英文名：Peginterferon alfa-2a Solution for Injection
健康人单次皮下注射PEG干扰素α-2a 180μg后3-6小时，血清2, 5-寡腺苷酸合成酶（2, 5-OAS，抗病毒活性指标）活性迅速升高。PEG干扰素α-2a所引起的2, 5-OAS血清活性可维持1周以上，且比单次皮下注射300万单位和1800万单位干扰素的活性高。与年轻人比较，62岁以上的老年人单次皮下注射PEG干扰素α-2a 180μg，所产生的血清2, 5-OAS活性强度和持续时间有所减低。
在正在进行的本品与利巴韦林联合应用的临床试验中，尚未发现两者药代动力学有交叉反应。 α-干扰素可以通过降低肝微粒体细胞色素P450酶的活性而影响机体的氧化代谢过程。但是，在健康男性中皮下注射派罗欣®180μg每周1次共4周后，未显示对美芬妥英、氨苯砜、异喹胍和甲磺丁脲等药物的药代动力学有影响。本品对细胸包素P450 3A4、2C9、2C19和2D6等同功酶的体内代谢活性也没有影响。
在同一研究中，发现茶碱的AUC（表示细胞色素P450 1A2活性的指标）出现了25%的升高。本品可中度抑制细胞色素P450 1A2活性。如果同时使用本品和茶碱，应监测茶碱血清浓度并适当调整茶碱用量。
Pegasys (Peginterferon alfa-2a) Indications And Usage
Pegasys (Peginterferon alfa-2a) , peginterferon alfa-2a, alone or in combination with COPEGUS, is indicated for the treatment of patients 5 years of age and older with chronic hepatitis C (CHC) virus infection who have 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 greater than 100 cells/mm.
The following points should be considered when initiating therapy with Pegasys (Peginterferon alfa-2a) and COPEGUS:
Pegasys (Peginterferon alfa-2a) Dosage And Administration
Pegasys (Peginterferon alfa-2a) is administered by subcutaneous injection in the abdomen or thigh. See COPEGUS Package Insert for all instructions regarding COPEGUS dosing and administration.
In patients with CrCL less than 30 mL/min, including patients with end-stage renal disease requiring hemodialysis, dose reduction to 135 mcg Pegasys (Peginterferon alfa-2a) is recommended. Signs and symptoms of interferon toxicity should be closely monitored. If severe adverse reactions or laboratory abnormalities develop, the dose of Pegasys (Peginterferon alfa-2a) may be reduced to 90 mcg until the adverse reactions abate. If intolerance persists after dose adjustment, Pegasys (Peginterferon alfa-2a) /COPEGUS therapy should be discontinued.
Renal function should be evaluated in all patients on COPEGUS. The dose of COPEGUS should be reduced for patients with creatinine clearance less than or equal to 50 mL/min
No data are available for pediatric subjects with renal impairment.
Discontinuation of therapy should be considered if the patient has failed to demonstrate at least a 2 log reduction from baseline in HCV RNA titer by 12 weeks of therapy or undetectable HCV RNA after 24 weeks of therapy .
During treatment, patients' clinical status and hepatic function should be closely monitored, and Pegasys (Peginterferon alfa-2a) treatment should be immediately discontinued if decompensation is observed .
Patients should be monitored for serious adverse reactions, some of which may become life threatening. Patients with persistently severe or worsening signs or symptoms should have their therapy withdrawn .
A patient should self-inject Pegasys (Peginterferon alfa-2a) only if the physician determines that it is appropriate and the patient agrees to medical follow-up as necessary and has been trained in proper injection technique
Pegasys (Peginterferon alfa-2a) should be inspected visually for particulate matter and discoloration before administration, and not used if particulate matter is visible or product is discolored. Vials, prefilled syringes, and disposable autoinjectors with particulate matter or discoloration should be returned to the pharmacist.
Discard the unused portion of Pegasys (Peginterferon alfa-2a) in single-use vials or prefilled syringes in excess of the labeled volume. Use only one vial or prefilled syringe or disposable autoinjector per dose.
