Pegasys
peginterferon alfa-2a · Injection, Solution · Subcutaneous
Uses
1 INDICATIONS AND USAGE PEGASYS is an inducer of the innate immune response indicated for the treatment of Chronic Hepatitis C (CHC) ( 1.1 ) Adult Patients: In combination therapy with other hepatitis C virus drugs for adults with compensated liver disease. PEGASYS monotherapy is indicated only if patient has contraindication or significant intolerance to other HCV drugs. Pediatric Patients: In combination with ribavirin for pediatric patients 5 years of age and older with compensated liver disease Chronic Hepatitis B (CHB) ( 1.2 ) Adult Patients: Treatment of adults with HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB) infection who have compensated liver disease and evidence of viral replication and liver inflammation Pediatric Patients: Treatment of non-cirrhotic pediatric patients 3 years of age and older with HBeAg-positive CHB and evidence of viral replication and elevations in serum alanine aminotransferase (ALT) 1.1 Chronic Hepatitis C (CHC) Adult Patients: PEGASYS, as part of a combination regimen with other hepatitis C virus (HCV) antiviral drugs, is indicated for the treatment of adults with CHC and compensated liver disease. For information about the safe and effective use of other HCV antiviral drugs to be used in combination with PEGASYS, refer to their prescribing information. PEGASYS monotherapy is only indicated for the treatment of patients with CHC and compensated liver disease if there are contraindications or significant intolerance to other HCV antiviral drugs. Pediatric Patients: PEGASYS in combination with ribavirin is indicated for the treatment of pediatric patients 5 years of age and older with CHC and compensated liver disease. Limitations of Use : PEGASYS alone or in combination with ribavirin without additional HCV antiviral drugs is not recommended for treatment of patients with CHC who previously failed therapy with an interferon-alfa. PEGASYS is not recommended for treatment of patients with CHC who have had solid organ transplantation [see Use in Specific Populations (8.8) ] . 1.2 Chronic Hepatitis B (CHB) Adult Patients: PEGASYS is indicated for the treatment of adults with HBeAg-positive and HBeAg-negative CHB infection who have compensated liver disease and evidence of viral replication and liver inflammation. Pediatric Patients: PEGASYS is indicated for the treatment of HBeAg-positive CHB in non-cirrhotic pediatric patients 3 years of age and older with evidence of viral replication and elevations in serum alanine aminotransferase (ALT).
Dosage and administration
2 DOSAGE AND ADMINISTRATION PEGASYS is administered by subcutaneous injection ( 2 ) In adult patients with CHC, PEGASYS is dosed as 180 mcg per week and the duration of treatment depends on indication, genotype, and whether it is administered with other HCV antiviral drugs ( 2.2 ). In adult patients with CHB, PEGASYS is dosed as 180 mcg per week for 48 weeks ( 2.4 ). In pediatric patients with CHC, PEGASYS is dosed as 180 mcg/1.73 m 2 × BSA per week, in combination with ribavirin, and the duration of treatment depends on genotype ( 2.3 ) In pediatric patients with CHB, PEGASYS is dosed as 180 mcg/1.73 m 2 × BSA per week for 48 weeks ( 2.5 ): Dosage modification is recommended in patients experiencing certain laboratory abnormalities, adverse reactions or renal impairment ( 2.6 , 12.3 ) 2.1 Dosage Overview Administer PEGASYS by subcutaneous injection once weekly in the abdomen or thigh for the treatment of: Adult patients with CHC without or with HIV coinfection [see Dosage and Administration (2.2) ]; Pediatric patients with CHC [see Dosage and Administration (2.3) ] ; Adult patients with CHB [see Dosage and Administration (2.4) ] ; and Pediatric patients with CHB [see Dosage and Administration (2.5) ]. For treatment of CHC, use PEGASYS in combination with other HCV antiviral drugs. For information about the recommended dosage and administration and the safe and effective use of these other HCV antiviral drugs, refer to their prescribing information. PEGASYS monotherapy is only indicated in the treatment of CHC if there are contraindications to or significant intolerance to other HCV antiviral drugs. For dosage modifications in patients with CHC or CHB: Due to neutropenia, thrombocytopenia, ALT elevation, and depression [see Dosage and Administration (2.6) ] . In patients with severe renal impairment (creatinine clearance less than 30 mL/minute) and in patients with creatinine clearance between 30 and 50 mL/minute [see Dosage and Administration (2.6) ] . For important administration instructions for all the PEGASYS injection presentations (i.e., vial and prefilled syringe) [ see Dosage and Administration (2.7) ]. 2.2 Recommended Dosage for Adults with CHC Dosage in Adults with CHC without HIV Coinfection Table 1 displays the recommended dosage and duration of PEGASYS and other HCV antiviral drugs in adults with CHC (without HIV coinfection) based on HCV genotype. For treatment of HCV genotype 1 with PEGASYS in combination with ribavirin or alone, discontinuation of treatment is recommended if at least a 2 log 10 reduction from baseline in HCV RNA has not been demonstrated by 12 weeks of therapy or if undetectable HCV RNA has not been achieved after 24 weeks of therapy [see Clinical Studies (14) ] . Refer to the prescribing information for specific HCV antiviral drugs used in combination with PEGASYS for information on stopping therapy based on treatment response. Immediately discontinue PEGASYS for hepatic decompensation (Child-Pugh score greater than 6 [class B and C]). Table 1 Recommended Dosage for PEGASYS for Adults with CHC Infection If PEGASYS is used in combination with other antiviral drugs for CHC, refer to the prescribing information of the other HCV antiviral drugs for the recommended dosage of the other HCV antiviral drugs and duration of the entire treatment regimen. Hepatitis C Virus Genotype PEGASYS Dosage PEGASYS Duration Genotypes 1, 4 If PEGASYS and ribavirin are used without other HCV antiviral drugs the recommended duration of therapy is 48 weeks. 180 mcg subcutaneous injection in thigh or abdomen once weekly Refer to the prescribing information of HCV antiviral drugs. Genotypes 2, 3 If PEGASYS and ribavirin are used without other HCV antiviral drugs the recommended duration of therapy is 24 weeks. Genotypes 5, 6 There are insufficient data for dosage recommendations If PEGASYS monotherapy is used for treatment of CHC, the recommended PEGASYS dosage is 180 mcg via subcutaneous injection in thigh or abdomen once weekly for 48 weeks. Dosage in Adults with CHC with HIV Coinfection The recommended PEGASYS dosage in adults with CHC and HIV coinfection is 180 mcg subcutaneously once weekly in the thigh or abdomen. If PEGASYS is used in combination with other antiviral drugs, refer to the prescribing information of the other HCV antiviral drugs for the recommended dosage of the other HCV antiviral drugs and duration of the entire treatment regimen (including PEGASYS). If PEGASYS and ribavirin are used without other HCV antiviral drugs, the recommended duration of therapy is 48 weeks (regardless of HCV genotype). 2.3 Recommended Dosage for Pediatric Patients with CHC PEGASYS is administered as 180 mcg/1.73 m 2 × BSA subcutaneously once weekly, to a maximum dose of 180 mcg, and should be given in combination with ribavirin. The recommended treatment duration for pediatric patients with HCV genotype 2 or 3 is 24 weeks and for other HCV genotypes is 48 weeks. Patients who initiate treatment prior to their 18 th birthday should maintain the recommended pediatric dosage (not the adult dosage) through the completion of therapy. Refer to the prescribing information of ribavirin for the recommended dosage and duration. 2.4 Recommended Dosage for Adults with CHB The recommended PEGASYS dosage in adults with CHB is 180 mcg subcutaneously once weekly in the thigh or abdomen for 48 weeks. 2.5 Recommended Dosage for Pediatrics Patients with CHB The recommended PEGASYS dosage in pediatric patients for HBeAg-positive CHB is 180 mcg/1.73 m 2 × BSA subcutaneously once weekly to a maximum dose of 180 mcg. The recommended duration of therapy is 48 weeks. Maintain the recommended pediatric dosage through the entire duration of therapy in patients who turn 18 years of age during therapy.
Dosage forms and strengths
3 DOSAGE FORMS AND STRENGTHS PEGASYS is a colorless to slightly yellowish solution available as: Injection: 180 mcg/mL in a single-dose vial Injection: 180 mcg/0.5 mL in a single-dose prefilled syringe Injection: 180 mcg/mL solution in a single-dose vial ( 3 ) 180 mcg/0.5 mL solution in a single-dose prefilled syringe ( 3 )
Contraindications
4 CONTRAINDICATIONS 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 )
Warnings and precautions
Refer to the prescribing information of the other HCV antiviral drugs, including ribavirin, for their Warnings and Precautions. Use with ribavirin Birth defects and fetal death: patients must have a negative pregnancy test prior to therapy, use 2 forms of effective contraception, and have monthly pregnancy tests ( 5.1 ) PEGASYS Clinically Significant Adverse Reactions or Risks Patients exhibiting the following events should be closely monitored and may require dose reduction or discontinuation of therapy: Neuropsychiatric reactions ( 5.2 ) Cardiovascular disorders ( 5.3 ) Bone marrow suppression ( 5.4 ) Autoimmune and endocrine disorders (including thyroid disorders; hyperglycemia) ( 5.5 , 5.6 ) Ophthalmologic disorders ( 5.7 ) Cerebrovascular disorders ( 5.8 ) Hepatic decompensation in cirrhotic patients. Exacerbation of hepatitis during hepatitis B treatment ( 5.9 ) Pulmonary disorders ( 5.10 ) Infections (bacterial, viral, fungal) ( 5.11 ) Colitis and pancreatitis ( 5.12 , 5.13 ) Hypersensitivity and serious skin reactions including Stevens-Johnson syndrome ( 5.14 ) Growth impairment with combination therapy in pediatric patients ( 5.15 ) Peripheral neuropathy when used in combination with telbivudine ( 5.16 ) 5.1 Pregnancy: Use with ribavirin Ribavirin may cause birth defects and/or death of the exposed fetus. Patients must avoid pregnancy (female patients or female partners of male patients) while taking PEGASYS and ribavirin combination therapy. Ribavirin therapy should not be started unless a confirmed negative pregnancy test has been obtained immediately prior to initiation of therapy. Women of childbearing potential and men must use two forms of effective contraception during treatment and for at least 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time [see Contraindications (4) , Patient Counseling Information (17) and ribavirin labeling] . 5.2 Neuropsychiatric Reactions Life-threatening or fatal neuropsychiatric reactions may manifest in all patients receiving therapy with PEGASYS and include suicide, suicidal ideation, homicidal ideation, depression, relapse of drug addiction, and drug overdose. These reactions may occur in patients with and without previous psychiatric illness. PEGASYS should be used with extreme caution in all patients who report a history of depression. Neuropsychiatric adverse events observed with alpha interferon treatment include aggressive behavior, psychoses, hallucinations, bipolar disorders, and mania. Physicians should monitor all patients for evidence of depression and other psychiatric symptoms. Patients should be advised to report any sign or symptom of depression or suicidal ideation to their prescribing physicians. In severe cases, therapy should be stopped immediately and psychiatric intervention instituted [see Boxed Warning , Adverse Reactions (6.1) and Dosage and Administration (2.6) ] . 5.3 Cardiovascular Disorders Hypertension, supraventricular arrhythmias, chest pain, and myocardial infarction have been observed in patients treated with PEGASYS. PEGASYS should be administered with caution to patients with pre-existing cardiac disease. Because cardiac disease may be worsened by ribavirin-induced anemia, patients with a history of significant or unstable cardiac disease should not receive PEGASYS/ribavirin [see ribavirin prescribing information] . 5.4 Bone Marrow Suppression PEGASYS suppresses bone marrow function and may result in severe cytopenias. Ribavirin may potentiate the neutropenia and lymphopenia induced by alpha interferons including PEGASYS. Very rarely, alpha interferons may be associated with aplastic anemia. It is advised that complete blood counts (CBC) be obtained pre-treatment and monitored routinely during therapy [see ribavirin prescribing information] . PEGASYS/ribavirin should be used with caution in patients with baseline neutrophil counts less than 1,500 cells/mm 3 , with baseline platelet counts less than 90,000 cells/mm 3 or baseline hemoglobin less than 10 g/dL. PEGASYS therapy should be discontinued, at least temporarily, in patients who develop severe decreases in neutrophil and/or platelet counts [see Dosage and Administration (2.6) ] . Severe neutropenia and thrombocytopenia occur with a greater incidence in HIV coinfected patients than monoinfected patients and may result in serious infections or bleeding [see Adverse Reactions (6.1) ] . Pancytopenia (marked decreases in RBCs, neutrophils and platelets) and bone marrow suppression have been reported in the literature to occur within 3 to 7 weeks after the concomitant administration of pegylated interferon/ribavirin and azathioprine. In this limited number of patients (n=8), myelotoxicity was reversible within 4 to 6 weeks upon withdrawal of both HCV antiviral therapy and concomitant azathioprine and did not recur upon reintroduction of either treatment alone. PEGASYS, ribavirin, and azathioprine should be discontinued for pancytopenia, and pegylated interferon/ribavirin should not be re-introduced with concomitant azathioprine. 5.5 Autoimmune Disorders Development or exacerbation of autoimmune disorders including myositis, hepatitis, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus have been reported in patients receiving alpha interferon. PEGASYS should be used with caution in patients with autoimmune disorders [see Boxed Warning ] . 5.6 Endocrine Disorders PEGASYS causes or aggravates hypothyroidism and hyperthyroidism. Hyperglycemia, hypoglycemia, and diabetes mellitus have been observed to develop in patients treated with PEGASYS. Patients with these conditions at baseline who cannot be effectively treated by medication should not begin PEGASYS therapy.
