Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Besremi 250 micrograms/0.5 mL solution for injection in pre-filled pen
⚠ This medicine appears to have been discontinued
The electronic medicines compendium (emc) no longer publishes a Summary of Product Characteristics for this product, which usually means it is no longer marketed in the UK. The patient leaflet below is kept for reference, but the product may not be available.
If you were prescribed this medicine, other products containing Ropeginterferon alfa-2b may still be available. Do not stop your treatment — ask your pharmacist or GP what to use instead.
What it is and what it is used for
for Besremi contains the active substance ropeginterferon alfa-2b, which belongs to the class of medicines called interferons. Interferons are produced by your immune system to block the growth of cancer cells. Besremi is used as monotherapy for the treatment of polycythaemia vera in adults. Polycythaemia vera is a type of cancer in which the bone marrow produces too many red blood cells, white blood cells and platelets (cells that help the blood to clot).
What you need to know before you take it
e Besremi Do not use Besremi if you are allergic to ropeginterferon alfa-2b or any of the other ingredients of this medicine (listed in section 6). if you have thyroid disease that is not controlled with medicines. if you have or had severe mental disorders (such as depression or suicidal thoughts or if you tried to kill yourself). if you have recently had severe heart problems (such as heart attack or stroke). if you have or had an autoimmune disease (such as rheumatoid arthritis, psoriasis or inflammatory bowel disease). if you had an organ transplantation and you take medicines which suppress your immune system. if you take telbivudine (a medicine used to treat hepatitis B infection). if you have advanced, uncontrolled liver disease. if you have severe kidney disease (with your kidneys working at less than 15% of their normal ability). Warnings and precautions Talk to your doctor before using Besremi: 1
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if you have thyroid disease. if you have diabetes or high blood pressure − your doctor may ask you to have an eye examination. if you have liver problems − you will have blood tests regularly to check how your liver is working if you are on a long-term Besremi therapy. if you have kidney problems. if you have psoriasis or other skin problems because they may get worse during treatment with Besremi.
Once you have started Besremi treatment, talk to your doctor: if you develop symptoms of depression (such as feelings of sadness, dejection, and suicidal thoughts). if you develop signs of a severe allergic reaction (such as difficulty in breathing, wheezing or hives) while using Besremi – if this is the case you will need to seek medical help immediately. if you develop symptoms of a cold or other respiratory infection (such as difficulty in breathing, cough, fever and chest pain). if you have changes in your vision − you must tell your doctor and have an immediate eye examination. Severe eye problems may occur during Besremi therapy. Your doctor will usually check your vision before starting your treatment. If you have health problems which may lead to eye problems such as diabetes or high blood pressure, you doctor should check your vision also during treatment. If your vision worsens, your doctor may decide to discontinue your treatment. Dental and gum disorders, which may lead to loss of teeth, can occur with interferon medicines. In addition, dry mouth could damage teeth and the lining of the mouth during long-term treatment with Besremi. You should brush your teeth thoroughly twice daily and have regular dental checks. It will need a certain time to reach your individual optimal dose of Besremi. Your doctor will decide if it is necessary to treat you with another medicine for an early reduction of your blood cell number to prevent blood clots and bleeding. Children and adolescents Do not give this medicine to children and adolescents because no information is available on the use of Besremi in this age group. Other medicines and Besremi Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. Do not use Besremi if you are taking telbivudine (for treating hepatitis B) since the combination of these medicines increases the risk of peripheral neuropathy (numbness, tingling, or burning sensations in the arms and legs). Tell your doctor if you are being treated with telbivudine. Tell your doctor especially if you are taking any of the following medicines: theophylline (a medicine used to treat respiratory diseases such as asthma) methadone (a medicine used to treat pain or opioid dependence) vortioxetine or risperidone (medicines used to treat mental disorders) anti-cancer medicines such as those stopping or slowing the growth of blood-forming cells in the bone marrow (e.g. hydroxycarbamide) medicines that work on the central nervous system to relieve pain, help you sleep, or have a calming effect (e.g. morphine, midazolam) Pregnancy, breast-feeding and fertility If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine. Pregnancy 2
The effect of Besremi during pregnancy is not known. The use of Besremi is not recommended during pregnancy. If you are a woman of childbearing potential, your doctor will discuss with you if effective birth control should be used during your treatment with Besremi. Breast-feeding It is not known if Besremi is present in breast milk. Your doctor will help you decide if you have to stop breast-feeding when you are using this medicine. Driving and using machines Do not drive or use machines if you feel dizzy, sleepy or confused while using Besremi. Besremi contains benzyl alcohol This medicine contains 5 mg benzyl alcohol in each 0.5 mL. Benzyl alcohol may cause allergic reactions. Ask your doctor or pharmacist for advice: if you are pregnant or breast-feeding. if you have a liver or kidney disease. This is because large amounts of benzyl alcohol can build-up in your body and may cause side effects (called "metabolic acidosis"). Besremi contains polysorbate 80 This medicine contains 0.025 mg of polysorbate 80 in each 0.5 mL. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergies. Besremi contains sodium This medicine contains less than 1 mmol sodium (23 mg) per mL, that is to say essentially 'sodiumfree'.
