HETRONIFLY 10 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

HETRONIFLY 10 mg/ml concentrate for solution for infusion

serplulimab

This medicinal product is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. The last section of this leaflet includes information on how to report side effects.

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.
• It is important that you carry the patient card with you during treatment.
• If you have any further questions, ask your doctor.
• If you get any side effects, talk to your doctor, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Hetronifly and what is it used for

Hetronifly is a cancer medicine that contains the active substance serplulimab. It is a monoclonal antibody, a type of protein designed to recognize and attack a specific target in the body called programmed death receptor 1 (PD-1), which is found on the surface of T and B lymphocytes (types of white blood cells that are part of the immune system, the body's natural defense). When PD-1 is activated by cancer cells, it can inhibit the activity of T lymphocytes. By blocking PD-1, Hetronifly prevents the inhibition of your T lymphocytes, which helps your immune system fight cancer.

Hetronifly is used to treat adult patients with a type of lung cancer called extensive-stage small cell lung cancer (ES-SCLC). It is used when the cancer:

• has spread inside the lungs (or to other parts of the body) and
• has not been previously treated.

If you have any questions about how Hetronifly works or why it has been prescribed for you, ask your doctor or pharmacist.

Hetronifly will be given in combination with chemotherapy. It is also important that you read the package leaflets of the specific chemotherapy you will be receiving. If you have any questions about these medicines, please ask your doctor.

2. What you need to know before you use Hetronifly

Do not use Hetronifly

If you are allergic to serplulimab or any of the other ingredients of this medicine.

If you are not sure if you are allergic, talk to your doctor or nurse before using Hetronifly.

Warnings and precautions

Talk to your doctor before starting treatment with Hetronifly if you have:

• an autoimmune disease (a disease in which the immune system attacks its own cells)
• liver problems
• kidney damage
• lung problems or breathing difficulties
• have had an organ transplant
• have had an allergic reaction to other cancer medicines that work in the same way (treatments with monoclonal antibodies)

If any of the above applies to you (or you are not sure), talk to your doctor before using Hetronifly.

When you are given Hetronifly, you may have some serious side effects (see section 4).

If you experience any of the following conditions, call or talk to your doctor immediately. Your doctor may give you other medicines that prevent more serious complications and help reduce your symptoms. Your doctor may stop the next dose of Hetronifly or interrupt your treatment with Hetronifly.

Tell your doctor immediatelyif you notice any of the following symptoms:

• lung inflammation: symptoms may include new or worsening cough, shortness of breath, or chest pain
• liver or bile duct inflammation: symptoms may include nausea or vomiting, decreased appetite, pain in the right side of the stomach, yellowing of the skin or whites of the eyes, numbness, dark urine, or bleeding or bruising more easily than usual
• intestinal inflammation: symptoms may include diarrhea or more frequent bowel movements than usual, or black, tarry, or sticky stools with blood or mucus, severe stomach pain, or pain when touched
• kidney inflammation: symptoms may include a decrease in the amount of urine you pass
• skin inflammation: symptoms may include rash, itching, blisters on the skin, or ulcers in the mouth or on other moist surfaces
• gland inflammation (especially of the thyroid, adrenal, pituitary, and pancreas): symptoms may include rapid heartbeat, extreme fatigue, weight gain or loss, dizziness or loss of consciousness, hair loss, feeling cold, constipation, persistent headache or unusual headaches, abdominal pain, nausea, and vomiting
• type 1 diabetes: symptoms may include high blood sugar, increased appetite or thirst, urinating more often than usual, rapid and deep breathing, confusion, or a sweet smell of breath, a sweet or metallic taste in the mouth, or a different smell of urine or sweat
• infusion-related reactions: symptoms may include chills or shaking, itching or rash, redness, shortness of breath or wheezing, dizziness, or fever
• heart muscle inflammation: symptoms may include chest pain, shortness of breath, or irregular heartbeat
• muscle problems: symptoms may include muscle pain, or muscle weakness or rapid fatigue
• brain inflammation (encephalitis): symptoms may include seizures, headache, fever, chills, vomiting, confusion, and memory problems
• eye inflammation, which may include changes in vision
• low platelet count: symptoms may include bleeding (nosebleeds or gum bleeding) and/or bruising

Children and adolescents

Hetronifly is not recommended for people under 18 years of age. This is because there is no information available on how it works in this age group.

