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FRONT

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PATIENT INFORMATION LEAFLET ® 81 mg

Powder for intravesical suspension BCG Immunotherapy

Read all of this leaflet carefully before you start receiving 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 nurse.

If any of the side effects gets serious tell your doctor or nurse.

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

What is in this leaflet

1.    What ImmuCyst 81 mg is and what it is used for

2.    What you need to know before you are given ImmuCyst 81 mg

3.    How ImmuCyst 81 mg is given

4.    Possible side effects

5.    How to store ImmuCyst 81 mg

6.    Contents of the pack and other information

1 WHAT IMMUCYST 81 MG IS AND WHAT IT IS USED FOR

ImmuCyst 81 mg is a specially prepared form of the bacterium that is used in the BCG (Bacillus Calmette-Guerin) injection that is given to people to protect them against tuberculosis (TB). However, the use of ImmuCyst 81 mg has nothing to do with the prevention of TB.

ImmuCyst 81 mg is a medication used for the treatment of certain cancers that are found on the surface of the urinary bladder wall. ImmuCyst 81 mg is also used in the prevention of recurrence of some of these cancers.

When ImmuCyst 81 mg is injected into the bladder it sets off a reaction in which cells of the immune (defensive) system in the bladder wall start to destroy surrounding cells including cancerous cells.

•    you know you have an aneurysm which is a swelling of the wall of an artery

•    you have any illness that may require treatment with drugs that weaken your immune system in the future (such as if you are awaiting an organ transplant)

•    you know you have a small bladder as there is a risk of bladder contracture (narrowing of the outlet of the bladder causing difficulty passing urine) after treatment with ImmuCyst 81 mg

•    you have a urinary tract infection (UTI) which causes the need to urinate more often than normal and pain whilst urinating, as treatment must stop until it is treated

•    you are to have a diagnostic test for TB (tuberculin skin test) as treatment with ImmuCyst 81 mg will alter the result. Your doctor may recommend that you take a tuberculin skin test before starting treatment with ImmuCyst 81 mg

•    you get flu-like symptoms (fever, cough, headache, aching muscles and tiredness) or you get an increase in urinary symptoms (e.g. burning or pain on urination) lasting more than 48 hours or increase in severity

•    you get urinary symptoms (such as urgency, frequency of urination or blood in urine), joint pain, eye complaints (such as pain, irritation or redness), cough, skin rash, jaundice (yellow skin and eyes), nausea (feeling sick) or vomiting (being sick).

Because ImmuCyst 81 mg contains live mycobacteria, excreted urine may also contain live bacteria. You should take appropriate action to protect family and close contacts from infection (see “After the administration” in section 3. HOW IMMUCYST 81 MG IS GIVEN). These measures are especially important if you are living with, or in close contact to, someone who is immunocompromised (on chemotherapy for example) as they could

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2 WHAT YOU NEED TO KNOW BEFORE YOU ARE GIVEN IMMUCYST 81 MG

You should not be given ImmuCyst 81 mg if:

•    you are allergic to BCG or any of the ingredients of this medicine (listed in section 6);

•    you have had bladder surgery or a catheter (tube) inserted in your bladder which caused bleeding within the past 14 days;

•    you have a weakened immune system, from treatment (chemotherapy, radiation therapy or other), or from disease, including HIV infection;

•    you have active TB infection;

•    you have any symptom or a history of BCG reaction affecting the whole body (see Warnings and precautions);

•    you have a high temperature of unknown cause, a urinary tract infection, or bloody urine. Treatment with ImmuCyst 81 mg will be delayed until these conditions resolve.

If you know any of the above apply to you, tell your doctor.

Warnings and precautions Systemic BCG reaction

Talk to your doctor immediately if you experience the symptoms of a systemic BCG reaction.

A systemic BCG reaction is a serious illness which may rarely occur in persons who have received BCG. It can cause death.

