December 27, 2011

FDA Hepatitis Update - Important updates to PegIntron labeling

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On December 22, 2011, the Food and Drug Administration approved revisions to the product labeling for PegIntron to include the use of PegIntron with hepatitis C virus (HCV) NS3/4A protease inhibitors for the treatment of genotype 1, chronic hepatitis C (CHC) infection. Additionally, the product labeling was update to include revisions to the text regarding the use of PegIntron in patients with neuropsychiatric disorders. Changes were made to the Medication Guide for consistency. The following changes were made to the product labeling.

The Indication and Usage section was update as follows:
PegIntron®, as part of a combination regimen, is indicated for the treatment of Chronic Hepatitis C in patients with compensated liver disease.

PegIntron in combination with REBETOL (ribavirin) and an approved Hepatitis C Virus (HCV) NS3/4A protease inhibitor is indicated in adult patients (18 years of age and older) with HCV genotype 1 infection (see the Package Insert of the specific HCV NS3/4A protease inhibitor for further information).

PegIntron in combination with REBETOL is indicated in patients with genotypes other than 1, pediatric patients (3-17 years of age), or in patients with genotype 1 infection where use of an HCV NS3/4A protease inhibitor is not warranted based on tolerability, contraindications or other clinical factors.

The Dosage and Administration section, PegIntron Combination Therapy and Discontinuation of Dosing subsections were updated as follows:


2.1 PegIntron Combination Therapy


The recommended dose of PegIntron is 1.5 mcg/kg/week. The volume of PegIntron to be injected depends on the strength of PegIntron and patient’s body weight (see Table 1).

should be taken with food. REBETOL should not be used in patients with creatinine clearance less than 50 mL/min.

See the Package Insert of the specific HCV NS3/4A protease inhibitor for information regarding dosing regimen and administration of the protease inhibitor in combination with PegIntron and ribavirin.

Duration of Treatment – Treatment with PegIntron/REBETOL of Interferon Alpha-naïve Patients

The treatment duration for patients with genotype 1 is 48 weeks. Discontinuation of therapy should be considered in patients who do not achieve at least a 2 log10 drop or loss of HCV-RNA at 12 weeks, or if HCV-RNA remains detectable after 24 weeks of therapy. Patients with genotype 2 and 3 should be treated for 24 weeks.

Duration of Treatment – Retreatment with PegIntron/REBETOL of Prior Treatment Failures

For patients with genotype 1 infection, PegIntron and REBETOL without an HCV NS3/4A protease inhibitor should only be used if there are contraindications, significant intolerance or other clinical factors that would not warrant use of an HCV NS3/4A protease inhibitor. The treatment duration for patients who previously failed therapy is 48 weeks, regardless of HCV genotype. Re-treated patients who fail to achieve undetectable HCV-RNA at Week 12 of therapy, or whose HCV-RNA remains detectable after 24 weeks of therapy, are highly unlikely to achieve SVR and discontinuation of therapy should be considered

2.4 Discontinuation of Dosing


See the Package Insert of the specific HCV NS3/4A protease inhibitor for information regarding discontinuation of dosing based on treatment futility.

In HCV genotype 1, interferon-alfa-naïve patients receiving PegIntron, alone or in combination with REBETOL, discontinuation of therapy is recommended if there is not at least a 2 log10 drop or loss of HCV-RNA at 12 weeks of therapy, or if HCV-RNA levels remain detectable after 24 weeks of therapy. Regardless of genotype, previously treated patients who have detectable HCV-RNA at Week 12 or 24, are highly unlikely to achieve SVR and discontinuation of therapy is recommended.

Warning and Precaution section was revised as follows:

Neuropsychiatric Events

Life-threatening or fatal neuropsychiatric events, including suicide, suicidal and homicidal ideation, depression, relapse of drug addiction/overdose, and aggressive behavior sometimes directed towards others have occurred in patients with and without a previous psychiatric disorder during PegIntron treatment and follow-up. Psychoses, hallucinations, bipolar disorders, and mania have been observed in patients treated with interferon alpha.

PegIntron should be used with caution in patients with a history of psychiatric disorders. Treatment with interferons may be associated with exacerbated symptoms of psychiatric disorders in patients with co-occurring psychiatric and substance use disorders. If treatment with interferons is initiated in patients with prior history or existence of psychiatric condition or with a history of substance use disorders, treatment considerations should include the need for drug screening and periodic health evaluation, including psychiatric symptom monitoring. Early intervention for re-emergence or development of neuropsychiatric symptoms and substance use is recommended.

Patients should be advised to report immediately any symptoms of depression or suicidal ideation to their prescribing physicians. Physicians should monitor all patients for evidence of depression and other psychiatric symptoms. If patients develop psychiatric problems, including clinical depression, it is recommended that the patients be carefully monitored during treatment and in the 6-month follow-up period. If psychiatric symptoms persist or worsen, or suicidal ideation or aggressive behavior towards others is identified, it is recommended that treatment with PegIntron be discontinued, and the patient followed, with psychiatric intervention as appropriate. In severe cases, PegIntron should be stopped immediately and psychiatric intervention instituted. Cases of encephalopathy have been observed in some patients, usually elderly, treated at higher doses of PegIntron.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

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