How to take it
Besremi Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. The dose will be set individually for you by your doctor for your condition. The usual starting dose of Besremi is 100 micrograms every 2 weeks. Your doctor will then increase your dose stepwise and may adjust your dose during treatment. Your doctor will reduce your starting dose to 50 micrograms if you have severe kidney problems. This medicine is for subcutaneous use which means that it is injected in the tissue under your skin. It should not be injected into an area of the body where the skin is irritated, reddened, bruised, infected, or scarred. If you are injecting this medicine yourself, you will get clear instructions on how to prepare and inject it. To prevent passing on infectious diseases, you should never share Besremi pre-filled pen with anyone else, even when the needle is changed. Details on how to prepare and inject Besremi are given in the Instructions for Use. Read them before you start using Besremi. If you use more Besremi than you should Tell your doctor as soon as possible.
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If you forget to use Besremi You should inject the dose as soon as you remember. However, if more than 2 days have passed since you missed the dose, leave out the dose and inject the next dose when it is due. Do not inject a double dose to make up for a forgotten dose. Check with your doctor or pharmacist if you are not sure. If you stop using Besremi Do not stop using Besremi before you have talked to your doctor. If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 4. Possible side effects Like all medicines, this medicine can cause side effects, although not everybody gets them. Contact your doctor immediately if you notice any of the following serious side effects during your treatment with Besremi: Common side effects (may affect up to 1 in 10 people): changes in your heartbeat (when the heart beats very fast and uneven) Uncommon side effects (may affect up to 1 in 100 people): attempted suicide, thoughts about killing yourself loss of vision which may be caused by bleeding in the retina (the retina is the light-sensitive layer in the eye), or by build-up of fat in or under the retina Rare side effects (may affect up to 1 in 1,000 people): loss of vision which may be caused by damage to the retina (such as obstruction of the blood vessels in the eye) or the optic nerve Very rare side effects (may affect up to 1 in 10,000 people): blindness breathing problems including shortness of breath, cough and chest pain which may be caused by lung infiltration, pneumonia (lung infection), pulmonary arterial hypertension (high blood pressure in the blood vessels bringing blood from the heart to the lungs) and pulmonary fibrosis (a lung disease where scars are formed in the lung tissue) Side effects with frequency not known (cannot be estimated from the available data): detachment of the retina (you may experience eye problems including changes in vision) Other side effects Very common side effects (may affect more than 1 in 10 people): decrease in the number of a type of white blood cells (called leucocytes) and in blood clotting cells (called platelets) joint or muscle pain flu-like symptoms, feeling tired in blood tests: increase of an enzyme called gamma-glutamyltransferase Common side effects (may affect up to 1 in 10 people): infection of the respiratory tract, runny or stuffy nose, fungal infections, flu decrease in the number or size of red blood cells increase or decrease in the thyroid gland activity, increase of thyroid stimulating hormone, inflammation of the thyroid gland increase of triglycerides (a type of lipid) in the blood, decreased appetite 4
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aggressive behaviour, feeling depressed, feeling anxious, problems with falling asleep or staying asleep, mood changes, lacking bodily energy or motivation headache, feeling dizzy, reduced sense of touch or sensation, feeling sleepy, sensation of tingling and 'pins and needles' dry eyes damage of the capillaries (very small blood vessels) in the body breathing problems diarrhoea, nausea, abdominal pain or stomach discomfort, constipation, dry mouth liver disorder, increase in certain liver enzymes (shown in blood tests) itching, hair loss, rash, redness of skin, psoriasis, dry and scaly skin, acne, thickening of the outer layer of the skin, increased sweating a disorder called Sjogren's syndrome where the body's immune system attacks glands that produce fluid (such as the tear and saliva glands), arthritis, pain in arms and legs, bone pain, painful sudden tightening of a muscle fever, weakness, chills, general health problems, irritation or redness at the site of injection, decreasing body weight in blood tests: antibodies which are produced by the body ́s immune system, increase of an enzyme called lactate dehydrogenase
Uncommon side effects (may affect up to 1 in 100 people): infection and re-infection with herpes, bacterial infections increase in the number of platelets autoimmune disorder of the thyroid gland, sarcoidosis (areas of inflamed tissue in different parts of the body) diabetes panic attack, hallucination (seeing, hearing or feeling things that are not there), feeling stressed, feeling nervous, lack of interest in activities, nightmare, irritability, confusion damage to the nervous system, migraine, mental disorder (health condition involving changes in thinking, emotion or behaviour), visual or sensory disturbances, shaky hands eye discomfort, eyelid eczema hearing loss, ringing in ears (tinnitus), spinning feeling (vertigo) heart disorders such as heart block (a disorder in the heart ́s electrical activity), blood clots in the blood vessels of the heart, leakage of the aortic valve high blood pressure, reduced blood supply to certain parts of the body, haematoma (collection of blood under the skin), flushing inflammation of lung tissue, coughing, nosebleed, sore throat inflammation of the stomach, abdominal wall disorder, intestinal gas, indigestion, painful swallowing, bleeding gums inflammation of the liver, damage to the liver, enlarged liver sensitivity to sunlight, peeling of the skin, nail disorder muscle weakness, neck pain, groin pain inflammation of the bladder, painful urination, increased need to urinate, inability to urinate sexual problems pain or itching at the site of injection, sensitivity to weather change non-acute porphyria (a liver disorder in which substances called porphyrins build up in the skin causing local skin damage, such as rashes, blisters, sores or discomfort, upon sun exposure) in blood tests: increase of uric acid, antibodies produced by the body ́s immune system against red blood cells Rare side effects (may affect up to 1 in 1,000 people): bipolar disorders (mood disorders with episodes of sadness and excitement), mania (extreme excitement or unreasonable enthusiasm) cardiomyopathy (diseases that affect the heart muscle), angina pectoris (a severe chest pain as a result of blockage of the heart vessels) liver failure 5
Very rare side effects (may affect up to 1 in 10,000 people): idiopathic or thrombotic thrombocytopenic purpura (increased bruising, bleeding, decreased platelets, anaemia and extreme weakness) myocardial ischemia (reduced blood flow to your heart muscle)
Possible side effects
with frequency not known (cannot be estimated from the available data): Vogt-Koyanagi-Harada disease (a rare disease that can lead to loss of vision, hearing and skin pigmentation), severe allergic reaction discolouration of the skin periodontal (affecting gums) and dental disorders, change in colour of the tongue Reporting of side effects If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.
