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Rebetol Intron A (Ribavirin / Interferon Alfa-2B) - Summary

 
 



CONTRAINDICATIONS AND WARNINGS

Combination REBETOL/INTRON A therapy is contraindicated in females who are pregnant and in the male partners of females who are pregnant. Extreme care must be taken to avoid pregnancy during therapy and for 6 months after completion of treatment in female patients, and in female partners of male patients who are taking combination REBETOL/INTRON A therapy. Females of childbearing potential and males must use two reliable forms of effective contraception during treatment and during the 6-month posttreatment follow-up period. Significant teratogenic and/or embryocidal effects have been demonstrated for ribavirin in all animal species studied. See CONTRAINDICATIONS and WARNINGS. REBETOL monotherapy is not effective for the treatment of chronic hepatitis C and should not be used for this indication. See WARNINGS.

Alpha interferons, including INTRON® A, cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many but not all cases these disorders resolve after stopping INTRON A therapy. See WARNINGS, and ADVERSE REACTIONS.

 

SUMMARY

REBETOL is Schering Corporation's brand name for ribavirin, a nucleoside analog with antiviral activity.

REBETOL (ribavirin, USP) Capsules is indicated in combination with INTRON A (interferon alfa-2b, recombinant) Injection for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with alpha interferon or who have relapsed following alpha interferon therapy.

Previously Untreated Patients Adults with compensated chronic hepatitis C and detectable HCV RNA (assessed by a central laboratory using a research-based RT-PCR assay) who were previously untreated with alpha interferon therapy were enrolled into two multicenter, double-blind trials (US and International) and randomized to receive REBETOL Capsules 1200 mg/day (1000 mg/day for patients weighing </=75 kg) plus INTRON A Injection 3 MIU TIW or INTRON A Injection plus placebo for 24 or 48 weeks followed by 24 weeks of off-therapy follow-up. The International study did not contain a 24-week INTRON A plus placebo treatment arm. The US study enrolled 912 patients who, at baseline, were 67% male, 89% caucasian with a mean Knodell HAI score (I+II+III) of 7.5, and 72% genotype 1. The International study, conducted in Europe, Israel, Canada, and Australia, enrolled 799 patients (65% male, 95% caucasian, mean Knodell score 6.8, and 58% genotype 1).

Study results are summarized in TABLE 3.

TABLE 3. Virologic and Histologic Responses: Previously Untreated Patients *
US Study International Study
24 weeks
of treatment
48 weeks
of treatment
24 weeks
of treatment
48 weeks
of treatment
INTRON A
plus
REBETOL
(N=228)
INTRON A
plus
Placebo
(N=231)
INTRON A
plus
REBETOL
(N=228)
INTRON A
plus
Placebo
(N=225)
INTRON A
plus
REBETOL
(N=265)
INTRON A
plus
REBETOL
(N=268)
INTRON A
plus
Placebo
(N=266)
Virologic
Response
-Responder1 65 (29) 13 (6) 85 (37) 27 (12) 86 (32) 113 (42) 46 (17)
-Nonresponder 147 (64) 194 (84) 110 (48) 168 (75) 158 (60) 120 (45) 196 (74)
-Missing data 16 (7) 24 (10) 33 (14) 30 (13) 21 (8) 35 (13) 24 (9)
Histologic
Response
-Improvement2 102 (45) 77 (33) 96 (42) 65 (29) 103 (39) 102 (38) 69 (26)
-No improvement 77 (34) 99 (43) 61 (27) 93 (41) 85 (32) 58 (22) 111 (41)
-Missing data 49 (21) 55 (24) 71 (31) 67 (30) 77 (29) 108 (40) 86 (32)
*Number (%) of patients
1 Defined as HCV RNA below limit of detection using a research-based RT-PCR assay at end of treatment and during follow-up period.
2 Defined as posttreatment (end of follow-up) minus pretreatment liver biopsy Knodell HAI score (I+II+III) improvement of >/=2 points.

Of patients who had not achieved HCV RNA below the limit of detection of the research-based assay by week 24 of REBETOL/INTRON A treatment, less than 5% responded to an additional 24 weeks of combination treatment.

Among patients with HCV genotype 1 treated with REBETOL/INTRON A therapy who achieved HCV RNA below the detection limit of the research-based assay by 24 weeks, those randomized to 48 weeks of treatment had higher virologic responses compared to those in the 24-week treatment group. There was no observed increase in response rates for patients with HCV nongenotype 1 randomized to REBETOL/INTRON A therapy for 48 weeks compared to 24 weeks.

