LCD/NCD Portal

L29181

 

GANCICLOVIR AND CIDOFOVIR

 

 

06/14/2011

 

 

Indications and Limitations of Coverage and/or Medical Necessity

 

Indications

 

• Ganciclovir (J1570 and J7310)

• Medicare will cover ganciclovir for the following FDA approved indications:

o 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.

o 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:

o 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:

o 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."

o 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:

o A) Physician is properly enrolled in Medicare.

o 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.

o The labeling lists the safe and effective, i.e. medically reasonable and necessary dosage and frequency.

o 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

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

o 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

o 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).

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

o Cidofovir is contraindicated in patients with hypersensitivity to cidofovir.

o 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.

o 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.

 

12x Hospital Inpatient (Medicare Part B only)

13x Hospital Outpatient

85x Critical Access Hospital

 

 

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.

 

0636 Pharmacy - Drugs Requiring Detailed Coding

 

 

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 FOCAL CHORIORETINITIS UNSPECIFIED

363.01 FOCAL CHOROIDITIS AND CHORIORETINITIS JUXTAPAPILLARY

363.03 FOCAL CHOROIDITIS AND CHORIORETINITIS OF OTHER POSTERIOR POLE

363.04 FOCAL CHOROIDITIS AND CHORIORETINITIS PERIPHERAL

363.05 FOCAL RETINITIS AND RETINOCHOROIDITIS JUXTAPAPILLARY

363.06 FOCAL RETINITIS AND RETINOCHOROIDITIS MACULAR OR PARAMACULAR

363.07 FOCAL RETINITIS AND RETINOCHOROIDITIS OF OTHER POSTERIOR POLE

363.08* FOCAL RETINITIS AND RETINOCHOROIDITIS PERIPHERAL

363.10 DISSEMINATED CHORIORETINITIS UNSPECIFIED

363.11 DISSEMINATED CHOROIDITIS AND CHORIORETINITIS POSTERIOR POLE

363.12 DISSEMINATED CHOROIDITIS AND CHORIORETINITIS PERIPHERAL

363.13 DISSEMINATED CHOROIDITIS AND CHORIORETINITIS GENERALIZED

363.14 DISSEMINATED RETINITIS AND RETINOCHOROIDITIS METASTATIC

363.15* 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.

 

 

Documentation Requirements

 

• Dilated indirect ophthalmoscopy should be performed 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.

o 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 underutilization guidelines for each drug must be documented in the medical record.

o These tests should be performed prior to each dose administration to support the treatment is medically necessary.

o 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.

o These follow up exams should be documented in the patient’s medical record and made available to Medicare upon request.

• J0740

o 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.

o 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.

 

 

Utilization Guidelines

 

• Dilated indirect ophthalmoscopy should be performed at:

o The time of the diagnosis of CMV retinitis.

o After completion of induction therapy.

o 1 month after the initiation of therapy.

o Monthly thereafter while the patient is on anti-CMV treatment.

• Ganciclovir (Cytovene)

o The recommended dose for Cytovene-IV should not be exceeded.

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

o 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. Cytovene capsules 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.

o 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.

o 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)

o ≥ 70 (5.0) 12 (5.0) 24.

o 50-69 (2.5) 12 (2.5) 24.

o 25-49 (2.5) 24 (1.25) 24.

o 10-24 (1.25) 24 (0.625) 24.

o <10 (1.25).

o 3 times per week following hemodialysis (0.625).

o 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.

o 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 performed 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.

o Serum creatinine or creatinine clearance values should be followed carefully to allow for dosage adjustments in renally impaired patients.

• Dose reduction in patients with renal impairment are required for Cytovene-IV and should be considered for Cytovene capsules.

o Dose reductions should be considered for those with neutropenia, anemia and/or thrombocytopenia.

o Ganciclovir should not be administered in patients with severe neutropenia (ANC less than 500/ul) or severe thrombocytopenia (platelets less than 25,000/ul).

• Ganciclovir (Vitrasert)

o 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.

o Following depletion of ganciclovir from the implant, as evidenced by progression of retinitis, the implant may be removed and another one inserted.

• Cidofovir (Vistide)

o 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.

o Patients receiving intravenous cidofovir:

 BUN.

 Creatinine.

 Urinalysis should be performed before each infusion.

o 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.

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

o 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)].

o 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.

o Dose adjustment:

 Changes in renal function during Vistide therapy:

• 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.

• Vistide must be discontinued for 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

o 0.25-0.5 mg/kg IV over one hour every 2 weeks.

o Continuation could be for 8 weeks with the goal of a blood BK PCR zero on 2 labs, then discontinuing the drug.

Treatment Logic

• Ganciclovir (Cytovene IV) is a synthetic guanine derivative and an active antiviral agent for cytomegalovirus (CMV) infections.

o 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.

o Cidofovir is available in IV form only. Cidofovir will not cure CMV infection.

 

 

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.

 

FSCO LCD 29181, Ganciclovir and Cidofovir, 06/14/2011. The official local coverage determination (LCD) is the version on the Medicare coverage database at www.cms.gov/medicare-coverage-database/.

 

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 adolescents. Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Disease Society of America. Retrieved 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 cystitis 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.

 

 

AMA CPT Copyright Statement

CPT codes, descriptions and other data only are copyright 2011 American Medical Association (or such other date of publication of CPT). All Rights Reserved. Applicable FARS/DFARS Clauses Apply.

 

CMS LCD L29181 GANCICLOVIR AND CIDOFOVIR