Print

Date Printed: August 22, 2017: 07:04 AM

Private Property of Blue Cross and Blue Shield of Florida.
This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J1000-42

Original Effective Date: 01/01/12

Reviewed: 12/14/16

Revised: 01/15/17

Subject: Capecitabine (Xeloda®) Tablets

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           

Position Statement

Dosage/ Administration

Billing/Coding

Reimbursement

Program Exceptions

Definitions

     

     

Related Guidelines

Other

References

Updates

 

Previous Version

           

DESCRIPTION:

Capecitabine (Xeloda) is an orally administered pro-drug of 5-fluorouracil. Both tumor cells and normal cells metabolize 5-fluorouracil into two metabolites: 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). FdUMP prevents the formation of thymidylate from uracil; thymidylate is the necessary precursor of thymidine triphosphate (dTTP), one of the four deoxyribonucleotides required for synthesis of DNA. A deficiency of this compound results in the inhibition of cellular division. FUTP is incorporated in place of uridine triphosphate (UTP) during RNA synthesis. This interferes with RNA processing and protein synthesis. Interference with DNA and RNA activity results in anti-neoplastic activity.

Capecitabine was the first oral anti-neoplastic agent approve by the US Food and Drug Administration for the treatment of metastatic breast cancer. It is also indicated for the first line treatment of metastatic colon cancer and as adjuvant treatment for colon cancer in persons with Dukes C colon cancer. In addition to its FDA-approved indications, capecitabine treatment is supported by referenced compendia (e.g., National Comprehensive Cancer Network) for off-label uses, including the treatment of anal cancer, brain metastases, cancer of unknown primary (occult primary), esophageal cancer, gastric cancer, hepatobiliary cancer, neuroendocrine tumors, renal cancer, ovarian cancer, pancreatic cancer, penile cancer, rectal cancer, and head and neck cancer.

POSITION STATEMENT:

Capecitabine (Xeloda) meets the definition of medical necessity when BOTH of the following are met:

1. Member meets ALL criteria for requested formulation:

a. Capecitabine tablet (generic)

i. Dosage does not exceed 2500 mg/m2/day

b. Xeloda® tablet

i. Member has a failure, contraindication, or intolerance to generic capecitabine

ii. Dosage does not exceed 2500 mg/m2/day

2. ONE of the following:

a. Capecitabine will be used to treat ANY of the following:

i. Anal carcinoma

ii. Appendiceal adenocarcinoma

iii. Breast cancer

iv. Brain metastases

v. Colon cancer

vi. Esophageal and esophagogastric junction cancer

vii. Gastric cancer

viii. Head and neck cancer

ix. Hepatobiliary cancer

x. Neuroendocrine tumor

xi. Occult primary tumors

xii. Ovarian cancer

xiii. Pancreatic adenocarcinoma

xiv. Penile Cancer

xv. Rectal cancer

xvi. Renal Cancer

xvii. Small bowel adenocarcinoma

b. Use is supported by an NCCN Compendium™ level of evidence 1 or 2A recommendation

c. Use is an FDA-approved indication

Approval duration: 1 year (all indications)

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved indications

Capecitabine should be administered with water 30 minutes after a meal. When used as monotherapy, the recommended dose is 1,250 mg/m2 twice daily for 14 days followed by a 1 week rest period in a 3 week cycle. Adjuvant therapy is recommended for a total of six months. When used in combination with docetaxel, the recommended dose is 1,250 mg/m2 twice daily for 14 days followed by a one week rest period, combined with docetaxel 75 mg/m2 as a 1 hour IV infusion every three weeks.

Dose Adjustments: reduce the dose by 25% in members with moderate renal impairment. Monitor in persons with mild to moderate hepatic impairment. Geriatric patients are more likely to experience adverse reactions and should be monitored closely. See prescribing information for adjustments due to adverse reactions.

Drug Availability: capecitabine is supplied as a 150- or 500 mg tablet.

PRECAUTIONS:

BOXED WARNING:

Individuals receiving capecitabine and oral coumarin-derivative anticoagulants (e.g., warfarin) should have their anticoagulant response (INR or prothrombin time) monitored frequently to adjust the anticoagulant accordingly. Altered coagulation parameters and/or bleeding, including death have occurred. The drug interaction may occur within days to several months after initiation of therapy or after stopping therapy with capecitabine. Individuals > 60 years of age with a diagnosis of cancer are more at risk.

