PLYZARI

Package leaflet: Information for the patient

Plyzari 6 mg/mL injection solution in a prefilled pen

Liraglutide
Generic medicine
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Plyzari is and what it is used for

What Plyzari is
Plyzari is a medicine used for weight loss that contains the active substance liraglutide. It is similar to a naturally occurring hormone called glucagon-like peptide-1 (GLP-1), which is released from the intestine after a meal. Plyzari acts on receptors in the brain that regulate appetite, producing a feeling of increased satiety and reduced hunger. This may help you eat less food and reduce body weight.

What Plyzari is used for
Plyzari is used for weight loss in addition to diet and exercise in adults aged 18 years and older with:

• a body mass index (BMI) of 30 kg/m² or higher (obesity), or
• a body mass index (BMI) of 27 kg/m² up to below 30 kg/m² (overweight) and weight-related health problems (such as diabetes, high blood pressure, abnormal blood lipid levels, or breathing problems during sleep known as obstructive sleep apnoea).
  BMI is a measure of body weight relative to height.

Continue using Plyzari only if you have lost at least 5% of your body weight after 12 weeks of treatment with a daily dose of 3.0 mg (see section 3). Consult your doctor before continuing.

Plyzari is used for weight loss in addition to a healthy diet and exercise in adolescents aged 12 years and older with:

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

Continue using Plyzari only if you have lost at least 4% of your BMI after 12 weeks of treatment with a daily dose of 3.0 mg or with the maximum tolerated dose (see section 3). Consult your doctor before continuing.

Plyzari is indicated in addition to a healthy diet and exercise for weight management in children aged 6 to <12 years with:

• obesity (diagnosed by a doctor), and
• body weight ≥45 kg.

Continue using Plyzari only if you have lost at least 4% of your BMI after 12 weeks of treatment with a daily dose of 3.0 mg or with the maximum tolerated dose (see section 3). Consult your doctor before continuing.

Diet and exercise
Your doctor will start you on a diet and exercise programme. Continue following this programme while using Plyzari.

2. What you need to know before using Plyzari

Do not use Plyzari

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

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Plyzari.
The use of Plyzari is not recommended if you have severe heart failure.
Experience with the use of this medicine in patients aged 75 years or older is limited. The use of Plyzari is not recommended if you are 75 years of age or older.
Experience with the use of this medicine in patients with kidney problems is limited. If you have kidney disease or are on dialysis, consult your doctor.
Experience with the use of this medicine in patients with liver problems is limited. If you have liver problems, consult your doctor.
The use of this medicine is not recommended if you have severe stomach or intestinal problems, such as delayed stomach emptying (called gastroparesis), or if you have inflammatory bowel disease.
If you know you are scheduled for surgery under anaesthesia (while asleep), inform your doctor that you are taking Plyzari.

Diabetic patients
If you have diabetes, do not use Plyzari as a substitute for insulin.

Pancreatitis (inflammation of the pancreas)
Talk to your doctor if you have or have had pancreatic disease.

Gallbladder inflammation and gallstones
If you lose weight substantially, you are at risk of developing gallstones, which may lead to inflammation of the gallbladder. Stop treatment with Plyzari and contact your doctor immediately if you experience severe pain in the upper part of the abdomen, usually worse on the right side under the ribs. The pain may radiate to your back or right shoulder. See section 4.

Thyroid disease
If you have thyroid disorders, including nodules or enlargement of the thyroid gland, consult your doctor.

Heart rate
Talk to your doctor if you experience palpitations (awareness of your heartbeat) or a sensation of increased heart rate at rest during treatment with Plyzari.

Fluid loss and dehydration
When you start treatment with Plyzari, you may lose body fluids or become dehydrated. This may be due to feeling unwell (nausea), vomiting, or diarrhoea. It is important to prevent dehydration by drinking plenty of fluids. If you have any questions or concerns, talk to your doctor, pharmacist, or nurse. See section 4.

