Byesilor

Package leaflet: Information for the user

Byesilor, 6 mg/ml, solution for injection in a pre-filled pen
Liraglutide
Please read all of this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you personally. Do not give it to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

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

1. What Byesilor is and what it is used for

What Byesilor is
Byesilor is a weight-loss medicine containing the active substance liraglutide. This substance mimics a naturally occurring hormone, glucagon-like peptide-1 (GLP-1), which is released from the intestines after a meal. Byesilor works by acting on receptors in the brain that regulate appetite, causing a feeling of fullness and reducing hunger. This may help reduce the amount of food consumed and lead to weight loss.

What Byesilor is used for
Byesilor is a medicine used to support weight loss, in combination with diet and exercise, in adults aged 18 years and older who have:

• a body mass index (BMI) of 30 kg/m² or higher (obesity), or
• a BMI of 27 kg/m² to less than 30 kg/m² (overweight) and have weight-related medical conditions (such as diabetes, high blood pressure, abnormal blood lipid levels, or sleep apnoea). Body Mass Index (BMI) is a measure of body weight relative to height.

Treatment with Byesilor should only be continued if body weight has decreased by at least 5% after 12 weeks of treatment at a dose of 3.0 mg/day (see section 3). To continue treatment, consult your doctor.

Byesilor may also be used as an adjunct to a healthy diet and increased physical activity for weight management in adolescents aged 12 years and older who have:

• obesity (diagnosed by a doctor)
• body weight above 60 kg

Treatment with Byesilor should only be continued if body mass index has decreased by at least 4% after 12 weeks of treatment at a dose of 3.0 mg/day or at the maximum tolerated dose (see section 3). To continue treatment, consult your doctor.

Diet and exercise
Your doctor will start you on a diet and exercise programme. You must follow these recommendations throughout your treatment with Byesilor.

2. Important information before using Byesilor

When not to use Byesilor

• if the patient is allergic to liraglutide or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Before starting treatment with Byesilor, discuss this with your doctor, pharmacist, or nurse.
The use of Byesilor in patients with severe heart failure is not recommended.
Experience with the use of this medicine in patients aged 75 years and older is limited. Use of this medicine is not recommended in patients aged 75 years and older.
Limited data are available on the use of this medicine in patients with renal impairment.
Patients with impaired kidney function or patients on dialysis should consult their doctor.
Limited data are available on the use of this medicine in patients with hepatic impairment.
Patients with impaired liver function should consult their doctor.
Use of this medicine is not recommended in patients with acute gastritis or enteritis causing delayed gastric emptying (gastroparesis) or with inflammatory bowel disease.
If the patient is to undergo surgery under anaesthesia, they should inform the doctor that they are taking Byesilor.

Diabetes patients
Patients with diabetes should not use Byesilor as a substitute for insulin.

Pancreatitis
If the patient has or has had a disease of the pancreas, they should consult their doctor.

Gallbladder inflammation and gallstones
During significant weight loss, patients are at risk of developing gallstones and, consequently, gallbladder inflammation. Treatment with Byesilor should be discontinued and medical advice sought immediately if sudden pain occurs in the upper part of the abdomen, usually stronger on the right side under the ribs. The pain may radiate to the back or right shoulder. See section 4.

Thyroid disease
In case of thyroid disease, including nodules and goitre, consult your doctor.

Heart rate
If palpitations (awareness of heartbeat) or a sensation of increased heart rate at rest occur during treatment with Byesilor, consult your doctor.

Fluid loss and dehydration
After starting treatment with Byesilor, loss of body fluids or dehydration may occur. This may be caused by nausea, vomiting, and diarrhoea. Patients should drink plenty of fluids to avoid dehydration. If in doubt or if you have any questions, consult your doctor, pharmacist, or nurse. See section 4.

Children and adolescents
The safety and efficacy of liraglutide in children under 12 years of age have not been studied.