CONTRAINDICATIONS

WARNINGS/PRECAUTIONS

BILLING/CODING INFORMATION:

HCPCS Coding

J8520

Capecitabine, oral, 150 mg

J8521

Capecitabine, oral, 500 mg

WW089

Capecitabine, 150 mg oral

WW096

Capecitabine, 500 mg oral

ICD-10 Diagnoses Codes That Support Medical Necessity (Effective 10/01/15)

C00.0 – C00.9

Malignant neoplasm of lip

C01

Malignant neoplasm of base of tongue

C02.0

Malignant neoplasm of dorsal surface of tongue

C02.1

Malignant neoplasm of border of tongue

C02.2 – C02.4

Malignant neoplasm of ventral surface of tongue, anterior two-thirds of tongue, part unspecified, lingual tonsil

C02.8

Malignant neoplasm of overlapping sites of tongue

C02.9

Malignant neoplasm of tongue, unspecified

C03.0 – C03.9

Malignant neoplasm of upper gum, lower gum, gum unspecified

C04.0 – C04.9

Malignant neoplasm of floor of mouth

C05.0 – C05.9

Malignant neoplasm of palate

C06.0 – C06.9

Malignant neoplasm of other and unspecified parts of mouth

C09.0 – C09.9

Malignant neoplasm of tonsil

C10.0 – C10.9

Malignant neoplasm of oropharynx

C11.0 – C11.9

Malignant neoplasm of nasopharynx

C12

Malignant neoplasm of pyriform sinus

C13.0 – C13.9

Malignant neoplasm of hypopharynx

C14.0 – C14.8

Malignant neoplasm of other and ill-defined sites in the lip, oral cavity and pharynx

C15.3 – C15.9

Malignant neoplasm of esophagus

C16.0 – C16.9

Malignant neoplasm of stomach

C17.0 – C17.2

Malignant neoplasm of duodenum, jejunum, ileum

C17.8 – C17.9

Malignant neoplasm of overlapping sites of small intestine or of unspecified site of small intestine

C18.0 – C18.9

Malignant neoplasm of colon

C19 – C21.8

Malignant neoplasm of rectosigmoid junction, rectum, anus and anal canal

C22.1

Intrahepatic bile duct carcinoma

C23 – C24.9

Malignant neoplasm of gallbladder and other and unspecified parts of biliary tract

C25.0 – C25.2

Malignant neoplasm of head, body, or tail of pancreas

C25.3

Malignant neoplasm of pancreatic duct

C25.4

Malignant neoplasm of endocrine pancreas

C25.7 – C25.9

Malignant neoplasm of other parts of pancreas, overlapping sites of pancreas, or unspecified part of pancreas

C30.0

Malignant neoplasm of nasal cavity

C31.0 – C31.1

Malignant neoplasm of maxillary or ethmoidal sinus

C32.0 – C32.9

Malignant neoplasm of larynx

C44.00 – C44.09

Unspecified malignant neoplasm of skin of lip

C48.1 – C48.2

Malignant neoplasm of specified or unspecified parts of peritoneum

C48.8

Malignant neoplasm of overlapping sites of retroperitoneum and peritoneum

C50.011 – C50.929

Malignant neoplasm of breast

C56.1 – C57.9

Malignant neoplasm of ovary, fallopian tube, broad ligament, parametrium and uterine adnexa, unspecified

C60.0 – C60.9

Malignant neoplasm of penis

C63.7

Malignant neoplasm of other specified male genital organs

C63.8

Malignant neoplasm of overlapping sites of male genital organs

C63.9

Malignant neoplasm of male genital organs , unspecified

C64.1 - C64.9

Malignant neoplasm of unspecified kidney, except renal pelvis

C65.1 - C65.9

Malignant neoplasm of unspecified renal pelvis

C76.0

Malignant neoplasm of head, face, and neck

C77.0

Secondary and unspecified malignant neoplasm of lymph nodes of head, face and neck

C78.00 – C78.02

Secondary malignant neoplasm of lung

C78.6

Secondary malignant neoplasm of retroperitoneum and peritoneum

C78.7

Secondary malignant neoplasm of liver and intrahepatic bile duct

C79.31

Secondary malignant neoplasm of brain

C79.51

Secondary malignant neoplasm of bone

C79.52

Secondary malignant neoplasm of bone marrow

C79.89

Secondary malignant neoplasm of other specified sites

C7A.00 – C7A.8

Malignant carcinoid tumor of other sites

C7B.00 – C7B.09

Secondary carcinoid tumor

C80.0 – C80.1

Disseminated malignant neoplasm, unspecified; Malignant (primary) neoplasm, unspecified

D37.01 – D37.09

Neoplasm of uncertain behavior of lip, tongue, salivary glands and pharynx

D37.1 – D37.9

Neoplasm of uncertain behavior of other digestive organs

D38.0

Neoplasm of uncertain behavior of larynx

D38.5 – D38.6

Neoplasm of uncertain behavior of other respiratory organs or unspecified respiratory organ

E16.0 – E16.8

Other disorders of pancreatic internal secretion

E34.0

Carcinoid syndrome

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

Medicare Advantage Products: No National Coverage Determination (NCD) was found at the time of the last guideline revised date. The following Local coverage determination (LCD) was found at fcso.com:L33826, Oral Anti-cancer Drugs.