Based on past clinical experience with BCG given in the bladder, a systemic BCG reaction can be defined as the presence of any of the following signs, if no other causes can be found for these signs:

• Fever of at least 39.5°C for at least 12 hours,

• Fever of at least 38.5°C for at least 48 hours,

•    Pneumonitis (inflammation of the lungs),

•    Hepatitis (severe liver illness),

•    Bacterial infection in the blood stream,

•    Inflammation of other organs (shown by a biopsy),

•    Blood clotting problems,

•    Difficulty breathing.

If you develop the symptoms of a BCG systemic reaction, your doctor will refer you to a specialist of infectious diseases.

BCG may persist in the urinary tract for several months after treatment with ImmuCyst 81 mg. Disseminated BCG infection may develop months or years after BCG therapy is given. Patients who receive medications which suppress the immune system after BCG therapy may be at higher risk of BCG infection. Other warnings

The stopper of the vial of ImmuCyst 81 mg contains latex, which may cause allergic reactions.

Some male genital or urinary BCG infections have required surgical removal of the testes.

Talk to your doctor or nurse before being given any dose of ImmuCyst 81 mg if:

•    you have any artificial joints (e.g. hip replacement)

•    you have any surgical implants (e.g. pacemaker fitted or replacement heart valve)

get a BCG infection from you (see above Warnings and Precautions for the symptoms of this serious condition).

If you have any question relating to the above information, please ask your doctor or nurse.

Children and adolescents

ImmuCyst 81 mg is not to be given to children.

Other medicines and ImmuCyst 81 mg

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

In particular, tell your doctor if you are having any treatments that affect your immune system. These include:

•    Anti-cancer medicines, e.g., methotrexate, ciclophosphamide, doxorubicin.

•    Medicines used to suppress rejection of transplants, e.g., ciclosporin.

•    Radiation treatment.

Also tell your doctor if you have been or are currently taking antibiotics (including anti-tuberculosis drugs) as they may affect how ImmuCyst 81 mg works. 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 receiving this medicine.

You should not be given ImmuCyst 81 mg if you are pregnant (or think you may be), or breast feeding unless your doctor has decided that it is in your best interests. Your doctor will advise you to take precautions to avoid becoming pregnant whilst being treated with ImmuCyst 8l mg. If you are breast feeding, you will be recommended to stop whilst being treated with ImmuCyst 81 mg. Driving and using machines

No studies on the effects on the ability to drive or use machines have been performed.

3 HOW IMMUCYST 81 MG IS GIVEN

ImmuCyst 81 mg is always given by a doctor or nurse.

The recommended course of treatment is:

•    one dose of ImmuCyst 81 mg into the bladder once a week for 6 weeks (total of 6 doses);

•    a break from treatment for 6 weeks, then one dose per week for l to 3 weeks (total of l to 3 doses);

•    then, six months after the start of your first treatment course, you will receive maintenance treatment of one dose per week for l to 3 weeks every 6 months (total of l8 doses);

•    up to 27 doses over a 3-year period.

Your doctor will decide how long your maintenance treatment will last.

Mode and route of administration:

This medication is administered into the bladder (intravesical route only):

•    Your doctor or nurse will insert a catheter (tube) into your bladder via the urethra (the passage through which you pass urine). If the bladder contains urine, it will be emptied through the catheter.

•    The doctor or nurse will connect to the catheter a pouch containing the ImmuCyst 81 mg solution. The solution will flow into your bladder. This process is called instillation.

•    Once the entire solution is in your bladder, the catheter will be removed.

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The following information is intended for healthcare professionals only: Take special care when using ImmuCyst 81 mg

Precautions

•    ImmuCyst 81 mg contains living, attenuated mycobacteria.

•    ImmuCyst 81 mg must never be prepared or used in the same room as medicines for systemic use or by the same persons who apply those.

•    Patients receiving ImmuCyst 8l mg treatment must not be treated in the vicinity of patients with known immunodeficiency.

•    Persons with a known immunodeficient condition must not be in contact with ImmuCyst 81 mg.

