Patient leaflet - Hetronifly 10 mg/ml concentrate for solution for infusion

1. What HETRONIFLY is and what it is used for

HETRONIFLY is a cancer medicine that contains the active substance serplulimab. It is a monoclonal

antibody, a type of protein that is designed to recognise and attach to a specific target in the body called programmed death‑1 (PD‑1) receptor which is found on the surface of T and B cells (types of white blood cells that form part of the immune system, the body’s natural defences). When PD‑1 is activated by cancer cells it can switch off the activity of T cells. By blocking PD‑1, HETRONIFLY prevents it from switching off your T cells which helps your immune system fight the cancer.

HETRONIFLY is used to treat adults with

extensive‑stage small cell lung cancer (ES‑SCLC) that has not previously been treated.
non‑small cell lung cancer (NSCLC) that has shown no changes in genes called EGFR (epidermal growth factor receptor), ALK (anaplastic lymphoma kinase) or ROS1 (c‑ros oncogene 1).
squamous non-small cell lung carcinoma that cannot be removed by surgery (unresectable), local advanced or spread to the other parts of the body.
oesophageal squamous cell carcinoma (OSCC) that cannot be removed by surgery (unresectable) or has spread to other parts of the body.

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

HETRONIFLY will be given in combination with chemotherapy. It is important that you also read the package leaflets for the specific chemotherapy you may be receiving. Ask your doctor If you have any questions about these medicines.

2. What you need to know before you are given HETRONIFLY

You should not be given 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 you are given HETRONIFLY.

Warnings and precautions

Talk to your doctor before you are given HETRONIFLY if you have:

an autoimmune disease (an illness where’s immune system attacks its own cells)
liver problems
kidney damage
lung problems or breathing problems
had an organ transplant
had an allergic reaction to other cancer medicines that work the same way (monoclonal antibody therapies)

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

When you are given HETRONIFLY you can have some serious side effects (See section 4).

If you have any of the following conditions, call or see your doctor straight away. Your doctor may give you other medicines that prevent more severe complications and to help reduce your symptoms. Your doctor may delay the next dose of HETRONIFLY or stop your treatment with HETRONIFLY.

Speak with 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, feeling less hungry, pain on the right side of your stomach, yellowing of skin or whites of eyes, drowsiness, dark urine or bleeding or bruising more easily than normal
inflammation of the intestines: symptoms may include diarrhoea or more bowel movements than usual, or stools that are black, tarry or sticky with blood or mucus, severe stomach pain or tenderness
inflammation of the kidneys: symptoms may include a decrease in the amount of urine you pass
inflammation of the skin: symptoms may include rash, itching, skin blistering or ulcers in the mouth or on other moist surfaces
inflammation of glands (especially the thyroid, adrenal, pituitary and pancreas): symptoms may include fast heart rate, extreme tiredness, weight gain or weight loss, dizziness or fainting, hair loss, feeling cold, constipation, headaches that will not go away or unusual headaches, abdominal pain, nausea and vomiting
type 1 diabetes: symptoms may include high blood sugar, feeling more hungry or thirsty than usual, passing urine more often than usual, fast and deep breathing, confusion, or a sweet smell to your breath, a sweet or metallic taste in your mouth or a different odour to your urine or sweat
infusion-related reactions: symptoms may include chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness or fever
inflammation of the heart muscle: symptoms may include chest pain, shortness of breath, or irregular heartbeat
inflammation or problems of the muscles: symptoms may include muscle pain, or muscle weakness or rapid fatigue
- inflammation of the brain (encephalitis): symptoms may include seizures, headache, fever, chills, vomiting, confusion and memory problems
- inflammation of the eyes, which may include changes in eyesight
- low number of platelets: symptoms may include bleeding (nose or gum bleeding) and/or bruising

Children and adolescents

HETRONIFLY is not recommended for anyone under the age of 18 years. This is because there is no information on how well it works in this age group.

Other medicines and HETRONIFLY

Tell your doctor if you are taking, have recently taken or might take any other medicines. This includes herbal medicines and medicines obtained without a prescription.

