BESREMI Solution for injection Ref.[28013] Active ingredients:

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 × 10⁹/L and leukocytes <10 × 10⁹/L). The maximum recommended single dose is 500 micrograms injected every two weeks. Phlebotomy as rescue treatment to normalise blood hyperviscosity may be necessary.

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.

During the clinical study program, one accidental case of overdose has been reported with ropeginterferon alfa-2b. The patient received a 10-time higher starting dose as recommended and developed flu-like symptoms for three days which were rated as non-serious. The patient recovered completely after paracetamol administration and temporary discontinuation of ropeginterferon alfa-2b therapy.

There is no antidote for the medicinal product available. In case of an overdose, close monitoring of the patient and symptomatic treatment, if necessary, are recommended.

3 years.

After first use:

The pre-filled pen may be stored for a maximum of 30 days in the refrigerator (2°C-8°C) when stored with the pen cap on and kept in the outer carton in order to protect from light. The pre-filled pen may be used up to two times within these 30 days. Any medicine remaining in the pre-filled pen after the second use and/or after 30 days must be discarded.

Store in a refrigerator (2°C-8°C).

Do not freeze.

Keep the pre-filled pen in the outer carton in order to protect from light.

For storage conditions after first opening of the medicinal product, see section 6.3.

The pre-filled pen is made of white polypropylene, with a grey push button and the strength “250 mcg/0.5 mL” highlighted in grey on the label. It delivers doses of 50 μg, 100 μg, 150 μg, 200 μg and 250 μg.

Besremi 250 micrograms/0.5 mL solution for injection in pre-filled pen is contains:

• 1 pre-filled pen and 2 injection needles.

Each pre-filled pen contains a cartridge (type 1 colourless glass) with a grey plunger (bromobutyl rubber) and a flanged cap (aluminium) with a stopper (bromobutyl rubber). The cartridge is sealed in a pen injector. Each cartridge contains 0.5 mL of solution.

Before use, the pre-filled pen should be brought to room temperature (15°C-25°C) for up to 15 minutes.

Since Besremi is a solution, it does not require resuspension before use. Inspect the solution before use. It may only be used if the solution is clear, colourless to pale yellow, with no particles visible.

The pre-filled pen label must always be checked before each injection to avoid medication errors between Besremi 250 micrograms/0.5 mL solution for injection and Besremi 500 micrograms/0.5 mL solution for injection. The 250 micrograms/0.5 mL pre-filled pen has a grey push button. The 500 micrograms/0.5 mL pre-filled pen has a blue push button.

A new, sterile needle as provided with the pre-filled pen must be carefully attached onto the pre-filled pen before each injection. Needles must be discarded immediately after use.

If the pre-filled pen is used for the first time, the pen is prepared for injection by turning the dose knob until the icon of a “drop” in the display window is seen. While holding the pre-filled pen with the needle pointing upwards, tap the pre-filled pen gently with the fingers so that any air bubbles rise towards the needle. Then press the push button until the display window shows “0”. This may be repeated up to six times. Once a droplet of liquid appears at the needle tip, the pre-filled pen and the needle are working properly.

The dose can be set in steps of 50 micrograms by rotating the dose knob. If a certain dose cannot be set, an insufficient quantity of medicinal product may be left in the pen and a new pen must be used.

The needle should be inserted into the skin. The push button should be pressed in completely and held down for at least 10 seconds before removing the needle.

To prevent possible transmission of disease or any kind of contamination, the use of Besremi pre-filled pen should remain strictly for a single patient, even when the needle is changed. The pre-filled pen may not be used more than twice and must be discarded 30 days after the first use, regardless of any medicinal product remaining in the pre-filled pen.

Empty pens must never be reused and must be properly discarded.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.