How to store it
Besremi Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the label and the outer carton after "EXP". The expiry date refers to the last day of that month. 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. Once opened, 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. Do not use this medicine if you notice that the pre-filled pen appears damaged, the solution is cloudy, has particles or flakes, or has any colour other than colourless to slightly yellow. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
Contents of the pack and other information
What Besremi contains The active substance is ropeginterferon alfa-2b. Each pre-filled pen of 0.5 mL solution contains 250 micrograms of ropeginterferon alfa-2b as measured on a protein basis, corresponding to 500 micrograms/mL. The other ingredients are sodium chloride, polysorbate 80, benzyl alcohol, anhydrous sodium acetate, glacial acetic acid, and water for injections. For benzyl alcohol, polysorbate 80 and sodium, see section 2 "Besremi contains benzyl alcohol", "Besremi contains polysorbate 80" and "Besremi contains sodium". What Besremi looks like and contents of the pack Besremi is presented as a solution for injection (injection) in a pre-filled pen. Each pre-filled pen contains 0.5 mL of solution. It is available in packs containing: 1 pre-filled pen and 2 injection needles (Type: mylife AutoProtect PRO 29G × 8mm)
- 3 pre-filled pens and 6 injection needles (Type: mylife AutoProtect PRO 29G × 8 mm). 6
Marketing Authorisation Holder and Manufacturer AOP Orphan Pharmaceuticals GmbH Leopold-Ungar-Platz 2 1190 Vienna Austria This leaflet was last revised in May 2026.
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Instructions for Use Please read this leaflet carefully before using the Besremi 250 micrograms pre-filled pen. If you have any further questions, ask your doctor or pharmacist. Your doctor or pharmacist will show you how to use the pen. The Besremi 250 micrograms pre-filled pen can be used to inject doses within the range of 50 to 250 micrograms in 5 microgram increments. The same pen can be used twice, as long as the sum of the two doses does not exceed 250 micrograms.Your doctor will tell you the dose you need. Please note down your injection dates and dose as instructed by your doctor. If you need a dose of more than 250 micrograms, you require two Besremi 250 microgram pre-filled pens. You must use a different injection site for each of the two pens. Your doctor or pharmacist will explain to you how to use the two pens. Store the pen in the outer carton in the refrigerator. Remove the pen from the refrigerator 15 minutes before the injection to let it reach room temperature. Find a quiet and well-lit area for the injection. You will need the following supplies for your injection:
- Besremi pre-filled pen
- Needle (Type: mylife AutoProtect PRO 29G × 8 mm)
- Alcohol wipe (not supplied)
- Optional: adhesive plaster (not supplied) The Besremi pre-filled pen comes with two or six needles (depending on the pack-size). Always use a new needle for each injection. Do not use the pen if it appears damaged. If at any time during the use of the pen, you feel you may have damaged it (e. g. by dropping it or using excessive force), do not continue to use the pen. Get a new pen and start over. Description Besremi 250 micrograms pre-filled pen
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Wash your hands before using Besremi. Check that the product has not expired. Remove the cap from the pen.
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Check the solution through the inspection windows along the sides of the cartridge holder. Do not use the pen if the solution is cloudy, has particles or flakes, or is any colour other than colourless to slightly yellow.
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Take a new needle and remove the protective foil. Place the pen straight and centrally arranged onto the needle to prevent it from buckling or bending. Make sure that it is firmly attached.
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Screw the needle onto the pen by turning the pen clockwise with gentle pressure until it stops.
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Remove the outer needle cap from the needle. Do not put the outer needle cap back on the needle until you have injected the medicine. Do not touch the needle tip at any time. If you have used your Besremi 250 micrograms prefilled pen once before and are using it a second time, continue directly with step 7. If you are using this pen for the first time, continue with preparation of the pen in step 5.
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If you are using this pen for the first time, prepare the pen for injection by turning the dose knob until you see the icon of a "drop" and the dot in the dosing window. The icon of a "drop" must be aligned with the dot in the dosing window.