Side effects
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 monoinfected subjects and in 19% of CHC/HIV subjects receiving PEGASYS alone or in combination with ribavirin. The most common serious adverse reactions (3% in CHC and 5% in CHC/HIV) was bacterial infection (e.g., sepsis, osteomyelitis, endocarditis, pyelonephritis, pneumonia). Other SAEs occurred at a frequency of less than 1% and included: suicide, suicidal ideation, aggression, anxiety, drug abuse and drug overdose, angina, hepatic dysfunction, fatty liver, cholangitis, arrhythmia, diabetes mellitus, autoimmune phenomena (e.g., hyperthyroidism, hypothyroidism, sarcoidosis, systemic lupus erythematosus, rheumatoid arthritis), 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. In clinical trials, 98 to 99 percent of subjects experienced one or more adverse reactions. 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. Table 7 displays pooled rates of adverse reactions occurring in greater than 5% of subjects in the PEGASYS monotherapy and PEGASYS/ribavirin combination therapy clinical trials. Overall, 11% of CHC monoinfected subjects receiving 48 weeks of therapy with PEGASYS either alone or in combination with ribavirin discontinued therapy; 16% of CHC/HIV coinfected subjects discontinued therapy. The most common reasons for discontinuation of therapy were psychiatric, flu-like syndrome (e.g., lethargy, fatigue, headache), dermatologic and gastrointestinal disorders, and laboratory abnormalities (thrombocytopenia, neutropenia, and anemia). Overall, 39% of subjects with CHC or CHC/HIV required modification of PEGASYS and/or ribavirin therapy. The most common reasons for dose modification of PEGASYS in CHC and CHC/HIV subjects was for neutropenia (20% and 27%, respectively) and thrombocytopenia (4% and 6%, respectively). The most common reason for dose modification of ribavirin in CHC and CHC/HIV subjects was anemia (22% and 16%, respectively). PEGASYS dose was reduced in 12% of subjects receiving 1000 mg to 1200 mg ribavirin for 48 weeks and in 7% of subjects receiving 800 mg ribavirin for 24 weeks. Ribavirin dose was reduced in 21% of subjects receiving 1000 mg to 1200 mg ribavirin for 48 weeks and in 12% of subjects receiving 800 mg ribavirin for 24 weeks. Chronic hepatitis C monoinfected subjects treated for 24 weeks with PEGASYS and 800 mg ribavirin were observed to have lower incidence of serious adverse reactions (3% vs. 10%), Hgb less than 10 g/dL (3% vs. 15%), dose modification of PEGASYS (30% vs. 36%) and ribavirin (19% vs. 38%) and of withdrawal from treatment (5% vs. 15%) compared to subjects treated for 48 weeks with PEGASYS and 1000 mg or 1200 mg ribavirin. The overall incidence of adverse reactions appeared to be similar in the two treatment groups. Table 7 Adverse Reactions Occurring in Greater Than or Equal to 5% of Subjects in Chronic Hepatitis C Clinical Trials (Pooled Studies 1, 2, 3, and Study 4) CHC Monotherapy (Pooled Studies 1-3) CHC Combination Therapy (Study 4) Body System PEGASYS 180 mcg 48 week Pooled studies 1, 2, and 3 ROFERON-A Either 3 MIU An induction dose of 6 million international units (MIU) three times a week for the first 12 weeks followed by 3 million international units three times a week for 36 weeks given subcutaneously. or 6/3 MIU of ROFERON-A 48 week PEGASYS 180 mcg + 1000 mg or 1200 mg Ribavirin 48 week Study 4 Intron ® A + 1000 mg or 1200 mg Rebetol ® 48 week N=559 N=554 N=451 N=443 % % % % Application Site Disorders Injection site reaction 22 18 23 16 Endocrine Disorders Hypothyroidism 3 2 4 5 Flu-like Symptoms and Signs Fatigue/Asthenia 56 57 65 68 Pyrexia 37 41 41 55 Rigors 35 44 25 37 Pain 11 12 10 9 Gastrointestinal Nausea/Vomiting 24 33 25 29 Diarrhea 16 16 11 10 Abdominal pain 15 15 8 9 Dry mouth 6 3 4 7 Dyspepsia <1 1 6 5 Hematologic Severe hematologic abnormalities (lymphocyte less than 500 cells/mm 3; hemoglobin less than 10 g/dL; neutrophil less than 750 cells/mm 3; platelet less than 50,000 cells/mm 3).
