LCD/NCD MedicationsL29181-LCD

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Local Coverage Determination (LCD) for Ganciclovir and Cidofovir (L29181)

Contractor Information

Contractor Name First Coast Service Options, Inc.

Contractor Number 09102

Contractor Type MAC - Part B

LCD Information

Document Information

LCD ID Number L29181

LCD Title Ganciclovir and Cidofovir

Contractor's Determination Number J0740

Primary Geographic Jurisdiction Florida

Oversight Region Region IV

AMA CPT/ADA CDT Copyright Statement

CPT only copyright 2002-2011 American Medical Association. All Rights Reserved. CPT is a registered trademark of the American Medical Association. Applicable FARS/DFARS Apply to Government Use. Fee schedules, relative value units, conversion factors and/or related components are not assigned by the AMA, are not part of CPT, and the AMA is not recommending their use. The AMA does not directly or indirectly practice medicine or dispense medical services. The AMA assumes no liability for data contained or not contained herein. The Code on Dental Procedures and Nomenclature (Code) is published in Current Dental Terminology (CDT). Copyright © American Dental Association. All rights reserved. CDT and CDT-2010 are trademarks of the American Dental Association.

Original Determination Effective Date

For services performed on or after 02/02/2009

Original Determination Ending Date

Revision Effective Date

For services performed on or after 06/14/2011

Revision Ending Date

CMS National Coverage Policy

CMS Manual System, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 15, Section 50.4.1

CMS Manual System, Pub. 100-08, Program Integrity Manual, Chapter 13, Section 5.1

Indications and Limitations of Coverage and/or Medical Necessity

Ganciclovir (Cytovene IV) is a synthetic guanine derivative and an active antiviral agent for cytomegalovirus (CMV) infections. The ganciclovir (Vitrasert) implant is a synthetic nucleoside analogue of 2′- deoxyguanosine, which inhibits assembly of virons. Ganciclovir is not a cure for CMV.

Cidofovir (Vistide) is an antiviral used to treat the symptoms of CMV infection of the eye. Cidofovir is available in IV form only. Cidofovir will not cure CMV infection.

Indications

Ganciclovir (J1570 and J7310)

Medicare will cover ganciclovir for the following FDA approved indications:

IV form

• Cytovene-IV is indicated for the induction and maintenance in the treatment of CMV retinitis in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS).

• Cytovene-IV is also indicated for the prevention of CMV disease in transplant recipients at risk for CMV disease

Implant form

• Ganciclovir (Vitrasert) implant is indicated for CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS). The intravitreal implant is designed to release ganciclovir over a period of 5 to 8 months. The implant provides localized treatment only and will not have any effect on extraocular CMV infection.

Cidofovir (J0740)

Medicare will cover cidofovir (Vistide) for the following FDA approved indications:

• Cidofovir is indicated, in combination with probenecid, for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS).

Medicare will also cover cidofovir for the following off-label indications:

• BK nephropathy or BK viremia for kidney transplant recipients.

Limitations

The CMS Manual System, Pub. 100-8, Program Integrity Manual, Chapter 13, Section 5.1 (http://www.cms.hhs.gov/manuals/downloads/pim83c13.pdf) outlines that "reasonable and necessary" services

are "ordered and/or furnished by qualified personnel." Services will be considered medically reasonable and

necessary only if performed by appropriately trained providers.

A qualified physician for this service/procedure is defined as follows: A) Physician is properly enrolled in Medicare.

B) Training and expertise must have been acquired within the framework of an accredited residency and/or fellowship program in the applicable specialty/subspecialty in the United States or must reflect equivalent education, training, and expertise endorsed by an academic institution in the United States and/or by the applicable specialty/subspecialty society in the United States.

"Drugs or biologicals approved for marketing by the FDA are considered safe and effective when used for indications specified on the labeling. The labeling lists the safe and effective, i.e. medically reasonable and necessary dosage and frequency. Therefore, doses and frequencies that exceed the accepted standard of recommended dosage and/or frequency, as described in the package insert, are considered not medically reasonable and necessary and, therefore, not reimbursable."

For the purpose of this LCD in defining immunocompromised patients, an expert in the field must have established an immune deficiency state to a degree that would place the patient at risk to develop a clinically significant manifestation of CMV retinitis.

Ganciclovir

Ganciclovir (Cytovene-IV) is contraindicated in patients with hypersensitivity to ganciclovir or acyclovir. Ganciclovir (Vitrasert) is contraindicated in patients with hypersensitivity to ganciclovir or acyclovir and in

patients with any contraindication for intraocular surgery, such as external infection or severe thrombocytopenia.

Cidofovir

Initiation of therapy with cidofovir is contraindicated in patients with a serum creatinine > 1.5mg/dL, a calculated creatinine clearance ≤ 55mL/min, or a urine protein ≥ 100mg/dL (equivalent to ≥ 2+ proteinuria).