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Hold the pen with the needle pointing upwards and make sure the dosing window is facing you. Do not point towards your face or anyone else's face. Tap the pen (cartridge holder) gently with your fingers to allow any air bubbles to rise to the top of the cartridge holder. Press the push button with your thumb until the "0" mark is aligned with the dot in the dosing window. You will see the window changes between the "drop" icon and the "0" mark, and you will hear gentle clicks when the button moves. If you look through the small gap at the top of the orange needle protective sleeve, you should see a droplet of liquid appearing at the needle tip. If you do not see a droplet at the needle tip, repeat steps 5 and 6 up to six times until a droplet appears. If you do not see the droplet after the seventh time, ask your doctor or pharmacist for advice. Between each 10-microgram mark, a dot without a number represents the intermediate 5-microgram dose. Set the dose your doctor advised by turning the dose knob until the prescribed dose is visible. The selected dose must align with the dot in the dosing window. If necessary, correct the dose by turning the dose knob up and down. If you are unable to reach the required dose setting by turning the dose knob, your pen may be out of sufficient medicine. Do not use any further force. Instead, get a new pen. Disinfect your skin in the injection area using an alcohol swab before the injection. Let the area dry before you inject the medicine. You must inject the medicine subcutaneously (under the skin). Your doctor will tell you where you must inject it. Possible injection sites are the belly (more than five centimetres away from the belly button) or the thigh. If you need two pens, use a different injection site for each pen (e. g. right and left side of belly or right and left thigh). Do not inject into irritated, reddened, bruised, infected or scarred skin in any way.
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Hold the pen so that the dosing window and the label are visible during the injection. Raise a fold of skin between the thumb and forefinger. Insert the needle at a 90 degrees angle until the orange protective sleeve on the needle is no longer visible.
Press the push button all the way down until the "0" mark is aligned with the dot in the dosing window. The soft clicking sounds will stop when the injection is complete. Continue pressing the push button while keeping the needle in your skin. Count slowly to 10. Do not lift or move the pen during injection. If the needle is removed earlier, you may see a stream of solution coming from the needle tip. If so, the full dose will not be delivered.
Carefully remove the needle from the skin by pulling straight upwards. Keep the injection site clean until the small injection wound has closed. Apply an adhesive plaster if needed.
Note:
- The orange protective sleeve locks automatically and the now visible red locking indicator covers the needle for your protection. If this is not the case, please ask your doctor or pharmacist.
- After removing the needle, a small droplet of liquid may remain on your skin. This droplet is normal and does not mean that you underdosed.
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Rotate the pen counterclockwise and dispose of the needle properly.
Note:
- Once the needle has been unscrewed, another red locking indicator covers the bottom of the needle for additional safety.
Note: Put the cap back on the pen securely. Reuse of the pen:
- Your doctor will tell you if you may use the pen for a second injection. In this case, put the pen back into the outer carton and store it in the refrigerator for the next use. Do not use the pen after 30 days. Disposal of the pen and needle:
- Discard the pen and needle after use according to local regulations or as instructed by your doctor or pharmacist.
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Frequently asked questions about Besremi 250 micrograms/0.5 mL solution for injection in pre-filled pen
How do I take Besremi 250 micrograms/0.5 mL solution for injection in pre-filled pen?
Besremi 250 micrograms/0.5 mL solution for injection in pre-filled pen comes as injection containing 250mcg / 0.5ml. Always follow the dose your doctor or pharmacist has given you, and read the leaflet that comes with the medicine.
What is the active substance in Besremi 250 micrograms/0.5 mL solution for injection in pre-filled pen?
The active substance in Besremi 250 micrograms/0.5 mL solution for injection in pre-filled pen is ropeginterferon alfa-2b.
Where does this information come from?
This leaflet reproduces the patient information leaflet approved for Besremi 250 micrograms/0.5 mL solution for injection in pre-filled pen, as published on the electronic medicines compendium (emc). The version printed inside your medicine’s packaging is the one that applies to you.
Can I get Besremi 250 micrograms/0.5 mL solution for injection in pre-filled pen without a prescription?
Whether a medicine is available over the counter or on prescription only depends on its licence. Check the leaflet, or ask your pharmacist — they can tell you straight away.
About this leaflet
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
- Source: electronic medicines compendium (emc), Datapharm
- Active substance: ropeginterferon alfa-2b
- Official document: view the original leaflet on emc →
⚕For healthcare professionals — Summary of Product Characteristics (SmPC)Full SmPC: dosage, interactions, contraindications, warnings+
4.1. Therapeutic indications
Besremi is indicated as monotherapy in adults for the treatment of polycythaemia vera without symptomatic splenomegaly.
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 × 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).
Race
No dose adjustment is necessary based on race (see section 5.2).
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 allows for adjustable dosing increments in the range of 50 to 250 micrograms or 50 to 500 micrograms.
4.3. Contraindications
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
• Pre-existing thyroid disease unless it can be controlled with conventional treatment
• Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation or suicide attempt
• Severe pre-existing cardiovascular disease, (i.e. uncontrolled hypertension, congestive heart failure (≥ NYHA class 2), serious cardiac arrhythmia, significant coronary artery stenosis, unstable angina) or recent stroke or myocardial infarction
• History or presence of autoimmune disease
• Immunosuppressed transplant recipients
• Combination with telbivudine (see section 4.5)
• Decompensated cirrhosis of the liver (Child-Pugh B or C)
• End stage renal disease (GFR < 15 mL/min)
4.4. Special warnings and precautions for use
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.
Dose titration phase
The recommended posology for the titration phase of ropeginterferon alfa-2b (see section 4.2) results in a prolonged time to reach the individual optimal dose compared to hydroxycarbamide. In a clinical study in polycythaemia vera, the end of the mean individual titration phase for ropeginterferon alfa-2b was reached after approximately 3.7 months, for hydroxycarbamide after approximately 2.6 months of treatment. Thus, other products (e.g. hydroxycarbamide) may be preferred in patients for whom an early reduction in elevated blood counts is necessary to prevent thrombosis and bleeding.
During the titration phase the efficacy to reduce the cardiovascular and thromboembolic risk of the underlying disease may not be fully established. Patients should be closely monitored, particularly during the titration phase; complete blood counts including determination of haematocrit level, leukocyte and platelet counts should be performed regularly also after the individual optimal dose has been established. Phlebotomy as rescue treatment to normalise blood hyperviscosity may be necessary.
Endocrine system
Before ropeginterferon alfa-2b therapy, any pre-existing thyroid disease needs to be treated and controlled with conventional therapy (see section 4.3). Patients who develop symptoms indicative of a thyroid dysfunction during ropeginterferon alfa-2b therapy, should evaluate their thyroid stimulating hormone (TSH) levels. If TSH levels can be controlled within the normal range, the therapy can be continued.
Diabetes mellitus have been observed with other interferon alfa medicinal products (see section 4.8). Patients with this condition who cannot be effectively controlled by medicinal products should not begin ropeginterferon alfa-2b therapy. Patients who develop this condition during treatment and cannot be controlled by medicinal products should discontinue ropeginterferon alfa-2b therapy.
Central nervous system (CNS)
CNS effects, particularly depression, have been observed in some patients treated with ropeginterferon alfa-2b during the clinical development program (see section 4.8). Other CNS effects, including suicidal ideation, attempted suicide, aggression, bipolar disorder, mania and confusion have been observed with other interferon alfa medicinal products. Patients should be closely monitored for any symptoms of psychiatric disorders and therapeutic management should be considered by the treating physician if such symptoms emerge. If psychiatric symptoms worsen, it is recommended to discontinue ropeginterferon alfa-2b therapy. Ropeginterferon alfa-2b must not be administered in patients with existence of or history of severe psychiatric disorders, particularly severe depression, suicidal ideation or suicide attempt (see section 4.3).
Cardiovascular system
Cardiac events including cardiomyopathy, myocardial infarction, atrial fibrillation and ischaemic coronary artery disorders have been associated with interferon alfa treatment (see section 4.8). Patients with pre-existing or a history of cardiovascular disorders should be closely monitored during ropeginterferon alfa-2b therapy. This medicinal product is contraindicated in patients with severe pre-existing cardiovascular disease or patients who had recently suffered from a stroke or myocardial infarction (see section 4.3).
Respiratory system
Respiratory disorders such as lung infiltration, pneumonitis, pneumonia or pulmonary arterial hypertension have been observed rarely in patients treated with interferon alfa (see section 4.8). Patients who develop respiratory symptoms should be monitored closely and if necessary, ropeginterferon alfa-2b therapy should be discontinued.
Visual system
Severe eye disorders such as retinopathy, retinal haemorrhage, retinal exudates, retinal detachment and retinal artery or vein occlusion which may result in blindness have been observed rarely in patients treated with interferon alfa (see section 4.8). Patients should have eye examinations before and during ropeginterferon alfa-2b therapy, specifically in those patients with retinopathy associated disease such as diabetes mellitus or hypertension. Any patient reporting a decrease or loss of vision or reporting other eye symptoms should have an immediate eye examination. Discontinuation of ropeginterferon alfa-2b should be considered in patients who develop new or worsening eye disorders.
Acute hypersensitivity
Serious, acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) have been rarely observed with other interferon alfa medicinal products. If this occurs, ropeginterferon alfa-2b therapy must be discontinued and appropriate medical therapy instituted immediately. Transient rashes do not necessitate interruption of treatment.
Liver function
Interferon alfa therapy has been associated with hepatotoxicity characterized by potentially significant increases in liver enzymes. Hepatic failure in hepatitis C virus infected patients was reported with other interferon alfa medicinal products (see section 4.8).
Increases in ALT (≥3 times the upper limit of normal), AST (≥3 times the upper limit of normal), GGT (≥3 times the upper limit of normal) and bilirubin (>2 times the upper limit of normal) levels have been observed in patients treated with ropeginterferon alfa-2b. These elevations were mostly transient and occurred during the first treatment year.
