ONCOTICE 2-8 x 10⁸ CFU POWDER FOR INTRAVESICAL SUSPENSION

Introduction

Package Leaflet: Information for the User

OncoTICE2‑8 x 108CFU

powder forsuspensionfor intravesical use

BCG Tice strain

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.

If you have any further questions, ask your doctor, pharmacist, or nurse.

• 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 experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is OncoTICE and what is it used for

OncoTICE belongs to a group of medicines called immunostimulants, which act on the body's defense system. Specifically, this medicine can stimulate your immune system.

OncoTICE is used to treat superficial bladder cancer. It is also used to prevent the disease from coming back after bladder surgery.

2. What you need to know before you use OncoTICE

Do not useOncoTICE:

• if you are allergic to the Bacillus Calmette-Guérin (BCG) or to any of the other components of this medicine (listed in section 6).
• if you have a urinary tract infection. If you have cystitis (inflammation of the bladder), you will first be given antibiotic treatment before starting OncoTICE. It is necessary that the antibiotic treatment is finished before starting OncoTICE.
• if you have blood in your urine.
• if you currently have tuberculosis.
• if you are being treated with anti-tuberculosis drugs, such as streptomycin, para-aminosalicylic acid, isoniazid, rifampicin, and ethambutol.
• if you have an altered immune system (reduced immunity to infectious diseases), whether congenital, acquired, caused by medications, or other treatments.
• if you are HIV positive.
• if you are pregnant or breastfeeding.
• if you have a fever and the cause is not known.
• if you have undergone any medical-surgical procedure in the bladder in the preceding week, due to the risk of systemic infection by the Calmette-Guérin (BCG) bacteria.

Warnings and precautions

Consult your doctor or pharmacist before starting to use OncoTICE.

• Before the first instillation of OncoTICE in the bladder, your doctor will probably perform a skin test (tuberculin test) to investigate if you have a tuberculosis infection.
• In case the bladder or urethra wall is damaged or injured during the introduction of the catheter, the treatment will have to be postponed until the injury heals. During the administration of OncoTICE, precautions are taken to not introduce contaminants into the urinary tract or unnecessarily traumatize the urinary mucosa.
• It is essential to rule out the presence of the HIV virus. A blood sample may be necessary to investigate this. Your doctor may also ask if there are any risk factors, such as having had unprotected sex, using dirty needles, or if you have used drugs or had blood transfusions.
• To protect your partner from transmission of the BCG bacteria, it is advised not to have sexual intercourse during the week following treatment with OncoTICE. If you use a condom, you can have sexual intercourse, as long as it is used correctly and does not break.
• You will be monitored after each OncoTICE instillation to avoid toxicity and systemic infection by the BCG bacteria.
• If accidental contamination of OncoTICE is suspected, a tuberculosis detection test will probably be performed at the time of the accident and 6 weeks later.
• If the tuberculin test is performed after treatment, the result may be positive.
• If you experience symptoms such as fever and weight loss of unknown origin, you should contact your doctor, as these symptoms could indicate a late outbreak of BCG infection. These symptoms can be delayed from months to years after the administration of the last dose of OncoTICE.

Using OncoTICE with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

The following medicines or therapies may reduce the effect of OncoTICE:

• Antibiotics, especially anti-tuberculosis drugs such as streptomycin, para-aminosalicylic acid (PAS), isoniazid, rifampicin, and ethambutol.
• Medicines that suppress the immune system (immunosuppressants).
• Medicines that suppress the production of bone marrow cells (bone marrow suppressants).
• Radiation therapy.

If you are using any of these medicines or treatments, your doctor will probably delay the treatment with OncoTICE until your current treatment is finished.

Note that these instructions may also apply to medicines that have been taken or used before or may be taken or used after.

Pregnancy and breastfeeding

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

OncoTICE should not be administered during pregnancy.

OncoTICE should not be administered during breastfeeding.

Driving and using machines

Very rarely, the ability to drive or use machines may be affected. However, try not to perform tasks that require special attention until you know how you tolerate the medicine.

3. How to use OncoTICE

OncoTICE should not be administered intravenously, subcutaneously, or intramuscularly.

OncoTICE should be administered directly into the bladder. OncoTICE should be applied by a doctor or nurse.

OncoTICE is administered in instillations in the bladder, usually once a week for 6 weeks, followed by one instillation per week for 3 consecutive weeks in months 3, 6, and 12 after the start of treatment. If necessary, the 3-week treatment schedule can be repeated every 6 months after the first year of treatment, but not for more than three years.

To administer OncoTICE, the contents of a vial, previously reconstituted, will be mixed with 50 ml of saline solution. First, your bladder will be emptied through the same catheter through which the OncoTICE solution will be instilled into the bladder. It is essential that you do not drink any liquid during the 4 hours before the start of treatment. The OncoTICE solution should remain in the bladder for two hours to obtain the optimal treatment result. In this way, the medicine will come into contact with the entire bladder wall. For this reason, you will be asked to move from time to time. It is very important not to urinate until the two hours of treatment have passed.

