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Ribavirin (Virazole)

Number: 0155



Policy
  1. Aetna considers ribavirin (Virazole) medically necessary for the treatment of respiratory syncytial virus (RSV) infection in immunosuppressed and high risk children and adults, and for the treatment of viral hemorrhagic fever (Crimean-Congo, Ebola, Lassa, and Marburg), Rift valley fever and Hantaan, a hanta virus.

  2. Aetna considers ribavirin in combination with interferon alpha or pegylated interferon alpha medically necessary for persons with chronic hepatitis C according to the criteria set forth in CPB 0404 - Interferons.  Clinical research suggests that there are synergistic effects of ribavirin and interferon alpha in the treatment of chronic hepatitis. 

  3. Aetna considers ribavirin monotherapy for the treatment of persons with chronic hepatitis C infection experimental and investigational because there is insufficient evidence to support the effectiveness of this approach.

  4. Aetna considers ribavirin experimental and investigational for all other indications (e.g., acute myeloid leukemia, hepatitis E infection, multiple sclerosis; not an all-inclusive list) because its effectiveness for indications other than the ones listed above has not been established.

See also CPB 0318 - Synagis (Palivizumab).

Background

Ribavirin is indicated for use in the treatment and prevention of certain viral infections in selected patients.  Ribavirin is marketed as a inhalation solution (Virazole), oral capsule (Rebetol) and tablet (Copegus), but can also be prepared for intravenous administration.

Mallet et al (2010) reported 2 patients in whom ribavirin therapy seemed to alter the natural history of chronic hepatitis E virus (HEV) infection.  A kidney and pancreas transplant recipient and a patient with idiopathic CD4(+) T lymphocytopenia, both with biopsy-proven chronic HEV infection were included in this study.  Patients received oral ribavirin, 12 mg/kg of body weight daily for 12 weeks.  Liver function tests, detection of HEV RNA (viremia and stool shedding) by reverse transcriptase polymerase chain reaction, and anti-HEV IgM and IgG antibodies wer performed.  Both patients had normalized liver function test results after 2 weeks of treatment and cleared HEV after 4 weeks of treatment.  Hepatitis E virus RNA remained undetectable in the serum and stools throughout follow-up (3 months and 2 months for the 1st and 2nd patient, respectively).  Side effects were considered mild.  The authors concluded that ribavirin is a potentially effective treatment of HEV infection and should be evaluated in patients with chronic HEV infection.  The main drawback of this study was that given the relatively short follow-up, the achievement of HEV eradication could not be claimed.

In a pilot study, Kamar and colleagues (2010) evaluated the ant-iviral effect of ribavirin monotherapy in patients with chronic HEV infection following kidney transplantation.  A total of 6 patients who received kidney transplants and were positive for HEV RNA (infected with HEV for 36.5 months; [range of 11 to 46 months]) were given ribavirin monotherapy for 3 months.  Ribavirin was given at 600 to 800 mg/day in 2 separate doses, based on the patient's ability to clear creatinine.  Median serum concentration of HEV RNA at baseline was 5.77 log copies/mL (range of 4.35 to 7.35 log copies/ml).  Three months after ribavirin therapy commenced, HEV RNA was undetectable in serum samples from all patients.  A sustained virologic response was observed in 4 patients; the other 2 patients relapsed at 1 and 2 months after ribavirin therapy ended.  At the end of the study, all patients had normal levels of alanine and aspartate aminotransferase.  Anemia was the main side effect caused by ribavirin therapy.  The authors concluded that ribavirin monotherapy inhibits the replication of HEV in vivo and might induce a sustained virological response in patients with chronic HEV infections.  They stated that further studies are needed to determine the optimal duration of ribavirin therapy.

Kamar et al (2014) noted that there is no established therapy for HEV infection.  In a retrospective, multi-center case-series study, these researchers evaluated the effects of ribavirin as monotherapy for solid-organ transplant (SOT) recipients with prolonged HEV viremia.  They examined the records of 59 patients who had received a solid-organ transplant (37 kidney-transplant recipients, 10 liver-transplant recipients, 5 heart-transplant recipients, 5 kidney and pancreas-transplant recipients, and 2 lung-transplant recipients).  Ribavirin therapy was initiated a median of 9 months (range of 1 to 82) after the diagnosis of HEV infection at a median dose of 600 mg per day (range of 29 to 1,200), which was equivalent to 8.1 mg/kg body weight/day (range of 0.6 to 16.3).  Patients received ribavirin for a median of 3 months (range of 1 to 18); 66 % of the patients received ribavirin for 3 months or less.  All the patients had HEV viremia when ribavirin was initiated (all 54 in whom genotyping was performed had HEV genotype 3).  At the end of therapy, HEV clearance was observed in 95 % of the patients.  A recurrence of HEV replication occurred in 10 patients after ribavirin was stopped.  A sustained virologic response, defined as an undetectable serum HEV RNA level at least 6 months after cessation of ribavirin therapy, occurred in 46 of the 59 patients (78 %).  A sustained virologic response was also observed in 4 patients who had a recurrence and were re-treated for a longer period.  A higher lymphocyte count when ribavirin therapy was initiated was associated with a greater likelihood of a sustained virologic response.  Anemia was the main identified side effect and required a reduction in ribavirin dose in 29 % of the patients, the use of erythropoietin in 54 %, and blood transfusions in 12 %.  The authors concluded that the findings of this retrospective, multi-center study showed that ribavirin as monotherapy may be effective in the treatment of chronic HEV infection; a 3-month course seemed to be an appropriate duration of therapy for most patients.

Unzueta and Rakela (2014) stated that HEV infection (genotype 3) has been described in developed countries as a cause of chronic hepatitis in recipients of SOT.  Immunosuppression seems to play a major role in the pathogenesis of chronic infections.  The current gold standard for the diagnosis of HEV infection is the detection of HEV RNA in serum, stools, or both.  In liver transplant recipients, HEV infection is considered an uncommon disease; however, a high index of suspicion is needed for patients with graft hepatitis of an unclear etiology.  Liver transplant recipients seem more likely to develop chronic HEV after an acute infection, and there is accelerated progression to advanced fibrosis and cirrhosis.  A decrease in immunosuppression is considered the first line of treatment, and pegylated interferon can be considered the second line of treatment for liver transplant recipients.  At the present time, there are not enough data to recommend treatment with ribavirin for adult liver transplant recipients, although this has been tried in other SOT populations.

An UpToDate review on “Hepatitis E virus infection” (Umashanker and Chopra, 2014) states that “Case reports and series have suggested a benefit from ribavirin monotherapy in solid-organ transplant recipients with chronic HEV, but prospective studies are needed to confirm these findings and to determine the dose, duration, and timing of ribavirin therapy”.

CPT Codes / HCPCS Codes / ICD-9 Codes
Other CPT codes related to the CPB:
90378 Respiratory syncytial virus, monoclonal antibody, recombinant, for intramuscular use, 50 mg, each
Other HCPCS codes related to the CPB:
J9213, J9214, J2915 Interferon alpha-2a, 2b, and n3
ICD-9 codes covered if selection criteria are met:
065.0 Crimean hemorrhagic fever [CHF Congo virus]
065.8 Other specified arthropod-borne hemorrhagic fever (e.g., mite-borne hemorrhagic fever)
066.3 Other mosquito-borne fever (e.g., Rift valley)
070.54 Chronic hepatitis C without mention of hepatic coma [not covered for ribavirin monotherapy]
078.89 Other specified diseases due to viruses (e.g., Marburg disease, Tanapox)
079.6 Respiratory syncytial virus (RSV)
466.11 Acute bronchiolitis due to respiratory syncytial virus (RSV)
079.81 Hantavirus
ICD-9 codes not covered for indications listed in the CPB:
070.43 Hepatitis E with hepatic coma
070.53 Hepatitis E without mention of hepatic coma
205.00 - 205.92 Acute myeloid leukemia
340 Multiple sclerosis
CPT Codes / HCPCS Codes / ICD-10 Codes
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
ICD-10 codes will become effective as of October 1, 2015 :
Other CPT codes related to the CPB:
90378 Respiratory syncytial virus, monoclonal antibody, recombinant for intramuscular use, 50 mg each
Other HCPCS codes related to the CPB:
J9213, J9214, J2915 Interferon alpha-2a, 2b, and n3
ICD-10 codes covered if selection criteria are met:
A92.0 - A92.9 Other mosquito-borne fever (e.g., Rift valley)
A96.2, A98.3 - A98.4
B33.24, B33.8
Other specified diseases due to viruses (e.g., Marburg disease, Tanapox)
A98.0 Crimean-Congo hemorrhagic fever
A98.8 Other specified viral hemorrhagic fevers (e.g., mite-borne hemorrhagic fever)
B18.2 Chronic viral hepatitis C [not covered for ribavirin monotherapy]
B33.4 Hantavirus (cardio)-pulmonary syndrome [HPS] [HCPS]
B97.4 Respiratory syncytial virus (RSV) as the cause of diseases classified elsewhere
J21.0 Acute bronchiolitis due to respiratory syncytial virus (RSV)
ICD-10 codes not covered for indications listed in the CPB:
B17.2 Acute hepatitis E
C92.00 - C92.92 Myeloid leukemia
G35 Multiple sclerosis


The above policy is based on the following references:
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