Oncotice powder for Instillation Fluid for intravesical use containing 2-8 x 10^8 Cfu Tice BCG – patient leaflet, side effects, dosage

1. What Oncotice is and what it is used for

Oncotice contains something called ‘BCG’ (‘Bacillus Calmette-Guérin’). This is a bacteria which has been specially altered, so that it can be used as a medicine.

Oncotice is used to:

• treat bladder cancer

• prevent bladder cancer from coming back after bladder

  surgery.

It comes as a powder which is mixed with saline (salt water). It is then run into your bladder through a tube. BCG is also used as a vaccine for TB (tuberculosis). Oncotice is a much stronger sort of BCG that can’t be used as a vaccine.

2. Before you are given Oncotice

Oncotice should not be given if:

• You have a urinary tract infection (UTI) or cystitis

  (inflammation of the bladder). This must be treated first.

• You have blood in your urine.

• You have or think you have TB (tuberculosis). Before you

  have Oncotice, your healthcare provider may do a skin reaction test, to see if you have TB. This is called a Tuberculin Test. If you have had Oncotice before, this may give you a positive result in this test.

• You are HIV-positive. You may need to have a blood test for HIV. Tell your healthcare provider if any of the following apply to you:
• you have been a drug user and have shared a needle
• you have had unsafe sex
• you have had a blood transfusion.

• you have problems with your immune system. This could be

  something which runs in the family or is caused by an illness or other medicines you are taking. Do not have Oncotice if any of the above apply to you. If you are not sure, talk to your healthcare provider before being given Oncotice. Take special care with Oncotice

Check with your healthcare provider before being given the medicine if:

• Your bladder wall or the tube that goes into your bladder

  from your kidneys (called the ureter) have been damaged during previous treatment. Treatment with Oncotice will not be given until this has healed.

If you are not sure if any of the above apply to you talk to your healthcare provider before being given Oncotice. Taking other medicines

Please tell your healthcare provider if you are taking or have recently taken any other medicine. This includes medicines obtained without a prescription, including herbal medicines. Do not have Oncotice and talk to your healthcare provider straight away if:

• You are taking medicines for TB.

The following can lower the effect of Oncotice:

• antibiotics

• medicines which affect the immune system

  (immuno-suppressants)

• medicines which affect the production of bone marrow cells

  (bone marrow suppressants)

• radiation treatment.

  If you are having any of these medicines or are having radiation treatment, your healthcare provider will probably delay giving you Oncotice.

  Using Oncotice with food and drink

  • Do not drink any liquid for 4 hours before you are given

    Oncotice.

  • Do not drink any liquid for 2 hours after you have been

    given Oncotice.

Pregnancy and breast-feeding

Do not have Oncotice if you are pregnant or breast-feeding. Ask your healthcare provider for advice before taking any medicine if you are pregnant or breast-feeding.

Driving and using machines

Oncotice will not affect your being able to drive or use any tools or machines.

Important information about some of the ingredients of Oncotice

• Oncotice contains lactose (a type of sugar). If you have been

  told by your healthcare provider that you cannot tolerate or digest some sugars, talk to your healthcare provider before being given this medicine.

• This medicine contains a very small amount of potassium

  (less than 1mmol or 39 mg per dose). This means it is essentially ‘potassium-free’.

3. How Oncotice is given

You will always be given Oncotice by a healthcare provider. Before it is given

• Do not drink any liquid the 4 hours before Oncotice is given

  to you.

• You will be asked to urinate immediately before Oncotice is

  given to you.

Being given your medicine

• First your genital area will be cleaned with a sterile solution.

• A healthcare provider will then pass a small flexible tube into

  your bladder. This will remove any urine that is still in your bladder.

• Oncotice is then run into your bladder through this tube. This

  will only take a few minutes.

• The tube will then be removed.

After it has been given

• Oncotice will be left in your bladder for 2 hours.

• During this time you should move around a little. This

  makes sure that the Oncotice is spread around your entire bladder wall.

• Do not drink any liquid for 2 hours after you have been given

  Oncotice.

• After 2 hours you will be asked to urinate, to empty your

  bladder. You should do this while sitting down to avoid splashing your urine around the toilet.

During the next 6 hours

• If you need to urinate again, also do this while sitting down.

• Every time you urinate, add two cups of household bleach to

  the toilet.

• Leave the bleach and urine to stand in the toilet for 15 minutes

  before flushing.

How often Oncotice is given

Oncotice is usually given once a week for 6 weeks. After this some people have ‘maintenance therapy’, where you may be given more doses. Your healthcare provider will talk to you about this.