It is essential that in the 6 hours after treatment, you urinate in a sitting position and that two cups of domestic bleach are added to the toilet after each urination. The bleach and urine should be left in the toilet for 15 minutes before flushing the water.

If you receive moreOncoTICEthan you should

The OncoTICE suspension is prepared from a vial by medical personnel, and it is unlikely that you will be given an excess of OncoTICE. However, if this happens, your doctor will carefully check that there are no symptoms of BCG infection. If necessary, you will receive anti-tuberculosis medications.

In case of accidental exposure, consult your doctor, pharmacist, or call the Toxicological Information Service, phone 91 562 04 20, indicating the medicine.

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

4. Possible side effects

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

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

• bladder inflammation
• pain when urinating, frequent urination, and blood in the urine. In general, these symptoms disappear within two days.
• flu-like symptoms, such as fever, fatigue, and general malaise (feeling unwell). These symptoms usually appear even 4 hours after treatment and last from 24 to 48 hours.

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

• joint pain
• arthritis
• muscle pain
• nausea and vomiting
• abdominal pain
• diarrhea

• lung inflammation
• anemia
• urinary incontinence
• urinary tract infection
• urinary urgency
• abnormalities in urine tests
• febrile chills.

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

• skin rash
• hepatitis with jaundice (yellowing of the skin or eyes)
• abnormalities in liver function tests
• decrease in the number of red blood cells or platelets, possibly associated with symptoms such as fatigue and/or bruising
• decrease in white blood cells
• pus in the urine
• difficulty urinating
• bladder constriction and blockage of urine flow
• BCG infection in the body (tuberculosis infections), with the possibility of late onset. Symptoms can be delayed from months to years after the last dose.

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

• cough
• inflammation of the epididymis (a duct located in the testicles).

Very rare side effects (may affect up to 1 in 10,000 people):

• hair loss
• increased sweating
• dizziness (feeling of spinning)
• headache
• increased muscle tension
• abnormal sensation such as itching, burning, tingling, or rash
• conjunctivitis
• loss of appetite
• indigestion and gas
• confusion
• drowsiness
• weight loss
• low blood pressure
• bronchitis
• difficulty breathing
• throat pain
• runny nose
• swelling of the lymph nodes
• kidney function impairment
• granuloma (nodule in an organ)
• inflammation of the glans
• inflammation of the testicles
• Reiter's syndrome (inflammation of the eyes, joints, and genitourinary system)
• lupus vulgaris (skin tuberculosis)
• inflammation of the prostate
• elevation of prostate-specific antigen (PSA) (prostate analysis)
• burning, itching, and pain in the female genital area
• back pain

• chest pain

• fluid retention in the limbs.

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

• allergic reactions
• inflammation of blood vessels, including blood vessels in the brain (vasculitis)
• abnormal arterial dilation due to bacterial infection (infectious aneurysm)
• infectious endophthalmitis (eye inflammation).

Reporting of side effects:

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible side effects not listed in this leaflet. You can also report them directly through the Spanish Medicines and Health Products Agency's Pharmacovigilance System for Human Use: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of OncoTICE

Keep in the refrigerator (between 2°C and 8°C). Keep in the original packaging to protect it from light.

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

OncoTICE is stored in the hospital according to the manufacturer's instructions on the packaging. The expiration date is printed on it.

Do not use this medicine after the expiration date stated on the packaging after EXP.

6. Contents of the pack and other information

Composition of OncoTICE

• The active substance is the Bacillus Calmette-Guérin (BCG). It is a bacteria adapted for OncoTICE. Each glass vial contains 2-8 x 10^8 colony-forming units (CFU).
• The other components are lactose monohydrate, L-asparagine monohydrate, citric acid monohydrate (E-330), dipotassium hydrogen phosphate, magnesium sulfate heptahydrate, iron(III) citrate, zinc formate, and ammonium hydroxide (E-527), glycerol (E-422).

Appearance and packaging of the product

OncoTICE is presented as a powder for preparing an instillation liquid, which, once prepared, is introduced into the bladder through a catheter.

OncoTICE is available in packs of 1 and 3 vials, each containing approximately 2-8 x 10^8 colony-forming units of Calmette-Guérin bacteria.

Marketing authorization holder and manufacturer

Marketing authorization holder

Merck Sharp & Dohme of Spain, S.A.

Josefa Valcárcel, 42

28027 Madrid, Spain

Phone: 91 321 06 00

Manufacturer

N.V. Organon

Kloosterstraat 6

5349 AB Oss, Netherlands

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem, Netherlands

Date of the last revision of this leaflet:12/2021.

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/