Liver disorders have been reported in patients after long-term ropeginterferon alfa-2b therapy (see section 4.8). Liver enzymes and hepatic function should be regularly controlled in patients with long-term ropeginterferon alfa-2b therapy. Treatment with ropeginterferon alfa-2b should be discontinued when, despite dose reduction, the increase in liver enzyme levels is progressive and clinically significant. In patients who develop evidence of hepatic decompensation during treatment, ropeginterferon alfa-2b should be discontinued. Ropeginterferon alfa-2b is contraindicated in patients with decompensated cirrhosis of the liver (see section 4.3).
Renal function
Regardless of the starting dose or degree of renal impairment, patients should be monitored. If renal function decreases during treatment, ropeginterferon alfa-2b therapy should be discontinued. Ropeginterferon alfa-2b is contraindicated in patients with end stage renal disease (see section 4.3).
Dental and periodontal disorders
Dental and periodontal disorders, which may lead to loss of teeth, have been reported with other interferon alfa medicinal products (see section 4.8). In addition, dry mouth could have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with ropeginterferon alfa-2b. Patients should brush their teeth thoroughly twice daily and have regular dental examinations.
Skin disorders
The use of ropeginterferon alfa-2b is associated with skin disorders (pruritus, alopecia, rash, erythema, psoriasis, xeroderma, dermatitis acneiform, hyperkeratosis, hyperhydrosis). In case of appearance or worsening of this skin disorders, the stop of the treatment must be envisaged.
Excipients
Besremi contains benzyl alcohol.
High volumes should be used with caution and only if necessary, especially in subjects with liver or kidney impairment because of the risk of accumulation and toxicity (metabolic acidosis).
Besremi contains polysorbate 80.
This medicinal product contains 0.025 mg of polysorbate 80 in each 0.5 mL. Polysorbates may cause allergic reactions.
Besremi contains less than 1 mmol sodium (23 mg) per mL, that is to say essentially 'sodium-free'.
4.5. Interaction with other medicinal products and other forms of interaction
Enzymes of the protein catabolism are considered to be involved in the metabolism of ropeginterferon alfa-2b. The involvement of transport proteins in absorption, distribution and elimination of ropeginterferon alfa-2b is not known. Interferon alfa has shown to influence the activity of cytochrome P450 (CYP) isozymes CYP1A2 and CYP2D6.
No interaction studies have been performed with ropeginterferon alfa-2b.
Interaction studies of other pegylated interferon alfa medicinal products
Co-administration of pegylated interferon alfa-2a with telbivudine in patients with hepatitis B increased the risk of developing peripheral neuropathy. A combination therapy with telbivudine and ropeginterferon alfa-2b is contraindicated (see section 4.3).
Administration of 180 micrograms of pegylated interferon alfa-2a once weekly for 4 weeks in healthy male subjects did not show any effect on mephenytoin, dapsone, debrisoquine and tolbutamide pharmacokinetics profiles, suggesting that pegylated interferon alfa-2a has no effect on in vivo metabolic activity of cytochrome P450 (CYP) 3A4, 2C9, 2C19 and 2D6 isozymes. In the same study, a 25% increase in the AUC of theophylline (CYP1A2 substrate) was observed, demonstrating that pegylated interferon alfa-2a is an inhibitor of CYP1A2 activity.
Co-administration of pegylated interferon alfa-2b showed no significant interaction with tolbutamide (CYP2C9 substrate), midazolam (CYP3A4 substrate), dapsone (N-acetyltransferase substrate) and modestly increased the exposure of caffeine (CYP1A2 substrate) and desipramine (CYP2D6 substrate).
Therefore, care should be taken when ropeginterferon alfa-2b is co-administered with CYP1A2 substrates notably those having a narrow therapeutic margin such as theophylline or methadone. Likewise, caution is recommended with CYP2D6 substrates (e.g. vortioxetine, risperidone) combined with ropeginterferon alfa-2b. Ropeginterferon alfa-2b may inhibit the activity of CYP1A2 and CYP2D6 and thus may increase the blood concentrations of these medicinal products.
No dose adaptions for ropeginterferon alfa-2b should be necessary when concomitantly administered with medicinal products metabolised via CYP2C9/19, CYP3A4 or by N-acetyltransferase.
Caution must be exercised when administering ropeginterferon alfa-2b in combination with other potentially myelosuppressive/chemotherapeutic agents.
Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with ropeginterferon alfa-2b.
4.6. Fertility, pregnancy and lactation
Women of childbearing potential/Contraception in females
Women of childbearing potential must use effective contraception during the treatment with ropeginterferon alfa-2b, unless otherwise discussed with the physician.
Pregnancy
There are no or limited amount of data from the use of interferon alfa in pregnant women.
Studies in animals have shown reproductive toxicity (see section 5.3).
As ropeginterferon alfa-2b may have the same effect, Besremi is not recommended during pregnancy and in women of childbearing potential not using contraception.
Breast-feeding
It is not known whether ropeginterferon alfa-2b is excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Besremi therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.
Fertility
There are no data on the effect of ropeginterferon alfa-2b therapy on the fertility of females or males.
4.7. Effects on ability to drive and use machines
Besremi has minor influence on the ability to drive and use machines. Patients who experience dizziness, somnolence or hallucination (see section 4.8) during Besremi therapy should avoid driving or using machines.