Other medicines and Hetronifly

Tell your doctor if you are using, have recently used, or might use any other medicines. This includes herbal medicines and medicines that do not require a prescription.

Tell your doctor if you are taking any medicine that suppresses your immune system, such as corticosteroids like prednisone. These medicines may interfere with how Hetronifly works. However, once you are being treated with Hetronifly, your doctor may give you corticosteroids to reduce any possible side effects of Hetronifly.

Corticosteroids may also be given to you before you receive Hetronifly in combination with chemotherapy to prevent and/or treat nausea, vomiting, and other side effects caused by chemotherapy.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, ask your doctor for advice before using this medicine.

Pregnancy

Do not use Hetronifly if you are pregnant, unless your doctor specifically recommends it. Hetronifly may harm your fetus.

Breastfeeding

It is not known if serplulimab passes into breast milk. You and your doctor will decide if you should breastfeed after receiving serplulimab.

Driving and using machines

Hetronifly may cause fatigue and other reactions. Do not drive or use machines after receiving Hetronifly unless you are sure you are well.

Hetronifly contains sodium

This medicine contains 22.5 mg of sodium (main component of cooking/table salt) in each 10 ml vial. This is equivalent to 1.1% of the maximum recommended daily intake of sodium for an adult.

3. How to use Hetronifly

You will receive treatment with Hetronifly in a hospital or clinic, under the supervision of an experienced doctor.

The recommended dose is 4.5 mg per kilogram of body weight every 3 weeks.

Your doctor will give you Hetronifly as an infusion (drip) into a vein. The first infusion is given over about 1 hour. Subsequent infusions take about 30 minutes.

If you use more Hetronifly than you should

There is no information on overdose with serplulimab. This medicine is given by a healthcare professional. The risk of overdose is low. In case of overdose, you will be closely monitored for signs and symptoms of adverse reactions. Your doctor will start the appropriate treatment.

If you miss a dose of Hetronifly

It is very important that you do not miss any dose of this medicine. If you miss a dose, call your doctor immediately to reschedule your appointment.

If you stop treatment with Hetronifly

Stopping treatment may interrupt the effect of the medicine. Do not stop treatment with Hetronifly unless you have discussed it with your doctor.

If you have any other questions about the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Be aware of the importance of symptoms of inflammation.

Hetronifly acts on your immune system and may cause inflammation in some parts of your body. This could cause serious damage to your body. Some inflammatory conditions may be life-threatening and require treatment or withdrawal of Hetronifly.

Tell your doctor immediatelyif you notice any symptoms of inflammation:

• lung inflammation: symptoms may include new or worsening cough, shortness of breath, or chest pain
• liver or bile duct inflammation: symptoms may include nausea or vomiting, decreased appetite, pain in the right side of the stomach, yellowing of the skin or whites of the eyes, numbness, dark urine, or bleeding or bruising more easily than usual
• intestinal inflammation: symptoms may include diarrhea or more frequent bowel movements than usual, or black, tarry, or sticky stools with blood or mucus, severe stomach pain, or pain when touched
• kidney inflammation: symptoms may include a decrease in the amount of urine you pass
• skin inflammation: symptoms may include rash, itching, blisters on the skin, or ulcers in the mouth or on other moist surfaces
• gland inflammation (especially of the thyroid, adrenal, pituitary, and pancreas): symptoms may include rapid heartbeat, extreme fatigue, weight gain or loss, dizziness or loss of consciousness, hair loss, feeling cold, constipation, persistent headache or unusual headaches, abdominal pain, nausea, and vomiting
• type 1 diabetes: symptoms may include high blood sugar, increased appetite or thirst, urinating more often than usual, rapid and deep breathing, confusion, or a sweet smell of breath, a sweet or metallic taste in the mouth, or a different smell of urine or sweat
• infusion-related reactions: symptoms may include chills or shaking, itching or rash, redness, shortness of breath or wheezing, dizziness, or fever
• heart muscle inflammation: symptoms may include chest pain, shortness of breath, or irregular heartbeat
• muscle problems: symptoms may include muscle pain, or muscle weakness or rapid fatigue
• brain inflammation (encephalitis): symptoms may include seizures, headache, fever, chills, vomiting, confusion, and memory problems
• eye inflammation, which may include changes in vision
• low platelet count: symptoms may include bleeding (nosebleeds or gum bleeding) and/or bruising

