To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: Peg-Intron (Peginterferon Alfa-2b)/Rebetol (Ribavirin) Combination Launched in U.S. for Chronic Hepatitis C URL: http://www.pslgroup.com/dg/207BC6.htm Doctor's Guide October 3, 2001
KENILWORTH, NJ -- October 3, 2001 -- Schering-Plough Corporation today announced the U.S. launch of combination therapy using Peg-Intron™ (peginterferon alfa-2b) Powder for Injection and Rebetol® (ribavirin, USP) Capsules for treating chronic hepatitis C. Rebetol Capsules, approved in July 2001 as a separately marketed product, currently are being shipped to trade customers and are expected to be available at pharmacies nationwide in two to three weeks. Rebetol is packaged in bottles containing either 42, 56, 70 or 84 capsules each. Peg-Intron, approved in January 2001, is available nationwide.
Rebetol Capsules are indicated for use only in combination with Peg-Intron for the treatment of chronic hepatitis C in patients with compensated liver disease who have not been previously treated with interferon alpha and are at least 18 years of age, or 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.
The safety and efficacy of Rebetol Capsules with interferons other than Peg-Intron or Intron A products have not been established.
Rebetol had been available in the United States only as a component of Rebetron™ Combination Therapy, which contains Rebetol Capsules and Intron A Injection in a single package. Schering-Plough will continue to market Rebetron Combination Therapy in the United States.
Rebetol is an oral formulation of ribavirin, a synthetic nucleoside analog. Schering-Plough has exclusive worldwide rights to market oral ribavirin for hepatitis C through a licensing agreement with ICN Pharmaceuticals, Inc. of Costa Mesa, California.
Peg-Intron, which is approved for dosing according to patient body weight, is the first and only pegylated interferon product approved for marketing in the United States. Peg-Intron is a longer-acting form of Intron A that uses proprietary Peg technology developed by Enzon, Inc. of Piscataway, New Jersey. Peg-Intron, recombinant interferon alfa-2b linked to a 12,000 dalton polyethylene glycol (Peg) molecule, is a once-weekly therapy designed to optimize the balance between antiviral activity and elimination half-life. Schering-Plough holds an exclusive worldwide license to Peg-Intron.
Intron A is a recombinant version of naturally occurring alpha interferon, which has been shown to exert both antiviral and immunomodulatory effects. Schering-Plough markets Intron A, the world's largest-selling alpha interferon, for 16 major antiviral and anticancer indications worldwide.
Rebetol monotherapy is not effective for the treatment of chronic hepatitis C virus infection and should not be used alone for this indication. The primary toxicity of ribavirin is hemolytic anemia. The anemia associated with Rebetol therapy may result in worsening of cardiac disease that has lead to fatal and nonfatal myocardial infarctions.
Patients with a history of significant or unstable cardiac disease should not be treated with Rebetol. Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin. In addition, ribavirin has a multiple-dose half-life of 12 days, and so it may persist in nonplasma compartments for as long as six months. Therefore, Rebetol therapy is contraindicated in women who are pregnant and in the male partners of women who are pregnant. Extreme care must be taken to avoid pregnancy during therapy and for six months after completion of treatment in both female patients and in female partners of male patients who are taking Rebetol therapy. At least two reliable forms of effective contraception must be utilized during treatment and during the six-month post-treatment follow-up period.
Alpha interferons, including Peg-Intron and Intron A, may 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 therapy with Peg-Intron or Intron A.
There are no new adverse events specific to Peg-Intron as compared to Intron A, however, the incidence of some (e.g., injection site reactions, fever, rigors, nausea) were higher. The most common adverse events associated with Peg-Intron were "flu-like" symptoms, occurring in approximately 50 percent of patients, which may decrease in severity as treatment continues. Application site disorders were common (47 percent), but all were mild (44 percent) or moderate (4 percent) and no patient discontinued, and included injection site inflammation and reaction (i.e., bruise, itchiness, irritation). Injection site pain was reported in 2 percent of patients receiving Peg-Intron. Alopecia (thinning of the hair) is also often associated with alpha interferons including Peg-Intron.
Psychiatric adverse events, which include insomnia, were common (57 percent) with Peg-Intron, but similar to IntronA (58 percent). Depression was most common at 29 percent. Suicidal behavior including ideation, suicidal attempts, and completed suicides occurred in 1 percent of patients during or shortly after completing treatment with Peg-Intron. Peg-Intron is contraindicated in patients with autoimmune hepatitis and decompensated liver disease.
The following serious or clinically significant adverse events have been reported at a frequency < 1 percent with Peg-Intron or interferon alpha: Severe decreases in neutrophil or platelet counts, hypothyroidism, hyperglycemia, hypotension, arrhythmia, ulcerative and hemorrhagic colitis, development or exacerbation of autoimmune disorders including thyroiditis, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, pulmonary disorders (dyspnea, pulmonary infiltrates, pneumonitis and pneumonia, some resulting in patient deaths), urticaria, angioedema, bronchoconstriction, anaphylaxis, retinal hemorrhages and cotton wool spots.
Renal failure patients should be closely monitored for signs and symptoms of interferon toxicity and Peg-Intron should be used with caution in patients with creatinine clearance < 50 mL/min. Patients on Peg-Intron therapy should have hematology and blood chemistry testing before the start of treatment and then periodically thereafter.
All patients receiving Intron A therapy experienced mild-to-moderate side effects. Some patients experienced more severe side effects, including neutropenia, fatigue, myalgia, headache, fever, chills and increased SGOT. Other frequently occurring side effects were nausea, vomiting, depression, alopecia, diarrhea and thrombocytopenia. Depression and suicidal behavior, including suicidal ideation and suicidal attempts, and completed suicides, have been reported in association with treatment with alfa interferons, including Intron A therapy.
Some four million Americans are infected with the hepatitis C virus (HCV) and approximately 70 percent of infected patients go on to develop chronic liver disease, according to the Centers for Disease Control and Prevention (CDC). Hepatitis C infection contributes to the deaths of an estimated 8,000 to 10,000 Americans each year and this toll is expected to triple by the year 2010, according to the CDC. The CDC has reported that HCV-associated end-stage liver disease is the most frequent indication for liver transplantation among adults.
SOURCE: Schering-Plough Corporation --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. P\S\L shall not be liable for any errors, omissions or delays in this content or any other content on its sites, newsletters or other publications, nor for any decisions or actions taken in reliance on such content. --------------------------------------------------------------------------------------------- This news story was printed from *Doctor's Guide to the Internet* located at http://www.docguide.com --------------------------------------------------------------------------------------- Return to News Story Page This site is maintained by webmaster@pslgroup.com Please contact us with any comments, problems or bugs. All contents Copyright (c) 1998 P\S\L Consulting Group Inc. All rights reserved.