed with a strong CYP3A4 inducer (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital): dose ≤ 240 mg/day.≤ 240 mg/day
- d: Dose supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence).
Continuation / Renewal Criteria
inv-15: Continued Therapy (Prostate Cancer) — Continuation criteria for prostate cancer
Continuation criteria for prostate cancer
Approval duration: 12 months.
Dose increase constraints
- a: If prescribed with a strong CYP2C8 inhibitor (e.g., gemfibrozil): new dose ≤ 80 mg/day.≤ 80 mg/day
- b: New dose ≤ 160 mg/day.≤ 160 mg/day
- c: If prescribed with a strong CYP3A4 inducer (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital): new dose ≤ 240 mg/day.≤ 240 mg/day
- d: New dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit evidence).
Coding and Key Clinical Thresholds
Provider Actions and Documentation Requirements
Prior authorization required for Xtandi
Prior authorization is required for requests for Xtandi (enzalutamide). Requests must document the diagnosis (CRPC or metastatic CSPC), prescriber specialty (oncologist or urologist), patient age (≥ 18 years), whether the member is receiving concurrent ADT or has had bilateral orchiectomy, dosing that meets the policy's maximums (including reduced max when given with a strong CYP2C8 inhibitor or increased max with a strong CYP3A4 inducer), and, if the brand Xtandi is requested, medical justification that the member cannot use generic enzalutamide (e.g., contraindication to excipients). Prescribed regimens must be FDA-approved or recommended by NCCN.
- Diagnosis: CRPC (progression despite bilateral orchiectomy or other ADT) or metastatic CSPC
- Prescriber: oncologist or urologist (or in consultation with one)
- Age: ≥ 18 years
- Concurrent therapy: GnRH analog prescribed concurrently or history of bilateral orchiectomy
- Dosing limits: ≤ 80 mg/day with strong CYP2C8 inhibitor; ≤ 160 mg/day standard; ≤ 240 mg/day with strong CYP3A4 inducer; or dose supported by guidelines/literature with evidence
- Brand request: medical justification required to show inability to use generic enzalutamide
No explicit step therapy sequence specified
The policy does not specify an explicit step-therapy sequence. It notes oral oncology generic redirection language in the revision history but contains no required prior agent(s) or failure steps to obtain enzalutamide.
- Policy language: “No explicit step therapy sequence described; policy notes generic redirection language in revision history.”
Submit supportive clinical documentation
Provider must submit supporting clinical documentation (such as office chart notes, laboratory results, or other clinical information) demonstrating the member meets all approval criteria, including diagnosis, ADT status, dosing rationale, and response when applicable.
- Examples: office chart notes, lab results, other clinical information
- Must support criteria such as diagnosis, concurrent ADT or orchiectomy, dosing limits, and positive response for continuation requests
Risk of denial if documentation not provided
Failure to provide the requested supporting documentation (office notes, laboratory results, or other clinical information) that demonstrates all approval criteria are met may result in denial of the request.
- Insufficient or missing documentation of diagnosis, ADT status, dosing justification, or treatment response can trigger a denial
Definitions
Background
Enzalutamide (Xtandi) is an androgen receptor inhibitor indicated for prostate cancer. Use for indications not addressed in this policy requires documentation per off‑label policies; see Section III for limits on non‑FDA approved uses.
Step Therapy
| Step | Description |
|---|---|
| 1 | No explicit step therapy sequence is specified in this policy. Revision history notes addition of generic redirection language for oral oncology (1Q 2021) and prior edits documenting dose and prescriber requirements, but the document does not define required prior agents or a stepwise fail-first sequence. |
Quantity Limits and Dose Strengths
Site of Care
No site-of-care restrictions in policy
The policy contains no site-of-care restrictions; there are no specified limitations on where treatment must be administered in this document.
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