Peginterferon Alfa-2a: uses, dosing, side effects & brands

In clinical trials, a broad variety of serious adverse reactions were observed in 1,010 subjects who received PEGASYS at doses of 180 mcg for 48 weeks, alone or in combination with ribavirin [see Boxed Warning and Warnings and Precautions (5) ] . The most common life-threatening or fatal events induced or aggravated by PEGASYS and ribavirin include depression, suicide, relapse of drug abuse/overdose, and bacterial infections, each occurring at a frequency of less than 1%. Hepatic decompensation occurred in 2% (10/574) of CHC/HIV subjects [see Warnings and Precautions (5.9) ] . Adult subjects: The most common adverse reactions (incidence greater than 40%) are fatigue/asthenia, pyrexia, myalgia, and headache ( 6.1 ) Pediatric subjects: The most common adverse reactions are similar to those seen in adults ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact pharma& agent at 1-888-814-7734 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug, and may not reflect the rates observed in clinical practice. Chronic Hepatitis C Adult Subjects In all hepatitis C studies, one or more serious adverse reactions occurred in 10% of CHC…

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 greater than 6 [class B and C]) in cirrhotic patients before treatment Hepatic decompensation with Child-Pugh score greater than or equal to 6 in cirrhotic CHC patients coinfected with HIV before treatment PEGASYS is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications which are sometimes fatal in neonates and infants. When PEGASYS is used in combination with other HCV antiviral drugs, the contraindications applicable to those agents are applicable to combination therapies. PEGASYS combination treatment with ribavirin is contraindicated in women who are pregnant and men whose female partners are pregnant [See Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ]. Refer to the prescribing information of the other HCV antiviral drugs, including ribavirin, for a list of their contraindications. Autoimmune hepatitis ( 4 ) Hepatic decompensation in patients with cirrhosis ( 4 ) Use in neonates/infants ( 4 ) Known hypersensitivity reactions such as urticaria, angioedema, bronchoconstriction and anaphylaxis to alpha interferons or any component of the product ( 4 ) Additional contraindications for use with other HCV antiviral drugs: When used in combination with other HCV antiviral drugs, all contraindications also apply to PEGASYS combination therapy ( 4 ) Ribavirin is contraindicated in pregnant women and men whose female partners are pregnant ( 4 , 8.1 )

Drugs metabolized by CYP1A2: monitor for increased serum levels of theophylline and adjust dose accordingly ( 7.2 ) Methadone: monitor for signs and symptoms of methadone toxicity ( 7.3 ) Nucleoside analogues: closely monitor for toxicities. Reduce or discontinue the dose of PEGASYS or ribavirin or both should the events worsen ( 7.4 ) Zidovudine: monitor for worsening neutropenia and/or anemia with PEGASYS and/or ribavirin ( 7.4 ) 7.1 Drugs Metabolized by Cytochrome P450 There was no effect on the pharmacokinetics of representative drugs metabolized by CYP 2C9, CYP 2C19, CYP 2D6 or CYP 3A4. Treatment with PEGASYS once weekly for 4 weeks in healthy subjects was associated with an inhibition of P450 1A2 and a 25% increase in theophylline AUC. 7.2 Theophylline Treatment with PEGASYS once weekly for 4 weeks in healthy subjects was associated with an inhibition of P450 1A2 and a 25% increase in theophylline AUC. Theophylline serum levels should be monitored and appropriate dose adjustments considered for patients given both theophylline and PEGASYS. 7.3 Methadone In a PK study of HCV subjects concomitantly receiving methadone, treatment with PEGASYS once weekly for 4 weeks was associated with methadone levels that were 10% to 15% higher than at baseline. The clinical significance of this finding is unknown; however, patients should be monitored for the signs and symptoms of methadone toxicity. The pharmacokinetics of concomitant administration of methadone and PEGASYS were evaluated in 24 PEGASYS naïve CHC subjects (15 male, 9 female) who received 180 mcg PEGASYS subcutaneously weekly. All subjects were on stable methadone maintenance therapy (median dose 95 mg, range 30 mg to 150 mg) prior to receiving PEGASYS. Mean methadone PK parameters were 10% to 15% higher after 4 weeks of PEGASYS treatment as compared to baseline. Methadone did not significantly alter the PK of PEGASYS as compared to a PK study of 6 chronic hepatitis C subjects not receiving methadone. 7.4 Nucleoside Analogues NRTIs In Study 7 among the CHC/HIV coinfected cirrhotic subjects receiving NRTIs cases of hepatic decompensation (some fatal) were observed [see Warnings and Precautions (5.9) ] . Patients receiving PEGASYS/ribavirin in combination with other HCV antiviral drugs and NRTIs should be closely monitored for treatment associated toxicities. Physicians should refer to prescribing information for other HCV antiviral drugs and the respective NRTIs for guidance regarding toxicity management. In addition, dose reduction or discontinuation of PEGASYS, ribavirin or both, should also be considered if worsening toxicities are observed [see Warnings and Precautions (5.3 , 5.9) and Dosage and Administration (2.6) ] . Zidovudine In Study 7, subjects who were administered zidovudine in combination with PEGASYS/ribavirin developed severe neutropenia (ANC less than 500 cells/mm 3 ) and severe anemia (hemoglobin less than 8 g/dL) more frequently than similar subjects not receiving zidovudine (neutropenia 15% vs. 9%) (anemia 5% vs. 1%). Discontinuation of zidovudine should be considered as medically appropriate. Dose reduction or discontinuation of PEGASYS, ribavirin or both should also be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh greater than 6). Refer to the prescribing information for specific HCV antiviral drugs used in combination with PEGASYS for information on drug interaction potential.