Posology : מינונים

4.2    Posology and method of administration

Treatment should be initiated under supervision of a physician experienced in the management of the disease.

Posology

Titration phase
The dose is titrated individually with a recommended starting dose of 100 micrograms (or 50 micrograms in patients under another cytoreductive therapy). The dose should be gradually increased by 50 micrograms every two weeks (in parallel, other cytoreductive therapy should be decreased gradually, as appropriate) until stabilisation of the haematological parameters is achieved (haematocrit <45%, platelets <400 x 109/L and leukocytes <10 x 109/L). The maximum recommended single dose is 500 micrograms injected every two weeks.

Maintenance phase
The dose at which stabilisation of the haematological parameters is achieved should be maintained in a two-week administration interval for at least 1.5 years. After that, the dose may be adapted and/or the administration interval prolonged up to every four weeks, as appropriate for the patient.

If adverse events develop during therapy, the administered dose should be reduced or treatment discontinued temporarily until adverse events abate; further, treatment should be re-initiated with a lower dose than the dose that caused adverse events.
If an increase of haematological parameters (haematocrit, platelets, leukocytes) is observed, the dose and/or dosing interval needs to be adapted individually.

Special populations

Hepatic impairment
In patients with compensated cirrhosis (i.e. Child-Pugh A), another pegylated interferon alfa medicinal product (pegylated interferon alfa-2a) has been shown to be safe. No ropeginterferon alfa-2b dose adjustment is required for adult patients with mild liver impairment.
The use of interferon alfa has not been evaluated in patients with decompensated cirrhosis (i.e., Child- Pugh B or C) and is contraindicated in these patients (see section 4.3).
Increased liver enzyme levels have been observed in patients treated with ropeginterferon alfa-2b.
When the increase in liver enzyme levels is progressive and persistent, the dose should be reduced. If the increase in liver enzymes is progressive and clinically significant despite dose reduction, or if there is evidence of hepatic decompensation, therapy should be discontinued (see section 4.4).

Renal impairment
The pharmacokinetic profile of other interferon alfa medicinal products (pegylated interferon alfa-2a and pegylated interferon alfa-2b) was evaluated in renal impaired patients (see section 5.2).
No dose adjustment for ropeginterferon alfa-2b is required for adult patients with mild (GFR 60- 89 mL/min) or moderate (GFR 30-59 mL/min) renal impairment. A reduced starting dose for ropeginterferon alfa-2b of 50 micrograms is recommended for patients with severe (GFR 15- 29 mL/min) renal impairment. Ropeginterferon alfa-2b is contraindicated in patients with end stage renal disease (GFR <15 mL/min) (see section 4.3).

Elderly
Adjustments in the recommended dose for ropeginterferon alfa-2b are not necessary when starting therapy in elderly patients (see section 5.2).

Obese or underweighted patients
The pharmacokinetic profile of ropeginterferon alfa-2b has not been determined in obese and underweighted patients. No recommendation on dose adjustment for ropeginterferon alfa-2b can be given for these patients.

Paediatric population
The safety and efficacy of Besremi in children and adolescents has not been established. No data are available (see section 4.4).

Method of administration
For subcutaneous use. The medicinal product is intended for long-term treatment and can be administered by a physician, nurse, family member or patient when trained in the administration of subcutaneous injections with the pre-filled pen. The instructions for use in the package leaflet should be followed.

The recommended injection site is the abdominal skin around but not within 5 cm of the navel or the thigh. Do not inject into an area where the skin is irritated, reddened, bruised, infected, or scarred. The pen can be adjusted to administer doses in 50 microgram intervals in the range of 50 to 250 micrograms or 50 to 500 micrograms.