•    The rubber stopper must not be removed from the vial. If leakage or oozing occurs, the area contaminated with the vial’s content must be washed with a 5% hypochlorite solution and then with water.

•    All instruments and materials which have been in contact with ImmuCyst 81 mg should be handled as infectious waste.

•    Materials in contact with ImmuCyst 81 mg must be sterilised appropriately or they have to be eliminated according to the rules for handling infectious waste.

•    Contact of contaminated instruments to urinary tract or the inadvertent injury of the mucous membrane of the urinary bladder or the urethra must be avoided during the intravesical administration of ImmuCyst 81 mg.

•    The intravesical administration of ImmuCyst 81 mg must not be started earlier than after 2 to 3 weeks following the performance of TUR.

If the doctor considers the catheterisation of the bladder as traumatic (e.g. a bleeding developed), ImmuCyst 8l mg must not be administered and the treatment should be postponed by at least 2 weeks.

The treatment should be continued at a later date as if there would not have been any interruption of the treatment regimen.

Reconstitution of freeze-dried product

DO NOT REMOVE THE RUBBER STOPPER FROM THE VIAL. HANDLE AS INFECTIOUS MATERIAL

The preparation of the ImmuCyst 81 mg should be done using aseptic technique.

A separate area for the preparation of the ImmuCyst 81 mg suspension

is recommended in order to avoid cross contamination

(e.g. in a biocontainment cabinet). The person responsible for mixing

the agent should wear gloves, eye protection, a mask and gown to

avoid inhalation of BCG organisms and inadvertent exposure of broken

skin to BCG organisms.

When handling and reconstituting ImmuCyst 81 mg, care should be taken so as to avoid needle stick injuries.

ImmuCyst 81 mg should not be handled by persons with an immunologic deficiency. ImmuCyst 81 mg is to be reconstituted only with sterile preservative-free normal saline to ensure proper dispersion of the organisms. For the reconstitution and further dilution of one dose of ImmuCyst 81 mg, 50 ml of sterile preservative-free normal saline are required.

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BACK

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After the administration:

•    Lie on your stomach for the first 15 minutes following the removal of the catheter. You may then get up and move around. This will ensure that the inside of your bladder is completely covered by ImmuCyst 81 mg.

•    Keep ImmuCyst 81 mg inside your bladder for, if possible, 2 hours. You may feel a burning sensation whilst urinating for the first time following treatment.

•    To lower the chance of contamination from the BCG in your urine you should urinate in a seated position for six hours following treatment.

•    Any urine passed during this time should be disinfected with an equal volume of household bleach for 15 minutes before flushing or disposal.

•    Unless otherwise specified by your doctor, drink plenty of fluids during the 48 hours following treatment and urinate frequently.

Frequency and duration of treatment

Follow the instructions of your treating doctor closely.

Never interrupt the treatment.

If you have any further questions on the use of this product, ask your doctor or nurse.

If you think you have been given more ImmuCyst 81 mg than you should

As ImmuCyst 81 mg is administered by a health-care professional it is most unlikely that you will be given the wrong dose. If you have any concerns about your dose or the use of this product speak to your doctor or nurse.

4 POSSIBLE SIDE EFFECTS

Like all medicines ImmuCyst 81 mg can sometimes cause side-effects, although not everybody gets them.

Some people have unpleasant side effects during their treatment with

ImmuCyst 81 mg. However, the side effects are usually easy to manage.

On your treatment days, they may be worse but they will get better in a few days. It is important for you to stay on ImmuCyst 81 mg for the whole treatment time. Completing the treatment helps to prevent the tumour from coming back.

Talk to your doctor or nurse about any side effects that you feel may prevent you from finishing the treatment.

