PROLEUKIN 18 MILLION IU POWDER FOR SOLUTION FOR INJECTION OR INFUSION - patient leaflet, side effects, dosage

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(b NOVARTIS

Also, Proleukin should not be given to you if blood tests show that:

• You have a low level of white blood cells, platelets or red blood cells.
• You have creatinine or bilirubin levels outside the normal range.
• If you have chest pain or irregular heart beat. In some patients an electrocardiogram (ECG) will be carried out at regular intervals.
• If you become short of breath or you start breathing faster during treatment.
• If you feel extremely tired or sleepy, because this may be a signal that you are losing consciousness.

If you get any of the symptoms listed above, tell your doctor immediately.

You should also take special care:

• If you have a fever, shivers, chills, nausea and/or diarrhoea.
• If you feel dizzy and notice a fast heart beat. This may be a sign that you have low blood pressure, often seen within 2 to 12 hours after starting Proleukin administration.
• If you have a bacterial infection, since Proleukin treatment puts you at a higher risk of infection.
• If you notice mood changes. These in general return to normal after stopping therapy.
• If you have diabetes. Your blood sugar levels may increase or decrease more than usual.
• If you have a very itchy red rash or if your skin gets extremely dry during the treatment with Proleukin.

If any of the symptoms listed above gets severe, tell your doctor.

Other medicines and Proleukin

Some medicines can decrease the effect of Proleukin, or increase side effects.

Tell your doctor or pharmacist if you are using any of the following medicines (or have recently used them).

• Chemotherapy medicines, called tamoxifen, interferon-alpha, cisplatin, vinblastine and/or dacarbazine, used to treat cancer.
• Medicines called glucocorticoids (a type of steroid), used to treat inflammatory reactions.
• Medicines called beta-blockers, used to treat high blood pressure.
• Medicines that affect the heart, central nervous system, liver, kidneys or bone marrow. Consult your doctor if you are not sure what these are.
• Contrast fluids used in Computerised Tomography (CT) scanning.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Children and adolescents (below 18 years)

Proleukin is not recommended for children and adolescents

younger than 18 years.

Older people (65 years and over)

Older patients may be more susceptible to the side effects of Proleukin. Medical staff should take extra care when treating older people.

Pregnancy and breast-feeding

• Tell your doctor before starting treatment if you are pregnant, if you suspect that you are pregnant, or if you intend to become pregnant. Your doctor will discuss with you the risks and benefits of taking Proleukin during pregnancy.
• Both male and female patients should use effective contraception while being treated with Proleukin in order to prevent pregnancy. This is done with most other medicines used to treat cancer.
• Stop breast-feeding during treatment with Proleukin as there is a possibility that serious side effects could affect the baby.

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

Driving and using machines

Do not drive or use any tools or machines because Proleukin has side effects which may influence your ability to carry out these activities.

Proleukin contains sodium

Proleukin contains less than 23 mg sodium per 1 ml, and can therefore be considered as ‘sodium-free’.

• 3. How Proleukin is used

Proleukin can be given to you:

• either as a drip into a vein (intravenous infusion). This should be carried out in the hospital, under supervision of a doctor or nurse experienced in the use of medicines to treat cancer,
• or by injection directly under the skin (subcutaneous injection). This can be administered in a hospital, in an outpatient’s de­partment or at home, under supervision of a doctor or nurse.

Before and during your Proleukin therapy, your doctor may perform regular blood tests and chest X-rays, to check your organs and your blood cell counts.

Follow all instructions given to you by your doctor or nurse carefully.

If you have been given more Proleukin than you should

If you have or think you have been given too much Proleukin, contact your doctor or nurse immediately. You might get some of the side effects described in section 4.

4. possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The side effects of this medicine usually disappear within two days after stopping the treatment.

Your doctor may consider it necessary to treat the side effects of Proleukin with other medicines.

Some side effects can be serious

Very common (may affect more than 1 in 10 people) or common (may affect up to 1 in 10 people):