Byesilor and other medicines
Tell your doctor, pharmacist, or nurse about all medicines the patient is currently taking, has recently taken, or plans to take.
In particular, inform your doctor, pharmacist, or nurse if:

• the patient is taking antidiabetic medicines of the sulfonylurea class (such as glimepiride or glibenclamide) or insulin – low blood sugar (hypoglycaemia) may occur when Byesilor is used together with these antidiabetic medicines. To prevent low blood sugar, the doctor may adjust the dose of the antidiabetic medicine. See section 4 – warning symptoms of low blood sugar. If insulin dose adjustment is needed, the doctor may recommend more frequent blood sugar monitoring.
• the patient is taking warfarin or other oral medicines that reduce blood clotting (anticoagulants). More frequent blood clotting tests may be necessary.

Pregnancy and breastfeeding
If the patient is pregnant, suspects she may be pregnant, or is planning a pregnancy, she should not use Byesilor. There are no data on the effects of liraglutide on the health of the unborn child.
Breastfeeding should not be undertaken during treatment with Byesilor. There is no information on whether liraglutide passes into human milk.

Driving and using machines
Liraglutide probably has no influence on the ability to drive and use machines.
However, dizziness may occur in some patients treated with liraglutide, mainly during the first 3 months of treatment (see section "Possible side effects"). If dizziness occurs, particular caution should be exercised when driving or operating machinery. For further information, consult your doctor.

Important information about certain ingredients of Byesilor
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. this medicine is considered "sodium-free".

3. How to use Byesilor

This medicine should always be used exactly as prescribed by your doctor. If you have any doubts,
you should consult your doctor, pharmacist, or nurse.
Your doctor will start by recommending a diet and exercise programme. You should follow these
recommendations throughout treatment with Byesilor.

What dose of medicine should be injected
Adults
Treatment starts with a low dose, which should be gradually increased over the first
five weeks of treatment.

• The initial dose of Byesilor is 0.6 mg once daily for at least one week.
• The dose should be gradually increased by 0.6 mg, as directed by your doctor, usually once a week, until the recommended dose of 3.0 mg once daily is reached. Your doctor will advise you on the dose of Byesilor to take in the following weeks of therapy. The usual dosing schedule is shown in the table below.

Week Injected dose
Week 1. 0.6 mg once daily
Week 2. 1.2 mg once daily
Week 3. 1.8 mg once daily
Week 4. 2.4 mg once daily
From week 5 onwards 3.0 mg once daily
After reaching the recommended dose of 3.0 mg in week 5, this dose should be maintained for the remainder of treatment. Do not further increase the dose.
Your doctor will regularly assess your treatment response.

Adolescents (≥ 12 years)
For adolescents aged 12 to 18 years, a similar dose-escalation schedule as for adults should be followed (see table above under Adults).
The dose should be gradually increased until reaching a dose of 3.0 mg (maintenance dose) or until the maximum dose tolerated by the patient is achieved. Daily doses higher than 3.0 mg are not recommended.

How and when to use Byesilor

• Before using the injection pen for the first time, your doctor or nurse will show you how to use it.
• Byesilor can be taken at any time of day, with or without food or drink.
• You should take Byesilor approximately at the same time each day – you may choose the most convenient time for yourself.

Injection site
Byesilor should be injected under the skin (subcutaneous injection).

• The best injection sites are the front of the waist (abdomen), thighs, or upper arms.
• You should change the injection site each day to reduce the risk of developing lumps.
• Do not inject the medicine into a vein or into a muscle.

Detailed instructions for use are provided on the reverse of this leaflet.

Patients with diabetes
If you have diabetes, you should inform your doctor. To prevent low blood sugar levels, your doctor may adjust the dose of your antidiabetic medicines.

• Byesilor must not be mixed with other injectable medicines (e.g. insulin).
• Byesilor should not be used in combination with other medicines that are GLP-1 receptor agonists (such as exenatide or lixisenatide).

Use of a higher than recommended dose of Byesilor
If you use more Byesilor than you should, contact your doctor immediately or go to hospital. Take the medicine packaging with you. You may require treatment. The following symptoms may occur:

• nausea
• vomiting
• low blood sugar (hypoglycaemia). Symptoms indicating low blood sugar – see the section on possible side effects under "Common".

Missed dose of Byesilor

• If less than 12 hours have passed since the scheduled time of administration, take the missed dose as soon as possible.
• However, if more than 12 hours have passed since the time when Byesilor should have been administered, skip the missed dose. Take the next dose the following day as usual.
• Do not take a double dose or increase the dose the next day to make up for a missed dose.