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

Other medicines and Plyzari
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
In particular, talk to your doctor, pharmacist, or nurse if:

• you are taking diabetes medicines called ‘sulfonylureas’ (such as glimepiride or glibenclamide) or if you are taking insulin – your blood sugar level may decrease (hypoglycaemia) when taking these medicines with Plyzari. Your doctor may adjust the dose of your diabetes medicines to prevent low blood sugar levels. See section 4 for signs of low blood sugar. If your insulin dose is adjusted, your doctor will recommend that you monitor your blood glucose levels more frequently.
• you are taking warfarin or other oral medicines to reduce blood clotting (anticoagulants). More frequent blood tests may be needed to monitor your blood’s ability to clot.

Pregnancy and breastfeeding
Do not use Plyzari if you are pregnant, suspect you may be pregnant, or are planning a pregnancy, as it is not known whether Plyzari could affect the unborn baby.
Do not breastfeed while using Plyzari. This is because it is not known whether Plyzari passes into breast milk.

Driving and using machines
It is unlikely that Plyzari will affect your ability to drive or operate machinery. However, some patients may experience dizziness while taking Plyzari, especially during the first 3 months of treatment (see section "Possible side effects"). If you feel dizzy, take special care when driving or using machines. For further information, consult your doctor.

Plyzari contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Plyzari

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your
doctor, pharmacist, or nurse.
Your doctor will start you on a diet and exercise programme. Continue this programme during your
treatment with Plyzari.

Amount to inject
Adults
Treatment will start at a low dose, which will be gradually increased over the first five weeks of
treatment.

• When you first start using Plyzari, the initial dose is 0.6 mg once daily for at least one week.
• Your doctor will instruct you to gradually increase the dose by 0.6 mg, usually every week, until reaching the recommended dose of 3.0 mg once daily. Your doctor will tell you how much Plyzari to use each week. Typically, you will be advised to follow the table below.

Once the recommended dose of 3.0 mg is reached during week 5 of treatment, continue using this
dose for the remainder of the treatment period. Do not increase the dose further.
Your doctor will regularly review your treatment.

Children and adolescents (from 6 to 18 years of age)
For children and adolescents aged 6 to under 18 years, the dose should be increased in a similar manner
as described in the table above for adults. The dose should be increased until reaching 3.0 mg (maintenance
dose) or the maximum tolerated dose. Daily doses higher than 3.0 mg are not recommended.

How and when to use Plyzari

• Before using the pen for the first time, your doctor or nurse will show you how to do it.
• You may use Plyzari at any time of day, with or without food and drinks.
• Use Plyzari approximately at the same time each day; choose a time of day that is convenient for you.

Where to inject
Plyzari is administered by subcutaneous injection (injection under the skin).

• The best areas for self-injection are the waist (abdomen), the front of the thighs, or the upper arms.
• Change the injection site each day to reduce the risk of lumps forming.
• Do not inject the medicine into a vein or muscle.

Injection needles are not included with the pen. For example, BD Ultra-Fine disposable needles or
NovoFine disposable thin needles up to 32 G in thickness and up to 8 mm in length may be used.
Detailed instructions for use are provided on the reverse of this leaflet.

Patients with diabetes
Inform your doctor if you have diabetes. Your doctor may adjust the dose of your diabetes medicines
to prevent low blood sugar levels.

• Do not mix Plyzari with other injectable medicines (e.g. insulins).
• Do not use Plyzari together with other medicines containing GLP-1 receptor agonists (such as exenatide or lixisenatide).

If you use more Plyzari than you should
If you use more Plyzari than you should, contact your doctor immediately or go to hospital. Take
the medicine package with you. You may require medical treatment. The following effects may occur:

• Feeling unwell (nausea)
• Being unwell (vomiting)
• Low blood sugar level (hypoglycaemia). See “Common side effects” for warning signs of low blood sugar.

If you forget to use Plyzari

• If you forget a dose and remember within 12 hours of your usual dosing time, inject the missed dose as soon as you remember.
• However, if more than 12 hours have passed since you should have used Plyzari, skip the missed dose and inject the next dose the following day at your usual time.
• Do not use a double dose or increase the dose the next day to make up for the missed dose.