4.8. Undesirable effects
Summary of the safety profile
The most common adverse reactions are leukopenia (20.2%), thrombocytopenia (18.5%), arthralgia (13.5%), fatigue (12.4%), increased gamma-glutamyltransferase (11.2%), influenza-like illness (11.2%), myalgia (10.7%), anaemia (9.6%), increased alanine aminotransferase (8.4%), neutropenia (7.9%), pyrexia (7.9%), increased aspartate aminotransferase (7.3%), pruritus (6.8%), pain in extremity (6.7%), alopecia (6.7%), headache (6.2%), diarrhoea (5.7%), injection site reaction (5.6%), chills (5.1%), and dizziness (5.1%).
Serious adverse reactions are depression (1.1%), atrial fibrillation (1.1%) and acute stress disorder (0.6%).
Tabulated list of adverse reactions
Following treatment-related adverse reactions were reported with ropeginterferon alfa-2b in clinical studies in 178 polycythaemia vera adult patients. Adverse reactions are listed by system organ class and frequency (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) or not known (cannot be estimated from available data).
System organ class
Frequency
Adverse reaction
Infections and infestations
common
respiratory tract infection, influenza, rhinitis, fungal skin infection
uncommon
oral herpes, herpes zoster, oral candidiasis, sinusitis, oesophageal candidiasis, vulvovaginal mycotic infection, hordeolum, onychomycosis
Blood and lymphatic system disorders
very common
leukopenia, thrombocytopenia
common
pancytopenia, neutropenia, anaemia
Immune system disorders
uncommon
sarcoidosis
very rare
idiopathic or thrombotic thrombocytopenic purpura#
not known
Vogt-Koyanagi-Harada disease#, acute hypersensitivity reactions#**
Endocrine disorders
common
hypothyroidism, hyperthyroidism, thyroiditis
uncommon
Basedow's disease, diabetes mellitus#
Metabolism and nutrition disorders
common
hypertriglyceridaemia, decreased appetite
Psychiatric disorders
common
depression, aggression#, insomnia, anxiety, mood altered, mood swings, mood disorders
uncommon
suicide attempt#, suicidal ideation#, confusional state#, acute stress disorder, hallucination, emotional distress, nervousness, nightmare, irritability
rare
bipolar disorder#, mania#
Nervous system disorders
common
headache, dizziness, hypoesthesia, somnolence, paraesthesia
uncommon
polyneuropathy, peripheral motor neuropathy, radiculopathy, migraine, mental impairment, tremor, aura
Eye disorders
common
dry eye
uncommon
retinal haemorrhage#, retinal exudates#, visual impairment, visual acuity reduced, vision blurred, ocular discomfort, eczema eyelids
rare
retinopathy#, optic neuropathy#, retinal artery occlusion#, retinal vein occlusion#,
very rare
blindness#
not known
retinal detachment#
Ear and labyrinth disorders
uncommon
deafness, tinnitus, vertigo
Cardiac disorders
common
atrial fibrillation
uncommon
myocardial infarction#, atrioventricular block, intracardiac thrombus, aortic valve incompetence, cardiovascular disorder
rare
cardiomyopathy#, angina pectoris#
very rare
myocardial ischemia#
Vascular disorders
common
microangiopathy
uncommon
Raynaud's phenomenon, hypertension, haematoma, flushing
Respiratory, thoracic and mediastinal disorders
common
dyspnoea
uncommon
pneumonitis, cough, epistaxis, throat irritation
very rare
lung infiltration#
not known
pulmonary fibrosis#, pneumonia#, pulmonary arterial hypertension#*
Gastrointestinal disorders
common
diarrhoea, nausea, abdominal pain, constipation, abdominal distension, dry mouth
uncommon
gastritis, abdominal wall disorder, flatulence, frequent bowel movements, odynophagia, gingival bleeding
not known
tooth disorder#, periodontal disease#
Hepatobiliary disorders
very common
gamma-glutamyltransferase increased
common
liver disorder, alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased
uncommon
hepatotoxicity, hepatitis toxic, hepatomegaly, porphyria non-acute
rare
hepatic failure#
Skin and subcutaneous tissue disorders
common
pruritus, alopecia, rash, erythema, psoriasis, xeroderma, dermatitis acneiform, hyperkeratosis, hyperhidrosis, dry skin
uncommon
photosensitivity reaction, skin exfoliation, nail dystrophy
not known
skin depigmentation#
Musculoskeletal and connective tissue disorders
very common
arthralgia, myalgia
common
Sjogren's syndrome, arthritis, pain in extremity, musculoskeletal pain, bone pain, muscle spasms
uncommon
muscular weakness, neck pain, groin pain
Renal and urinary disorders
uncommon
cystitis haemorrhagic, dysuria, micturition urgency, urinary retention
Reproductive system and breast disorders
uncommon
erectile dysfunction, haematospermia
General disorders and administration site conditions
very common
Influenza-like illness, fatigue
common
pyrexia, injection site reaction, asthenia, chills, general physical health deterioration, injection site erythema
uncommon
injection site pain, injection site pruritus, sensitivity to weather change
not known:
tongue hyperpigmentation#
Investigations
common
antithyroid antibody positive, blood thyroid stimulating hormone increased, body temperature increased, antinuclear antibody positive, blood lactate dehydrogenase increased, weight decreased
uncommon
platelet count increased, blood uric acid increased, Coombs test positive
#Reported as adverse reactions during treatment with other interferon alfa medicinal products.
