VIRAZOLE SUMMARY
VIRAZOLE®
(Ribavirin for Inhalation Solution, USP)
Rx Only
Virazole® is a brand name for ribavirin, a synthetic nucleoside with antiviral activity. VIRAZOLE for inhalation solution is a sterile, lyophilized powder to be reconstituted for aerosol administration. Each 100 mL glass vial contains 6 grams of ribavirin, and when reconstituted to the recommended volume of 300 mL with sterile water for injection or sterile water for inhalation (no preservatives added), will contain 20 mg of ribavirin per mL, pH approximately 5.5. Aerosolization is to be carried out in a Small Particle Aerosol Generator (SPAG-2) nebulizer only.
VIRAZOLE is indicated for the treatment of hospitalized infants and young children with severe lower respiratory tract infections due to respiratory syncytial virus. Treatment early in the course of severe lower respiratory tract infection may be necessary to achieve efficacy.
Only severe RSV lower respiratory tract infection should be treated with VIRAZOLE. The vast majority of infants and children with RSV infection have disease that is mild, self-limited, and does not require hospitalization or antiviral treatment. Many children with mild lower respiratory tract involvement will require shorter hospitalization than would be required for a full course of VIRAZOLE aerosol (3 to 7 days) and should not be treated with the drug. Thus the decision to treat with VIRAZOLE should be based on the severity of the RSV infection.
The presence of an underlying condition such as prematurity, immunosuppression or cardiopulmonary disease may increase the severity of clinical manifestations and complications of RSV infection.
Use of aerosolized VIRAZOLE in patients requiring mechanical ventilator assistance should be undertaken only by physicians and support staff familiar with this mode of administration and the specific ventilator being used (see WARNINGS, and DOSAGE AND ADMINISTRATION).
RSV infection should be documented by a rapid diagnostic method such as demonstration of viral antigen in respiratory tract secretions by immunofluorescence3,4 or ELISA5 before or during the first 24 hours of treatment. Treatment may be initiated while awaiting rapid diagnostic test results. However, treatment should not be continued without documentation of RSV infection.
Non-culture antigen detection techniques may have false positive or false negative results. Assessment of the clinical situation, the time of year and other parameters may warrant reevaluation of the laboratory diagnosis.
Non-Mechanically-Ventilated Infants
: In two placebo controlled trials in infants hospitalized with RSV lower respiratory tract infection, aerosolized VIRAZOLE treatment had a therapeutic effect, as judged by the reduction in severity of clinical manifestations of disease by treatment day 3.3,4 Treatment was most effective when instituted within the first 3 days of clinical illness. Virus titers in respiratory secretions were also significantly reduced with VIRAZOLE in one of these original studies.4 Additional controlled studies conducted since these initial trials of aerosolized VIRAZOLE in the treatment of RSV infection have supported these data.
Mechanically-Ventilated Infants
: A randomized, double-blind, placebo controlled evaluation of aerosolized VIRAZOLE at the recommended dose was conducted in 28 infants requiring mechanical ventilation for respiratory failure caused by documented RSV infection.6 Mean age was 1.4 months (SD, 1.7 months). Seven patients had underlying diseases predisposing them to severe infection and 21 were previously normal. Aerosolized VIRAZOLE treatment significantly decreased the duration of mechanical ventilation required (4.9 vs. 9.9 days, p=0.01) and duration of required supplemental oxygen (8.7 vs 13.5 days, p=0.01). Intensive patient management and monitoring techniques were employed in this study. These included endotracheal tube suctioning every 1 to 2 hours; recording of proximal airway pressure, ventilatory rate, and F1 O2 every hour; and arterial blood gas monitoring every 2 to 6 hours. To reduce the risk of VIRAZOLE precipitation and ventilator malfunction, heated wire tubing, two bacterial filters connected in series in the expiratory limb of the ventilator (with filter changes every 4 hours), and water column pressure release valves to monitor internal ventilator pressures were used in connecting ventilator circuits to the SPAG-2.
Employing these techniques, no technical difficulties with VIRAZOLE administration were encountered during the study. Adverse events consisted of bacterial pneumonia in one case, staphyloccus bacteremia in one case and two cases of post-extubation stridor. None were felt to be related to VIRAZOLE administration.
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NEWS HIGHLIGHTSMedia Articles Related to Virazole (Ribavirin)
InterMune Announces Modification To On-Going Phase 2b Study Of ITMN-191 In Patients With Chronic HCV Infection
Source: Liver Disease / Hepatitis News From Medical News Today [2009.11.18]
InterMune, Inc. (Nasdaq: ITMN) announced that the on-going Phase 2b study conducted by Roche of ITMN-191 (RG7227) combined with standard of care (SOC) PEGASYS® (peginterferon alfa-2a) and COPEGUS® (ribavirin) in HCV treatment-naive patients has been modified. The Phase 2b study has four dosage cohorts: SOC; 300mg q8h plus SOC; 600mg q12h plus SOC and 900mg q12h plus SOC. To date, approximately 175 patients have been enrolled in the study.
AASLD: Treating Before Transplant Cuts HCV Recurrence (CME/CE)
Source: MedPage Today Gastroenterology [2009.11.06]
BOSTON (MedPage Today) -- In patients with advanced liver disease related to hepatitis C, a course of pegylated interferon and ribavirin (Rebetol) before liver transplant may help them avoid recurrence of infection, a researcher said here.
SCYNEXIS' SCY-635 Demonstrates Positive Antiviral Activity In Combination With Approved And Investigational Anti-HCV Agents
Source: Liver Disease / Hepatitis News From Medical News Today [2009.11.04]
Drug discovery company SCYNEXIS, Inc. presented positive data from an in vitro study evaluating the antiviral activity of SCY-635 in combination with approved and investigational non-nucleoside polymerase inhibitors, nucleoside polymerase inhibitors, protease inhibitors, ribavirin and interferon alpha 2b. SCY-635 exhibited additive to synergistic antiviral activity when combined with each of the six compounds tested and all combinations exhibited greater-than-anticipated antiviral activity.
Bristol-Myers Squibb And ZymoGenetics Present Final Phase 1b Results For PEG-Interferon Lambda In Hepatitis C
Source: Liver Disease / Hepatitis News From Medical News Today [2009.11.03]
Bristol-Myers Squibb Company (NYSE: BMY) and ZymoGenetics, Inc. (NASDAQ: ZGEN) today presented final results from a Phase 1b clinical trial of PEG-Interferon lambda administered with ribavirin in relapsed and treatment-naïve hepatitis C virus (HCV) patients. The poster included data on 56 patients in the study. Antiviral activity was observed at all dose levels tested.
Published Studies Related to Virazole (Ribavirin)
A phase III study of the safety and efficacy of viramidine versus ribavirin in treatment-naive patients with chronic hepatitis C: ViSER1 results. [2009.09]
Pegylated interferon (peg-IFN) and ribavirin (RBV) are effective in eradicating the hepatitis C virus in more than half of patients. However, anemia arising from RBV-induced hemolysis can prompt dose reductions and lower sustained virologic response (SVR) rates... These results suggest fixed-dose VRD given 600 mg BID is insufficient to treat patients with chronic hepatitis C; a weight-based dosing trial of viramidine is currently under way.
Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. [2009.08.06]
BACKGROUND: Treatment guidelines recommend the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus (HCV) infection. However, these regimens have not been adequately compared... CONCLUSIONS: In patients infected with HCV genotype 1, the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferon-ribavirin regimens or between the two doses of peginterferon alfa-2b. (ClinicalTrials.gov number, NCT00081770.) 2009 Massachusetts Medical Society
Predictability of sustained virological response to pegylated interferon alpha-2b Plus ribavirin therapy by week-8 viral response in HIV-positive patients with chronic hepatitis C virus infection. [2009.07]
Chronic hepatitis C is frequent and aggressive in HIV-positive patients. Identification of early predictors of response to anti-HCV therapy is needed for a lower rate of response and higher discontinuations, compared to HCV mono-infected subjects...
Effect of dietary purines on the pharmacokinetics of orally administered ribavirin. [2009.06]
Ribavirin is found to be absorbed in the intestine through the human concentrative nucleoside transporter 2 (hCNT2). Cellular uptake of ribavirin was strongly inhibited by purine nucleoside in an in vitro study...
Retreating chronic hepatitis C with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results. [2009.06]
CONCLUSION: Retreatment of PEG-IFN and RBV nonresponders with CIFN and RBV is safe and efficacious and can be considered a retreatment strategy for patients failing previous therapy with PEG-IFN/RBV, especially in interferon-sensitive patients with lower baseline fibrosis scores.
Clinical Trials Related to Virazole (Ribavirin)
Peg-Ifn Dose Evaluations for Previously Untreated Subjects With Chronic Hepatitis C Infected With Genotype 1 (Study P03471AM1)(COMPLETED) [Completed]
The objective is to compare the safety and efficacy of the following three treatment regimens
in previously untreated adult subjects with chronic hepatitis C infected with Genotype 1: (1)
PEG-Intron 1. 5 µg/kg/wk in combination with weight based REBETOL (800-1400 mg/day); (2)
PEG-Intron 1µg/kg/wk in combination with weight based REBETOL (800-1400 mg/day); and (3)
PEGASYS 180 µg/wk plus COPEGUS 1000-1200 mg/day.
