CurrentCentenePolicy CP.PHAR.60

Capecitabine (Xeloda)

Defines medical necessity criteria, dosing limits, approved FDA and NCCN-recommended (off-label) indications, continued therapy requirements, formulary/generic use expectations, approval durations, and coding implications for capecitabine (Xeloda) under Centene lines of business (HIM, Medicaid).

Policy Summary

PayerCentene

PolicyCapecitabine (Xeloda)

Policy CodePolicy CP.PHAR.60

Change TypeRevised / coding update / clarification (2021–2025)

Effective Date05.01.11

Next Review Date

Key ActionProvider must submit documentation showing the member meets all approval criteria, including diagnosis, oncologist involvement, age, prior use when applicable, and response to therapy for continuation requests.

POLICY UPDATE CHANGES

Added NCCN-supported indications and reorganized indications between FDA-approved and off-label sections across multiple annual reviews (2021–2025).

Added HCPCS code J8522 and removed J8520 and J85211 (coding update applied Aug 07 2024).

Revised medical justification language to require generic capecitabine use unless contraindicated or clinically significant adverse effects are experienced; applied this requirement to continued therapy criteria (2Q 2021).

6FDA approved indications listed

20+NCCN-recommended/off-label indications

6Initial approval duration (months)

12Continued approval duration (months)

Coverage Summary

Scope: This policy defines medical necessity criteria and coverage stance for capecitabine (Xeloda) and aligns coverage to FDA-approved indications and NCCN-recommended uses. The drug is considered covered with criteria when prescribed for FDA-approved or NCCN-recommended indications, with indication-specific dosing limits and documentation requirements.

Coverage stance and key requirements: Capecitabine is expected to be the generic product unless contraindicated or the member experiences clinically significant adverse effects. Initial approvals are issued for 6 months and continued therapy approvals for 12 months. Dosing limits are specified by indication (examples: colorectal single-agent ≤ 1,250 mg twice daily on Days 1–14 every 21 days; colorectal continued therapy total daily max ≤ 2,500 mg; breast and colorectal continued therapy total daily max ≤ 2,500 mg; gastric/esophageal total daily max ≤ 2,000 mg; pancreatic total daily max ≤ 1,660 mg), and all prescribed regimens must be FDA-approved or recommended by NCCN.

Key thresholds & durations

Initial approval duration6 months

Continued approval duration12 months

Colorectal initial dose (single-agent)≤ 1,250 mg twice daily on Days 1–14 of a 21‑day cycle (adjuvant: max 8 cycles)

Breast initial dose≤ 1,250 mg/m2 twice daily on Days 1–14 of a 21‑day cycle

Gastric/Esophageal initial doseOptions including ≤ 1,000 mg twice daily on Days 1–14 every 21 days or 625 mg twice daily on Days 1–21 (max 8 cycles)

Pancreatic initial dose830 mg twice daily on Days 1–21 of a 28‑day cycle (max 6 cycles) when used with gemcitabine

Initial Therapy Criteria

Initial Approval Criteria - Colorectal Cancer; Initial Approval Criteria - Breast Cancer; Initial Approval Criteria - Gastric / Esophageal / Gastroesophageal Junction Cancer; Initial Approval Criteria - Pancreatic Cancer; Initial Approval Criteria - NCCN Recommended Uses (Off-label)

Covered when ALL of the following are met:

ALL of the following

ALL of the following
- Diagnosis of colorectal cancer
- Prescribed by or in consultation with an oncologist
- Age > 18 years
- Member must use generic capecitabine, unless contraindicated or clinically significant adverse effects are experienced

Other Diagnoses / Formulary Handling

Other diagnoses/indications (Formulary/non-formulary handling)

When requested use is not specifically listed:

ANY of the following

For drugs on formulary/PDL, refer to no coverage criteria policy HIM.PA.33 (Marketplace) or CP.PMN.255 (Medicaid)
For drugs NOT on formulary/PDL, refer to non-formulary policy HIM.PA.103 (Marketplace) or CP.PMN.16 (Medicaid)
If requested use is not listed and prior criteria do not apply, refer to off-label use policy HIM.PA.154 (Marketplace) or CP.PMN.53 (Medicaid)

Continuation Therapy Criteria

Continuation-specific numeric thresholds

Colorectal continued therapy max≤ 2,500 mg total daily on Days 1–14 every 21 days (adjuvant: max 8 cycles)

Perioperative colorectal with radiation (continued)≤ 1,650 mg total daily

Breast continued therapy max≤ 2,500 mg total daily on Days 1–14 every 21 days

Gastric/Esophageal continued therapy max≤ 2,000 mg total daily on Days 1–14 every 21 days

Pancreatic continued therapy max≤ 1,660 mg total daily on Days 1–21 every 28 days (max 6 cycles)

Unproven / Off-Label Evidence Requirements

Off-label uses: Requests for off-label (non-FDA) indications must be supported by recognized practice guidelines (such as NCCN) or peer-reviewed literature. The policy requires that prescribers submit supporting evidence to demonstrate that the dosing and regimen are supported by those sources.

NCCN-related note: Several indications are covered as NCCN-recommended off-label uses (listed in the NCCN group within the policy) and dosing for these uses must either be within FDA maximum limits or be supported by practice guidelines or peer-reviewed literature with prescriber-submitted evidence.

Applicable Codes

HCPCS - Covered product coding (informational)HCPCS

J8522

Capecitabine, oral, per 500 mg (HCPCS added Aug 2024 as per document)

Provider Actions / Prior Authorization

Prior Authorization

Prior authorization required with dosing limits

Prior authorization is required. Requests must meet the policy's indication-specific dosing and regimen limits (e.g., colorectal, breast, gastric/esophageal, pancreatic and NCCN-recommended uses) and, for off-label uses, be supported by practice guidelines or peer-reviewed literature submitted by the prescriber. Affected billing code: J8522.

Documentation Required

Support clinical documentation

Provider must submit supporting clinical documentation (office notes, lab results, or other clinical information) demonstrating the member meets all approval criteria, including diagnosis, involvement or consultation with an oncologist, patient age, prior use when applicable, and documentation of response to therapy for continuation requests. Include relevant labs and office notes as needed.

Clinical Evidence & References

Primary references: Xeloda Prescribing Information (Genentech; December 2022) and the National Comprehensive Cancer Network Drugs and Biologics Compendium (accessed February 5, 2024).

Notes: Annual review entries and policy updates cite dosing and contraindication changes informed by the prescribing information updates (PI updates noted in 2023 and subsequent annual reviews).

Background

Background: Capecitabine (Xeloda) is an oral nucleoside metabolic inhibitor with antineoplastic activity. The policy aligns coverage to FDA-approved indications and NCCN-recommended uses and specifies indication-specific dosing regimens and maximum total daily doses.

Dosing and product preference: FDA- and guideline-aligned dosing limits are specified by indication (examples include colorectal single-agent 1,250 mg PO twice daily Days 1–14 every 21 days; pancreatic with gemcitabine 830 mg PO twice daily Days 1–21 every 28 days up to 6 cycles). The policy expects use of a generic capecitabine product unless contraindicated or clinically significant adverse effects occur.

Revision History

02.22.21annual_review

Medical justification language revised to require use of generic capecitabine unless contraindicated and added this requirement to continued therapy criteria; added NCCN-supported indication of squamous cell skin cancer; removed differentiation for neuroendocrine tumor sites and removed single-agent/temozolomide neuroendocrine pancreas prescribing criterion.

02.22.22annual_review

Added maintenance therapy and 'unresponsive to preoperative systemic therapy' uses in breast cancer per NCCN; collapsed off-label criteria for neuroendocrine tumor of the pancreas into the off-label criteria set.

01.10.23annual_review

Policy Summary

PayerCentene

PolicyCapecitabine (Xeloda)

Policy CodePolicy CP.PHAR.60

Change TypeRevised / coding update / clarification (2021–2025)

Effective Date05.01.11

Next Review Date

On This Page

Prescriber must document medical justification for brand if applicable

Request must meet one of the following dosing/regimen options

Monotherapy (unresectable or metastatic disease, or adjuvant treatment): Dose does not exceed 1,250 mg twice a day on Days 1 to 14, every 21 days; if adjuvant treatment: maximum of 8 cycles
Combination with oxaliplatin-containing regimen (unresectable or metastatic disease, or adjuvant treatment): Dose does not exceed 1,000 mg twice a day on Days 1 to 14, every 21 days
Perioperative treatment options
- With concomitant radiation therapy: Dose does not exceed 825 mg twice a day
- Without radiation therapy: Dose does not exceed 1,250 mg twice a day
Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)

Prescribed regimen must be FDA-approved or recommended by NCCN

ALL of the following

Diagnosis of gastric, esophageal, or gastroesophageal junction cancer
Prescribed by or in consultation with an oncologist
Age > 18 years
Member must use generic capecitabine, unless contraindicated or clinically significant adverse effects are experienced
Dose/regimen options
- Dose does not exceed 1,000 mg twice a day on Days 1 to 14, every 21 days
- Dose does not exceed 625 mg twice a day on Days 1 to 21 (maximum of 8 cycles)
- Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)
Prescribed regimen must be FDA-approved or recommended by NCCN

ALL of the following

Diagnosis of pancreatic cancer
Prescribed by or in consultation with an oncologist
Age > 18 years
Member must use generic capecitabine, unless contraindicated or clinically significant adverse effects are experienced
Dose/regimen
- Dose does not exceed 830 mg twice a day on Days 1 to 21, every 28 days (maximum of 6 cycles)
- Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)
Prescribed regimen must be FDA-approved or recommended by NCCN

Billing Rule

Generic use expectation

Use of generic capecitabine is expected. Brand capecitabine should only be used if contraindicated or if the patient experiences clinically significant adverse effects; the prescriber must document the medical justification for brand selection.

Prior Authorization

Approval durations

Initial approvals are granted for 6 months. Continued therapy approvals are granted for 12 months.

Per updated prescribing information, updated FDA-approved indications for colorectal and breast cancer; added gastric/esophageal/gastroesophageal junction and pancreatic cancer criteria (removed from off-label list); collapsed off-label criteria for anal carcinoma into NCCN off-label set; added ampullary adenocarcinoma and extrapulmonary neuroendocrine carcinoma to NCCN off-label list; removed criterion excluding severe renal impairment as a contraindication per PI updates (contraindication removed).

01.18.24annual_review

Added NCCN-supported indication of endometrial carcinoma and vulvar cancer into the off-label (NCCN-recommended) criteria set; references reviewed and updated.

08.07.24coding_update

Added HCPCS code J8522 and removed HCPCS codes J8520 and J85211.

01.13.25annual_review

Added NCCN-supported indications of cervical cancer and vaginal cancer into the off-label (NCCN-recommended) criteria set; revised language for extrapulmonary neuroendocrine carcinoma criteria (changed 'and' to 'or' regarding large or small cell carcinoma); references reviewed and updated.

05.25document_metaLatest

Policy last reviewed 05.25 (2Q 2025 annual review reflected in policy history).