• Blood disorders: low levels of white blood cells (leucopenia) with symptoms of fever or increased risk of infections; low levels of platelets in your blood with bruises and spontaneous bleeding (thrombocytopenia); low levels of red blood cells (anaemia) with symptoms such as fatigue and pale skin; blood clotting disorders with sudden onset of shortness of breath, bloody sputum, leg pain or easy bleeding; high level of white blood cells called eosinophils which may cause heart or lung problems due to inflammation.
• Heart and circulation problems: heart attack (myocardial ischemia); disorders of heart and blood vessels, such as abnormal or insufficient pumping force of the heart (heart failure); awareness of an abnormal heart beat (palpitations); chest pain; low blood pressure (hypotension) or high blood pressure (hypertension) associated with dizziness, blurred vision or constant headache; irregular heart beat (arrhythmia); fast heart beat (tachycardia); blue colour to the lips, tongue and skin due to oxygen deficiency in the blood (cyanosis).
• Breathing and lung problems: coughing; shortness of breath (dyspnoea) or chest discomfort; accumulation of water in the lung (pulmonary oedema); deficiency of oxygen in the organs (hypoxia); coughing up blood (haemoptysis).
• Acute inflammation present throughout the entire body, frequently associated with fever and elevated white blood cell count or low white blood cell count and lower-than-average temperature, and vomiting are possible signs of blood poisoning.
• Kidney and urine problems: low urine production (oliguria), with high levels of urea and creatinine in the blood with symptoms such as vomiting, inability to produce urine, sleepiness, poor muscle tone or difficult breathing; blood in the urine (haematuria); kidney failure associated with fatigue, sleepiness, loss of appetite, vomiting or swollen legs.
• Digestive and organ problems: stomach, intestine and rectal bleeding (resulting in black stools); vomiting blood (haematemesis); swelling of the belly (ascites); difficulty in swallowing (dysphagia); abdominal swelling, discomfort, possible signs of enlargement of the liver and/or of the spleen.
• Nerve problems: sudden unconsciousness or fainting (syncope); loss of ability to speak.

Continued overleaf

6 NOVARTIS

THE FOLLOWING INFORMATION IS INTENDED FOR HEALTHCARE PROFESSIONALS ONLY

Proleukin ®

18 million IU powder for solution for injection or infusion aldesleukin

Special precaution for storage

Keep out of the sight and reach of children.

Do not use Proleukin after the expiry date which is stated on the pack.

Store the unopened vials in a refrigerator (2°C to 8°C). Do not freeze. Store in the original package in order to protect from light.

Shelf-life following reconstitution

Reconstituted solution of Proleukin can be stored for 24 hours in a refrigerator (2°C to 8°C), if not used immediately.

Diluted solution of Proleukin should be used within 48 hours after reconstitution, including duration of the infusion.

How to prepare and administer Proleukin

• — Use a sterilised injection syringe and injection needle.

• — Inject 1.2 ml Water for Injections into the vial of Proleukin. Direct the Water for Injections against the side of the vial to avoid excessive foaming.

• — Swirl gently to allow the powder to dissolve completely. Do not shake.

• — The solution contains 18 million IU or 1.1 mg Proleukin (aldesleukin) per millilitre.

The solution is now ready for subcutaneous administration or should be further diluted for administration by intravenous infusion.

Instructions for proper use of Proleukin

Subcutaneous (s.c.) administration

• — Once reconstituted, the product should be used within 24 hours.

• — The product should be brought to room temperature before administration and used immediately.

• — The appropriate dose can then be withdrawn and injected subcutaneously.

• — Proleukin should be injected into subcutaneous tissue. The best areas for injection are loose and soft (flabby) areas away from joints, nerves, bones and other important structures.

• — The injection site should be changed at regular intervals if Proleukin is administered subcutaneously. This helps prevent pain and redness at the injection site.

One treatment cycle usually lasts four weeks.

• - Week 1

Days 1 to 5: a dose of 18 million IU Proleukin every day

Days 6 and 7: no Proleukin treatment

• - Weeks 2, 3 and 4

Days 1 and 2: a dose of 18 million IU each day

Days 3, 4 and 5: a dose of 9 million IU every day

Days 6 and 7: no Proleukin treatment

After one week without Proleukin administration, a second 4-week cycle should be given.

If the condition of the patient has improved or stabilised, treatment with Proleukin can be continued with additional 4-week cycles.

Depending on the response to the treatment, a higher or lower dose may be suggested.

Intravenous (i.v.) administration

• – With a sterile syringe, withdraw the appropriate dose of the Proleukin solution from the vial.

• – Dilute as necessary to up to 500 ml with glucose 50 mg/ml (5%) solution for infusion, containing 1 mg/ml (0.1%) human albumin. The human albumin should be mixed with the glucose solution prior to the addition of the reconstituted aldesleukin.

• – The appropriate dose can then be administered intravenously, giving a daily dose of 18 million IU/m over 24 hours, for 5 days.

As for all injections, check for the presence of particles or discolouration before administration. Do not use Proleukin if you see particulate matter in the solution or if the solution is cloudy or more than slightly yellow in colour.