Cidofovir is contraindicated in patients receiving agents with nephrotoxic potential. Such agents must be discontinued prior to starting therapy with Vistide.

Cidofovir is contraindicated in patients with hypersensitivity to cidofovir.

Cidofovir is contraindicated in patients with a history of clinically severe hypersensitivity to probenecid or other sulfa containing medications.

Direct intraocular injection of Vistide is contraindicated. Administering Vistide by intraocular injection may result in significant decreases in intraocular pressure and vision impairment.

Coding Information

Bill Type Codes:

Contractors may specify Bill Types to help providers identify those Bill Types typically used to report this service. Absence of a Bill Type does not guarantee that the policy does not apply to that Bill Type. Complete absence of all Bill Types indicates that coverage is not influenced by Bill Type and the policy should be assumed to apply equally to all claims.

999x Not Applicable

Revenue Codes:

Contractors may specify Revenue Codes to help providers identify those Revenue Codes typically used to report this service. In most instances Revenue Codes are purely advisory; unless specified in the policy services reported under other Revenue Codes are equally subject to this coverage determination. Complete absence of all Revenue Codes indicates that coverage is not influenced by Revenue Code and the policy should be assumed to apply equally to all Revenue Codes.

99999 Not Applicable

CPT/HCPCS Codes

J0740 INJECTION, CIDOFOVIR, 375 MG

J1570 INJECTION, GANCICLOVIR SODIUM, 500 MG J7310 GANCICLOVIR, 4.5 MG, LONG-ACTING IMPLANT

ICD-9 Codes that Support Medical Necessity

042* HUMAN IMMUNODEFICIENCY VIRUS (HIV) DISEASE

078.5* CYTOMEGALOVIRAL DISEASE

363.00 - 363.08* FOCAL CHORIORETINITIS UNSPECIFIED - FOCAL RETINITIS AND RETINOCHOROIDITIS PERIPHERAL

363.10 - 363.15* DISSEMINATED CHORIORETINITIS UNSPECIFIED - DISSEMINATED RETINITIS AND RETINOCHOROIDITIS PIGMENT EPITHELIOPATHY

V42.0* KIDNEY REPLACED BY TRANSPLANT

*Please note that when billing procedure code J0740 and J7310, a diagnosis of 042 must and 078.5 must be billed, in addition to a diagnosis from the range 363.00-363.08 or 363.10-363.15.

* V42.0 should be billed for J0740 only when it has been administered for the off-label indication of BY nephropathy or BK viremia.

Diagnoses that Support Medical Necessity

N/A

ICD-9 Codes that DO NOT Support Medical Necessity

Any diagnosis not listed under ICD-9 codes that support medical necessity

XX000 Not Applicable

ICD-9 Codes that DO NOT Support Medical Necessity Asterisk Explanation

Diagnoses that DO NOT Support Medical Necessity N/A

General Information

Documentations Requirements

Dilated indirect ophthalmoscopy should be preformed at the time of diagnosis of CMV retinitis, after completion of induction therapy, 1 month after the initiation of therapy and monthly thereafter while the patient is on anti-CMV treatment. These tests should be documented in the medical record and made available to Medicare upon request.

All coverage criteria listed in the indications and limitations and utilization guidelines section of this LCD must be documented in the medical record and made available to Medicare upon request.

All laboratory test listed as necessary under utilization guidelines for each drug must be documented in the medical record. These tests should be preformed prior to each dose administration to support the treatment is medically necessary. For patients receiving cidofovir, the medication record must support that the patient is receiving the required IV hydration and the required probenecid with each cidofovir administration.

Patients who are HIV+ should be advised to have ophthalmologic follow up exams at a minimum of every 4-6 weeks while being treated with Cytovene IV. These follow up exams should be documented in the patient’s medical record and made available to Medicare upon request.

J0740

For the off-label indication, the medical record must show a biopsy proven BK virus nephropathy or a baseline kidney function, if the disease is severe on biopsy or BK PCR blood does not respond to a reduction of immunosuppression. If being used for patients at risk for BK virus nephropathy, the medical record must show rising BK blood and urine PCR occurring despite a reduction in immunosuppression.

Appendices

Utilization Guidelines Dilated indirect ophthalmoscopy should be preformed at the time of the diagnosis of CMV retinitis, after completion of induction therapy, 1 month after the initiation of therapy and monthly thereafter while the patient is on anti-CMV treatment.

Ganciclovir (Cytovene)

The recommended dose for Cytovene-IV should not be exceeded. The recommended infusion rate for Cytovene-IV solution should not be exceeded.

