BlueCross BlueShield of Tennessee Medical Policy Manual



50242-0051-XX RITUXAN 10MG/ML Solution (GENENTECH)

50242-0053-XX RITUXAN 10MG/ML Solution (GENENTECH)


Rituximab is a genetically engineered monoclonal antibody which binds specifically to the human CD20 antigen. The CD20 antigen is expressed on greater than 90% of B-cell non-Hodgkin’s lymphomas and is found on the abnormal B-cells of chronic lymphocytic leukemia (CLL).  Additionally, B-cells expressing the CD20 antigen are believed to play a role in the pathogenesis of rheumatoid arthritis.

In binding with the CD-20 antigen on B lymphocytes, rituximab likely recruits immune effector functions to mediate B-cell lysis, possibly through complement-dependent cytotoxicity (CDC) or antibody-dependent cell mediated cytotoxicity (AIDCC).  Rituximab has also been shown to induce apoptosis in the DHL-4 human B-cell lymphoma line.


See also: Rituximab Biosimilar Products







Initial therapy - 375 mg/m² weekly x 8 doses; OR 375 mg/m² cycle 1, then 500 mg/m² every 28 days cycles 2-6 (6 total doses)

Renewal therapy - 375 mg/m² once weekly for 4 doses per 6 month period; OR 375mg/ m² every 8 weeks

NHL, PTLD, Waldenström’s, Castleman’s or HL  

Initial therapy -  375 mg/m2 once weekly for 4 - 8 doses in a 6 month period

Renewal therapy - 375 mg/m² once weekly for 4 doses per 6 month period; OR 375mg/ m² every 8 weeks

Pediatric Aggressive B-cell Lymphoma


375 mg/m2 once to twice during the first week of the induction

cycle (typically 21-day cycle)


375 mg/m2 once weekly on day-1 of the consolidation cycle (typically 21-day cycle)


RCYVE – 375mg/m2 on day-1 of each 21-day cycle

RICE – 375 mg/m2 on days 2 and 3 of courses 1 and 2, and on day 1 only of course 3 if needed.

*Note: dosing and dosing schedules are highly variable and dependent on regimen used, please refer to NCCN for different protocols.

CNS Lymphoma


Initial: 375 mg/m2 once weekly for 4 - 8 doses in a 6 month period

Renewal Therapy:375 mg/m² once weekly for 4 doses per 6 month period; OR

375 mg/ m² every 8 weeks


10-40 mg weekly to every 3 weeks


375 mg/m2 once weekly for 4 - 8 doses in a 6 month period


1,000 mg on days 1 and 15, repeated every 24 weeks. May repeat up to every 16 weeks in patients requiring more frequent dosing based on clinical evaluation.

Pemphigus Vulgaris


Administer 1,000 mg on days 1 and 15 in combination with tapering doses of glucocorticoids


Administer 500 mg at month 12 and repeat every 6 months thereafter or based on clinical evaluation.


Administer 1000 mg upon relapse, resumption of glucocorticoids may be considered.

*Subsequent infusions (maintenance and relapse) should be no sooner than 16 weeks after the previous infusion.



375 mg/m² weekly x 4 doses, initially


Pediatric - 250 mg/m² on days 1 and 15, then 250 mg/m² every 6 months thereafter based on clinical evaluation

Adult - 500 mg on days 1 and 15, then 500 mg every 6 months thereafter based on clinical evaluation.

*Initial MAINTENANCE infusions should be no sooner than 16 weeks and no later than 24 weeks after the previous infusion if rituximab was used for initial induction therapy.

*Initial MAINTENANCE infusions should be initiated within 4 weeks following disease control when initial induction occurred with other standard of care immunosuppressants.

AIHA, Thrombocytopenia or Immunotherapy Toxicity Treatment

375 mg/m² weekly x 4 doses in a 6 month period


375 mg/m² weekly x 4 doses, then 375 mg/m² monthly x 4 months


Coverage will be provided for 6 months (12 months initially for pemphigus vulgaris) and may be renewed unless otherwise specified.

Maintenance therapy for oncology indications may be renewed for up to a maximum of 2 years except for the following:

Relapse therapy for pemphigus vulgaris must be at least 16 weeks past a prior infusion.

Refer to DOSAGE LIMITS below


BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.


We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.


For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).


Joly, B. S., Coppo, P., Veyradier, A. (2017, May). Thrombotic thrombocytopenic purpura. Blood, 129 (21), 2836-2846.

Lexi-Comp Online. (2020). AHFS DI. Rituximab. Retrieved August 13, 2020 from Lexi-Comp Online with AHFS.

MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2020, July). Rituximab. Retrieved August 13, 2020 2020 from MICROMEDEX Healthcare Series.

Moghadam-Kia, S., Aggarwal, S., Oddis, C. V. (2015). Treatment of inflammatory myopathy: emerging therapies and therapeutic targets. Expert Review of Clinical Immunology. (11)11, 1265-1275.

National Comprehensive Cancer Network. (2020). NCCN Drugs & Biologics Compendium®. Rituximab. Retrieved August 13, 2020 from the National Comprehensive Cancer Network.

Oddis, C. V., Reed, A. M., Aggarwal, R., Rider, L. G., Ascherman, D. P., Levesque, M. C., et al. (2013, February). Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: A randomized, placebo-phase trial. Arthritis Rheumatology, 65 (2), 314-324.

Pemphigus & Pemphigoid Foundation. (2017) For Medical Professionals - Diagnostic Testing.  Retrieved September 17, 2018 from

Pemphigus. ARUP Consult©. Retrieved October 2, 2019, from: 

Trebst, C., Jarius, S., Berthele, A., Paul, F., Schippling, S., Wildemann, B., et al. (2013). Update on the diagnosis and treatment of neuromyelitis optica: Recommendations of the Neuromyelitis Optica Study Group (NEMOS). Journal of Neurology. (2014) 261, 1-16.

U. S. Food and Drug Administration. (2020, March). Center for Drug Evaluation and Research. Rituxan® (rituximab) injection for intravenous use. Retrieved August 13, 2020 from




Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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Maximum billable units per dose and over time by indication as a Medical Benefit; 1 billable unit = 100 mg 



Oncology Indications:

Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL)

Initial therapy - Loading dose: 100 units x 1 dose

Subsequent doses - 130 units every 28 days x 5 doses per 6 months

Renewal therapy - 100 units per dose every 8 weeks x 4 doses per 6 months

Immunotherapy Toxicity Treatment

100 units per dose weekly x 4 doses in a 6 months period

All other oncology indications

Initial therapy -  100 units per dose weekly x 8 doses per 6 months

Renewal therapy - 100 units per dose every 8 weeks x 4 doses per 6 months

Non Oncology Indications:

Pemphigus Vulgaris

Initiation - 100 units every 14 days x 2 doses in a 12 month period

Maintenance - 50 units every 16 weeks

Rheumatoid Arthritis (RA )

100 units per dose every 14 days x 2 doses in a 16 week period


Induction - 100 units per dose weekly x 4 doses in a 4 month period

Initial Maintenance - 100 units x 2 doses in a 6 month period

Subsequent Maintenance - 50 units every 6 months


100 units per dose weekly x 4 doses, then 100 units monthly x 4 months

All other non-oncology indications

100 units per dose weekly x 4 doses in a 6 month period