One treatment cycle usually consists of:

• – Days 1 to 5: a daily dose of 18 million IU/m of body surface area over 24 hours as a continuous infusion. The line will remain in the vein throughout the therapy.

• – Over the next 2 to 6 days: no Proleukin treatment.

• – Then, another 5 consecutive days of continuous infusion.

After three weeks without Proleukin administration, a second cycle as described above should follow.

If the condition of the patient has improved or stabilised after completing two cycles, treatment with Proleukin might be continued as five days of therapy every 4 weeks. Up to four maintenance cycles can be administered.

Depending on the response to the treatment, a higher or lower dose may be suggested.

Each vial is for single use only.

Disposal

Do not throw away any medicine via wastewater or household waste.

Any unused solution, vial, syringe and needle should be disposed of in an appropriate way. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

• Decreased or increased thyroid activity (hypo- or hyperthyroidism) with symptoms such as weight gain, weight loss, sweating or loss of hearing; high blood calcium level (hypercalcaemia) with symptoms such as feeling sick (nausea), vomiting or constipation.
• Difficulty breathing, tiredness, vomiting, drowsiness possible signs of high level of lactic acid in the blood.
• Feeling cold due to low body temperature (hypothermia); low level of calcium (hypocalcaemia) with possible muscle weakness, twitching or tingling of fingers; high level of potassium (hyperkalaemia) in the blood associated with cramps, abnormal heart rhythm, dizziness and headache.

If you experience any of the effects listed above, contact your doctor immediately or go to the nearest emergency unit.

Uncommon (may affect up to 1 in 100 people), rare (may affect up to 1 in 1,000 people) or not known (frequency cannot be estimated from the available data):

• Blood disorders: low levels of white blood cells with signs and symptoms of sudden high fever, severe sore throat, and more frequent infections (agranulocytosis or neutropenia); formation of blood clot (thrombosis); bleeding (haemorrhage).
• Heart problems: irregular heart beat; disease of the heart muscle with symptoms such as chest pain, fever or malaise; loss of consciousness (sudden loss in cardiac function); chest discomfort or pain (abnormal accumulation of fluid around the heart).
• Lung problems: sudden onset of breathing difficulty due to blood clots in the lung (pulmonary embolism); extreme difficulty in breathing (adult respiratory distress syndrome).
• Serious allergic reactions: anaphylaxis, leading to swelling of the face and throat and difficulty breathing (Quincke’s oedema); high fever, skin rash with small blisters, joint pain and/or eye inflammation (Stevens Johnson syndrome)
• Digestive and organ problems: recurring (severe) inflammation of the bowels (Crohn’s disease) accompanied with diarrhoea, pain in lower abdomen, fever, and weight loss; inflammation of the pancreas (pancreatitis) accompanied with severe pain in upper abdomen radiating to the back; constipation, swollen abdomen, abdominal pain (intestinal obstruction); upper abdominal pain (cholecystitis); liver failure with abdominal pain, fatigue, yellowish skin and eyes or dark yellow urine; a group of symptoms consisting of severe abdominal pain, nausea, fever, vomiting (gastrointestinal perforation).
• Nerve problems: seizures (convulsions or fits); paralysis; coma; disturbances of the sight (optic neuropathy); central nervous lesion with tingling, numbness (paraesthesia) or loss of control of movement; weakness or paralysis of limbs or face, difficulty speaking (cerebrovascular bleeding/cere­brovascular accident/ leucoencephalo­pathy).
• Low glucose level (hypoglycaemia) associated with symptoms such as feeling hungry, sweating, dizziness, heart palpitations.
• Muscle problems: muscle spasms, fever, red-brown urine possible signs of muscle disorder (rhabdomyolysis): pain or weakness in muscles.

If you experience any of the effects listed above, contact your doctor immediately or go to the nearest emergency unit.

Other side effects

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

• Loss of appetite (anorexia).
• Difficulty in sleeping (insomnia)
• Anxiety; confusion; dizziness; headache; drowsiness (somnolence).
• Cough.
• Feeling sick (nausea) with or without vomiting; diarrhoea; mouth sores with inflammation (stomatitis).
• Redness of the skin (erythema), skin rash; peeling; itching, sweating.
• Reactions on injection site, such as pain and inflammation.
• Flu-like symptoms (fever, chills, malaise, fatigue); pain; weight loss, weight gain.
• Fluid accumulation (oedema).

If any of these gets severe, tell your doctor or pharmacist.