Drug interactions
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.
Use in specific populations
Pediatric patients: Safety and efficacy in CHC pediatric patients less than 5 years old and CHB pediatric patients less than 3 years old have not been established ( 8.4 ) Geriatric patients: Neuropsychiatric, cardiac, and systemic (flu-like) adverse reactions may be more severe ( 8.5 ) Patients with hepatic impairment: Clinical status and hepatic function should be closely monitored and treatment should be immediately discontinued if decompensation occurs ( 8.6 ) Patients with renal impairment: PEGASYS dose should be reduced in patients with creatinine clearance less than 30 mL/min ( 2.6 , 8.7 ) CHB: Safety and efficacy have not been established in hepatitis B patients coinfected with HCV or HIV ( 8.9 ) 8.1 Pregnancy Pregnancy Exposure Registry – Use with ribavirin A ribavirin Pregnancy Registry has been established to monitor maternal and fetal outcomes of pregnancies of female patients and female partners of male patients exposed to ribavirin during pregnancy or who become pregnant within 6 months following cessation of treatment with ribavirin. Healthcare providers and patients are encouraged to report such cases by calling 1-800-593-2214. Risk Summary There are no adequate and well-controlled studies of PEGASYS in pregnant women to inform a drug-associated risk. Based on animal reproduction studies, PEGASYS can cause fetal harm and should be assumed to have abortifacient potential. Non-pegylated interferon alfa-2a treatment caused abortion when given to pregnant rhesus monkeys (see Data ). The background risk of major birth defects and miscarriage in the indicated population is 3% and 4-22%, respectively. In the U.S. general population, the estimated background risk for major birth defects and miscarriage in the clinically recognized pregnancies is 2-4% and 15-20%, respectively. PEGASYS combination treatment with ribavirin is contraindicated in women who are pregnant and in the male partners of women who are pregnant [see Contraindications (4) , Warnings and Precautions (5.1) , and ribavirin labeling] . Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin [see ribavirin labeling]. Data Animal Data – Groups of 8 or 9 pregnant rhesus monkeys were given non-pegylated interferon alfa-2a by daily intramuscular injection over days 22 to 70 of gestation at doses of 1, 5 and 25 million IU/day. Two, 3 and 6 monkeys aborted in the low, mid and high dose groups compared with 1 in the control group. Maternal toxicity, characterized by transient body weight loss, was seen at all dose levels. There were too few remaining pregnancies to assess teratogenic potential but no developmental abnormalities were observed in surviving fetuses. 8.2 Lactation There is no information regarding the presence of peginterferon alfa-2a in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for adverse reactions from the drugs in nursing infants, a decision must be made whether to discontinue nursing or discontinue PEGASYS. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for PEGASYS and any potential adverse effects on the breastfed child from PEGASYS or from the underlying maternal condition. The Centers for Disease Control and Prevention recommends that HIV-infected mothers not breastfeed their infants to avoid potential transmission of HIV; therefore, CHC- and CHB-infected mothers coinfected with HIV should not breastfeed their infants. 8.3 Females and Males of Reproductive Potential Pregnancy Testing Females of reproductive potential must undergo pregnancy testing before initiation of treatment with PEGASYS or with PEGASYS in combination with ribavirin or with other HCV drugs [see Warnings and Precautions (5.17) ] . Females of reproductive potential receiving PEGASYS in combination with ribavirin must have a routine pregnancy test performed monthly during treatment and for at least 6 months following treatment. Female partners of male patients receiving PEGASYS in combination with ribavirin must have a routine pregnancy test performed monthly during treatment and for at least 6 months posttherapy [see Warnings and Precautions (5.17) , ribavirin prescribing information] . Contraception Females Because of the abortifacient potential of PEGASYS, females of reproductive potential should be advised to use effective contraception during therapy [see Warnings and Precautions (5.17) ] . However, when receiving PEGASYS in combination with ribavirin, women of reproductive potential and their partners must use effective contraception during treatment and for at least 6 months after the last dose [see ribavirin prescribing information] . Infertility Females Based on its mechanism of action and studies in female monkeys, PEGASYS can cause disruption of the menstrual cycle [see Nonclinical Toxicology (13.1) ] . No female fertility study has been performed. 8.4 Pediatric Use PEGASYS is indicated for the treatment of CHC in pediatric patients 5 to 17 years of age and for the treatment of CHB in pediatric patients 3 to 17 years of age [see Indications and Usage (1.1) , (1.2) , Dosage and Administration (2.3) , (2.5) , Clinical Studies (14.1) , (14.4) ]. The use of PEGASYS for the treatment of pediatric patients 5 to 17 years of age with CHC is based on one clinical trial in 114 previously untreated CHC subjects 5 to 17 years of age with compensated liver disease and detectable HCV RNA [see Clinical Trials Experience (6.1) , Clinical Studies (14.1) ] . The safety and efficacy of PEGASYS in pediatric patients with CHC below the age of 5 years have not been established.
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry – Use with ribavirin A ribavirin Pregnancy Registry has been established to monitor maternal and fetal outcomes of pregnancies of female patients and female partners of male patients exposed to ribavirin during pregnancy or who become pregnant within 6 months following cessation of treatment with ribavirin. Healthcare providers and patients are encouraged to report such cases by calling 1-800-593-2214. Risk Summary There are no adequate and well-controlled studies of PEGASYS in pregnant women to inform a drug-associated risk. Based on animal reproduction studies, PEGASYS can cause fetal harm and should be assumed to have abortifacient potential. Non-pegylated interferon alfa-2a treatment caused abortion when given to pregnant rhesus monkeys (see Data ). The background risk of major birth defects and miscarriage in the indicated population is 3% and 4-22%, respectively. In the U.S. general population, the estimated background risk for major birth defects and miscarriage in the clinically recognized pregnancies is 2-4% and 15-20%, respectively. PEGASYS combination treatment with ribavirin is contraindicated in women who are pregnant and in the male partners of women who are pregnant [see Contraindications (4) , Warnings and Precautions (5.1) , and ribavirin labeling] . Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin [see ribavirin labeling]. Data Animal Data – Groups of 8 or 9 pregnant rhesus monkeys were given non-pegylated interferon alfa-2a by daily intramuscular injection over days 22 to 70 of gestation at doses of 1, 5 and 25 million IU/day. Two, 3 and 6 monkeys aborted in the low, mid and high dose groups compared with 1 in the control group. Maternal toxicity, characterized by transient body weight loss, was seen at all dose levels. There were too few remaining pregnancies to assess teratogenic potential but no developmental abnormalities were observed in surviving fetuses.
Pediatric use
8.4 Pediatric Use PEGASYS is indicated for the treatment of CHC in pediatric patients 5 to 17 years of age and for the treatment of CHB in pediatric patients 3 to 17 years of age [see Indications and Usage (1.1) , (1.2) , Dosage and Administration (2.3) , (2.5) , Clinical Studies (14.1) , (14.4) ]. The use of PEGASYS for the treatment of pediatric patients 5 to 17 years of age with CHC is based on one clinical trial in 114 previously untreated CHC subjects 5 to 17 years of age with compensated liver disease and detectable HCV RNA [see Clinical Trials Experience (6.1) , Clinical Studies (14.1) ] . The safety and efficacy of PEGASYS in pediatric patients with CHC below the age of 5 years have not been established. The use of PEGASYS for the treatment of pediatric patients 3 to 17 years of age with CHB is based on one clinical trial in 161 previously untreated CHB subjects 3 to 17 years of age of whom 111 were assigned to treatment with PEGASYS [ see Clinical Trials Experience (6.1) , Clinical Studies (14.4) ] . PEGASYS has not been studied in pediatric CHB patients with liver cirrhosis and the safety and efficacy of PEGASYS in pediatric patients with CHB below the age of 3 years have not been established. PEGASYS contains benzyl alcohol. In neonates and infants, benzyl alcohol has been reported to be associated with an increased incidence of neurological and other complications which are sometimes fatal in neonates and infants [see Contraindications (4) ] .
Geriatric use
8.5 Geriatric Use Younger patients have higher virologic response rates than older patients. Clinical studies of PEGASYS alone or in combination with ribavirin did not include sufficient numbers of subjects aged 65 or over to determine whether they respond differently from younger subjects. Adverse reactions related to alpha interferons, such as CNS, cardiac, and systemic (e.g., flu-like) effects may be more severe in the elderly and caution should be exercised in the use of PEGASYS in this population. PEGASYS is excreted by the kidney, and the risk of toxic reactions to this therapy may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function. PEGASYS should be used with caution in patients with creatinine clearance less than or equal to 50 mL/min. The dose of PEGASYS should be reduced for patients with creatinine clearance less than 30 mL/min [see Dosage and Administration (2.6) and Use in Specific Populations (8.7) ] .