If you notice the following side effects, see your doctor immediately:

• BCG infection (see Warning and Precautions for typical symptoms

of the condition) which happens because the BCG bacteria have got into

your blood and could result in the following:

•    Serious infections of the blood (septicemia with shock), occasionally fatal

•    Infections of the eyes, lungs, liver (shown by an abnormal liver function test), bones, bone marrow, kidneys, lymph nodes, peritoneum (membrane lining the abdomen and its organs), testicles (orchitis or epididymitis) and the prostate (granulomatous prostatitis)

•    Infection of an already present aneurysm (a swelling of the wall of an artery)

•    Infection of surgical implants (e.g. replacement heart valve or pacemaker) or artificial joints (e.g. replacement hip)

•    Joint disorders (arthritis or arthralgia), eye disorders (including conjunctivitis, uveitis, iritis, keratitis, granulomatous chorioretinitis), urinary disorders (urethritis), skin rash. These symptoms have been reported as isolated conditions or in combination (Reiter’s syndrome; this is more likely to happen if you are a carrier of the HLA-B27 tissue antigen).

Side effect information from clinical trials

Very common reactions (affects more than 1 user in 10) are:

•    Pain or burning during urination (dysuria), traces of blood in the urine (haematuria), sudden and unstoppable need to urinate (urinary urgency) and frequent urge to urinate (urinary frequency)

•    Feeling generally unwell (malaise), fever, chills Common reactions (affects 1 to 10 users in 100) are:

•    Urinary tract infection (UTI), bladder inflammation (cystitis), bladder cramps and pain, inability to hold urine (urinary incontinence) and difficulty passing urine (bladder contracture)

•    Loss of appetite (anorexia), feeling sick (nausea), being sick (vomiting), diarrhoea

•    Liver lesions (hepatic lesions),

•    Heart problems (cardiac disorders)

•    Skin rash

•    Joint pain (arthralgia) and muscle pain (myalgia), inflammation of joints (arthritis)

•    Feeling tired (fatigue)

Uncommon (affects 1 to 10 users in 1,000) are:

•    Generalised (systemic) infections, lung (pulmonary) infections, local infections

•    Reduced number of red blood cells (anaemia), insufficient number of white blood cells in the blood (leukopenia), abnormally low number of platelets which are the blood components involved in blood clotting (thrombocytopenia), blood clotting and bleeding disorder (coagulopathy)

•    Headaches, dizziness

•    Abdominal pain, constipation

•    Inflammation of mucous membranes of your mouth or intestinal tract (mucositis, stomatitis or ulcers)

•    Liver disease (granulomatous hepatitis)

•    Skin abscess, hypersensitivity skin reaction (causing itchy, inflamed skin and/or rash)

•    Kidney disorders (renal toxicity)

•    Urinary obstruction

•    Visible skin particles in urine

•    Genital pain, flank (side) pain

Other side effects that have occurred in people using ImmuCyst 81 mg:

•    Serious lung disease (pneumonia, interstitial lung disease)

•    Purple-reddish lumps on the skin (erythema nodosum)

•    Serious kidney disease including:

•    renal abscess

•    renal insufficiency

•    kidney infection (pyelonephritis)

•    kidney inflammation (nephritis including tubulointerstitial nephritis, interstitial nephritis and glomerulonephritis)

•    Difficulty in urinating including the presence of blood clots in the bladder (vesical tamponade) and constant urge to urinate (feeling of incomplete emptying of the bladder)

•    Flu-like symptoms (fever, cough, headache, aching muscles and tiredness)

•    Abnormal blood tests: abnormal or increased blood creatinine or blood urea nitrogen

Reporting of side effects

If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the internet at www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

5 HOW TO STORE IMMUCYST 81 MG

Keep this medicine out of the sight and reach of children.

The information in section 5 and 6 is primarily for healthcare professionals. ImmuCyst 81 mg should be kept in a refrigerator at a temperature between 2° and 8°C. Do not use after the expiry date stated on the vial. The expiry date refers to the last day of that month.

At no time should the freeze-dried or reconstituted ImmuCyst 81 mg be exposed to sunlight, direct or indirect. Exposure to artificial light should be kept to a minimum.