Common (may affect up to 1 in 10 people):

• Nose, throat and pulmonary infections; stuffed nose (nasal congestion).
• Nose bleeding (epistaxis)
• Dehydration with signs such as dryness of the mouth or feeling thirsty.
• Mood changes, e.g. irritability, excitement and restlessness (agitation), depression, observation of things which are not there (hallucinations).
• Loss of control of movements, observation of itching and tingling of fingers or toes without cause (paraesthesia, neuropathy).
• Loss of taste.
• Lethargy with signs of lack of energy, tiredness and sleepiness.
• Stomach discomfort after meal (dyspepsia); constipation.
• Inflammation of the lips (cheilitis); inflammation of the stomach resulting in stomach ache and nausea (gastritis).
• Loss of hair (alopecia); itchy rash.
• Muscle pain; joint pain.
• Eye inflammations (conjunctivitis) with itching redness and swelling.
• Swelling and reddening of a vein (phlebitis).
• Inflammation of mucous membranes (mucositis); swelling with nodes (nodules) on site of injection.
• High level of blood glucose (hyperglycaemia) with signs such as excessive thirst, hunger, urination or fatigue.
• Blood tests indicating a change in liver function e.g. high level of bilirubin (hyperbilirubi­naemia) or liver enzymes in the blood (liver transaminase, alkaline phosphatase and lactate dehydrogenase).

If any of these gets severe, tell your doctor or pharmacist.

Uncommon (may affect up to 1 in 100 people):

• Allergy reactions (hypersensitivity) leading to runny eyes, runny nose, skin rash or distress.
• Muscle weakness (myasthenia)
• Skin discolouration (vitiligo).

If any of these gets severe, tell your doctor or pharmacist.

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

• Diabetes.
• Skin rash with small blisters filled with fluid (vesiculobullou­s rash).
• Tissue damage (necrosis) at injection site.

If any of these gets severe, tell your doctor or pharmacist.

Inflammation of the blood vessels (vasculitis ) in the skin, brain, and rest of the body, has also been reported.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist.

This includes any possible side effects not listed in this leaflet.

You can also report side effects directly via the Yellow Card Scheme at:.

By reporting side effects you can help provide more information on the safety of this medicine.

5. how to store proleukin

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 pack after EXP. The expiry date refers to the last day of that month. Store the unopened vials in a refrigerator (2°C to 8°C). Do not freeze. Store in the original package in order to protect from light.

Your doctor, nurse or pharmacist knows how to store Proleukin properly.

6. contents of the pack and other informationwhat proleukin contains the active substance is aldesleukin, providing 18 million international units (iu) (1.1 mg) per millilitre of solution reconstituted as recommended.

the other ingredients are mannitol (e421), sodium laurilsulfate, sodium dihydrogen phosphate dihydrate and disodium hydrogen phosphate dihydrate.

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06/09/2017 08:30

Read all of this leaflet carefully before you are given 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 or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

What is in this leaflet:

What Proleukin is and what it is used for

What you need to know before you are given Proleukin

How Proleukin is used

Possible side effects

How to store Proleukin

Contents of the pack and other information

1. What Proleukin is and what it is used for

Proleukin is the brand name of aldesleukin. It is a synthetic protein, very similar to a protein produced by the body called interleukin-2 (IL-2). This protein is part of the immune system.

IL-2 activates certain white blood cells in the body called lymphocytes, which fight against diseases and infections.

IL-2 stimulates the production of lymphocytes in the body, and enhances the body’s defences.

Proleukin is used to treat kidney cancer which has spread to other organs (also called metastatic renal cell carcinoma ).

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

Your doctor may carry out tests before you are treated with Proleukin. He/she may perform a blood test to check the level of sugar in your blood and check your kidney and liver function. He/she may also test your heart, respiratory and mental performance. He/she will check your response to the treatment at regular intervals and take any necessary action.

You should not be given Proleukin

• If you are allergic (hypersensitive) to aldesleukin or any of the other ingredients of this medicine (listed in section 6).
• If you are confined to bed for more than half the day.
• If it is less than 24 months since your kidney cancer was diagnosed and you have cancer symptoms, even if the cancer has spread to other organs.
• If you have a history of heart disease.
• If you have an infection for which you are taking antibiotics.
• If you have a shortage of oxygen in your blood.
• If you have serious problems with your liver, kidneys or any other organs.
• If you suffer from seizures (convulsions or fits), or from brain cancer that has not been successfully treated.
• If you have had an organ transplant.
• If you currently use medicines called corticosteroids to treat inflammatory reactions or if you may require these during Proleukin therapy.
• If you have had rheumatoid arthritis, Crohn’s disease or any other disease caused by your own immune system.

If any of the above applies to you, talk to your doctor. You should not be given Proleukin.