Having sex in the week after having Oncotice

If you have sexual intercourse during the week after being given the medicine, you must use a condom. This will lower the chance of the BCG bacteria being passed to your partner. If you have more Oncotice than you should

Oncotice is made up from a standard bottle by your healthcare provider. It is unlikely that you will receive too much Oncotice. If you do have too much, your healthcare provider will check carefully to see whether you have BCG infection. If necessary you will need to have treatment for TB.

4. Possible side effects

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

OncoTICE^® powder for suspension

2-8 X 10⁸ CFU Tice^® BCG

Information for the patient

1. 1.

   NAME OF THE MEDICINAL PRODUCT

   OncoTICE^® powder for instillation fluid for intravesical use containing 2-8 x 10⁸ CFU Tice BCG.

2. 2.

   QUALITATIVE AND QUANTITATIVE COMPOSITION

   OncoTICE BCG 12.5mg per vial containing 2-8 x 10⁸ CFU Tice BCG.

   After reconstitution in 50 ml saline the suspension contains 0.4-1.6 x 10⁷ CFU/ml.

   OncoTICE is a freeze-dried preparation containing attenuated bacilli of Mycobacterium bovis, prepared from a culture of Bacillus Calmette-Guérin (BCG). For excipients, see section 6.1.

3. 3.

   PHARMACEUTICAL FORM

   Powder for instillation fluid for intravesical use.

4. 4. CLINICAL PARTICULARS

4.1 Therapeutic indications

OncoTICE is indicated for treatment of primary or concurrent carcinoma-in-situ of the urinary bladder and for the prevention of recurrence of high grade and/or relapsing superficial papillary transitional cell carcinoma of the urinary bladder (Stage Ta (grade 2 or 3) or T1 (grade 1, 2 or 3)) after transurethral resection.

OncoTICE is only recommended for stage Ta grade 1 papillary tumours, when there is judged to be a high risk of tumour recurrence.

4.2 Posology and method of administration

For preparation of the OncoTICE suspension see section 6.6.

Posology

Adults and the elderly

The contents of one vial of OncoTICE, reconstituted and diluted as indicated, are instilled into the urinary bladder.

Induction treatment

Weekly instillation with OncoTICE during the first 6 weeks. When used as an adjuvant therapy after TUR of a superficial urothelial cell carcinoma of the bladder (see “Therapeutic indications”), treatment with OncoTICE should be started between 10 and 15 days after performing the TUR. Treatment should not be started until mucosal lesions after TUR have healed. Treatment should also be delayed in cases of gross haematuria or major bladder irritability.

Maintenance treatment

Maintenance treatment consists of weekly instillation with OncoTICE during 3 consecutive weeks at months 3, 6, and 12 after initiation of the treatment. The need for maintenance treatment every 6 months beyond the first year of treatment should be evaluated on the basis of tumour classification and clinical response.

Paediatric population

No data are available

Method of administration

Intravesical instillation

Insert a catheter via the urethra into the bladder and drain the bladder completely. Connect the 50ml syringe containing the prepared OncoTICE suspension to the catheter and instil the suspension into the bladder. If a closed-system transfer device is not available, the 50 ml OncoTICE suspension is instilled into the bladder by gravity flow. After instillation, remove the catheter. The instilled OncoTICE suspension must remain in the bladder for a period of 2 hours. During this period care should be taken that the instilled OncoTICE suspension has sufficient contact with the whole mucosal surface of the bladder. Therefore, the patient should not be immobilised or, in case of a bed-ridden patient, should be turned over from back to abdomen and vice versa every 15 minutes. After two hours, have the patient void the instilled suspension in a sitting position.

Urine should be voided in a sitting position for 6 hours after treatment and two cups of household bleach should be added to the toilet before flushing. The bleach and urine should be left to stand in the toilet for 15 minutes before flushing.

NOTE: The patient must not ingest any fluid for a period starting 4 hours prior to instillation, until bladder evacuation is permitted (i.e., 2 hours after instillation).

4.3 Contra-indications

Urinary tract infections. Therapy with OncoTICE should be interrupted until the bacterial culture from urine becomes negative and therapy with antibiotics and/or urinary antiseptics is stopped.

Gross haematuria. In these cases OncoTICE therapy should be stopped or postponed until the haematuria has been successfully treated or has resolved.

In patients with a positive Tuberculin test, OncoTICE instillations are contra-indicated only if there is supplementary medical evidence for an active tuberculous infection.

Treatment with anti-tuberculosis drugs like streptomycin, para-amino-salicylic acid (PAS), isoniazid (INH), rifampicin and ethambutol.