Overdosage
There is limited experience with overdosage. The maximum dose received by any patient was 7 times the intended dose of PEGASYS (180 mcg/day for 7 days). There were no serious reactions attributed to overdosages. Weekly doses of up to 630 mcg have been administered to patients with cancer. Dose-limiting toxicities were fatigue, elevated liver enzymes, neutropenia, and thrombocytopenia. There is no specific antidote for PEGASYS. Hemodialysis and peritoneal dialysis are not effective.
Description
Peginterferon alfa-2a, is a covalent conjugate of recombinant alfa-2a interferon (approximate molecular weight [MW] 20,000 daltons) with a single branched bis-monomethoxy polyethylene glycol (PEG) chain (approximate MW 40,000 daltons). The PEG moiety is linked at a single site to the interferon alfa moiety via a stable amide bond to lysine. Peginterferon alfa-2a has an approximate molecular weight of 60,000 daltons. Interferon alfa-2a is produced using recombinant DNA technology in which a cloned human leukocyte interferon gene is inserted into and expressed in Escherichia coli . PEGASYS is a sterile, preservative-free, colorless to slightly yellowish solution available as an injection and is administered subcutaneously. Each vial of 180 mcg/mL peginterferon alfa-2a (expressed as the amount of interferon alfa-2a) also contains acetic acid (0.05 mg), benzyl alcohol (10 mg), polysorbate 80 (0.05 mg), sodium acetate trihydrate (2.62 mg), and sodium chloride (8 mg) at pH 6 ± 0.5. Each prefilled syringe of 180 mcg/0.5 mL peginterferon alfa-2a (expressed as the amount of interferon alfa-2a) also contains acetic acid (0.0231 mg), benzyl alcohol (5 mg), polysorbate 80 (0.025 mg), sodium acetate trihydrate (1.3085 mg), and sodium chloride (4 mg) at pH 6 ± 0.5.
Mechanism of action
12.1 Mechanism of Action Pegylated recombinant human interferon alfa-2a is an inducer of the innate antiviral immune response [see Microbiology (12.4) ] .
How supplied
(peginterferon alfa-2a) injection is a sterile, preservative-free, colorless to slightly yellowish solution administered subcutaneously. Each PEGASYS Single-Dose Vial Package Contains: A box containing 180 mcg per 1 mL solution in a single-dose vial. (NDC 82154-0449-1) Each PEGASYS Prefilled Syringe Monthly Convenience Pack Contains: A box containing four 180 mcg per 0.5 mL (½ cc) single-dose prefilled syringes with 4 needles. Each prefilled syringe is supplied with a 27-gauge, ½-inch needle with a needle-stick protection device. (NDC 82154-0451-4) Storage and Handling Store in the refrigerator at 2°C to 8°C (36°F to 46°F). Do not leave PEGASYS out of the refrigerator for more than 24 hours. Do not freeze or shake. Protect from light. Vials and prefilled syringes are for single use only. Discard any unused portion remaining in the vial, prefilled syringe. Disposal Instructions If home use is prescribed, a puncture-resistant container for the disposal of used needles and syringes should be supplied to the patients. Patients should be thoroughly instructed in the importance of proper disposal and cautioned against any reuse of any needles and syringes. The full container should be disposed of according to the directions provided by the physician [see FDA-Approved Medication Guide ] .
Storage
Storage and Handling Store in the refrigerator at 2°C to 8°C (36°F to 46°F). Do not leave PEGASYS out of the refrigerator for more than 24 hours. Do not freeze or shake. Protect from light. Vials and prefilled syringes are for single use only. Discard any unused portion remaining in the vial, prefilled syringe.
