PEGASYS Indications and Important Safety Information
INDICATIONS AND USAGE
PEGASYS® (peginterferon alfa-2a), alone or in combination with COPEGUS® (ribavirin, USP), is indicated for the treatment of patients 5 years of age and older with chronic hepatitis C (CHC) virus infection with compensated liver disease and have not been previously treated with interferon alpha. Efficacy has been demonstrated in subjects with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A) and in adult subjects with clinically stable HIV disease and CD4 count >100 cells/mm3.
- PEGASYS in combination with COPEGUS 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).
- PEGASYS in combination with COPEGUS is indicated in patients with HCV genotypes other than 1, pediatric patients (5-17 years of age), or in patients with HCV genotype 1 infection where use of an HCV NS3/4A protease inhibitor is not warranted based on tolerability, contraindications or other clinical factors.
The following points should be considered when initiating therapy with PEGASYS and COPEGUS:
- Use of PEGASYS monotherapy is not recommended for treatment of CHC unless a patient has a contraindication to or significant intolerance to ribavirin. Combination therapy provides substantially better response rates than monotherapy.
- Safety and efficacy have not been demonstrated for treatment longer than 48 weeks.
- The safety and efficacy have not been established in liver or other organ transplant recipients.
PEGASYS is indicated for the treatment of adult patients with HBeAg positive and HBeAg negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation.
IMPORTANT SAFETY INFORMATION
Alpha interferons, including PEGASYS, 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. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping PEGASYS therapy.
Use with ribavirin. Ribavirin, including COPEGUS, may cause birth defects and/or death of the fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with ribavirin therapy may result in a worsening of cardiac disease. [See COPEGUS Package Insert for additional information and other WARNINGS.]
PEGASYS is contraindicated in patients with known hypersensitivity reactions such as urticaria, angioedema, bronchoconstriction, anaphylaxis, or Stevens-Johnson syndrome to alpha interferons, including PEGASYS, or any of its components; autoimmune hepatitis; hepatic decompensation (Child-Pugh score >6 [class B and C]) in cirrhotic patients before treatment; hepatic decompensation with Child-Pugh score ≥6 in cirrhotic CHC patients coinfected with HIV before treatment.
PEGASYS is also contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal.
PEGASYS/ribavirin combination therapy is additionally contraindicated in women who are pregnant, men whose female partners are pregnant, patients with known hypersensitivity (urticaria, angioedema, bronchoconstriction, and anaphylaxis) to ribavirin or to any component of the tablet, patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia), and combination with didanosine (reports of fatal hepatic failure, as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis have been reported in clinical trials).
Patients exhibiting the following events, some of which may be life-threatening, should be closely monitored, and therapy withdrawn in those with persistently severe or worsening signs or symptoms:
- Use with ribavirin: Ribavirin may cause birth defects and/or death of the exposed fetus. Patients must have a negative pregnancy test prior to therapy, use 2 or more forms of contraception, and have monthly pregnancy tests. The primary toxicity of ribavirin is hemolytic anemia. Fatal and nonfatal myocardial infarctions have been reported in patients with anemia caused by ribavirin. Patients with a history of significant or unstable cardiac disease should not use ribavirin
- Neuropsychiatric reactions; cardiovascular disorders; bone marrow suppression; pancytopenia (with concomitant use of azathioprine); autoimmune disorders; endocrine disorders; ophthalmologic disorders; cerebrovascular disorders; hepatic failure and hepatitis exacerbations; pulmonary disorders; infections; colitis; pancreatitis; hypersensitivity and serious skin reactions, including Stevens-Johnson syndrome; impact on growth in pediatric patients; peripheral neuropathy (in combination with telbivudine)
The most common life-threatening or fatal events (<1%) include depression, suicide, relapse of drug abuse/overdose, and bacterial infections. Hepatic decompensation occurred in 2% of CHC/HIV subjects.
The most common serious adverse event was bacterial infection. Other serious adverse events occurred, including: suicide, suicidal ideation, aggression, anxiety, drug abuse and drug overdose, angina, hepatic dysfunction, fatty liver, cholangitis, arrhythmia, diabetes mellitus, autoimmune phenomena, peripheral neuropathy, aplastic anemia, peptic ulcer, gastrointestinal bleeding, pancreatitis, colitis, corneal ulcer, pulmonary embolism, coma, myositis, cerebral hemorrhage, thrombotic thrombocytopenic purpura, psychotic disorder, and hallucination.
For hepatitis C subjects, the most commonly reported adverse reactions were psychiatric reactions, including depression, insomnia, irritability, anxiety, and flu-like symptoms such as fatigue, pyrexia, myalgia, headache, and rigors. Other common reactions were anorexia, nausea and vomiting, diarrhea, arthralgias, injection site reactions, alopecia, and pruritus.
The safety profile observed in pediatric subjects was similar to that seen in adults, the most prevalent adverse events were influenza-like illness, upper respiratory tract infection, headache, gastrointestinal disorder, skin disorder, and injection-site reaction. Most of the adverse events reported in the study were mild or moderate in severity. Severe adverse events (hyperglycemia and cholecystectomy) were reported in 2 subjects.
Chronic Hepatitis C with HIV Coinfection (Adult Patients):
The adverse event profile of HCV/HIV coinfected adult subjects treated with PEGASYS/ribavirin was generally similar to that shown for monoinfected patients. Events occurring more frequently in coinfected subjects were neutropenia, anemia, thrombocytopenia, weight decrease, and mood alteration.
Chronic Hepatitis B:
The most common or important serious adverse events, all of which occurred at a frequency of less than or equal to 1%, in the hepatitis B studies were infections (sepsis, appendicitis, tuberculosis, influenza), hepatitis B flares, and thrombotic thrombocytopenic purpura. The most commonly observed adverse reactions in patients treated with PEGASYS were pyrexia, headache, fatigue, myalgia, alopecia, and anorexia.
You may report side effects to the FDA at 1-800-FDA-1088 or www.FDA.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.
Please see PEGASYS full Prescribing Information for Boxed WARNINGS and additional Important Safety Information.
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