Tell your doctor immediately if you experience any of the following side effects that have been reported in clinical trials with patients receiving Hetronifly.

The following side effects have been reported in clinical trials with Hetronifly in combination with chemotherapy:

Very common (may affect more than 1 in 10 people)

• lung infection (pneumonia)
• decrease in white blood cell count (leukocytes, neutrophils, and lymphocytes), red blood cell count (anemia), or platelet count (thrombocytopenia)
• reduction in thyroid gland activity (may cause fatigue or weight gain) or overactivity of the thyroid gland
• blood tests with high glucose levels (hyperglycemia or diabetes mellitus)
• blood tests with high uric acid levels (hyperuricemia) or lipid levels (hyperlipidemia)
• blood tests with abnormal electrolyte levels (potassium, sodium, calcium, magnesium, phosphate, or chloride)
• blood tests with low protein levels (hypoproteinemia)
• decreased appetite
• sleeping problems
• abnormal heart rhythm
• cough
• nausea
• constipation
• abdominal pain
• diarrhea
• vomiting
• high liver enzyme levels in the blood (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase)
• rash
• hair loss
• muscle and bone pain
• fever
• weakness
• high alkaline phosphatase levels in the blood

Common (may affect up to 1 in 10 people)

• urinary tract infection
• upper respiratory tract infection
• abnormal coagulation test results
• infusion-related reaction
• thyroid gland inflammation, abnormal thyroid function test
• weight loss
• low blood sugar levels
• peripheral nerve damage that causes numbness, dizziness, headache, or altered sensations (paresthesia)
• a regular heartbeat that is faster than normal, slow heartbeat, conduction disorders, heart failure, increased levels of substances in the brain (natriuretic peptide) that may be a sign of heart failure
• high blood pressure, blood vessel inflammation
• lung inflammation, shortness of breath, chest pain
• mouth inflammation, indigestion, difficulty swallowing, abdominal distension, gastrointestinal disorder
• high bilirubin levels in the blood (breakdown product of hemoglobin), liver damage
• itching, skin inflammation, excessive sweating
• joint pain (arthralgia), pain in arms or legs, musculoskeletal disorder
• glucose in the urine, protein in the urine, red or white blood cells in the urine, kidney damage
• high urea or creatinine levels in the blood
• feeling tired, general malaise, swelling
• high levels of heart damage markers (troponin), myoglobin, or creatine phosphokinase in the blood

Uncommon (may affect up to 1 in 100 people)

• severe infection, skin infection, intestinal infection, lip infection, brain and cerebral cortex infection caused by the herpes simplex virus
• lymph node inflammation
• anaphylactic reaction
• decreased secretion of hormones produced by the adrenal glands, other thyroid disorders, overactivity of the adrenal glands, inflammation of the pituitary gland located at the base of the brain
• abnormal lipoproteins in the blood
• brain inflammation, neurotoxicity, motion sickness, motor dysfunction
• blurred vision
• heart muscle disease, reduced blood flow to the heart muscle (myocardial ischemia), myocardial tissue ischemia, fluid accumulation in the pericardium, heart muscle inflammation, high levels of heart damage markers
• dry mouth, intestinal inflammation, stomach inflammation, pancreas inflammation, gum bleeding
• thick and sometimes scaly skin growth, changes in skin color, dry skin
• auto-inflammatory muscle disease (myositis), joint inflammation
• chills

Other side effects with frequency not known (cannot be estimated from the available data)

• muscle inflammation (myositis)

Reporting of side effects

If you experience any side effects, talk to your doctor, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Hetronifly

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 carton and on the label of the vial after CAD and EXP. The expiry date is the last day of the month indicated.

