PEG-INTRON® treatment for hepatitis C

PEG-INTRON/REBETOL® (Ribavirin, USP) Capsules combination therapy utilizes pegylation which represents the most recent advance in the treatment of chronic hepatitis C. PEG-INTRON/REBETOL combination therapy is approved by the FDA for the treatment of chronic hepatitis C in patients not previously treated with alpha interferons who have compensated liver disease and are at least 18 years of age.

PEG-INTRON/REBETOL combination therapy consists of two separate medications, PEG-INTRON®, which is injected and REBETOL®, which is taken orally.

PEG-INTRON® is a "pegylated" or modified form of alpha interferon that works by helping to boost the immune system to fight viruses, similar to how naturally produced interferon works in the human body. For more information about pegylation, including the benefits of pegylated interferon, see About Pegylation.

REBETOL® is an antiviral drug (ie, a drug that fights against viruses). By itself, REBETOL® is not very effective against the hepatitis C virus but in combination with PEG-INTRON®, it is much more effective than PEG-INTRON® alone. It is not known how the two products work together to fight the hepatitis C virus.

The National Institutes of Health has recognized that the highest response rates in the treatment of chronic hepatitis C have been achieved with combination therapy with ribavirin and pegylated alpha interferons.

PEG-INTRON/REBETOL combination therapy is associated with some serious side effects and cannot be used by certain patients, including pregnant women and men whose partners are pregnant. For further information about the possible side effects of PEG-INTRON® and PEG-INTRON/REBETOL combination therapy, see the Medication Guide

WARNING
Alpha interferons, including PEG-INTRON®, 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 Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy.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 PEG-INTRON therapy.

Ribavirin causes hemolytic anemia. Anemia associated with REBETOL therapy may exacerbate cardiac disease that has led to fatal and nonfatal myocardial infarctions. Patients with a history of significant or unstable cardiac disease should not be treated with REBETOL®. It is advised that complete blood counts (CBC) be obtained at baseline and at weeks 2 and 4 of therapy or more frequently if clinically indicated.

REBETOL and combination REBETOL/PEG-INTRON therapy must not be used by women, or male partners of women, who are or may become pregnant during therapy and during the 6 months after stopping therapy. REBETOL and combination REBETOL/PEG-INTRON therapy should not be initiated until a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Women of childbearing potential and men must use effective contraception (at least two reliable forms) during treatment and during the 6-month post treatment follow-up period. Significant teratogenic and/or embryocidal effects have been demonstrated for ribavirin in all animal species in which adequate studies have been conducted. These effects occurred at doses as low as one twentieth of the recommended human dose of REBETOL®. If pregnancy occurs in a patient or partner of a patient during treatment or during the 6 months after treatment stops, physicians are encouraged to report such cases by calling (800) 727-7064.

PEG-INTRON®
There are no new adverse events specific to PEG-INTRON® as compared to INTRON® A (Interferon alfa-2b, recombinant) for Injection, however, the incidence of some (eg, 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% of patients, which may decrease in severity as treatment continues. Application site disorders were common (47%), but all were mild (44%) or moderate (4%) and no patient discontinued, and included injection site inflammation and reaction (ie, bruise, itchiness, irritation). Injection site pain was reported in 2% 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%) with PEG-INTRON®, but similar to INTRON® A (58%). Depression was most common at 29%. Suicidal behavior including ideation, suicidal attempts, and completed suicides occurred in 1% of patients during or shortly after completing treatment with PEG-INTRON®.

PEG-INTRON®/REBETOL® is contraindicated in patients with autoimmune hepatitis, decompensated liver disease, and in patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia).

The following serious or clinically significant adverse events have been reported at a frequency < 1% 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, RA, 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.

In the PEG-INTRON/REBETOL combination trial the incidence of serious adverse events was 17% in the PEG-INTRON/REBETOL groups compared to 14% in the INTRON A/REBETOL group. The incidence of severe adverse events in the PEG-INTRON/REBETOL combination therapy trial was 23% in the INTRON A/REBETOL group and 31-34% in the PEG-INTRON/REBETOL groups. Dose reductions due to adverse reactions occurred in 42% of patients receiving PEG-INTRON® (1.5 mg/kg)/REBETOL® and in 34% of those receiving INTRON® A/REBETOL®.

PEG-INTRON® is indicated for use alone or in combination with REBETOL® for the treatment of chronic hepatitis C in patients with compensated liver disease who have not been previously treated with interferon alpha and who are at least 18 years of age.