PEG-INTRON® treatment for hepatitis C

PEG-INTRON® (peginterferon alfa-2b) Powder for Injection, when used alone for the treatment of chronic hepatitis C, is usually prescribed once a week for one year. When used as monotherapy, PEG-INTRON® has been proven in clinical studies to be twice as effective (24% vs 12%) as INTRON® A (Interferon alfa-2b, recombinant) for Injection, in terms of the percentage of patients who had their viral load reduced to undetectable levels 6 months after treatment.*

During treatment, your doctor will carefully follow viral levels and do other tests to see if your liver is getting better with treatment.

A successful course of therapy with PEG-INTRON® may provide you with a period of remission and a lower risk of developing cirrhosis and/or liver cancer. Therefore, it is very important that you follow your treatment plan as long as it takes to see if you are improving. Follow-up with your doctor is also very important. Even if you have no sign of the virus in your body at the end of treatment, you may suffer a relapse (your infection may return). If this happens, you may need another course of therapy.

PEG-INTRON® is indicated for use alone or in combination with REBETOL® (Ribavirin, USP) Capsules for the treatment of chronic hepatitis C in patients not previously treated with interferon alpha who have compensated liver disease and are at least 18 years of age. For information on combination therapy with PEG-INTRON® and REBETOL®, see About PEG-INTRON/REBETOL Combination Therapy.

* Randomized study comparing treatment with PEG-INTRON® (0.5, 1.0, or 1.5 mcg/kg QW SC) to treatment with INTRON® A (3 MIU TIW SC) in 1219 adults with chronic hepatitis from HCV infection. The patients were not previously treated with interferon therapy, had compensated liver disease, detectable HCV RNA, elevated ALT, and liver histopathology consistent with chronic hepatitis. Patients were treated for 48 weeks with 24 weeks of follow-up. Seventy percent of all patients were infected with HCV genotype I, and 74% of all patients had high baseline levels of HCV RNA (more than 2 million copies/mL of serum), two factors known to predict poor response to treatment.

WARNING
Alpha interferons, including PEG-INTRON® and 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 PEG-INTRON or INTRON A therapy.

REBETOL monotherapy is not effective for the treatment of chronic hepatitis C and should not be used alone for this indication.

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 PEG-INTRON/REBETOL or INTRON A 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 PEG-INTRON/REBETOL or INTRON A 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 posttreatment 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 µg/kg)/REBETOL® and in 34% of those receiving INTRON® A/REBETOL®.
REBETOL® should not be used in patients with creatinine clearance < 50 ml/min.

INTRON® A
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, SUICIDAL ATTEMPTS, AND COMPLETED SUICIDES, HAVE BEEN REPORTED IN ASSOCIATION WITH TREATMENT WITH ALFA INTERFERONS, INCLUDING INTRON A THERAPY.