If you stop using Plyzari
Do not stop treatment with Plyzari without first talking to your doctor.
If you have any questions about how to use this medicine, ask your doctor, pharmacist, or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects
Rarely, some serious allergic reactions (anaphylaxis) have been reported in patients using Plyzari. Seek immediate medical attention if you experience symptoms such as breathing difficulties, swelling of the face and throat, or rapid heartbeat.
Pancreatitis (inflammation of the pancreas) has been reported uncommonly in patients using Plyzari. Pancreatitis is a serious condition that may be life-threatening.
If you experience any of the following serious side effects, stop taking Plyzari and contact your doctor immediately:

• Severe and persistent pain in the abdomen (stomach area), possibly radiating to the back, along with nausea and vomiting, which may be signs of inflammation of the pancreas (pancreatitis).

Other side effects
Very common: affects more than 1 in 10 people

• Feeling unwell (nausea), discomfort (vomiting), diarrhoea, constipation, headache – these usually resolve after a few days or weeks.

Common: affects up to 1 in 10 people

• Stomach and intestinal problems such as indigestion (dyspepsia), inflammation of the stomach lining (gastritis), stomach discomfort, upper abdominal pain, heartburn, abdominal swelling, gas (flatulence), belching, and dry mouth
• Feeling weak or tired
• Altered taste sensation
• Dizziness
• Difficulty sleeping (insomnia). This usually occurs during the first 3 months of treatment
• Gallstones
• Skin rash
• Injection site reactions (such as bruising, pain, irritation, itching, and skin rash)
• Low blood sugar level (hypoglycaemia). Signs of low blood sugar may occur suddenly and may include: cold sweating, cold and pale skin, headache, rapid heartbeat, nausea, feeling very hungry, vision changes, drowsiness, weakness, nervousness, anxiety, confusion, difficulty concentrating, and tremor. Your doctor will advise you on how to manage low blood sugar levels and what to do if you notice these signs
• Increased levels of pancreatic enzymes such as lipase and amylase.

Uncommon: affects up to 1 in 100 people

• Fluid loss (dehydration). This is more likely to occur at the beginning of treatment and may be caused by vomiting, nausea, and diarrhoea
• Delayed stomach emptying
• Inflammation of the gallbladder
• Allergic reactions including skin rash
• General feeling of malaise
• Rapid heartbeat.

Rare: affects up to 1 in 1,000 people

• Reduced kidney function
• Acute kidney failure. Signs may include reduced urine volume, metallic taste in the mouth, and increased tendency to bruise.

Not known: frequency cannot be estimated from the available data

• Intestinal obstruction. A severe form of constipation with additional symptoms such as stomach pain, bloating, vomiting, etc.
• Subcutaneous nodules may be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis; the frequency of this occurrence is not known).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Plyzari

Keep this medicine out of the sight and reach of children.
Do not use Plyzari after the expiry date stated on the pen label and on the carton after
'Exp.'. The expiry date refers to the last day of that month.
Before first use:
Store in a refrigerator (2°C - 8°C). Do not freeze.
After starting to use the pen:
The pen can be stored for 1 month at temperatures below 30°C or in the refrigerator (2°C - 8°C). Do not freeze.
When not in use, keep the pen with the cap on to protect the medicine from light.
Do not use the medicine if the solution is not clear and colourless or almost colourless.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Plyzari contains

• The active substance is liraglutide. 1 mL of injectable solution contains 6 mg of liraglutide. A pre-filled pen contains 18 mg of liraglutide.
• The other excipients are disodium citrate dihydrate, propylene glycol, phenol and water for injections. Additionally, hydrochloric acid and/or sodium hydroxide may have been added to adjust the pH.

Description of the appearance of Plyzari and contents of the pack
Plyzari is supplied as a clear, colourless or almost colourless injectable solution in a pre-filled pen. Each pen contains 3 mL of solution and is capable of delivering doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg and 3.0 mg.
Plyzari is available in packs containing 1, 3 or 5 pens. Not all pack sizes may be marketed.
Needles are not included.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Zentiva Italia S.r.l.
Via P. Paleocapa, 7
20121 Milano
Italy

Manufacturer
Pharmadox
Healthcare Ltd.
KW20A Kordin
Industrial Park,
Paola PLA 3000,
Malta.