Pegasys (Peginterferon alfa-2a) Contraindications
Pegasys (Peginterferon alfa-2a) is contraindicated in patients with:
Pegasys (Peginterferon alfa-2a) 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.
Pegasys (Peginterferon alfa-2a) /COPEGUS combination therapy is additionally contraindicated in:
Pegasys (Peginterferon alfa-2a) Warnings And Precautions
Patients should be monitored for the following serious conditions, some of which may become life threatening. Patients with persistently severe or worsening signs or symptoms should have their therapy withdrawn .
Life-threatening or fatal neuropsychiatric reactions may manifest in all patients receiving therapy with Pegasys (Peginterferon alfa-2a) 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 (Peginterferon alfa-2a) 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 .
Pegasys (Peginterferon alfa-2a) suppresses bone marrow function and may result in severe cytopenias. Ribavirin may potentiate the neutropenia and lymphopenia induced by alpha interferons including Pegasys (Peginterferon alfa-2a) . 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 .
Pegasys (Peginterferon alfa-2a) /COPEGUS should be used with caution in patients with baseline neutrophil counts less than 1,500 cells/mm, with baseline platelet counts less than 90,000 cells/mm or baseline hemoglobin less than 10 g/dL. Pegasys (Peginterferon alfa-2a) therapy should be discontinued, at least temporarily, in patients who develop severe decreases in neutrophil and/or platelet counts .
Severe neutropenia and thrombocytopenia occur with a greater incidence in HIV coinfected patients than monoinfected patients and may result in serious infections or bleeding .
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 (Peginterferon alfa-2a) , COPEGUS, and azathioprine should be discontinued for pancytopenia, and pegylated interferon/ribavirin should not be re-introduced with concomitant azathioprine .
Chronic hepatitis C (CHC) patients with cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including Pegasys (Peginterferon alfa-2a) . Cirrhotic CHC patients coinfected with HIV receiving highly active antiretroviral therapy (HAART) and interferon alfa-2a with or without ribavirin appear to be at increased risk for the development of hepatic decompensation compared to patients not receiving HAART. In Study 6 , among 129 CHC/HIV cirrhotic subjects receiving HAART, 14 (11%) of these subjects across all treatment arms developed hepatic decompensation resulting in 6 deaths. All 14 subjects were on NRTIs, including stavudine, didanosine, abacavir, zidovudine, and lamivudine. These small numbers of patients do not permit discrimination between specific NRTIs for the associated risk.
Exacerbations of hepatitis during hepatitis B therapy are not uncommon and are characterized by transient and potentially severe increases in serum ALT. Chronic hepatitis B subjects experienced transient acute exacerbations (flares) of hepatitis B (ALT elevation greater than 10-fold higher than the upper limit of normal) during Pegasys (Peginterferon alfa-2a) treatment (12% and 18%) and post-treatment (7% and 12%) in HBeAg negative and HBeAg positive subjects, respectively. Marked transaminase flares while on Pegasys (Peginterferon alfa-2a) therapy have been accompanied by other liver test abnormalities. Patients experiencing ALT flares should receive more frequent monitoring of liver function. Pegasys (Peginterferon alfa-2a) dose reduction should be considered in patients experiencing transaminase flares. If ALT increases are progressive despite reduction of Pegasys (Peginterferon alfa-2a) dose or are accompanied by increased bilirubin or evidence of hepatic decompensation, Pegasys (Peginterferon alfa-2a) should be immediately discontinued .