Patients with Normal Renal function

Treatment of CMV retinitis in patients with normal renal function:

Induction Treatment: (Cytovene-IV) The recommended initial dosage for patients with normal renal function is 5mg/kg every 12 hours for 14-21 days. The infusion is given at a constant rate over 1 hour. Cytovenecapsules should not be used for induction treatment.

Maintenance Treatment: (Cytovene-IV) Following induction treatment, the recommended maintenance dosage of Cytovene-IV solution is 5mg/kg given as a constant-rate infusion over one hour once daily, 7 days per week, or 6mg/kg once daily, 5 days per week.

Prevention of CMV disease in transplant recipients with normal renal function

Cytovene-IV: The recommended initial dosage of Cytovene-IV solution for patients with normal renal function is 5mg/kg, given at a constant rate over one hour, every 12 hours for 7-14 days, followed by 5mg/kg once daily, 7 days per week or 6mg/kg once daily, 5 days per week.

Patients with Renal Impairment

Cytovene IV – Refer to the table below for recommended doses and adjust dosing interval as indicated.

Creatinine Clearance* (mL/min)( Cytovene-IV Induction Dose (mg/kg)) Dosing Interval (hours)( Cytovene- IV Maintenance dose (mg/kg)) Dosing Interval (hours)

≥ 70 (5.0) 12 (5.0) 24

50-69 (2.5) 12 (2.5) 24

25-49 (2.5) 24 (1.25) 24

10-24 (1.25) 24 (0.625) 24

<10 (1.25) 3 times per week following hemodialysis (0.625) 3 times per week following hemodialysis

• *Creatinine clearance can be related to serum creatinine by the formulas given below.

• Dosing for patients undergoing hemodialysis should not exceed 1.25mg/kg 3 times per week, following each hemodialysis session. Cytovene-IV should be given shortly after the dialysis session, since dialysis has been shown to reduce plasma levels by approximately 50%.

Creatinine clearance for males =

(140-age [yrs]) (body wt [kg])/(72) (serum creatinine [mg/dL])

Creatinine clearance for females = 0.85x male value

Blood counts and platelet counts should be preformed frequently, especially in patients in whom ganciclovir or nucleoside analogues have previously resulted in cytopenia, or in whom neutrophil counts are less than 1000 cells/ul at the beginning of treatment. Serumcreatinineorcreatinineclearancevaluesshouldbefollowed carefully to allow for dosage adjustments in renally impaired patients.

DosereductioninpatientswithrenalimpairmentarerequiredforCytovene-IV and should be considered for Cytovene capsules. Dose reductions should be considered for those with neutropenia, anemia and/or thrombocytopenia. Ganciclovirshouldnotbeadministeredinpatientswithsevereneutropenia (ANC less than 500/ul) or severe thrombocytopenia (platelets less than 25,000/ul).

Ganciclovir (Vitrasert)

Each Vitrasert implant contains a minimum of 4.5mg of ganciclovir and is designed to release the drug over a 5 to 8 month period of time. Following depletion of ganciclovir from the implant, as evidenced by progression of retinitis, the implant may be removed and another one inserted.

Cidofovir (Vistide)

Due to potential for increased nephrotoxicity, doses greater than the recommended dose must not be administered and the frequency or rate of administration must not be exceeded.

Patients receiving intravenous cidofovir: BUN, creatinine and urinalysis should be performed before each infusion.

Induction Therapy

The recommended induction dose of Vistide for patients with a serum creatinine of ≤ 1.5mg/dL, a calculated creatinine clearance > 55mL/min, and a urine protein < 100mg/dL (equivalent to < 2+ proteinuria) is 5mg/kg body weight (given as an intravenous infusion at a constant rate over one hour) administered once weekly for two consecutive weeks.

Maintenance doses: 5mg/kg (given as an intravenous infusion) administered continuously over a one hour period, once every 2 weeks.

The most appropriate dose of cidofovir for patients with a serum creatinine >1.5mg/mL or a creatinine clearance

≤ 55mL/min is not known. The following doses (in mg per kg of body weight are recommended when the benefits or cidofovir exceed the potential risks:

Creatinine Clearance (mL/min) ( Induction dose (once weekly for 2 weeks)) Maintenance dose (once every 2 weeks)

41-55 ( 2mg per kg body weight) 2mg per kg body weight

30-40 ( 1.5 mg per kg body weight) 1.5 mg per kg body weight 20-29 ( 1mg per kg body weight) 1 mg per kg body weight

≤ 19( 05.mg per kg body weight) 0.5 mg per kg body weight

Creatinine clearance for males =

[140-age (years)] X [body wt (kg)]/ 72 X [serum creatinine (mg/dL)]

Creatinine clearance for females =

[140-age (years)] X [body wt (kg)] X 0.85 /72 X [serum creatinine (mg/dL)]

Maintenance Therapy

The recommended maintenance dose of Vistide is 5mk/kg body weight (given as an intravenous infusion at a constant rate over one hour), administered once every two weeks.