PEG-Interferon a-2b + Ribavirin for Treatment of Patients With Chronic Hepatitis C Who Have Previously Failed to Achieve a Sustained Virologic Response Following Interferon Alfa or Interferon a-2b + Ribavirin Therapy [Completed]
HRN-003 STUDY SYNOPSIS
OBJECTIVE: To compare the Sustained Virologic Response (SVR) of PEGIntron plus ribavirin
among patients receiving a fixed dose of PEGIntron versus weighted-adjusted dosing.
OVERVIEW OF STUDY DESIGN: This is a multi-center, randomized, open-label clinical trial using
PEGIntron weight-adjusted dose by subcutaneous injection weekly + ribavirin by mouth twice
daily for 48 weeks OR PEGIntron fixed dose by subcutaneous injection weekly + ribavirin by
mouth twice daily for 48 weeks.
STUDY POPULATION: 600 Adult patients with chronic hepatitis C virus infection who have
previously failed to achieve a sustained virologic response following interferon alfa or
interferon alfa-2b plus ribavirin therapy.
DOSAGE AND ADMINISTRATION: Eligible participants will be randomized to receive PEGIntron
weight-adjusted dose (1. 5 mg/kg) by subcutaneous injection weekly + ribavirin 400 mg by mouth
twice daily for 48 weeks OR PEGIntron fixed dose (150 mg if weight > than 80 kg or 100 mg if
weight < 80 KG) by subcutaneous injection weekly + ribavirin 400 mg by mouth twice daily for
48 weeks.
EFFICACY EVALUATIONS: Laboratory analysis, quality of life assessments, and change in study
medication doses will be obtained.
SAFETY EVALUATIONS: Assessment of laboratory evaluations, vital signs, incidence and severity
of adverse experiences and progression of disease, as measured by HCV viral load.
STUDY DESIGN
This is a treatment protocol to evaluate the antiviral efficacy, safety and tolerability
polyethylene glycol (PEG) conjugated interferon alfa-2b (PEGIntron) for the treatment of
chronic hepatitis C virus infection in patients who have previously failed to achieve a
sustained virologic response following interferon alfa or interferon alfa-2b plus ribavirin
therapy. Patients will be stratified according to their response to the previous course of
therapy (i. e. non-reponse or relapse virologic pattern
This is a multi-center, randomized, open-label clinical trial that will involve approximately
25 sites with an anticipated enrollment of 600 patients over a six-month period.
Eligible participants will be randomized to receive PEGIntron weight-adjusted dose (1. 5
mg/kg) by subcutaneous injection weekly + ribavirin 400 mg by mouth twice daily for 48 weeks
OR PEGIntron fixed dose (150 mg if weight > than 80 kg or 100 mg if weight < 80 KG) by
subcutaneous injection weekly + ribavirin 400 mg by mouth twice daily for 48 weeks.
- Group A: PEGIntron weight -adjusted dose (1. 5 mg/kg) by subcutaneous injection weekly
+ ribavirin 400 mg by mouth twice daily for 48 weeks (Total therapy x 48weeks).
- Group B: PEGIntron fixed dose (150 mg if weight > than 80 kg or 100 mg if weight < 80
KG) by subcutaneous injection weekly + ribavirin 400 mg by mouth twice daily for an
additional 48 weeks (Total therapy x 48 weeks).
REPEAT Study - A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) Therapy in Combination With COPEGUS (Ribavirin) in Patients With Chronic Hepatitis C (CHC) Who Did Not Respond to Previous PegIntron (Peginterferon Alfa-2b (12KD))/Ribavirin Combination Therapy [Completed]
This 4 arm study is designed for patients with CHC who have not responded to peginterferon
alfa-2b (12KD)/ribavirin combination therapy. In these patients, the effects of lengthening
the duration of treatment, as well as including an initial 12-week period of high-dose
PEGASYS (360 micrograms sc), are compared with the standard combination therapy of PEGASYS
(180 micrograms sc) and ribavirin (1000-1200mg po). The anticipated time on study treatment
is 1-2 years and the target sample size is 500+ individuals.
Infergen and Ribavirin Treatment of Patients With HCV Who Achieved Partial Response to Peginterferon-Alfa and Ribavirin [Active, not recruiting]
This is a 60-to-72 week multicenter study to evaluate Infergen and Ribavirin in patients with
Chronic Hepatitis C Virus after partial response to treatment using peginterferon-alfa and
Ribavirin therapy. The study will be conducted at approximately 50 sites across the United
States.
Trial of Peg-Interferon Plus Epoetin-Alfa for Treatment of Chronic Hepatitis C Virus Infection [Completed]
The purpose of this study is to determine if the use of epoetin-alpha will allow patients
with chronic hepatitis C virus infection to be treated with higher doses of
peginterferon-alpha-2b and ribavirin, thus increasing chances at lower viral levels and
raising sustained virologic response.
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