*Class label for interferon medicinal products, see below pulmonary arterial hypertension.
**e.g. urticaria, angioedema, bronchoconstriction or anaphylaxis.
Description of selected adverse reactions
Most common adverse reactions
The most common adverse reactions (including number of patients, incidence rate, severity grade, necessity for dose adaptation and outcome) reported during the ropeginterferon alfa-2b clinical development program are summarised in Table 1.
Table 1. Most common adverse reactions during ropeginterferon alfa-2b treatment.
ADR
>10% PT
N (%)
N = 178
IR
CTCAE intensity grade ≥3
N (%)
Dose reduced
N (%)
Medicinal Product interrupted
N (%)
Medicinal Product discontinued
N (%)
Recovered
N (%)
Leukopenia
36 (20.2)
21.2
3 (8.3)
24 (66.7)
7 (19.4)
n.r.
35 (97.2)
Thrombo-cytopenia
33 (18.5)
11.2
4 (12.1)
13 (39.4)
3 (9.1)
1 (3.0)
30 (90.9)
Arthralgia
24 (13.5)
5.2
1 (4.2)
5 (20.8)
5 (20.8)
1 (4.2)
22 (91.7)
Fatigue
22 (12.4)
6.6
n.r.
4 (18.2)
1 (4.5)
1 (4.5)
21 (95.5)
Gamma-glutamyl-transferase increased
20 (11.2)
7.9
7 (35.0)
9 (45.0)
5 (25.0)
n.r.
17 (85.0)
Influenza like illness
20 (11.2)
4.9
n.r.
4 (20.0)
3 (15.0)
n.r.
19 (95.0)
Myalgia
19 (10.7)
3.5
n.r.
6 (31.6)
1 (5.3)
n.r.
17 (89.5)
No CTCAE grade 5 (death) adverse reactions reported for these preferred terms; 1 AE grade 4 (life-threating or disabling) reported for Gamma-glutamyltransferase increased. Abbreviations: CTCAE, common terminology criteria for adverse events; n.r., not reported; ADR, adverse drug reaction; PT, preferred term; IR, incidence rate of mean adverse events per 100 patients per year; n, number of patients.
N (%) number and percentage of patients with given AE
Gastrointestinal disorders
Gastrointestinal disorders have been reported with other interferon alfa medicinal products and have been reported in 15.7% of patients with ropeginterferon alfa-2b treatment. The most common gastrointestinal disorders reported in these studies were diarrhoea (5.1%; incidence rate: 2.8 [events/100 patients per year]) and nausea (4.5%; incidence rate: 1.2 events/100 patients per year]).
CNS
In the clinical development program of ropeginterferon alfa-2b, two cases of serious depression (1.1%; incidence rate: 0.4 events/100 patients per year) occurred. The patients recovered completely after permanent medicinal product discontinuation. One patient who experienced serious acute stress disorder (0.6%; incidence rate: 0.2 events/100 patients per year) with moderate intensity recovered completely after the dose of ropeginterferon alfa-2b was reduced. CNS effects including suicide attempt, suicidal ideation, aggression, bipolar disorder, mania and confusion have been reported with interferon alfa (see section 4.4).
Cardiovascular system
During ropeginterferon alfa-2b therapy, three cases of atrial fibrillation (1.1%; incidence rate: 0.3 events/100 patients per year) with intensity grade 1 to 3 occurred in two patients. Ropeginterferon alfa-2b treatment was continued, and the patients received appropriate medicinal products to treat these events. Patients recovered from the two events; one event was ongoing at the time of assessment.
Respiratory system
Cases of pulmonary arterial hypertension (PAH) have been reported with interferon alfa, notably in patients with risk factors for PAH (such as portal hypertension, HIV infection, cirrhosis). Events were reported at various time points typically several months after starting treatment with interferon alfa.
Visual system
Serious eye disorders have been reported with interferon alfa such as retinopathy, retinal haemorrhage, retinal exudates, retinal detachment and retinal artery or vein occlusion (see section 4.4).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme Website: www.mhra. gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9. Overdose
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.
🇷🇴 Known in Romania as
Medicines sold in Romania with the same active substance: Cunoscut în România ca
- BESREMI 250 mcg/0,5 ml prescriptionROPEGINTERFERON ALFA-2B · injection / infusion
Same active substance. The strength, the form and whether you need a prescription can differ. Always ask a pharmacist before you switch. Romanian medicines in the UK →
🇵🇱 Known in Poland as
Medicines sold in Poland with the same active substance: W Polsce znany jako
- BesremiRopeginterferonum alfa-2b · injection / infusion
Same active substance. The strength, the form and whether you need a prescription can differ. Always ask a pharmacist before you switch. Polish medicines in the UK →
💬 Ask about this leaflet
Ask anything about Besremi 250 micrograms/0.5 mL solution for injection in pre-filled pen. The assistant answers only from this leaflet — if the leaflet does not cover it, it will say so. It does not give medical advice.
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