Hetronifly

Patient information leaflet

HETRONIFLY 10 mg/ml concentrate for solution for infusion

serplulimab
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before receiving this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• It is important that you carry your patient card with you during treatment.
• If you have any questions, ask your doctor.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor. See section 4.

Contents of this leaflet

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

1. What Hetronifly is and what it is used for

Hetronifly is an antitumour medicinal product containing the active substance serplulimab. It is a
monoclonal antibody, a type of protein designed to recognise and bind to a specific target in the body
called programmed death receptor-1 (PD-1), which is found on the surface of T and B cells (types of
white blood cells that are part of the immune system, the body's natural defences). When the PD-1
receptor is activated by tumour cells, it can suppress the activity of T cells. By blocking PD-1, Hetronifly
prevents this suppression, thereby helping the immune system to fight cancer.
Hetronifly is used to treat adults with a type of lung cancer called extensive-stage small cell lung
cancer (ES-SCLC). It is used when the cancer:

• has spread within 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 this medicine has been prescribed for
you, speak to your doctor or pharmacist.
Hetronifly is administered in combination with chemotherapy. It is important to also read the package
leaflets for the specific chemotherapy you are receiving. Ask your doctor if you have any questions
about these medicines.

2. What you should know before using Hetronifly

Do not use Hetronifly
If you are allergic to serplulimab or to any of the other ingredients of this medicine.
If you are unsure whether you are allergic, discuss this with your doctor or nurse before receiving
Hetronifly.

Warnings and precautions
Talk to your doctor before using Hetronifly if you have:

• an autoimmune disease (a condition in which the immune system attacks your own cells)
• liver problems
• kidney damage
• lung or breathing problems
• received an organ transplant
• previously experienced an allergic reaction to other anticancer medicines that work in the same way (monoclonal antibody therapies)

If any of these conditions apply to you (or if you have any doubts), you should discuss them with your doctor
before Hetronifly is administered.
Administration of Hetronifly may cause serious side effects (see section 4).
If any of the following conditions occur, call or consult your doctor immediately. Your doctor may
administer other medicines to prevent more serious complications and help reduce your symptoms.
Your doctor may delay your next dose of Hetronifly or discontinue treatment with Hetronifly.

Contact your doctor immediately if you notice any of the following symptoms:

• inflammation of the lungs: symptoms may include new or worsening cough, shortness of breath, or chest pain
• inflammation of the liver and bile ducts: symptoms may include nausea or vomiting, loss of appetite, pain on the right side of the stomach, yellowing of the skin or whites of the eyes, drowsiness, dark urine, or bleeding or bruising more easily than normal
• inflammation of the intestine: symptoms may include diarrhoea or more frequent bowel movements than usual, black, tarry, or sticky stools with blood or mucus, severe pain or tightness in the stomach
• inflammation of the kidneys: symptoms may include reduced amount of urine passed
• skin inflammation: symptoms may include rashes, itching, blisters, or ulcers in the mouth or other mucous membranes
• inflammation of glands (especially thyroid, adrenal glands, pituitary gland, and pancreas): symptoms may include rapid heartbeat, extreme tiredness, weight gain or weight loss, dizziness or fainting, hair loss, feeling cold, constipation, persistent headache or unusual headache, abdominal pain, nausea, and vomiting
• type 1 diabetes: symptoms may include high blood sugar, increased hunger or thirst, urinating more frequently than usual, rapid and deep breathing, confusion, sweet-smelling breath, sweet or metallic taste in the mouth, or unusual odour of urine or sweat
• infusion-related reactions: symptoms may include chills or shaking, itching or skin rash, flushing, shortness of breath or laboured breathing, dizziness, or fever
• inflammation of the heart: symptoms may include chest pain, shortness of breath, or irregular heartbeat
• inflammation or problems with muscles: symptoms may include muscle pain, muscle weakness, or rapid fatigue
• inflammation of the brain (encephalitis): symptoms may include seizures, headache, fever, chills, vomiting, confusion, and memory disturbances
• eye inflammation, which may lead to changes in vision
• low platelet count: symptoms may include bleeding (from nose or gums) and/or bruising

Children and adolescents
Hetronifly is not recommended for patients under 18 years of age. This is because there is no information
on its efficacy in this age group.

Other medicines and Hetronifly
Inform your doctor if you are taking, have recently taken, or might take any other medicines, including
natural products and those obtained without a prescription.
Inform your doctor if you are taking other medicines that weaken the immune system, such as
corticosteroids (e.g., prednisone). These medicines may interfere with the action of Hetronifly. However,
once you are on Hetronifly treatment, your doctor may administer corticosteroids to reduce possible side
effects of Hetronifly. Corticosteroids may also be given before receiving 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, suspect you may be pregnant, planning to become pregnant, or are breastfeeding,
please consult your doctor before taking this medicine.