Tell your doctor if you are taking other medicines that weaken your immune system, examples include cortisone derivatives, such as prednisone. These medicines may interfere with the way HETRONIFLY works. However, once you are treated with HETRONIFLY, your doctor may give you corticosteroids to reduce possible side‑effects with HETRONIFLY. Corticosteroids may also be given to you before receiving HETRONIFLY in combination with chemotherapy to prevent and/or treat nausea, vomiting, and other side effects caused by chemotherapy.

Pregnancy and breast‑feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Pregnancy

You must not use HETRONIFLY if you are pregnant unless your doctor specifically recommends it.

HETRONIFLY can harm your unborn baby.

Breast-feeding

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

Driving and using machines

HETRONIFLY may cause fatigue and other adverse reactions. Do not drive or use machines after you have been given HETRONIFLY unless you are sure you are feeling 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 recommended maximum daily dietary intake of sodium for an adult.

HETRONIFLY contains polysorbate 80

This medicine contains 2.0 mg of polysorbate 80 in each 10 ml vial. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergies.

3. How you are given HETRONIFLY

HETRONIFLY will be given to you in a hospital or clinic under the supervision of an experienced doctor.

The recommended dose of HETRONIFLY is

4.5 mg per kg of your bodyweight every 3 weeks for extensive stage small cell lung cancer and non-small cell lung cancer.
- 3 mg per kg of your bodyweight every 2 weeks for oesophageal squamous cell carcinoma.

Your doctor will give you HETRONIFLY via an infusion (drip) into your vein. The first infusion is given over a period of about 1 hour. The next infusions are given over a period of 30 minutes.

If you take more HETRONIFLY than you should

There is no information on overdose with serplulimab. This medicine is given to you by an experienced professional. Chance of an overdose is low. In case of overdose, you will be closely monitored for signs or symptoms of adverse reactions. Your doctor will start appropriate treatment.

If you miss an appointment to get HETRONIFLY

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

If you stop receiving HETRONIFLY

Stopping treatment may stop the effect of the medicine. Do not stop treatment with HETRONIFLY unless you have discussed this with your doctor.

If you have any further questions about your treatment, ask your doctor.

4. Possible side effects

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

Be aware of important symptoms of inflammation.

HETRONIFLY acts on your immune system and may cause inflammation in parts of your body. This may seriously damage your body. Some inflammatory conditions may be life‑threatening and need treatment or withdrawal of HETRONIFLY (see section 2).

Serious side effects

Speak with your doctor immediately if you notice any of the following serious symptoms. They may be signs of a serious, possibly fatal, condition. Getting medical treatment right away may help keep these problems from becoming more serious.

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, feeling less hungry, pain on the right side of your stomach, yellowing of skin or whites of eyes, drowsiness, dark urine or bleeding or bruising more easily than normal
inflammation of the intestines (uncommon): symptoms may include diarrhoea or more bowel movements than usual, or stools that are black, tarry or sticky with blood or mucus, severe stomach pain or tenderness
inflammation of pancreas (uncommon): symptoms may include abdominal pain, nausea and vomiting
inflammation of the heart muscle (uncommon): symptoms may include chest pain, shortness of breath, or irregular heartbeat
myasthenia gravis and myasthenic syndromes (rare): symptoms may include muscle weakness and tiring easily

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GRP-020 BBBC5248 GR01 0000 0 0000000 Other side effects

Talk to your doctor if you get any of the following side effects that have been reported in clinical trials with patients receiving HETRONIFLY in combination with chemotherapy:

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

infection of the lung (pneumonia)
decrease in the number of white blood cells (leukocytes, neutrophils, lymphocytes), red blood cells (anaemia) or platelets (thrombocytopenia)
reduced thyroid gland activity (can cause tiredness or weight gain) or overactive thyroid gland activity
blood tests showing high levels of glucose (hyperglycaemia or type 1 diabetes mellitus)
blood tests showing high levels of uric acid (hyperuricaemia) or lipids (hyperlipidaemia)
blood tests showing abnormal levels of electrolyte (potassium, sodium, calcium, magnesium, phosphate, or chloride)
blood tests showing low levels of protein (hypoproteinaemia)
reduced appetite
weight loss
trouble sleeping
abnormal heart rhythm
cough
chest pain
nausea
constipation
diarrhoea
vomiting
increased liver enzyme levels in the blood (alanine aminotransferase, aspartate aminotransferase)
rash
hair loss
pain in the muscles and bones
protein in the urine
fever
weakness
increased level of creatinine in the blood

Common (may affect up to 1 in 10 people)

infection of urinary tract
infection of the airways or respiratory tract
skin infection
abnormal coagulation function test
decrease in the number of white blood cells (granulocytes)
low number of white blood cells with fever
infusion-related reaction
inflammation of thyroid gland
low blood sugar level
dizziness, headache, disorder of sensation (paraesthesia), damage to the peripheral nervous system causing numbness
a regular cardiac rhythm in which heart beats faster than normal, slow heartbeat, conduction defects, heart failure, increased level of troponin, myocardial injury
high or low blood pressure, inflammation of the blood vessels
shortness of breath, a blood clot (usually from a leg vein) travels to your lungs and blocks an artery, difficulty speaking
inflammation of the mouth mucosa, indigestion, difficulty swallowing, abdominal distension or pain, gastrointestinal disorder, dry mouth, inflammation of the stomach
increased blood level of gamma-glutamyltransferase
increased blood bilirubin (breakdown product of haemoglobin)
- itchiness, inflammation of the skin
- inflammation of the joint
- positive red blood cells in the urine, renal injury
- increased level of urea in the blood
- overall discomfort, swelling
- increased level of alkaline phosphatase, myoglobin, creatine phosphokinase or amylase in the blood

Uncommon (may affect up to 1 in 100 people)

severe infection
anaphylactic reaction
decreased secretion of hormones produced by the adrenal glands
abnormal thyroid function test, other thyroid disorder, inflammation of the pituitary gland situated at the base of the brain, reduced parathyroid gland activity
abnormal lipoprotein in the blood
feeling of spinning, inflammation of the brain, neurotoxicity, brain stroke, change in the taste of foods, memory impairment
blurred vision, inflammation of cornea or conjunctiva
a reduction in blood flow to the heart muscle (myocardial ischaemia), a collection of fluid in the pericardium
blood clot in the veins
lungs cannot oxygenate blood
gingival bleeding, inflammation of the oesophagus, ulcer in the stomach
uneven skin pigmentation, thickened, sometimes scaly skin patches with changes in colour, dry skin, excessive sweating
increased frequency of urination, difficulty urinating
chills
increased level of lipase in the blood

Rare (may affect up to 1 in 1,000 people)

infection of stomach and intestine, infection of the brain and brain covering caused by herpes simplex virus
inflammation of the lymph node
overactive adrenal gland
motor dysfunction
a condition in which the muscles become weak and tire easily (myasthenia gravis and myasthenic syndrome)
disease of heart muscle
inflammation of the muscles (myositis)
a severe and possibly fatal skin disease characterised by blistering, peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands or feet) with or without a rash (toxic epidermal necrolysis)

Reporting of side effects

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 the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you 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 which is stated on the outer carton and vial label after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C to 8°C).

Do not freeze.

Store in the original package in order to protect from light.

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

Do not use this medicine if you notice visible particles.

Do not throw away any medicines via wastewater or household waste. Your healthcare professional will dispose any medicines that are no longer being used. These measures will help protect the environment.

6. Contents of the pack and other information

What HETRONIFLY contains

The active substance is serplulimab.

Each ml of concentrate contains 10 mg of serplulimab. One vial of 10 ml 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.

What HETRONIFLY looks like and contents of the pack

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

Marketing Authorisation Holder

Accord Healthcare Limited

Sage House, 319 Pinner Road

North Harrow, Middlesex

HA1 4HF

United Kingdom

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