Patient information
Advise the patient to read the FDA-approved patient labeling ( Medication Guide and Instructions for Use ) Patients receiving PEGASYS alone or in combination with an approved HCV antiviral drug should be directed in its appropriate use, informed of the benefits and risks associated with treatment, and referred to FDA-approved patient labeling ( Medication Guide and Instructions for Use ). Pregnancy Patients must be informed that ribavirin must not be used by women who are pregnant or by men whose female partners are pregnant. ribavirin therapy should not be initiated until a report of a negative pregnancy test has been obtained immediately before starting therapy. Female patients of childbearing potential and male patients with female partners of childbearing potential must be advised of the teratogenic/embryocidal risks and must be instructed to practice effective contraception during ribavirin therapy and for 6 months post-therapy. Patients should be advised to notify the healthcare provider immediately in the event of a pregnancy [see Contraindications (4) and Warnings and Precautions (5.1) ] . Women of childbearing potential and men must use two forms of effective contraception during treatment and during the 6 months after treatment has been stopped; routine monthly pregnancy tests must be performed during this time [see Contraindications (4) , Warnings and Precautions (5.1) , Use in Specific Populations (8.1) , and ribavirin prescribing information] . To monitor maternal and fetal outcomes of pregnant women exposed to ribavirin, the ribavirin Pregnancy Registry has been established. Patients should be encouraged to register by calling 1-800-593-2214. Flu-like symptoms Inform patients that flu-like symptoms are very common in patients taking PEGASYS. Symptoms may include tiredness, weakness, fever, chills, muscle aches, joint pain, and headaches. Inform patients that some of these symptoms may be decreased by injecting PEGASYS in the evening. Also inform patients which over-the-counter medicines can be taken to help prevent or decrease some of the symptoms. Laboratory Evaluations and Hydration Patients should be advised that laboratory evaluations are required before starting therapy and periodically thereafter [see Warnings and Precautions (5.17) ] . Patients should be instructed to remain well hydrated, especially during the initial stages of treatment. General Information Patients should be questioned about prior history of drug abuse before initiating PEGASYS; as relapse of drug addiction and drug overdoses have been reported in patients treated with interferons. Patients should be informed that it is not known if therapy with PEGASYS will prevent transmission of HBV infection to others or prevent cirrhosis, liver failure or liver cancer that might result from HBV infection. Patients should be informed that the effect of treatment of hepatitis C infection on transmission is not known, and that appropriate precautions to prevent transmission of the hepatitis C virus during treatment or in the event of treatment failure should be taken. Patients who develop dizziness, confusion, somnolence, and fatigue should be cautioned to avoid driving or operating machinery. Patients should be advised to avoid drinking alcohol to reduce the chance of further injury to the liver. Patients should not switch to another brand of interferon without consulting their healthcare provider. Dosing Instructions Patients should be advised to take their prescribed dose of PEGASYS on the same day and approximately same time each week. Patients should also be advised that if they miss a dose, but remember within 2 days, to take their missed dose as soon as they remember and then to take their next dose on the day they normally do. If they remember when more than 2 days have passed, patients should be advised to consult their healthcare provider. Patients should also be advised to consult their healthcare provider if the full dose is not received (e.g., leakage around the injection site). Patients must be instructed on the use of aseptic techniques when administering PEGASYS. Appropriate training for preparation using the vial and prefilled syringe must be given by a healthcare provider, including a careful review of the PEGASYS Medication Guide and Instructions for Use for the vial and prefilled syringe. Patients should be instructed to allow the vial and prefilled syringe to come to room temperature and for condensation on the outside of the prefilled syringe to disappear before use. The following instructions should be given: Vial: warm the refrigerated medicine by gently rolling in the palms of the hands for about one minute. Pre-filled syringe: lay the syringe on a flat clean surface and wait a few minutes until it reaches room temperature. If condensation water is observed on the outside of the syringe, wait another few minutes until it disappears. Patients should be advised not to shake the vial and prefilled syringe as foaming may occur. Patients should be advised to choose a different place on either the thigh or abdomen each time an injection is made.
Label text from the FDA structured product label by pharmaand GmbH (revised Sep 2, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Peginterferon Alfa-2a in 2 products
Pegasys NDC products (2)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 82154-0449 | Peginterferon Alfa-2a 180 ug/mL Injection, Solution | pharmaand GmbH | BLA |
| 82154-0451 | Peginterferon Alfa-2a 180 ug/.5mL Injection, Solution | pharmaand GmbH | BLA |
Frequently asked questions
What is Pegasys used for?
1 INDICATIONS AND USAGE PEGASYS is an inducer of the innate immune response indicated for the treatment of Chronic Hepatitis C (CHC) ( 1.1 ) Adult Patients: In combination therapy with other hepatitis C virus drugs for adults with compensated liver disease. PEGASYS monotherapy is indicated only if patient has contraindication or significant intolerance to other HCV drugs. Pediatric Patients: In…
What are the side effects of Pegasys?
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… See the full label for the complete list.
Who makes Pegasys?
Pegasys is listed by 1 labeler in the FDA NDC directory, including pharmaand GmbH.