Stopping Byesilor treatment
Do not stop using Byesilor without consulting your doctor.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Serious adverse reactions
Severe allergic reactions (anaphylaxis) have been reported rarely in patients treated with liraglutide.
If symptoms such as difficulty breathing, swelling of the face and throat, or rapid heartbeat occur,
seek medical attention immediately.
Inflammation of the pancreas (pancreatitis) has been reported not infrequently in patients treated
with liraglutide. Pancreatitis may have a severe course, potentially life-threatening.
Treatment with Byesilor should be discontinued and medical advice should be sought immediately if
any of the following serious adverse reactions occur:

• Severe and persistent abdominal pain (in the stomach area) which may radiate to the back, along with nausea and vomiting, as these may be symptoms of pancreatitis.

Other adverse reactions
Very common: may occur in more than 1 in 10 people

• Nausea, vomiting, diarrhoea, constipation, headache – these symptoms usually resolve after a few days or weeks.

Common: may occur in no more than 1 in 10 people

• Gastrointestinal disorders such as indigestion (dyspepsia), inflammation of the stomach lining, gastric discomfort, upper abdominal pain, heartburn, bloating, gas, belching and dry mouth
• Feeling of weakness or fatigue
• Taste disturbances
• Dizziness
• Difficulty sleeping (insomnia). These symptoms usually occur during the first 3 months of treatment.
• Gallstones
• Rash
• Injection site reactions (such as bruising, pain, irritation, itching and rash)
• Low blood sugar (hypoglycaemia). Symptoms of low blood sugar may appear suddenly and may include cold sweats, cold pale skin, headache, palpitations, nausea, intense hunger, blurred vision, drowsiness, weakness, nervousness, restlessness, confusion, difficulty concentrating and tremor. Your doctor will provide information on how to treat symptoms caused by low blood sugar and what to do if symptoms occur.
• Increased levels of pancreatic enzymes such as lipase and amylase.

Uncommon: may occur in no more than 1 in 100 people

• Fluid loss (dehydration). These symptoms are more likely at the beginning of treatment and may be caused by vomiting, nausea and diarrhoea.
• Delayed gastric emptying
• Inflammation of the gallbladder
• Allergic reactions, including skin rash
• General malaise
• Increased heart rate.

Rare: may occur in no more than 1 in 1000 people

• Impaired kidney function
• Acute kidney failure. Symptoms may include reduced urine output, metallic taste in the mouth and easy bruising.

Frequency not known: cannot be estimated from available data

• Bowel obstruction. Severe form of constipation with additional symptoms such as abdominal pain, bloating, vomiting, etc.
  Reporting of adverse reactions
  If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49 21 301, fax: 22 49 21 309, website: https://smz.ezdrowie.gov.pl
  Adverse reactions can also be reported to the marketing authorization holder.
  Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Byesilor

Keep this medicine out of the sight and reach of children.
Do not use Byesilor after the expiry date stated on the label of the syringe and cardboard
container following "EXP". The expiry date refers to the last day of the month indicated.
Before first use:
Store in a refrigerator (2°C - 8°C). Do not freeze. Keep away from the freezer compartment.
After first use of the syringe:
The syringe can be stored for up to one month at temperatures below 30°C or in the
refrigerator (2°C - 8°C). Do not freeze. Keep away from the freezer compartment.
When the syringe is not in use, it should be capped to protect it from light.
Do not use this medicine if the solution is not clear and colourless.
Medicines must not be disposed of via the sewage system or household waste. Ask your
pharmacist how to dispose of medicines no longer required. These measures will help
protect the environment.

6. Contents of the packaging and other information

What the medicine Byesilor contains

• The active substance is liraglutide. 1 ml of injection solution contains 6 mg of liraglutide. One pre-filled semi-automatic injector contains 18 mg of liraglutide.
• The other ingredients are: disodium phosphate dihydrate, propylene glycol, phenol, sodium hydroxide (for pH adjustment), concentrated hydrochloric acid (for pH adjustment), and water for injections.