DEFINITIONS:

DPD: Dihydropyrimidine dehydrogenase (DPD) is an enzyme involved in the breakdown of the pyrimidines, uracil and thymine. A deficiency in DPD is a result of mutations in the DPYD gene. The deficiency causes excess uracil and thymine; however it is unknown how excess pyrimidines are related to signs and symptoms of the disorder. Fluoropyrimidine toxicity may result in individuals with deficiency of DPD because the medications are broken down by the enzyme.

RELATED GUIDELINES:

Assays of Genetic Expression in Tumor Tissue as a Technique to Determine Prognosis in Patients with Breast Cancer, 05-86000-26
Bevacizumab (Avastin®) Injection, 09-J0000-66

Brachytherapy-Oncologic Applications, 04-77260-20

Carboplatin (Paraplatin®) IV, 09-J0000-93

Docetaxel (Taxotere®) IV, 09-J0000-95

Genetic Testing for Hereditary Breast or Ovarian Cancer, 05-82000-30

Genetic Testing for Inherited Susceptibility to Colon Cancer Including Microsatellite Instability, 08-82000-31

Gonadotropin Releasing Hormone Analogs and Antagonists, 09-J0000-48

Intensity-Modulated Radiation Therapy (IMRT), 04-77260-22

Oxaliplatin (Eloxatin®) IV, 09-J1000-00

Positron Emission Tomography (PET Scan) Oncologic Applications, 04-78000-17

Tumor Markers, 05-86000-22

OTHER:

Table 1: Common Terminology Criteria for Adverse Events v4.0 (CTCAE)

Grade

Description

1

Mild; asymptomatic or mild symptoms; clinical diagnostic observations only; intervention not indicated

2

Moderate; minimal, local or noninvasive intervention indicated; limited age-appropriate instrumental activities of daily living

3

Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living

4

Life-threatening consequences; urgent intervention indicated

5

Death related to adverse event

REFERENCES:

  1. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc; 2016 [cited 2016 Nov 21]. In: STAT!Ref Online Electronic Medical Library [Internet]. Available from: http://online.statref.com/.
  2. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2016 [cited 2016 Nov 21]. Available from: http://www.clinicalpharmacology.com/.
  3. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2014 Nov 3]. Available from: http://clinicaltrials.gov/.
  4. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2016 Nov 21]. Available from: http://www.thomsonhc.com/.
  5. National Cancer Institute. Common Terminology Criteria for Adverse Events. Available at: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Accessed 11/18/15.
  6. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Anal Cancer, v.1.2017 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  7. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Breast Cancer, v.2.2016 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  8. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Central Nervous System Cancer, v.1.2016 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  9. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Colon Cancer, v.1.2017 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  10. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Esophageal and Esophagogastric Junction Cancer, v.2.2016 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  11. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Gastric Cancer, v.3.2016 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  12. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Head and Neck Cancer, v.2.2016 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  13. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Hepatobiliary Cancers, v.2.2016 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  14. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Neuroendocrine Tumors, v.2.2016 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  15. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Occult Primary (Cancer of Unknown Primary[CUP]) v.2.2017 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  16. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Ovarian Cancer, v.1.2016 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  17. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Pancreatic Adenocarcinoma, v.2.2016 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  18. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Rectal Cancer, v.1.2017 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  19. NCCN Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2016 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.
  20. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2016 [cited 2016 Nov 28]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  21. Xeloda (capecitabine) tablet [package insert]. Genentech, Inc. San Francisco, CA. March 2015 [cited 2016 Nov 21]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a1de8bba-3b1d-4c9d-ab8a-32d2c05e67c8/.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 12/14/16.

GUIDELINE UPDATE INFORMATION:

01/01/12

New Medical Coverage Guideline.

01/15/14

Review and revision to guideline; consisting of updating the position statement, dosage/administration section, precautions section, references, coding, and program exceptions.

07/15/14

Revision to guideline; consisting of adding language requiring failure of generic capecitabine.

01/15/15

Review and revision to guideline; consisting of position statement, coding, references.

11/01/15

Revision: ICD-9 Codes deleted.

01/15/16

Review and revision to guideline; consisting of updating position statement, dosing, warnings, coding, references.

01/15/17

Review and revision to guideline; consisting of updating position statement, coding, and references.

Date Printed: August 22, 2017: 07:04 AM