Once reconstituted, the product should be used immediately. The reconstituted product must not be used if any cloudiness or precipitation (lumps) can be seen in it.

If there is an unavoidable delay between reconstitution and administration, this delay should not exceed 2 hours at a temperature between 2° and 25°C. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6 CONTENTS OF THE PACK AND OTHER INFORMATION

340mm

What Immucyst 81 mg contains

The active substance(s) is:

Attenuated Mycobacterium bovis suspension*:

81 mg or approximately 1.8 to 15.9 x I0⁸ CFU** per instillation dose when resuspended

* Live Bacillus Calmette-Guerin (Connaught) strain ** Colony Forming Units

The other ingredient is monosodium glutamate. No preservative is added.

What ImmuCyst 81 mg looks like and contents of pack ImmuCyst 81 mg is a white powder in a 5 ml glass vial.

ImmuCyst 81 mg comes in packs of I vial.

Marketing Authorisation Holder

Alliance Pharmaceuticals Limited

Avonbridge House

Bath Road

Chippenham

Wiltshire SNI5 2BB

Manufacturer

Sanofi Pasteur Limited, Toronto, Ontario, Canada This leaflet was last revised in: October 2016

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ImmuCyst® is a registered trademark of Sanofi Pasteur Limited.

Alliance, Alliance Pharmaceuticals and associated devices are registered trademarks of Alliance Pharmaceuticals Limited.

© Alliance Pharmaceuticals Limited 20I6

Three options for intravesicular administration are possible:

Option 1:

•    Using a 5 ml sterile syringe and needle, draw up 3 ml of sterile preservative-free saline solution.

•    Prepare the surface of the ImmuCyst 8I mg vial using a suitable antiseptic.

•    Using the same syringe and needle, pierce the rubber stopper in the vial of freeze-dried material with the needle.

•    Holding the vial of freeze-dried material upright, pull the plunger of the syringe back to the 5 ml marking on the barrel. This will create a mild vacuum in the vial.

•    Release the plunger and allow the vacuum to pull the saline from the syringe into the vial of freeze-dried material.

•    After all the saline has passed into the freeze-dried material, remove the needle and syringe.

•    Shake the vial gently until a fine, even suspension results. Avoid foaming since this will prevent withdrawal of the proper dose. Any reconstituted product, which exhibits flocculation or clumping that cannot be dispersed with gentle shaking should not be used.

•    Withdraw the entire contents of the reconstituted material from the vial into the same 5 ml syringe. Return the vial to an upright position before removing the syringe from the vial.

•    Further dilute the reconstituted material from the vial (I dose) with sterile preservative-free normal saline to a final volume of 50 ml for intravesical instillation.

•    The reconstituted product is then transferred to a bladder syringe. Option 2:

Follow instructions as above except the entire contents from the reconstituted

vial is added to a saline bladder irrigation bag instead of a bladder syringe.

Option 3:

Use a 50 ml (closed system) saline bladder irrigation bag to reconstitute ImmuCyst 8I mg and instill the solution as per the manufacturer’s instructions. Reconstituted product

The product should be used immediately after reconstitution.

Reconstituted product should not be exposed to direct or indirect sunlight. Exposure to artificial light should also be kept to a minimum.

If there is an unavoidable delay between reconstitution and administration, this delay should not exceed 2 hours at a temperature between 2°C and 25°C. Any reconstituted product that exhibits flocculation or clumping that cannot be dispersed with gentle shaking should not be used.

Instructions for Disposal

Unused product, packaging, and all equipment and materials used for instillation of the product (e.g. syringes, catheters) should be placed immediately in a container for biohazardous materials and disposed of according to local requirements applicable to biohazardous materials.

Urine voided during the 6-hour period following ImmuCyst 8I mg instillation should be disinfected with an equal volume of 5% hypochlorite solution (undiluted household bleach) and allowed to stand for I5 minutes before flushing.

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