Relapse Patients Patients with compensated chronic hepatitis C and detectable HCV RNA (assessed by a central laboratory using a research-based RT-PCR assay) who had relapsed following one or two courses of interferon therapy (defined as abnormal serum ALT levels) were enrolled into two multicenter, double-blind trials (US and International) and randomized to receive REBETOL 1200 mg/day (1000 mg/day for patients weighing </=75 kg) plus INTRON A 3 MIU TIW or INTRON A plus placebo for 24 weeks followed by 24 weeks of off-therapy follow-up. The US study enrolled 153 patients who, at baseline, were 67% male, 92% caucasian with a mean Knodell HAI score (I+II+III) of 6.8, and 58% genotype 1. The International study, conducted in Europe, Israel, Canada, and Australia, enrolled 192 patients (64% male, 95% caucasian, mean Knodell score 6.6, and 56% genotype 1).

Study results are summarized in TABLE 4.

TABLE 4. Virologic and Histologic Responses: Relapse Patients *
US Study International Study
INTRON A
plus
REBETOL
(N=77)
INTRON A
plus
Placebo
(N=76)
INTRON A
plus
REBETOL
(N=96)
INTRON A
plus
Placebo
(N=96)
Virologic
Response
-Responder1 33 (43) 3 (4) 46 (48) 5 (5)
-Nonresponder 36 (47) 66 (87) 45 (47) 91 (95)
-Missing data 8 (10) 7 (9) 5 (5) 0 (0)
Histologic
Response
-Improvement2 38 (49) 27 (36) 49 (51) 30 (31)
-No improvement 23 (30) 37 (49) 29 (30) 44 (46)
-Missing data 16 (21) 12 (16) 18 (19) 22 (23)
*Number (%) of patients
1 Defined as HCV RNA below limit of detection using a research-based RT-PCR assay at end of treatment and during follow-up period.
2 Defined as posttreatment (end of follow-up) minus pretreatment liver biopsy Knodell HAI score (I+II+III) improvement of >/=2 points.

Virologic and histologic responses were similar among male and female patients in both the previously untreated and relapse studies.


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NEWS HIGHLIGHTS

Media Articles Related to Rebetol Intron A (Ribavirin)

Results from studies in chronic hepatitis C patients with HIV-1 co-infection and liver transplant recipients
Source: Liver Disease / Hepatitis News From Medical News Today [2014.11.13]
AbbVie has announced results from studies in chronic hepatitis C patients with human immunodeficiency virus type 1 (HIV-1) co-infection (TURQUOISE-I) and liver transplant recipients (CORAL-I) at...

Results from Phase 2 PEARL-I study in genotype 4 chronic hepatitis C patients
Source: Liver Disease / Hepatitis News From Medical News Today [2014.11.13]
AbbVie has announced detailed results from its open-label Phase 2b study, PEARL-I, which demonstrated that 100 percent of genotype 4 (GT4) patients who were new to therapy (n=42/42) or who had...

Study examines life expectancy among patients with chronic hepatitis C virus infection and cirrhosis
Source: Liver Disease / Hepatitis News From Medical News Today [2014.11.11]
Patients with chronic hepatitis C virus infection and advanced fibrosis or cirrhosis who attained sustained virological response (SVR) had survival comparable with that of the general population...

Olysio gains additional FDA approval as once-daily, all-oral treatment combination for chronic hepatitis C
Source: Liver Disease / Hepatitis News From Medical News Today [2014.11.07]
Janssen Therapeutics, Division of Janssen Products, LP (Janssen) has announced the U.S.

more news >>

Published Studies Related to Rebetol Intron A (Ribavirin)

The combination of MK-5172, peginterferon, and ribavirin is effective in treatment-naive patients with hepatitis C virus genotype 1 infection without cirrhosis. [2014]
without cirrhosis... CONCLUSIONS: Once-daily MK-5172 (100 mg) with PR for 24 or 48 weeks was highly

[Efficacy and safety of ribavirin aerosol in children with hand-foot-mouth disease]. [Article in Chinese] [2014]
with hand-foot-mouth disease (HFMD)... CONCLUSIONS: Ribavirin aerosol can be effectively and safely used for treating

Seizures during pegylated interferon and ribavirin therapy for chronic Hepatitis C: observations from the WIN-R trial. [2011.03]
BACKGROUND: Seizures are reported as an uncommon side effect of interferon therapy. AIM: To determine the frequency and presentation of seizures occurring during pegylated interferon-alpha (PEG-IFNalpha) and ribavirin therapy for chronic hepatitis C... CONCLUSIONS: Seizures occur infrequently in patients receiving PEG-IFNalpha-2b plus ribavirin, and appear to be associated with other risk factors including antidepressant use.