Dose adjustment:

ChangesinrenalfunctionduringVistidetherapy: The maintenance dose of Vistide must be reduced from 5mg/kg to 3mg/kg for an increase in serum creatinine of 0.3-0.4 mg/dL above baseline. Vistidemustbediscontinuedfor an increase in serum creatinine of ≥ 0.5 mg/dL above baseline or development of ≥ 3+ proteinuria.

Probenecid must be administered orally with each Vistide dose (Induction and Maintenance doses). 2 grams must be administered 3 hours prior to the Vistide dose and 1 gram administered at 2 hours and 8 hours after completion of the 1 hour Vistide infusion (for a total of 4 grams administered).

Patients must receive at least one liter of 0.9% (normal) saline solution intravenously with each infusion of Vistide. The normal saline solution should be infused over a 1-2 hour period immediately before the Vistide infusion. Patients who can tolerate the additional fluid load should receive a second liter. If administered, the second liter of saline should be initiated either at the start of the Vistide infusion or immediately afterwards, and infused over a 1-3 hour period.

Serum creatinine and urine protein must be monitored within 48 hours prior to each dose. White blood cell counts with differential should be monitored prior to each dose. Patients with proteinuria: intravenous hydration should be administered and the test repeated. Intraocular pressure, visual acuity and ocular symptoms should be monitored periodically.

For J0740 off-label administration for BK nephropathy or BK viremia dosing is recommended at 0.25-0.5 mg/kg IV over one hour every 2 weeks. Continuation could be for 8 weeks with the goal of a blood BK PCR zero on 2 labs, then discontinuing the drug.

Sources of Information and Basis for Decision

Cytovene-IV (ganciclovir sodium for injection) prescribing information. Roche Pharmaceuticals. Retrieved from http://www.rocheusa.com/products/Cytovene/ on 1/12/06.

Dunn, J. (2003). Cytomegalovirus Retinitis in 2003. The Hopkins HIV Report. Retrieved from http://hopkins- aids.edu/publications/report/may03_4.html on 3/20/06.

Fisher, S. (2006). Infections complicating solid organ transplantation. Surgical clinics of North America. (86)5. National Guideline Clearinghouse. Treating opportunistic infections among HIV-infected adults and adolscents.

Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious

Disease Society of America. Retirved from http://www.guideline.gov on 2/9/06.

Roache, L. (2003). Rethinking CMV retinitis. American Academy of Ophthalmology. Retrieved from http://www.aao.org on 2/9/06.

Savona, MR; Newton, D., et al. (2007). Low dose cidofovir treatment of BK virus-associated hemorrhagic cysistis in recipients of hematopoietic stem cell transplant. Bone Marrow Transplantation, 39; 783-787.

USP DI® Drug Information for Health Care Professionals. Ganciclovir (Implantation- ophthalmic), Ganciclovir( systemic), Cidofovir( systemic). Retrieved from http://www.thomsonhc.com on 3/21/06.

Vistide (cidofovir injection) package insert. Gilead Sciences, Inc. 2000.

Advisory Committee Meeting Notes This Local Coverage Determination (LCD) does not reflect the sole opinion of the contractor or Contractor Medical Director. Although the final decision rests with the contractor, this LCD was

developed in cooperation with advisory groups, which includes representatives from numerous societies.

Start Date of Comment Period

End Date of Comment Period

Start Date of Notice Period 07/01/2009

Revision History Number 2

Revision History Explanation Revision Number:2 Start Date of Comment Period:N/A

Start Date of Notice Period:07/01/2011 Revised Effective Date:06/14/2011

LCR B2011-083

June 2011 Connection

Explanation of Revision: Based on an outside request to clarify our current training statement outlined in this

LCD, language under the “Limitations” section of the LCD has been deleted and replaced with a revised statement regarding the qualification and training. Revisions will be effective based on process date.

Revision Number:1

Start Date of Comment Period:N/A Start Date of Notice Period:07/1/2009 Revised Effective Date: 06/19/2009

LCR B2009-073

June 2009 Update

Explanation of Revision: LCD revised to add the off-label indication of BK nephropathy and BK viremia for kidney transplant patients for HCPCS J0740. ICD-9-CM code V42.0 has been added as medically reasonable and necessary for HCPCS code J0740. The effective date of this revision is based on date of service.

Revision Number:Original

Start Date of Comment Period:N/A Start Date of Notice Period:12/04/2008 Revised Effective Date:02/02/2009

LCR B2009-

December 2008 Bulletin

This LCD consolidates and replaces all previous policies and publications on this subject by the carrier predecessors of First Coast Service Options, Inc. (Triple S and FCSO).

For Florida (00590) this LCD (L29181) replaces LCD L23190 as the policy in notice. This document (L29181) is effective on 02/02/2009.

Reason for Change