Chronic hepatitis C (CHC) genotype 1

Peginterferon alpha-2b should be administered as a once weekly subcutaneous injection. The dose administered in adults depends on whether it is used in combination therapy (bitherapy or tritherapy) or as monotherapy.

Peginterferon alpha-2b combination therapy (bitherapy or tritherapy)

Bitherapy (peginterferon alpha-2b with ribavirin): applies to all adult and paediatric patients 3 years of age and older.

Tritherapy (peginterferon alpha-2b with ribavirin and boceprevir): applies to adult patients with genotype 1 CHC.

Adults – Dose to be administered

Peginterferon alpha-2b 1.5 micrograms/kg/week in combination with ribavirin capsules.

The intended dose of 1.5 μg/kg of peginterferon alpha-2b to be used in combination with ribavirin may be delivered in weight categories with the peginterferon alpha-2b strengths according to Table 1. Ribavirin capsules are to be administered orally each day in two divided doses with food (morning and evening).

Table 1. Dosing for combination therapy*:

^a 2 morning, 2 evening
^b 2 morning, 3 evening
^c 3 morning, 3 evening
^d 3 morning, 4 evening
* Refer to the SmPC of boceprevir for details about the dose of boceprevir to be administered in tritherapy.

Adults – Duration of treatment – Naïve patients

Tritherapy: Refer to the SmPC for boceprevir.

Bitherapy: Predictability of sustained virological response – Patients infected with virus genotype 1 who fail to achieve undetectable HCV-RNA or demonstrate adequate virological response at week 4 or 12 are highly unlikely to become sustained virological responders and should be evaluated for discontinuation.

• Genotype 1:
  • Patients who have undetectable HCV-RNA at treatment week 12, treatment should be continued for another nine month period (i.e., a total of 48 weeks).
  • Patients with detectable but ≥2 log decrease in HCV-RNA level from baseline at treatment week 12 should be reassessed at treatment week 24 and, if HCV-RNA is undetectable, they should continue with full course of therapy (i.e. a total of 48 weeks). However, if HCV-RNA is still detectable at treatment week 24, discontinuation of therapy should be considered.
  • In the subset of patients with genotype 1 infection and low viral load (<600,000 IU/ml) who become HCV-RNA negative at treatment week 4 and remain HCV-RNA negative at week 24, the treatment could either be stopped after this 24 week treatment course or pursued for an additional 24 weeks (i.e. overall 48 weeks treatment duration). However, an overall 24 weeks treatment duration may be associated with a higher risk of relapse than a 48 weeks treatment duration.
• Genotypes 2 or 3: It is recommended that all patients be treated with bitherapy for 24 weeks, except for HCV/HIV co-infected patients who should receive 48 weeks of treatment.
• Genotype 4: In general, patients infected with genotype 4 are considered harder to treat and limited study data (n=66) indicate they are compatible with a duration of treatment with bitherapy as for genotype 1.

Duration of treatment

For patients who exhibit virological response at week 12, treatment should be continued for at least another three-month period (i.e., a total of six months). The decision to extend therapy to one year of treatment should be based on prognostic factors (e.g., genotype, age >40 years, male gender, bridging fibrosis).

Dose modification for all patients (monotherapy and combination therapy)

If severe adverse reactions or laboratory abnormalities develop during treatment with peginterferon alpha-2b monotherapy or combination therapy, the dosages of peginterferon alpha-2b and/or ribavirin must be modified as appropriate, until the adverse reactions abate. Dose reduction of boceprevir is not recommended. Boceprevir must not be administered in the absence of peginterferon alpha-2b and ribavirin. As adherence might be of importance for outcome of therapy, the dose of peginterferon alpha-2b and ribavirin should be kept as close as possible to the recommended standard dose.
Guidelines were developed in clinical trials for dose modification.