Impaired immune response irrespective of whether this impairment is congenital or caused by disease, drugs or other therapy.

Positive HIV serology.

Pregnancy and lactation.

4.4 Special warnings and special precautions for use

Before the first intravesical instillation of OncoTICE, a Tuberculin test (PPD) should be performed. If the test is positive, OncoTICE instillations are contraindicated only if there is supplementary medical evidence for an active tuberculous infection.

Traumatic catheterisation or other injuries to the urethra or bladder mucosa can promote systemic BCG infection. Administration of OncoTICE should be delayed in such patients until mucosal damage has healed.

It is recommended that patients known to be at risk of HIV infection be adequately screened prior to commencing therapy.

Patients should be monitored for the presence of symptoms of systemic BCG infection and signs of toxicity after each intravesical treatment.

OncoTICE should not be administered intravenously, subcutaneously or intramuscularly.

In order to protect the partner, the patient should be recommended to either refrain from intercourse within one week after OncoTICE instillation, or to use a condom.

The use of OncoTICE may sensitise patients to tuberculin resulting in a positive reaction to PPD.

Reconstitution and preparation of the OncoTICE suspension for instillation and administration should be performed under aseptic conditions.

Spillage of OncoTICE suspension may cause Tice BCG contamination. Any spilled OncoTICE suspension should be cleaned by covering with paper towels soaked with tuberculocidal disinfectant, such as household bleach, for at least 10 minutes. All waste materials should be disposed of as biohazard material

Accidental exposure to Tice BCG could occur through self-inoculation, by dermal exposure through an open wound, or by inhalation or ingestion of OncoTICE suspension. Tice BCG exposure should not produce significant adverse health outcomes in healthy individuals. However, in case of suspected, accidental self-inoculation, PPD skin testing is advised at the time of the accident and six weeks later to detect skin test conversion.

4.5 Interaction with other medicinal products and other forms of interaction

Tice BCG is sensitive to most antibiotics and in particular to the routinely used anti-tuberculosis drugs like streptomycin, para-amino salicylic acid (PAS), isoniazid (INH), rifampicin and ethambutol. Therefore, the anti-tumour activity of OncoTICE may be influenced by concomitant therapy with antibiotics. If a patient is being treated with an antibiotic it is recommended to postpone the intravesical instillation until the end of the antibiotic-treatment (see also “Contra-indications”).

Immunosuppressants and/or bone marrow depressants and/or radiation may interfere with the development of the immune response and thus with the anti-tumour efficacy and should therefore not be used in combination with OncoTICE.

4.6 Pregnancy and lactation

OncoTICE instillation for carcinoma of the bladder is contraindicated during pregnancy and lactation (see section 4.3).

4.7 Effects on ability to drive and use machines

Not relevant

4.8 Undesirable effects

The side effects of intravesical OncoTICE therapy are generally mild and transient. Toxicity and side-effects appear to be directly related to the cumulative CFU count of BCG administered with the various instillations. Approximately 90% of patients develop local irritative symptoms in the bladder. Pollakiuria and dysuria are reported very frequently. The cystitis and typical inflammatory reactions (granulomas) which occur in the mucosa of the bladder after instillation of BCG, and which cause these symptoms, may be an essential part of the anti-tumour activity of the BCG. In most cases, the symptoms disappear within two days after instillation and the cystitis does not require treatment. During maintenance treatment with BCG, the symptoms of cystitis may be more pronounced and prolonged. In these cases, when severe symptoms are present, isoniazid (300 mg daily) and analgesics can be given until disappearance of symptoms.

Table 1 Side effects reported during post-marketing surveillance

Table 1 Side effects reported during post-marketing surveillance (Continued)

Information for the Doctor Information for the Doctor

NEC = not elsewhere classified

¹ High Level Term instead of Preferred Term

² Granuloma NOS has been observed in various organs including the aorta, bladder, epididymis, gastrointestinal tract, kidney, liver, lungs, lymphnodes, peritoneum, prostate

³ Only isolated cases reported during post-marketing surveillance

Also commonly observed are malaise, a low to medium grade fever and/or influenza-like symptoms (fever, rigors, malaise and myalgia) which may accompany the localised, irritative toxicities that often reflect hypersensitivity reactions and be treated symptomatically. These symptoms usually appear within 4 hours after instillation and last for 24 to 48 hours. Fever higher than 39°C typically resolves within 24 to 48 hours when treated with antipyretics (preferably paracetamol) and fluids. However, it is frequently not possible to distinguish these uncomplicated febrile reactions from early systemic BCG infection and antituberculosis treatment may be indicated. Fever above 39°C that does not resolve within 12 hours despite antipyretic therapy must be considered as systemic BCG-infection, necessitating clinical confirmatory diagnostics and treatment.