Pediatric subjects treated with Pegasys (Peginterferon alfa-2a) plus COPEGUS combination therapy showed a delay in weight and height increases after 48 weeks of therapy compared with baseline. Both weight and height for age z-scores as well as the percentiles of the normative population for subject weight and height decreased during treatment. At the end of 2 years follow-up after treatment, most subjects had returned to baseline normative growth curve percentiles for weight and height (mean weight for age percentile was 64% at baseline and 60% at 2 years post-treatment; mean height percentile was 54% at baseline and 56% at 2 years post-treatment). At the end of treatment, 43% of subjects experienced a weight percentile decrease of 15 percentiles or more, and 25% experienced a height percentile decrease of 15 percentiles or more on the normative growth curves. At 2 years post-treatment, 16% of subjects remained 15 percentiles or more below their baseline weight curve and 11% remained 15 percentiles or more below their baseline height curve.
Before beginning Pegasys (Peginterferon alfa-2a) or Pegasys (Peginterferon alfa-2a) /COPEGUS combination therapy, standard hematological and biochemical laboratory tests are recommended for all patients. Pregnancy screening for women of childbearing potential must be performed. Patients who have pre-existing cardiac abnormalities should have electrocardiograms administered before treatment with Pegasys (Peginterferon alfa-2a) /COPEGUS.
After initiation of therapy, hematological tests should be performed at 2 weeks and 4 weeks and biochemical tests should be performed at 4 weeks. Additional testing should be performed periodically during therapy. In adult clinical studies, the CBC (including hemoglobin level and white blood cell and platelet counts) and chemistries (including liver function tests and uric acid) were measured at 1, 2, 4, 6, and 8 weeks, and then every 4 to 6 weeks or more frequently if abnormalities were found.
The entrance criteria used for the clinical studies of Pegasys (Peginterferon alfa-2a) may be considered as a guideline to acceptable baseline values for initiation of treatment:
Pegasys (Peginterferon alfa-2a) Adverse Reactions
In clinical trials, a broad variety of serious adverse reactions were observed in 1,010 subjects who received Pegasys (Peginterferon alfa-2a) at doses of 180 mcg for 48 weeks, alone or in combination with COPEGUS . The most common life-threatening or fatal events induced or aggravated by Pegasys (Peginterferon alfa-2a) and COPEGUS 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 .
The following adverse reactions have been identified and reported during post-approval use of Pegasys (Peginterferon alfa-2a) therapy. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and lymphatic system disorders:
Ear and labyrinth disorders:
Metabolism and nutrition disorders:
Skin and subcutaneous tissue disorders:
Pegasys (Peginterferon alfa-2a) Drug Interactions
There was no effect on the pharmacokinetics of representative drugs metabolized by CYP 2C9, CYP 2C19, CYP 2D6 or CYP 3A4.
Treatment with Pegasys (Peginterferon alfa-2a) once weekly for 4 weeks in healthy subjects was associated with an inhibition of P450 1A2 and a 25% increase in theophylline AUC.
In a PK study of HCV subjects concomitantly receiving methadone, treatment with Pegasys (Peginterferon alfa-2a) 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 (Peginterferon alfa-2a) were evaluated in 24 Pegasys (Peginterferon alfa-2a) naïve chronic hepatitis C (CHC) subjects (15 male, 9 female) who received 180 mcg Pegasys (Peginterferon alfa-2a) subcutaneously weekly. All subjects were on stable methadone maintenance therapy (median dose 95 mg, range 30 mg to 150 mg) prior to receiving Pegasys (Peginterferon alfa-2a) . Mean methadone PK parameters were 10% to 15% higher after 4 weeks of Pegasys (Peginterferon alfa-2a) treatment as compared to baseline. Methadone did not significantly alter the PK of Pegasys (Peginterferon alfa-2a) as compared to a PK study of 6 chronic hepatitis C subjects not receiving methadone.
Pegasys (Peginterferon alfa-2a) Use In Specific Populations
The safety and effectiveness of Pegasys (Peginterferon alfa-2a) , alone or in combination with COPEGUS in patients below the age of 5 years have not been established.
Pegasys (Peginterferon alfa-2a) 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 .
Renal function should be evaluated in all patients prior to initiation of Pegasys (Peginterferon alfa-2a) by estimating the patient's creatinine clearance.
A clinical trial evaluated treatment with Pegasys (Peginterferon alfa-2a) and COPEGUS in 50 CHC subjects with moderate (creatinine clearance 30 – 50 mL/min) or severe (creatinine clearance less than 30 mL/min) renal impairment or end stage renal disease (ESRD) requiring chronic hemodialysis (HD). In 18 subjects with ESRD receiving chronic HD, Pegasys (Peginterferon alfa-2a) was administered at a dose of 135 mcg once weekly. Dose reductions and temporary interruptions of Pegasys (Peginterferon alfa-2a) (due to Pegasys (Peginterferon alfa-2a) -related adverse reactions, mainly anemia) were observed in up to 22% ESRD/HD subjects during treatment; and 17% of these subjects discontinued Pegasys (Peginterferon alfa-2a) due to Pegasys (Peginterferon alfa-2a) -related adverse reactions. Only one-third of ESRD/HD subjects received Pegasys (Peginterferon alfa-2a) for 48 weeks. Subjects with severe (n=14) or moderate (n=17) renal impairment received Pegasys (Peginterferon alfa-2a) 180 mcg once weekly. Pegasys (Peginterferon alfa-2a) discontinuation rates were 36% and 0% in subjects with severe and moderate renal impairment, respectively, compared to 0% discontinuation rate in subjects with normal renal function.
Based on the pharmacokinetic and safety results from this trial, patients with creatinine clearance less than 30 mL/min should receive a reduced dose of Pegasys (Peginterferon alfa-2a) , and patients with creatinine clearance less than or equal to 50 mL/min should receive a reduced dose of COPEGUS. In addition, patients with any degree of renal impairment should be carefully monitored for laboratory abnormalities (especially decreased hemoglobin) and adverse reactions, and should undergo careful monitoring of creatinine clearance. Patients with clinically significant laboratory abnormalities or adverse reactions which are persistently severe or worsening should have therapy withdrawn .
Pegasys (Peginterferon alfa-2a) Overdosage
There is limited experience with overdosage. The maximum dose received by any patient was 7 times the intended dose of Pegasys (Peginterferon alfa-2a) (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 (Peginterferon alfa-2a) . Hemodialysis and peritoneal dialysis are not effective.
Pegasys (Peginterferon alfa-2a) Description
Pegasys (Peginterferon alfa-2a) , 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 .
Pegasys (Peginterferon alfa-2a) is a sterile, preservative-free, colorless to light yellow injectable solution 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.
Each Autoinjector containing 180 mcg/0.5 mL peginteferon 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.
Each Autoinjector containing 135 mcg/0.5 mL peginteferon 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.
Because the autoinjectors are designed to deliver the full content, autoinjectors should only be used for patients who need the full dose (180 or 135 mcg). If the required dose is not available in an autoinjector, prefilled syringes, or vials should be used to administer the required dose. The autoinjector is for subcutaneous administration only.
Pegasys (Peginterferon alfa-2a) Clinical Pharmacology
Maximal serum concentrations (C) and AUC increased in a nonlinear dose related manner following administration of 90 to 270 mcg of Pegasys (Peginterferon alfa-2a) . Maximal serum concentrations (C) occur between 72 to 96 hours post-dose.
Week 48 mean trough concentrations (16 ng/mL; range 4 to 28) at 168 hours post-dose are approximately 2-fold higher than week 1 mean trough concentrations (9 ng/mL; range 0 to 15). Steady-state serum levels are reached within 5 to 8 weeks of once weekly dosing. The peak to trough ratio at week 48 is approximately 2. The mean systemic clearance in healthy subjects given Pegasys (Peginterferon alfa-2a) was 94 mL/h, which is approximately 100-fold lower than that for interferon alfa-2a (ROFERON-A). The mean terminal half-life after subcutaneous dosing in subjects with chronic hepatitis C was 160 hours (range 84 to 353 hours) compared to 5 hours (range 3.7 to 8.5 hours) for ROFERON-A.
Pegasys (Peginterferon alfa-2a) Clinical Studies
The safety and effectiveness of Pegasys (Peginterferon alfa-2a) for the treatment of hepatitis C virus infection were assessed in three randomized, open-label, active-controlled clinical studies. All subjects were adults, had compensated liver disease, detectable hepatitis C virus (HCV), liver biopsy diagnosis of chronic hepatitis, and were previously untreated with interferon. All subjects received therapy by subcutaneous injection for 48 weeks, and were followed for an additional 24 weeks to assess the durability of response. In studies 1 and 2, approximately 20% of subjects had cirrhosis or bridging fibrosis. Study 3 enrolled subjects with a histological diagnosis of cirrhosis (78%) or bridging fibrosis (22%).
In Study 1 (n=630), subjects received either ROFERON-A (interferon alfa-2a) 3 MIU three times a week, Pegasys (Peginterferon alfa-2a) 135 mcg once weekly or Pegasys (Peginterferon alfa-2a) 180 mcg once weekly. In Study 2 (n=526), subjects received either ROFERON-A 6 MIU three times a week for 12 weeks followed by 3 MIU three times a week for 36 weeks or Pegasys (Peginterferon alfa-2a) 180 mcg once weekly. In Study 3 (n=269), subjects received ROFERON-A 3 MIU three times a week, Pegasys (Peginterferon alfa-2a) 90 mcg once weekly or Pegasys (Peginterferon alfa-2a) 180 mcg once each week.
In all three studies, treatment with Pegasys (Peginterferon alfa-2a) 180 mcg resulted in significantly more subjects who experienced a sustained response (defined as undetectable HCV RNA [less than 50 IU/mL] using the COBAS AMPLICORHCV Test, version 2 and normalization of ALT on or after study week 68) compared to treatment with ROFERON-A. In Study 1, response to Pegasys (Peginterferon alfa-2a) 135 mcg was not different from response to 180 mcg. In Study 3, response to Pegasys (Peginterferon alfa-2a) 90 mcg was intermediate between Pegasys (Peginterferon alfa-2a) 180 mcg and ROFERON-A.
Matched pre- and post-treatment liver biopsies were obtained in approximately 70% of subjects. Similar modest reductions in inflammation compared to baseline were observed in all treatment groups.
Of the subjects who did not demonstrate either undetectable HCV RNA or at least a 2 log drop in HCV RNA titer from baseline by 12 weeks of Pegasys (Peginterferon alfa-2a) 180 mcg therapy, 2% (3/156) achieved a sustained virologic response .
Averaged over Study 1, Study 2, and Study 3, response rates to Pegasys (Peginterferon alfa-2a) were 23% among subjects with viral genotype 1 and 48% among subjects with other viral genotypes. The treatment response rates were similar in men and women.
In Study 7, subjects with CHC/HIV were randomized to receive either Pegasys (Peginterferon alfa-2a) 180 mcg subcutaneous once weekly plus an oral placebo, Pegasys (Peginterferon alfa-2a) 180 mcg once weekly plus COPEGUS 800 mg by mouth daily or ROFERON-A (interferon alfa-2a), 3 MIU subcutaneous three times a week plus COPEGUS 800 mg by mouth daily. All subjects received 48 weeks of therapy and sustained virologic response (SVR) was assessed at 24 weeks of treatment-free follow-up. COPEGUS or placebo treatment assignment was blinded in the Pegasys (Peginterferon alfa-2a) treatment arms. All subjects were adults, had compensated liver disease, detectable hepatitis C virus, liver biopsy diagnosis of chronic hepatitis C, and were previously untreated with interferon. Subjects also had CD4+ cell count greater than or equal to 200 cells/mmor CD4+ cell count greater than or equal to 100 cells/mm but less than 200 cells/mmand HIV-1 RNA less than 5,000 cells/mm, and stable status of HIV. Approximately 15% of subjects in the study had cirrhosis. Results are shown in
Treatment response rates are lower in CHC/HIV subjects with poor prognostic factors (including HCV genotype 1, HCV RNA greater than 800,000 IU/mL, and cirrhosis) receiving pegylated interferon alpha therapy. Geographic region is not a prognostic factor for response. However, poor prognostic factors occur more frequently in the US population than in the non-US population.