This medicinal product is authorised in the European Economic Area countries under the following names:
Austria: Luntin 6 mg/ml Injektionslösung in einem Fertigpen
Sweden, Norway, Germany: Nevolat
Spain: Plyzari 6mg/ml solución inyectable en pluma precargada
Poland, Czech Republic, Italy, Portugal: Plyzari
Netherlands: Nevolat 6 mg/ml oplossing voor injectie in een voorgevulde pen
Hungary: Nevolat 6 mg/ml oldatos injekció előretöltött injekciós tollban
France: LIENDAX 6 mg/mL, solution injectable en stylo prérempli

Instructions for use of Plyzari 6 mg/mL solution for injection in a pre-filled pen Read these instructions carefully before using the Plyzari pre-filled pen. Do not use the pen without having received adequate training from your doctor or nurse. Begin by checking the pen to ensure it contains Plyzari 6 mg/mL, then refer to the illustrations below to learn about the different parts of the pen and the needle. If you are blind or have severe visual impairment, do not use this pen without assistance. Ask for help from a person with good eyesight who has been trained in the use of the Plyzari pre-filled pen. The pen is a pre-filled pen with selectable dose. It contains 18 mg of liraglutide and delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, and 3.0 mg. BD Ultra fine™ or NovoFine® disposable needles are recommended for use with this pen. Needles are not included in the package. Important information Pay special attention to these notes, as they are important for the safe use of the pen.	Pre-filled pen with injectable liraglutide and needle (example)
1 Preparing the pen with a new needle • Check the name and colored label on the pen to ensure it contains Plyzari. This is particularly important if you use more than one type of injectable medicine. Using the wrong medicine may be harmful to your health. • Remove the cap from the pen.
Check that the solution in the pen is clear and colourless. Look through the pen window. If the solution appears cloudy or opalescent, do not use the pen.
Take a new needle and remove the protective seal.

Press the needle straight onto the pen and rotate it until
it is securely fastened.
Remove the outer needle cap and keep it for later use.
You will need it after the injection to safely remove the
needle from the pen.

Remove and discard the inner needle cap.
If you try to reattach it, you could accidentally prick yourself with the needle.
A drop of solution may appear at the tip of the needle. This is normal, but you must still perform a flow check if you are using a new pen for the first time.
Do not attach a new needle to the pen until you are ready to administer the injection.
Always use a new needle for each injection.

This prevents needle blockages, contamination, infection, and incorrect dosing.
Never use a bent or damaged needle.

2 Flow check

• Perform a flow check before giving your first injection with each new pen. If your pen has already been used, go directly to step 3, 'Dose selection'.

• Rotate the dose selector to the symbol until the dose counter shows the flow check symbol.
• Hold the pen with the needle pointing upward. Press and hold the injection button until the dose counter returns to 0. The 0 must align with the dose indicator. A drop of solution should appear at the tip of the needle.

A small drop may remain at the tip of the needle,
but it will not be injected.
If no drop appears, repeat step 2, "Flow check with each new pen," up to six times. If still no drop appears, replace the needle and repeat step 2, "Flow check with each new pen," once more.
If no drop appears, discard the pen and use a new one.
Always make sure a drop appears at the tip of the needle before using a new pen for the first time.