Pregnancy
Do not use Hetronifly during pregnancy unless specifically recommended by your doctor.
Hetronifly may harm the unborn child.

Breastfeeding
It is not known whether serplulimab passes into breast milk. You and your doctor will decide whether to
breastfeed after receiving serplulimab.

Driving and using machines
Hetronifly may cause fatigue and other adverse reactions. Do not drive or operate machinery after
receiving Hetronifly if you are not sure you feel well.

Hetronifly contains sodium
This medicine contains 22.5 mg of sodium (a main component of table salt) per 10 ml vial. This corresponds to 1.1% of the maximum daily recommended sodium intake for an adult.

3. How to use Hetronifly

Hetronifly is administered in a hospital or clinic setting under the supervision of an experienced doctor.
The recommended dose is 4.5 mg per kg of body weight every three weeks.
Your doctor will administer Hetronifly as an intravenous infusion (drip). The first infusion will be given over approximately 1 hour. Subsequent infusions may be given over a period of 30 minutes.
If you are given more Hetronifly than you should be
There is no information available on overdose with serplulimab. This medicine is administered by an experienced healthcare professional, so the likelihood of an overdose is low. In the event of an overdose, the patient will be closely monitored for any signs or symptoms of adverse reactions. The doctor will initiate appropriate treatment.
If you miss an appointment for Hetronifly administration
It is very important not to miss a dose of this medicine. If you miss an appointment, contact your doctor immediately to reschedule.
If you stop treatment with Hetronifly
Stopping treatment may interrupt the medicine's effect. Do not discontinue treatment with Hetronifly without discussing it with your doctor.
If you have any questions about how to use this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Be aware of the main symptoms of inflammation.
Hetronifly acts on the immune system and may cause inflammation in certain parts of the body.
This can seriously damage the body. Some inflammatory conditions may be life-threatening and require specific treatment or discontinuation of Hetronifly (see section 2).

Serious side effects
Contact your doctor immediately if you notice any of the following serious symptoms. They may be signs of a serious, potentially fatal condition. Receiving immediate medical care may help prevent these problems from worsening:

• Inflammation of the lungs (common): symptoms may include new or worsening cough, shortness of breath, or chest pain
• Inflammation of the liver and bile ducts (common): symptoms may include nausea or vomiting, loss of appetite, pain on the right side of the abdomen, yellowing of the skin or whites of the eyes, drowsiness, dark urine, or bleeding or bruising more easily than normal
• Inflammation of the intestine (uncommon): symptoms may include diarrhoea or more frequent bowel movements than usual, or black, tarry, sticky stools with blood or mucus, severe pain or tightness in the stomach
• Inflammation of the pancreas (uncommon): symptoms may include abdominal pain, nausea, and vomiting
• Inflammation of the heart (uncommon): symptoms may include chest pain, shortness of breath, or irregular heartbeat

Other side effects
Contact your doctor immediately if you experience any of the following side effects, which have been reported in clinical studies of patients receiving Hetronifly in combination with chemotherapy.

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

• Lung infection (pneumonia)
• Decrease in white blood cells (leukocytes, neutrophils, lymphocytes), red blood cells (anaemia), or platelets (thrombocytopenia)
• Underactive thyroid (may cause tiredness or weight gain) or overactive thyroid
• Blood tests showing high levels of glucose (hyperglycaemia or diabetes mellitus)
• Blood tests showing high levels of uric acid (hyperuricaemia) or lipids (hyperlipidaemia)
• Blood tests showing abnormal levels of electrolytes (potassium, sodium, calcium, magnesium, phosphate, or chloride)
• Blood tests showing low levels of proteins (hypoproteinaemia)
• Loss of appetite
• Sleep problems (insomnia)
• Irregular heartbeat
• Cough
• Nausea
• Constipation
• Abdominal pain
• Diarrhoea
• Vomiting
• Increased levels of liver enzymes in the blood (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase)
• Skin rash
• Hair loss
• Muscle and bone pain
• Fever
• Weakness
• Increased levels of alkaline phosphatase in the blood

Common (may affect up to 1 in 10 people)

• Urinary tract infection
• Upper respiratory tract infection
• Abnormal blood coagulation tests
• Infusion-related reaction
• Inflammation of the thyroid, abnormal thyroid function tests
• Weight loss
• Hypoglycaemia
• Peripheral nervous system damage causing numbness, dizziness, headache, sensation disturbances (paraesthesia)
• A regular heartbeat with a faster-than-normal heart rate, slow heartbeat, conduction defects, heart failure, increased levels of brain natriuretic peptide (a possible sign of heart failure)
• High blood pressure, inflammation of blood vessels
• Inflammation of the mouth lining, indigestion, difficulty swallowing, abdominal bloating, gastrointestinal disturbances
• Increased bilirubin in the blood (a breakdown product of haemoglobin)
• Itching, skin inflammation, excessive sweating
• Joint pain (arthralgia), pain in arms or legs, musculoskeletal disorders
• Glucose in urine, presence of proteins in urine, presence of red or white blood cells in urine, kidney damage
• Increased levels of urea or creatinine in the blood
• Feeling of tiredness, general malaise, swelling
• Increased blood levels of myocardial necrosis marker (troponin), myoglobin, or creatine phosphokinase

Uncommon (may affect up to 1 in 100 people)

• Severe infection, skin infection, intestinal infection, lip infection, brain and meningeal infection caused by herpes simplex virus
• Swollen lymph nodes
• Anaphylactic reaction
• Decreased secretion of hormones produced by adrenal glands, other thyroid disorders, overactive adrenal glands, inflammation of the pituitary gland located at the base of the brain
• Abnormal blood lipoproteins
• Brain inflammation, neurotoxicity, motion sickness, motor dysfunction
• Blurred vision
• Heart muscle disease, reduced blood flow to the heart muscle (myocardial ischaemia), tissue myocardial ischaemia, fluid accumulation in the pericardium, increased levels of myocardial necrosis marker
• Dry mouth, stomach inflammation, bleeding gums
• Growth of thickened, sometimes scaly skin, changes in skin colour, dry skin
• Autoimmune muscle inflammation (autoimmune myositis), joint inflammation
• Chills

Other side effects reported with unknown frequency (cannot be estimated from available data)

• Muscle inflammation (myositis)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor. You can also report side effects directly via the national reporting system listed in Annex V. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Hetronifly

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the outer packaging and on the vial label after the word EXP. The expiry date refers to the last day of that month.
Store this medicine in the refrigerator at a temperature between 2 °C and 8 °C.
Do not freeze.
Keep in the original packaging to protect it from light.
Once diluted, the product must be used immediately. The diluted solution must not be frozen. If not used immediately, the diluted solution has been shown to be stable for 24 hours when stored in the refrigerator (from 2 °C to 8 °C), including up to 6 hours at room temperature (at 25 °C or below).
Do not use this medicine if you see visible particles.
Do not dispose of any medicine via wastewater or household waste. Healthcare professionals will dispose of unused medicines properly. These measures will help protect the environment.

6. Package contents and other information

What Hetronifly contains
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 components are monohydrate citric acid, sodium citrate, sodium chloride (see section 2:
Hetronifly contains sodium), mannitol, polysorbate 80, water for injections.
Description of the appearance of Hetronifly and contents of the pack
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 liquid, colourless to slightly yellow, clear to slightly opalescent. Each pack contains 1 vial.
Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona, s/n
Edifici Est, 6a Planta
08039 Barcelona
Spain
Manufacturer
Baggerman Farmanet N.V.
Barrierweg 3g
Eindhoven
Noord-Brabant
5622 CL
The Netherlands
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.
This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

The following information is intended exclusively 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 (at or below 25 °C).
• Prior to administration, visually inspect the product for particulate matter and discoloration. The concentrate is a solution that ranges from colorless to slightly yellow and from clear to slightly opalescent. Discard the vial if visible particles are observed.
• Confirm the product dose and calculate the required volume of Hetronifly.
• Using a sterile syringe, withdraw from the intravenous bag a volume of 9 mg/ml (0.9%) sodium chloride injection solution equivalent to the volume of product to be infused, and discard this volume.
• Using a syringe, withdraw the required volume of Hetronifly from the vial and inject it into the bag containing 9 mg/ml (0.9%) sodium chloride injection solution, to prepare a diluted solution with a final concentration between 1.0 and 8.0 mg/ml. Mix the diluted solution by gently inverting the bag.
• Administer the infusion solution intravenously using a sterile, non-pyrogenic administration set equipped with an in-line or add-on low protein-binding filter of 0.2 to 5.0 μm.
• Set the initial infusion rate at 100 ml per hour (25 drops per minute are recommended). The infusion rate may be adjusted if infusion-related reactions occur. If no infusion-related adverse reactions occur during the first infusion, subsequent infusions may be administered over 30 minutes (± 10 minutes).
• From a microbiological standpoint, the product should be used immediately after dilution. The diluted solution must not be frozen. If not used immediately, the diluted solution may be stored for up to 24 hours at a temperature between 2 °C and 8 °C. This 24-hour storage period may include up to 6 hours at room temperature (≤ 25 °C). If refrigerated, vials and/or intravenous bags must be brought to room temperature before use.
• At the end of the infusion, flush the infusion line with 9 mg/ml (0.9%) sodium chloride solution according to the hospital’s standard operating procedure.
• Do not co-administer other medicinal products through the same infusion line.
• To improve traceability of biological medicinal products, the name and batch number of the administered medicinal product must be clearly recorded in the patient’s medical record.

Any unused medicinal product and waste material derived from this medicinal product must be disposed of in accordance with
local applicable regulations.