Of the subjects who did not demonstrate either undetectable HCV RNA or at least a 2 log reduction from baseline in HCV RNA titer by 12 weeks of Pegasys (Peginterferon alfa-2a) and COPEGUS combination therapy, 2% (2/85) achieved an SVR.
In CHC subjects with HIV coinfection who received 48 weeks of Pegasys (Peginterferon alfa-2a) alone or in combination with COPEGUS treatment, mean and median HIV RNA titers did not increase above baseline during treatment or 24 weeks post-treatment.
The safety and effectiveness of Pegasys (Peginterferon alfa-2a) for the treatment of chronic hepatitis B were assessed in controlled clinical trials in HBeAg positive (Study 8) and HBeAg negative (Study 9) subjects with chronic hepatitis B.
Subjects were randomized to Pegasys (Peginterferon alfa-2a) 180 mcg subcutaneous once weekly, Pegasys (Peginterferon alfa-2a) 180 mcg subcutaneous once weekly combined with lamivudine 100 mg once daily by mouth or lamivudine 100 mg once daily by mouth. All subjects received 48 weeks of their assigned therapy followed by 24 weeks of treatment-free follow-up. Assignment to receipt of Pegasys (Peginterferon alfa-2a) or no Pegasys (Peginterferon alfa-2a) was not masked.
All subjects were adults with compensated liver disease, had chronic hepatitis B virus (HBV) infection, and evidence of HBV replication (serum HBV greater than 500,000 copies/mL for Study 8 and greater than 100,000 copies/mL for Study 8) as measured by PCR (COBAS AMPLICOR HBV Assay). All subjects had serum alanine aminotransferase (ALT) between 1 and 10 times the upper limit of normal (ULN) and liver biopsy findings compatible with the diagnosis of chronic hepatitis.
The results observed in the Pegasys (Peginterferon alfa-2a) and lamivudine monotherapy groups are shown in .
Pegasys (Peginterferon alfa-2a) co-administered with lamivudine did not result in any additional sustained response when compared to Pegasys (Peginterferon alfa-2a) monotherapy.
Conclusions regarding comparative efficacy of Pegasys (Peginterferon alfa-2a) and lamivudine treatment based upon the end of follow-up results are limited by the different mechanisms of action of the two compounds. Most treatment effects of lamivudine are unlikely to persist 24 weeks after therapy is withdrawn.
Pegasys (Peginterferon alfa-2a) How Supplied/storage And Handling
Storage and Handling
Store in the refrigerator at 2°C to 8°C (36°F to 46°F). Do not leave Pegasys (Peginterferon alfa-2a) out of the refrigerator for more than 24 hours. Do not freeze or shake. Protect from light. Vials, prefilled syringes and autoinjectors are for single use only. Discard any unused portion remaining in the vial, prefilled syringe.
If home use is prescribed, a puncture-resistant container for the disposal of used needles, syringes and autoinjectors 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, syringes and autoinjectors. The full container should be disposed of according to the directions provided by the physician .
Pegasys (Peginterferon alfa-2a) Patient Counseling Information
Patients should be advised to take their prescribed dose of Pegasys (Peginterferon alfa-2a) 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 (Peginterferon alfa-2a) . Appropriate training for preparation using the vial, prefilled syringe or autoinjector must be given by a healthcare provider, including a careful review of the Pegasys (Peginterferon alfa-2a) Medication Guide and Instructions for Use for the vial, prefilled syringe and autoinjector.
Patients should be instructed to allow the vial, prefilled syringe or autoinjector to come to room temperature and for condensation on the outside of the prefilled syringe or autoinjector to disappear before use. The following instructions should be given:
Patients should be advised not to shake the vial, prefilled syringe or autoinjector 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.
PEGASYS CONVENIENCE PACK 1KIT/BOX