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Treatment should be initiated only by a physician experienced in the treatment of patients with hepatitis B or C.
Please refer also to the ribavirin Summary of Product Characteristics (SPC) when Pegasys is to be used in combination with ribavirin.
Dose to be administered and duration of treatment
Chronic hepatitis B:
The recommended dosage and duration of Pegasys for both HBeAg-positive and HBeAg-negative chronic hepatitis B is 180 micrograms once weekly for 48 weeks by subcutaneous administration in the abdomen or thigh.
Chronic hepatitis C – treatment-naïve patients:
The recommended dose for Pegasys is 180 micrograms once weekly by subcutaneous administration in the abdomen or thigh given in combination with oral ribavirin or as monotherapy.
The dose of ribavirin to be used in combination with Pegasys s given in Table 1.
The ribavirin dose should be administered with food.
Duration of treatment
The duration of combination therapy with ribavirin for chronic hepatitis C depends on viral genotype. Patients infected with HCV genotype 1 who have detectable HCV RNA at week 4 regardless of pre-treatment viral load should receive 48 weeks of therapy.
Treatment for 24 weeks may be considered in patients infected with
- genotype 1 with low viral load (LVL) ( 800,000 IU/mL) at baseline or
- genotype 4
who become HCV RNA negative at week 4 and remain HCV RNA negative at week 24. However, an overall 24 weeks treatment duration may be associated with a higher risk of relapse than a 48 weeks treatment duration (see section 5.1). 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. Overall 16 weeks of treatment may be associated with a lower chance of response and is associated with a higher risk of relapse than a 24 week treatment duration (see section 5.1). 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 (see Table 1).
Available data for patients infected with genotype 5 or 6 are limited; therefore combination treatment with 1000/1200 mg of ribavirin for 48 weeks is recommended.
Table 1: Dosing Recommendations for Combination therapy for HCV Patients
|
Genotype
|
Pegasys Dose
|
Ribavirin Dose
|
Duration
|
|
Genotype 1 LVL with RVR*
|
180 micrograms
|
<75 kg = 1000 mg
 75 kg = 1200 mg
|
24 weeks or
48 weeks
|
|
Genotype 1 HVL with RVR*
|
180 micrograms
|
<75 kg = 1000 mg
75 kg = 1200 mg
|
48 weeks
|
|
Genotype 4 with RVR*
|
180 micrograms
|
<75 kg = 1000 mg
75 kg = 1200 mg
|
24 weeks or
48 weeks
|
|
Genotype 1 or 4 without RVR*
|
180 micrograms
|
<75 kg = 1000 mg
75 kg = 1200 mg
|
48 weeks
|
|
Genotype 2 or 3 without RVR**
|
180 micrograms
|
800 mg
|
24 weeks
|
|
Genotype 2 or 3 LVL with RVR**
|
180 micrograms
|
800 mg(a)
|
16 weeks(a) or 24 weeks
|
|
Genotype 2 or 3 HVL with RVR**
|
180 micrograms
|
800 mg
|
24 weeks
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*RVR = rapid viral response (HCV RNA undetectable) at week 4 and HCV RNA undetectable at week 24;
**RVR = rapid viral response (HCV RNA negative) by week 4
LVL= 800,000 IU/mL; HVL= > 800,000 IU/mL
(a) It is presently not clear whether a higher dose of ribavirin (e.g.1000/1200 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 retreating non-responding and relapsing patients.
The recommended duration of Pegasys monotherapy is 48 weeks.
Chronic hepatitis C – treatment-experienced patients:
The recommended dose of Pegasys in combination with ribavirin is 180 mcg once weekly by subcutaneous administration. For patients <75 kg and 75 kg, 1000 mg daily and 1200 mg daily of ribavirin,respectively, and regardless of genotype, should be administered.
Patients who have detectable virus at week 12 should stop therapy. The recommended total duration of therapy is 48 weeks. If patients infected with virus genotype 1, not responding to prior treatment with PEG-IFN and ribavirin are considered for treatment, the recommended total duration of therapy is 72 weeks (see section 5.1).
HIV-HCV co-infection
The recommended dosage for Pegasys, alone or in combination with ribavirin, is 180 micrograms once weekly subcutaneously for 48 weeks. For patients infected with HCV genotype 1 <75 kg and 75 kg, 1000 mg daily and 1200 mg daily of ribavirin,respectively, should be administered. Patients infected with HCV genotypes other than genotype 1 should receive 800 mg daily of ribavirin. A duration of therapy less than 48 weeks has not been adequately studied.
Predictability of response and non-response – treatment-naïve patients
Early virological response by week 12, defined as a 2 log viral load decrease or undetectable levels of HCV RNA has been shown to be predictive for sustained response (see Tables 2 and 6).
Table 2: Predictive Value of Week 12 Virological Response at the Recommended Dosing Regimen while on Pegasys Combination Therapy
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Genotype
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Negative
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Positive
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|
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No response by week 12
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No sustained response
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Predictive Value
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Response by week 12
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Sustained response
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Predictive Value
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|
Genotype 1
(N= 569)
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102
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97
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95%
(97/102)
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467
|
271
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58%
(271/467)
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|
Genotype 2 and 3
(N=96)
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3
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3
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100%
(3/3)
|
93
|
81
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87%
(81/93)
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The negative predictive value for sustained response in patients treated with Pegasys in monotherapy was 98%.
A similar negative predictive value has been observed in HIV-HCV co-infected patients treated with Pegasys monotherapy or in combination with ribavirin (100% (130/130) or 98% (83/85), respectively). Positive predictive values of 45% (50/110) and 70% (59/84) were observed for genotype 1 and genotype 2/3 HIV-HCV co-infected patients receiving combination therapy.
Predictability of response and non-response – treatment-experienced patients
In non-responder patients re-treated for 48 or 72 weeks, viral suppression at week 12 (undetectable HCV RNA defined as <50 IU/mL) has been shown to be predictive for sustained virological response. The probabilities of not achieving a sustained virological response with 48 or 72 weeks of treatment if viral suppression was not achieved at week 12 were 96% (363 of 380) and 96% (324 of 339), respectively. The probabilities of achieving a sustained virological response with 48 or 72 weeks of treatment if viral suppression was achieved at week 12 were 35% (20 of 57) and 57% (57 of 100), respectively.
Dose adjustment for adverse reactions
General
Where dose adjustment is required for moderate to severe adverse reactions (clinical and/or laboratory) initial dose reduction to 135 micrograms is generally adequate. However, in some cases, dose reduction to 90 micrograms or 45 micrograms is necessary. Dose increases to or towards the original dose may be considered when the adverse reaction abates (see section 4.4 for use and section 4.8).
Haematological (see also Table3)
Dose reduction is recommended if the neutrophil count is < 750/mm3. For patients with Absolute Neutrophil Count (ANC) < 500/mm3 treatment should be suspended until ANC values return to > 1000/mm3. Therapy should initially be re-instituted at 90 micrograms Pegasys and the neutrophil count monitored.
Dose reduction to 90 micrograms is recommended if the platelet count is < 50,000/mm3. Cessation of therapy is recommended when platelet count decreases to levels < 25,000/mm3.
Specific recommendations for management of treatment-emergent anaemia are as follows: ribavirin should be reduced to 600 milligrams/day (200 milligrams in the morning and 400 milligrams in the evening) if either of the following apply: (1) a patient without significant cardiovascular disease experiences a fall in haemoglobin to < 10 g/dl and ![]()
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