the first time. The presence of the drop ensures the flow of the solution. If the drop does not appear, no medication will be injected, even if the dose counter moves. This situation may indicate a blocked or damaged needle. If you do not check the flow before the first injection with each new pen, you may not receive the prescribed dose and may not achieve the desired effect of Plyzari.
3 Selecting the dose • Rotate the dose selector until the dose counter displays the dose (0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3.0 mg). If you select the wrong dose, you can correct it by rotating the dose selector forward or backward. The maximum dose that can be selected on the pen is 3.0 mg. The dose selector changes the dose. Only the dose counter and the dose indicator show how many mg have been selected for each dose. You may select up to 3.0 mg per dose. When less than 3.0 mg remains in the pen, the dose counter will stop before reaching 3.0. The dose selector will produce a different click when rotated forward, backward, or beyond the remaining mg. Do not count the clicks of the pen. Before injecting the medication, always use the dose counter and dose indicator to verify how many mg have been selected. Do not count the clicks of the pen. Do not use the pen scale, which only approximately indicates how much solution remains in the pen. Only doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3.0 mg should be selected using the dose selector. The selected dose must align precisely with the dose indicator to ensure an accurate dose is delivered.
How much solution is left? • The pen scale shows approximately how much solution remains in the pen. • To see exactly how much solution is left, use the dose counter: rotate the dose selector until the dose counter stops. If it shows 3.0, at least 3.0 mg remains in the pen. If the dose counter stops before reaching 3.0 mg, this means there is not enough solution left for a full 3.0 mg dose. If you need more medication than remains in the pen: Only after receiving specific training or instructions from your doctor or nurse, you may split the dose between the pen currently in use and a new pen. Use a calculator to plan the doses according to your doctor’s or nurse’s instructions. Be very careful to calculate the correct dose. If you are unsure how to split the dose between two pens, select and inject your required dose using a new pen.
4 Injecting the dose • Insert the needle into the skin as shown to you by your doctor or nurse. • Make sure you can see the dose counter. Do not cover it with your fingers, to avoid interrupting the injection.
Press and hold the injection button until the dose counter returns to 0. The 0 must align with the dose indicator. You may hear or feel a click.

Continue to press the injection button
while keeping the needle in the skin until the
dose counter returns to 0 and count
slowly to 6.

• If the needle is removed too early, you may notice a stream of solution leaking from the needle tip. In this case, the full dose will not have been delivered.

Remove the needle from the skin.
If bleeding occurs at the injection site, apply light
pressure. Do not rub the area.
After injection, you may see a drop of solution
on the needle tip. This is normal and
does not affect the administered dose.
Always check the dose counter to know

how many mg you are injecting. Keep pressing the
injection button until the dose counter
displays 0.
How to identify a blocked or damaged needle?

• If a 0 does not appear on the dose counter after continuously pressing the injection button, you may have used a blocked or damaged needle.
• In this case, no medication will have been administered – even if the dose counter has moved from the originally set dose.

How to manage a blocked needle?
Replace the needle as described in step 5 “After
injection” and repeat all steps starting from
step 1 “Preparing the pen with a new
needle”. Make sure to select the full required dose.
Never touch the dose counter during
injection to avoid interrupting the injection.

5 After injection

• Insert the needle tip into the outer cap placed on a flat surface, without touching the needle or the outer needle cap.
• When the needle is covered, press the outer needle cap down completely, carefully.
• Unscrew the needle and dispose of it carefully.

Replace the pen cap on the pen after each use to protect the solution from light. Always dispose of the needle after each injection to ensure comfortable injections and prevent blocked needles. If the needle is blocked, it will not deliver any medication. When the pen is empty, discard it without the attached needle as instructed by your doctor, nurse, pharmacist, or local authorities. Never attempt to re-cover the inner needle cap. You could prick yourself with the needle. Always remove the needle from the pen after each injection. This can prevent needle blockages, contamination, infection, solution leakage, and incorrect dosing.
Other important information • Always keep the pen and needles out of sight and reach of others, especially children. • Never share the pen and needles with other people. • Caregivers must be very careful when handling used needles to prevent needle-stick injuries and cross-infections. • Change the injection site daily to reduce the risk of developing lumps.
Pen maintenance • Do not leave the pen in a car or in other places where it could overheat or become too cold. • Do not inject Plyzari if it has been frozen. Product that has been frozen may not produce the desired effect of the medicine. • Do not expose the pen to dust, dirt, or liquids. • Do not wash, immerse, or lubricate the pen. If necessary, clean it with a neutral detergent on a damp cloth. • Do not drop the pen or hit it against hard surfaces. If the pen is dropped or if you suspect a problem, attach a new needle and check the solution flow before injection. • Do not attempt to refill the pen. When empty, it must be discarded. • Do not attempt to repair or disassemble the pen.