What Byesilor looks like and contents of the pack
Byesilor is a clear and colourless solution for injection in a pre-filled semi-automatic injector. It is supplied as a cartridge closed with a bromobutyl rubber stopper and a colourless type I glass insert, contained in a pen-type injector with a light blue body, a purple button, and a white dose-dialling knob with a grey cap.
Each injector contains 3 ml of solution, sufficient for 30 doses of 0.6 mg, 15 doses of 1.2 mg, 10 doses of 1.8 mg, 7 doses of 2.4 mg, or 6 doses of 3.0 mg.
Byesilor is available in packs containing 1, 2, 3, 5 or 10 (2x5) pre-filled semi-automatic injectors. Not all pack sizes may be marketed.
The pack does not contain needles.

Marketing Authorisation Holder:
Ranbaxy (Poland) Sp. z o.o.
Idzikowskiego Street 16
00-710 Warsaw
tel. 22 642 07 75

Manufacturer/Importer:
Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132JH Hoofddorp
The Netherlands

This medicine is authorised for marketing in the European Economic Area countries and in the United Kingdom (Northern Ireland) under the following names:
Belgium: Byesilor 6 mg/ml solution for injection in a pre-filled pen
Byesilor 6 mg/ml solution injectable en stylo prérempli
Byesilor 6 mg/ml Injektionslösung im Fertigpen
Germany: Byesilor 6 mg/ml Injektionslösung im Fertigpen
Spain: Byesilor 6 mg/ml solución inyectable en pluma precargada EFG
Italy: Byesilor
Netherlands: Byesilor 6 mg/ml solution for injection in a pre-filled pen
Poland: Byesilor
Before using the injector,
Do not use
with
This injector
Important information