Telaprevir is effective given every 8 or 12 hours with ribavirin and peginterferon alfa-2a or -2b to patients with chronic hepatitis C. [2011.02]
BACKGROUND &#38; AIMS: Recent studies have shown that 12 weeks of treatment with telaprevir, administered every 8 hours (q8h), combined with pegylated interferon (peginterferon) alfa-2a plus ribavirin significantly increased the rate of hepatitis C virus (HCV) eradication (sustained virologic response [SVR]) in patients infected with HCV genotype 1 compared with approved therapy. We investigated the efficacy, safety, tolerability, and pharmacokinetics of telaprevir given q8h or every 12 hours (q12 h) in combination with peginterferon alfa-2a or alfa-2b... CONCLUSIONS: A high proportion (>80%) of patients achieved an SVR regardless of the telaprevir dosing frequency (q8 h or q12 h) or type of peginterferon alfa used (alfa-2a or alfa-2b). Copyright (c) 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Antiviral re-treatment of IFN-ribavirin non-responders for recurrent post-transplantation hepatitis C. [2011.01]
BACKGROUND: The aim of the study was to compare the efficacy and tolerability of pegylated interferon (PEG-IFN) plus ribavirin (RIB) and PEG-IFN monotherapy after unsuccessful initial therapy with interferon-alpha2b (IFN) plus RIB after recurrent post-transplantation hepatitis C... CONCLUSIONS: Both treatment arms showed to be effective, well tolerated and lead to an improvement in histologic outcome. Because of lower rates in side effects and equal outcome, PEG-IFN monotherapy is an adequate option for antiviral re-treatment. (c) 2010 John Wiley & Sons A/S.

more studies >>

Clinical Trials Related to Rebetol Intron A (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 g/kg/wk in combination with weight based REBETOL (800-1400 mg/day); (2) PEG-Intron 1g/kg/wk in combination with weight based REBETOL (800-1400 mg/day); and (3) PEGASYS 180 g/wk plus COPEGUS 1000-1200 mg/day.

Extended Treatment With PEG-Intron and Rebetol in Patients With Genotype 1 Chronic Hepatitis C and Slow Virologic Response (Study P03685AM3) [Active, not recruiting]
This is a controlled, randomized, parallel-groups, open-label, multinational study designed to evaluate the efficacy and safety of PEG-Intron plus Rebetol in subjects with chronic hepatitis C. It is designed to evaluate whether 72 weeks of treatment with PEG-Intron plus Rebetol is more effective than 48 weeks of treatment in subjects with Genotype 1 chronic hepatitis C who exhibit a slow response to treatment.

Peg-Intron and Rebetol Therapy in Treatment of Naive Hepatitis C Patients: A Comparison of Race and Genotype on Treatment Outcome (Study P04212)(COMPLETED) [Completed]
This is a multicenter clinical trial designed to compare the efficacy of 48 weeks of therapy with pegylated (PEG)-Interferon/ribavirin in Southeastern Asian patients with genotype 1 chronic hepatitis C with 48 weeks of therapy with PEG-Interferon/ribavirin in Caucasian patients with genotype 1 chronic hepatitis C. This study is also designed to provide a randomized comparison of 24 weeks versus 48 weeks of therapy with PEG-Interferon/ribavirin in Southeastern Asian patients with genotypes 6-9. The primary endpoint is sustained virologic response, as defined by negative hepatitis C virus (HCV) ribonucleic acid (RNA) in serum at 24 weeks after therapy completion.

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).

Ribavirin for Hemorrhagic Fever With Renal Syndrome in Germany [Not yet recruiting]
This is a treatment protocol using IND Ribavirin-there is no control group. Hemorrhagic Fever with Renal Syndrome (HFRS) is caused by a virus acquired by contact with chronically infected rodent hosts. HFRS is present throughout Europe and caused mainly by Puumala and Dobrava viruses. Treatment consists mainly of supportive care with careful attention to control of blood pressure and fluid balance and/or dialysis. Early initiation of IND Intravenous Ribavirin has been shown to be an effective treatment for HFRS and may prevent the need for dialysis. It is important to initiate therapy based on a diagnosis consistent with HFRS and a history that makes exposure likely. This study will monitor the clinical events that occur with HFRS as well as the safety and efficacy of Ribavirin.

more trials >>


Page last updated: 2014-11-30

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