• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Besremi is and what it is used for
2. What you need to know before you use Besremi
3. How to use Besremi
4. Possible side effects
5. How to store Besremi
6. Contents of the pack and other information

• 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).

Talk to your doctor before using Besremi:

• 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.

Do not give this medicine to children and adolescents because no information is available on the use of Besremi in this age group.

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)

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

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.

Do not drive or use machines if you feel dizzy, sleepy or confused while using Besremi.

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”).

This medicine contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially ‘sodium-free’.

Tell your doctor as soon as possible.

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.

Do not stop using Besremi before you have talked to your doctor.

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)

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
• 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

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)

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

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 Cart Scheme Website: www.mhra.goc.uk/yellowcard or seachr for MHRA Yellow Cart in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

• 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 and sodium, see section 2 “Besremi contains benzyl alcohol” and “Besremi contains sodium”.

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 Clickfine 8mm)