Pre-filled semi-automatic injector with Byesilor and needle (example)
1 Preparing the injector with a new needle Check the name and color of the label on the injector to confirm it contains the medicine Byesilor. This is particularly important when using several types of injectable medicines. Using the wrong medicine may pose a health risk. Remove the injector cap.
Check whether the solution in the injector is clear and colourless. Look through the viewing window of the injector. Do not use the injector if the solution is cloudy.
Take a new needle and peel off the paper tab.
Attach the needle directly onto the injector. Screw it on firmly until securely in place.
Remove the outer needle shield and keep it for later. It will be needed after injection for safe removal of the needle from the injector.
Remove the inner needle shield and dispose of it. Attempting to reattach it may result in accidental needlestick. A small drop of solution may appear at the needle tip. This is normal, but during first use of the injector, flow check should be performed. Do not attach a new needle to the injector until ready to administer the injection. Always use a new needle for each injection. This helps prevent needle blockage, contamination, infection, and inaccurate dosing. Never use a bent or damaged needle.
2 Checking the flow Before first use of each new injector, perform a flow check. If the injector has already been used, proceed to step 3 “Setting the dose”. Turn the dose selector knob to the flow check symbol ( ).
Hold the injector with the needle pointing upwards. Press and hold the dose button until the dose counter returns to 0. The number 0 must align with the dose indicator. A drop of solution should appear at the needle tip. A small drop may remain at the needle tip, but it will not be injected. If no drop appears, repeat step 2 “Checking the flow” up to 6 times. If still no drop appears, replace
the needle and repeat step 2 “Checking the flow” once more. If no drop still appears, discard the injector and use a new one. Before first use of a new injector, always ensure a drop of solution appears at the needle tip. This confirms that the solution flow is not blocked. If no drop appears, the medicine will not be delivered, even though the dose counter may move. This may indicate that the needle is blocked or damaged. Using a new injector without performing the flow check before first injection may result in not receiving the prescribed dose and lack of intended effect of Byesilor.
3 Setting the dose Turn the dose selector knob until the dose counter shows the correct dose (0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3.0 mg). If an incorrect dose is selected, turn the knob forward or backward to correct it. The maximum dose that can be set on the injector is 3.0 mg. The dose selector knob allows dose adjustment. Only the dose counter and dose indicator show how many mg have been selected. Up to 3.0 mg can be set per dose. If the injector contains less than 3.0 mg of medicine, the dose counter will stop before reaching 3.0. The clicking sound of the dose selector knob differs when turning forward and backward and when exceeding the remaining mg of medicine. Do not count the clicks of the injector. Always verify the selected mg dose using the dose counter and dose indicator before injection. Do not count clicks. Do not use the injector scale. This scale only shows an approximate amount of solution remaining in the injector. Use the dose selector knob only to select doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3.0 mg. The selected dose must be exactly aligned with the dose indicator to ensure correct dosing. Do not align the dose indicator with “mg”.	Warning: Turning the dose selector knob forward causes it to extend automatically, as shown in the illustration, which is a normal phenomenon.
How much solution remains? The scale on the injector shows an approximate amount of solution remaining in the injector. To accurately check how much solution remains, use the dose counter: turn the dose selector knob until the dose counter stops.
If 3.0 is visible, at least 3.0 mg of medicine remains in the injector. If the dose counter stops before 3.0 mg, this means the injector does not contain enough solution to deliver a full 3.0 mg dose. If more medicine is needed than remains in the current injector The dose may be divided between the current and a new injector only if trained by a doctor or nurse. Use a calculator to determine doses according to instructions provided by the doctor or nurse. Calculations must be performed very carefully. If in doubt about how to divide the dose between two injectors, select and inject the required dose using a new injector.
4 Administering the dose Insert the needle under the skin as instructed by your doctor or nurse. Ensure the dose counter is visible. Do not cover it with fingers, as this may interrupt the injection.
Press and hold the dose button until the dose counter shows 0. The number 0 must align with the dose indicator. You may hear or feel a click.	B
Keep the needle in the skin after the dose counter returns to 0 and slowly count to 6. If the needle is removed too early, you may see the solution leaking from the needle tip. This means the full dose was not delivered.
Remove the needle from the skin. If bleeding occurs at the injection site, gently press it. Do not rub the area. After injection, a drop of solution may appear at the needle tip. This is normal and does not affect the delivered dose. Always observe the dose counter to monitor the number of mg delivered. Hold the dose button pressed until the dose counter shows 0. How to check if the needle is blocked or damaged? If 0 does not appear on the dose counter despite continuous
pressure on the dose button, the needle may be blocked or damaged. In such a case – no medicine was delivered – even if the dose counter moved and shows a different dose than initially set. What to do if the needle becomes blocked? Replace the needle as described in step 5 “After injection” and repeat all steps starting from step 1 “Preparing the injector with a new needle”. Ensure the full required dose is selected. Do not touch the dose counter during injection, as this may interrupt the injection.
5 After injection Place the needle tip into the outer needle shield on a flat surface, without touching the needle or the outer needle shield.
After inserting the needle, carefully push the outer needle shield fully onto the needle. Unscrew the needle and dispose of it carefully according to instructions provided by your doctor, nurse, pharmacist or local authorities.
After each use, replace the cap on the injector to protect the solution from light. Always remove the needle after each injection to ensure comfortable future injections and prevent needle blockage. If the needle is blocked, the medicine will not be delivered. When the injector is empty, dispose of it without the needle attached, according to instructions from your doctor, nurse, pharmacist or local authorities. Never attempt to reattach the inner shield to the needle. This may result in accidental needlestick. Always remove the needle from the injector after each injection. This helps prevent needle blockage, contamination, infection, solution leakage and inaccurate dosing.
Other important information The injector and needles must always be stored out of sight and reach of others, especially children. Never share your injector or needles with other people. Caregivers must exercise particular caution when removing and disposing of used needles – to eliminate the risk of needlestick injury and cross-infection.

Caring for the injection device

• Do not leave the injection device in a car or any other place where it may be exposed to excessively high or low temperatures.
• Do not inject Byesilor if it has been frozen. In such a case, the intended effect of the medicine may not be achieved.
• Do not expose the injection device to dust, dirt, or liquids.
• Do not wash, soak, or lubricate the injection device. The device may be cleaned with a cloth moistened with a mild detergent.
• Do not drop the injection device or strike it against hard surfaces. If the injection device has been dropped or if malfunction is suspected, always attach a new needle and check the solution flow before administering the injection.
• Do not refill the injection device. After it is empty, it should be discarded.
• Do not attempt to repair or disassemble the injection device.