PEGASYS

In these patients, tolerability to combination therapy and additional prognostic factors such as degree of fibrosis should be taken into account when deciding on treatment duration. Shortening the treatment duration in patients with genotype 1 and high viral load (HVL) (>800 000 IU/mL) at baseline who become HCV RNA negative at week 4 and remain HCV RNA negative at week 24 should be considered with even more caution since the limited data available suggest that this may significantly negatively impact the sustained virologic response.

Patients infected with HCV genotype 2 or 3 who have detectable HCV RNA at week 4, regardless of pre-treatment viral load should receive 24 weeks of therapy. Treatment for only 16 weeks may be considered in selected patients infected with genotype 2 or 3 with LVL (≤ 800 000 IU/mL) at baseline who become HCV negative by week 4 of treatment and remains HCV negative by week 16.

1). In these patients, tolerability to combination therapy and the presence of additional clinical or prognostic factors such as degree of fibrosis should be taken into account when considering deviations from standard 24 weeks treatment duration.

Shortening the treatment duration in patients infected with genotype 2 or 3 with HVL (> 800 000 IU/mL) at baseline who become HCV negative by week 4 should be considered with more caution as this may significantly negatively impact the sustained virological response (SVR) (see Table 1).

Available data for patients infected with genotype 5 or 6 are limited; therefore, combination treatment with 1 000/1 200 mg of ribavirin for 48 weeks is recommended. g. 1 000/1 200 mg/day based on body weight) results in higher SVR rates than does the 800 mg/day, when treatment is shortened to 16 weeks.

The ultimate clinical impact of a shortened initial treatment of 16 weeks instead of 24 weeks is unknown, taking into account the need for […]

Chronic hepatitis C in prior non-responder patients Overall, the safety profile for Pegasys in combination with ribavirin in prior non-responder patients was similar to that in naïve patients. In a clinical trial of non-responder patients to prior pegylated interferon alfa-2b/ribavirin, which exposed patients to either 48 or 72 weeks of treatment, the frequency of withdrawal for adverse events or laboratory abnormalities from Pegasys treatment and ribavirin treatment was 6% and 7%, respectively, in the 48 week arms and 12% and 13%, respectively, in the 72 week arms.

Similarly for patients with cirrhosis or transition to cirrhosis, the frequencies of withdrawal from Pegasys treatment and ribavirin treatment were higher in the 72-week treatment arms (13% and 15%) than in the 48-week arms (6% and 6%).

Patients who withdrew from previous therapy with pegylated interferon alfa- 2b/ribavirin because of haematological toxicity were excluded from enrolling in this trial. In another clinical trial, non-responder patients with advanced fibrosis or cirrhosis (Ishak score of 3 to 6) and baseline platelet counts as low as 50,000 cells/mm3 were treated for 48 weeks.

4). Chronic hepatitis C and HIV co-infection In HIV-HCV co-infected patients, the clinical adverse reaction profiles reported for Pegasys, alone or in combination with ribavirin, were similar to those observed in HCV mono-infected patients.

For HIV-HCV patients receiving Pegasys and ribavirin combination therapy other undesirable effects have been reported in ≥ 1% to ≤ 2% of patients: hyperlactacidaemia/lactic acidosis, influenza, pneumonia, affect lability, apathy, tinnitus, pharyngolaryngeal pain, cheilitis, acquired lipodystrophy and chromaturia.

Pegasys treatment was associated with decreases in absolute CD4+ cell counts within the first 4 weeks without a reduction in CD4+ cell percentage. The decrease in CD4+ cell counts was reversible upon dose reduction or cessation of therapy.

The use of Pegasys had no observable negative impact on the control of HIV viraemia during therapy or follow-up. Limited safety data are available in co-infected patients with CD4+ cell counts <200/μL. Tabulated list of adverse reactions Table 9 summarises the undesirable effects reported with Pegasys monotherapy in CHB or CHC adult patients and with Pegasys in combination with ribavirin in CHC patients.

Undesirable effects reported in clinical studies are grouped according to frequency as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1°000 to < 1/100), rare (≥ 1/10°000 to < 1/1°000), very rare (< 1/10°000).

For spontaneous reports of undesirable effects from post-marketing experience, the frequency is not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in decreasing order of seriousness.

Table 9:

Undesirable effects reported with Pegasys monotherapy or in combination with ribavirin in clinical trials and post marketing Body system Very common Common Uncommon Rare Very rare Frequency not known Infections and infestations Bronchitis, upper respiratory infection, oral candidiasis, herpes simplex, fungal, viral and bacterial infections Pneumonia, skin infection Endocarditis , otitis externa Sepsis Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm Blood and lymphatic system disorders Thrombocyt openia, anaemia, lymphadeno pathy Pancytopeni a Aplastic anaemia Pure red cell aplasia Body system Very common Common Uncommon Rare Very rare Frequency not known Immune […]

If necessary, an inter-disciplinary approach including a mental health care provider or addiction specialist should be considered to evaluate, treat and follow the patient. Patients should be closely monitored during therapy and even after treatment discontinuation.

Early intervention for re-emergence or development of psychiatric disorders and substance use is recommended. 1). 1). It is important to consider the treatment with Pegasys +/- ribavirin induced a growth inhibition during treatment, the reversibility of which is uncertain.

1). Whenever possible the child should be treated after the pubertal growth spurt, in order to reduce the risk of growth inhibition. There are no data on long-term effects on sexual maturation Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Laboratory tests prior to and during therapy Prior to beginning Pegasys therapy, standard haematological and biochemical laboratory tests are recommended for all patients. The following may be considered as baseline values for initiation of treatment: - Platelet count ≥ 90 000 cells/mm3 - ANC ≥ 1 500 cells/mm3 - Adequately controlled thyroid function (TSH and T4) Haematological tests should be repeated after 2 and 4 weeks and biochemical tests should be performed at 4 weeks.

Additional testing should be performed periodically during therapy (including glucose monitoring). 8). Progressive decreases after 8 weeks of therapy were infrequent. 2), reached normal values by 8 weeks in the majority of patients and returned to baseline in all patients after about 16 weeks.

8). 2). The occurrence of anaemia (haemoglobin <10 g/dL) has been observed in up to 15% of CHC patients in clinical trials on the combined treatment of Pegasys with ribavirin. 8). The risk of developing anaemia is higher in the female population.

Caution should be exercised when administering Pegasys in combination with other potentially myelosuppressive agents. Pancytopenia and bone marrow suppression have been reported in the literature to occur within 3 to 7 weeks after the administration of a peginterferon and ribavirin concomitantly with azathioprine.

5). The use of Pegasys and ribavirin combination therapy in CHC […]