Store in a refrigerator (between 2 °C and 8 °C).

Do not freeze.

Store in the original package to protect from light.

The product, once diluted, must be used immediately. The diluted solution must not be frozen. If not used immediately, the diluted solution has demonstrated stability for 24 hours in a refrigerator (between 2 °C and 8 °C), which may include up to 6 hours at room temperature (less than or equal to 25 °C).

Do not use this medicine if you notice visible particles.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Hetronifly

The active substance is serplulimab.

Each ml of concentrate contains 10 mg of serplulimab. A 10 ml vial contains 100 mg of serplulimab.

The other ingredients are citric acid monohydrate, sodium citrate, sodium chloride (see section 2: Hetronifly contains sodium), mannitol, polysorbate 80, water for injections.

Appearance and Package Contents of the Product

Hetronifly is a concentrate for solution for intravenous infusion, supplied in a glass vial with a rubber stopper. The vial contains 10 mg/ml of serplulimab. The concentrate is a clear to opalescent, colorless to pale yellow liquid. Each carton contains 1 vial.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona, s/n

Edifici Est, 6a Planta

08039 Barcelona

Spain

Manufacturer

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50, Pabianice, 95-200, Poland

Accord Healthcare Single Member S.A.,

64th Km National Road Athens Lamia, Schimatari, 32009, Greece

Date of Last Revision of this Leaflet:

Other Sources of Information

Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu.

The leaflet for this medicine can be found in all languages of the European Union/European Economic Area on the European Medicines Agency website.

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This information is intended only for healthcare professionals:

Preparation and Administration of the Infusion

Aseptic handling must be ensured during the preparation of the infusion.

• Do not shake the vial.
• Allow the vial to reach room temperature (less than or equal to 25 °C).
• Visually inspect the product for particles or color changes before administration. The concentrate is a clear to opalescent, colorless to pale yellow solution. Discard the vial if visible particles are observed.
• Confirm the dose of the product and calculate the required volume of Hetronifly.
• Withdraw the necessary volume of sodium chloride injection solution at a concentration of 9 mg/ml (0.9%) corresponding to the volume of the product in the target intravenous infusion bag using a sterile syringe and discard.
• Use a syringe to withdraw the required volume of Hetronifly from the vial and inject into the sodium chloride injection solution at a concentration of 9 mg/ml (0.9%) to prepare a diluted solution with a final concentration of 1.0 to 8.0 mg/ml. Gently mix the infusion by manual rotation.
• Administer the solution for infusion by intravenous route using a sterile, non-pyrogenic infusion set with low protein binding of 0.2 to 5.0 μm or add an in-line filter.
• Adjust the initial infusion rate to 100 ml per hour (a rate of 25 drops per minute is recommended). The infusion rate may be adjusted if infusion-related reactions occur. If no infusion-related adverse reactions occur during the first infusion, the duration of subsequent administrations may be reduced to 30 minutes (± 10 minutes).
• From a microbiological point of view, the product, once diluted, must be used immediately. The diluted solution must not be frozen. If not used immediately, the diluted solution may be stored for 24 hours between 2 °C and 8 °C. This 24-hour period may include up to 6 hours at room temperature (less than or equal to 25 °C). If refrigerated, the vials and/or intravenous bags must be allowed to reach room temperature before use.
• After administration of the infusion, flush the line with a sodium chloride 9 mg/ml (0.9%) solution in accordance with the hospital's routine operating procedure.
• No other medicines should be administered simultaneously through the same intravenous line.
• In order to improve the traceability of biological medicinal products, the name and batch number of the administered medicinal product must be clearly recorded in the patient's file.

The disposal of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations.