CurrentCentenePolicy CP.PHAR.60

Capecitabine (Xeloda) (PDF)

Defines medical necessity criteria, dosing limits, approved and NCCN-recommended off-label indications, DPYD testing requirement, generic use preference, continuation criteria, approval durations, contraindications/boxed warnings, and coding implications for capecitabine across HIM/ICHRA and Medicaid lines of business.

Policy Summary

PayerCentene

PolicyCapecitabine (Xeloda) (PDF)

Policy CodePolicy CP.PHAR.60

Change TypeMaterial changes to criteria, indications, coding, and approval duration

Effective Date05.01.11

Next Review Date

Key ActionProvider must submit documentation (office notes, lab results, etc.) supporting that member meets all approval criteria.

SourceLink

POLICY UPDATE CHANGES

Added criterion to confirm that a homozygous or compound heterozygous DPYD variant is not present, unless immediate treatment is necessary.

Extended initial approval duration from 6 to 12 months.

Added gastric/esophageal/gastroesophageal junction cancer and pancreatic cancer criteria as FDA-approved indications (removed from off-label list).

Added HCPCS code J8522 and removed J8520 and J8521.

Added ICHRA line of business.

5FDA Indications listed

qNCCN off-label count (a–q)

12Approval duration (months)

J8522Current HCPCS code

Coverage Summary

Policy CP.PHAR.60: Capecitabine (Xeloda) is covered with criteria. Coverage aligns with FDA-approved indications and NCCN-recommended off-label uses, requires confirmation that a homozygous or compound heterozygous DPYD variant is not present prior to initiating therapy (unless immediate treatment is necessary), and mandates generic-first use unless contraindicated or clinically significant adverse effects occur. Approval duration is 12 months.

Quick facts / high-level thresholds

Age threshold>= 18 years

Approval duration12 months

Current HCPCS codeJ8522 (Capecitabine, oral, 50 mg)

DPYD/DPD testing requirementConfirm homozygous or compound heterozygous DPYD variants are not present prior to initiating capecitabine unless immediate treatment is necessary

Generic-first ruleMember must use generic capecitabine unless contraindicated or clinically significant adverse effects occur

Initial Therapy Criteria

Initial Approval Criteria

Covered when ALL of the following are met:

ALL of the following

Diagnosis of colorectal cancer
Used in subsection A (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

Continuation Therapy Criteria

Continued Therapy (All Indications)

Covered when ALL of the following are met:

ALL of the following

Currently receiving medication via Centene benefit, or documentation supports member has received Xeloda for at least 30 days
Member is responding positively to therapy
Member must use generic capecitabine, unless contraindicated or clinically significant adverse effects are experienced
If request is for a dose increase, new dose must meet one of
- Colorectal cancer monotherapy: New dose does not exceed 2,500 mg/m2 total daily dose on Days 1 to 14, every 21 days (if adjuvant: max 8 cycles)

Provider Actions / Prior Authorization

Prior Authorization

Prior authorization requirement

Requests require confirmation of the diagnosis, that the drug is prescribed by or in consultation with an oncologist, patient age ≥ 18 years, confirmation that a homozygous or compound heterozygous DPYD variant is not present (unless immediate treatment is necessary), use of generic capecitabine unless contraindicated, adherence to specified dose limits or guideline-supported dosing, and that approvals are granted for 12 months.

Documentation Required

Support clinical documentation

Submit clinical documentation (office/chart notes, lab results, and other clinical information) demonstrating the diagnosis, oncologist involvement, age, dosing regimen and that dosing falls within policy limits or is supported by practice guidelines/peer‑reviewed literature. When applicable, include DPYD test results or documentation addressing DPYD status per policy guidance.

Applicable Codes

HCPCS J-code for capecitabineHCPCS

J8522

Capecitabine, oral, 50 mg

Safety, Evidence, and Background

Capecitabine is an orally administered nucleoside metabolic inhibitor with antineoplastic activity. The policy aligns coverage with FDA-approved indications and NCCN recommendations and includes safety provisions addressing dihydropyrimidine dehydrogenase (DPD) deficiency; patients with homozygous or compound heterozygous DPYD variants (complete or near-complete DPD deficiency) are at increased risk of severe or fatal toxicity, and updated labeling advises testing for DPYD variants prior to initiating capecitabine unless immediate treatment is necessary.

Evidence sources: Xeloda Prescribing Information (Genentech, Inc.; October 2025) and the NCCN Drugs & Biologics Compendium (accessed January 29, 2026).

Boxed warnings / DPYD (contraindication) quick reference

Boxed warning updateBoxed warnings updated for patients with complete DPD deficiency (risk of severe/fatal toxicity)

DPYD variant confirmation requirementPolicy adds requirement to confirm a homozygous or compound heterozygous DPYD variant is not present prior to initiation unless immediate treatment is necessary

DPYD definition / rationaleHomozygous or compound heterozygous DPYD variants can cause complete or near-complete DPD deficiency, increasing risk of severe toxicity (eg, mucositis, diarrhea, neutropenia, neurotoxicity)

Definitions

DPYD: Gene encoding dihydropyrimidine dehydrogenase; homozygous or compound heterozygous variants can cause complete or near-complete DPD deficiency, increasing risk of severe toxicity with capecitabine.

NCCN: National Comprehensive Cancer Network; guideline source referenced for off-label/recommended uses.

Revision History

05.26.2026P&T approval (annual review)Latest

2Q 2026 annual review; updated boxed warnings for patients with complete DPD deficiency and added criterion requiring confirmation that a homozygous or compound heterozygous DPYD variant is not present unless immediate treatment is necessary (per Appendix D).

05.26.2026P&T approval (annual review)Latest

Extended initial approval duration from 6 months to 12 months for this maintenance medication (chronic condition).

05.26.2026

Policy Summary

PayerCentene

PolicyCapecitabine (Xeloda) (PDF)

Policy CodePolicy CP.PHAR.60

Change TypeMaterial changes to criteria, indications, coding, and approval duration

Effective Date05.01.11

Next Review Date

Key ActionProvider must submit documentation (office notes, lab results, etc.) supporting that member meets all approval criteria.

SourceLink

On This Page

Confirmation that a homozygous or compound heterozygous DPYD variant is not present, unless immediate treatment is necessary

See Appendix D; added per 2Q 2026 annual review

Request meets one of

Monotherapy (unresectable or metastatic disease, or adjuvant treatment): Dose does not exceed 1,250 mg/m2 twice a day on Days 1 to 14, every 21 days
If adjuvant treatment: maximum of 8 cycles
In combination with oxaliplatin-containing regimen (unresectable or metastatic disease, or adjuvant treatment): Dose does not exceed 1,000 mg/m2 twice a day on Days 1 to 14, every 21 days
Perioperative options
- With concomitant radiation therapy: Dose does not exceed 825 mg/m2 twice a day
- Without radiation therapy: Dose does not exceed 1,250 mg/m2 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

Initial Approval Criteria - Breast Cancer

Covered when ALL of the following are met:

ALL of the following

Diagnosis of breast cancer and one of the following: a) Disease is recurrent, advanced, metastatic, or unresponsive to preoperative systemic therapy; OR b) Xeloda is prescribed as adjuvant or maintenance therapy
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
Confirmation that a homozygous or compound heterozygous DPYD variant is not present, unless immediate treatment is necessary
Dose options
- Dose does not exceed 1,250 mg/m2 twice a day on Days 1 to 14, every 21 days
- 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

Initial Approval Criteria - Gastric/Esophageal/Gastroesophageal Junction Cancer

Covered when ALL of the following are met:

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
Confirmation that a homozygous or compound heterozygous DPYD variant is not present, unless immediate treatment is necessary
Dose options
- Dose does not exceed 625 mg/m2 twice a day on Days 1 to 21, every 21 days
  Maximum of 8 cycles
- Dose does not exceed 1,000 mg/m2 twice a day on Days 1 to 14, every 21 days
- 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

Initial Approval Criteria - Pancreatic Cancer

Covered when ALL of the following are met:

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
Confirmation that a homozygous or compound heterozygous DPYD variant is not present, unless immediate treatment is necessary
Dose options
- Dose does not exceed 830 mg/m2 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

Initial Approval Criteria - NCCN Recommended Uses (off-label)

Covered when ALL of the following are met:

ALL of the following

Prescribed for one of the following diagnoses: ampullary adenocarcinoma; anal carcinoma; appendiceal neoplasms and cancers; cervical cancer; gestational trophoblastic neoplasia; head and neck cancer (nasopharynx, advanced head and neck cancer, occult primary tumors); hepatobiliary cancer (extrahepatic cholangiocarcinoma, gallbladder cancer, intrahepatic cholangiocarcinoma); neuroendocrine tumor of the pancreas, gastrointestinal tract, lung, or thymus; extrapulmonary neuroendocrine carcinoma (large OR small carcinoma OR mixed neuroendocrine-non-neuroendocrine neoplasm); occult primary cancer; ovarian/fallopian tube/primary peritoneal cancer; penile cancer; small bowel adenocarcinoma; squamous cell skin cancer; thymoma or thymic carcinoma; vaginal cancer; vulvar 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
Confirmation that a homozygous or compound heterozygous DPYD variant is not present, unless immediate treatment is necessary
Dose is within FDA maximum limit for any FDA approved indication OR 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

Other diagnoses/indications (fallback)

If not specifically listed above or if recent label change occurred:

ANY of the following

If label change within last 6 months not yet reflected in policy, refer to no coverage or non-formulary policies depending on formulary status (HIM.PA.33, CP.PMN.255, HIM.PA.103, CP.PMN.16)
If requested use is not listed in section III and above does not apply, refer to off-label use policy (HIM.PA.154 or CP.PMN.53)

Colorectal cancer with oxaliplatin: New dose does not exceed 2,000 mg/m2 total daily dose on Days 1 to 14, every 21 days

Colorectal perioperative

With concomitant radiation therapy: New dose does not exceed 1,650 mg/m2 total daily dose
Without radiation therapy: New dose does not exceed 2,500 mg/m2 total daily dose

Breast cancer: New dose does not exceed 2,500 mg/m2 total daily dose on Days 1 to 14, every 21 days

Gastric/Esophageal options

New dose does not exceed 1,250 mg/m2 total daily dose on Days 1 to 21, every 21 days (max 8 cycles)
New dose does not exceed 2,000 mg/m2 total daily dose on Days 1 to 14, every 21 days

Pancreatic cancer: New dose does not exceed 1,660 mg/m2 total daily dose on Days 1 to 21, every 28 days (max 6 cycles)

New 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

Relevant laboratory results

DPYD testing results or documentation

Documentation Required

DPYD variant confirmation

Confirmation that a homozygous or compound heterozygous DPYD variant is not present is required prior to initiating capecitabine unless immediate treatment is necessary. If immediate treatment is necessary, the prescriber may submit a rationale and supporting evidence; note that currently available DPYD tests vary in design and an FDA‑authorized test is not available.

DPYD confirmation required before initiation unless immediate treatment is necessary
Prescriber may submit rationale/evidence if treatment cannot be delayed
Available DPYD tests may vary and no FDA‑authorized test is currently available

Billing Rule

Use generic product

Generic capecitabine is preferred. Members must use generic capecitabine unless contraindicated or clinically significant adverse effects occur. This generic‑first preference applies to both initial and continued therapy.

Documentation Required

Off-label supporting evidence

For off‑label or NCCN‑recommended uses or for dosing outside FDA limits, the prescriber must submit supporting practice guidelines or peer‑reviewed literature to justify the requested regimen.

Submit practice guideline citations or peer‑reviewed literature supporting the off‑label/NCCN‑recommended use or non‑standard dose

Testing noteFDA advises testing for DPYD variants prior to initiating capecitabine, but an FDA-authorized test is not currently available; available tests vary in accuracy and design

When exception allowedIf immediate treatment is necessary, prescriber may initiate therapy without confirmed absence of homozygous/compound heterozygous DPYD variants

P&T approval (annual review)

Added gastric/esophageal/gastroesophageal junction cancer and pancreatic cancer as FDA-approved indications (removed from off‑label list) per updated prescribing information and RT4 changes.

08.07.2024Coding update

Coding update: added HCPCS code J8522 (Capecitabine, oral, 50 mg) and removed HCPCS codes J8520 and J8521.

02.??.????Administrative update

Non-material administrative addition: added ICHRA line of business.