Systemic BCG infections could be due to traumatic catheterisation, bladder perforation or premature BCG instillation after extensive TUR of a superficial carcinoma of the bladder. These systemic infections may be manifested by pneumonitis, hepatitis, cytopenia, vasculitis, infective aneurysm and/or sepsis after a period of fever and malaise during which symptoms progressively increase. Patients with symptoms of therapy-induced systemic BCG infection should be adequately treated with anti-tuberculosis drugs according to treatment schedules used for tuberculosis infections. In these cases, further treatment with Tice BCG is contraindicated.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions 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.

4.9 Overdose

Overdosage occurs when more than one vial of OncoTICE is administered per instillation. In case of overdosage, the patient should be closely monitored for signs of systemic BCG infection and if necessary treated with anti-tuberculosis drugs.

1. 5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

OncoTICE is an immunostimulating agent (ATC code L 03-AX03).

It has anti-tumor activity, but the exact mechanism of action is not known. Study data suggest that an active non-specific immune response takes place. BCG invokes a local inflammatory response involving a variety of immune cells, such as macrophages, natural killer cells and T cells.

5.2 Pharmacokinetic Properties

For the treatment and recurrence prophylaxis of bladder cancer, the attachment of BCG to the bladder wall after voiding has been shown to be important. This allows a targeted pharmacological effect at the site of application.

5.3 Preclinical safety data

As a result of the wide clinical application of BCG vaccination in the preceding decades the risks of BCG in human subjects are well-characterised. Intra-vesical administration to dogs has been found to be safe and without significant toxicity. No evidence of birth defects, genetic damage or carcinogenecity in humans are available from the extensive adverse reaction literature of BCG used as a vaccine.

1. 6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose

Asparagine

Citric Acid (E330)

Dibasic Potassium Phosphate

Magnesium Sulfate

Iron Ammonium Citrate

Glycerol (E422)

Zinc formate

Ammonium Hydroxide (E527)

6.2 Incompatibilities

OncoTICE is incompatible with hypo and hypertonic solutions. OncoTICE should only be mixed with physiological saline as described in section 6.6. Other incompatibility studies have not been performed.

6.3 Shelf life

12 months

In-use stability of the reconstituted product has been demonstrated for 2 hours at 2-8°C protected from light. From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

6.4 Special precautions for storage

Store at 2-8°C, protect from light.

6.5 Nature and contents of containers

2 ml Type 1 glass vials in packs of 1 and 3.

6.6 Special precautions for disposal and other handling

OncoTICE contains live, attenuated mycobacteria. Because of the potential risk for transmission, it should be prepared, handled and disposed of as a biohazard material (see section 4.4).

Perform the following procedures under aseptic conditions using sterile physiological saline solution as the diluent and suitable techniques to ensure protection of the health care worker. The use of closed-system transfer device products may be considered when transferring OncoTICE from primary packaging to instillation equipment.

Reconstitution

Transfer 50ml of the diluent into a sterile container and add 1ml from the sterile container to the vial. Ensure that the needle is inserted through the center of the rubber stopper. Allow to stand for a few minutes then gently swirl until a homogenous suspension is obtained. Forceful agitation should be avoided.

Preparation of the solution for instillation

Transfer the reconstituted contents of the vial back into the container. Rinse the vial by transferring 1ml from the container back into the vial, then add back to the container. If a closed-system transfer device is not available, dilute the reconstituted 1ml suspension in sterile physiological saline up to a volume of 49ml. Then rinse the empty vial with 1ml of sterile physiological saline. Add the rinse fluid to the reconstituted suspension for a final volume of 50ml. Mix the suspension carefully.

The suspension, with a total volume of 50ml is now ready for instillation; it contains a total of 2-8 x 10⁸ CFU of Tice BCG.

1. 7.

   MARKETING AUTHORISATION HOLDER

   Merck Sharp & Dohme (UK) Limited

   120 Moorgate

   London

   EC2M 6UR

   UK

2. 8.

   MARKETING AUTHORISATION NUMBER

   PL 53095/0003

3. 9.

   DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

   28 April 1998/28 April 2003

4. 10.

   LAST REVISED

   August 2025

© 2025 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. All rights reserved.

II-082[TIL]

XXXXXXXX/XX-X TKBA

For Position Only

If you notice the following side effects, see your healthcare provider straight away:

• a high temperature (fever) above 39 °C that lasts for more

  than 12 hours, even after taking medicines like paracetamol to lower your temperature.

• signs of a BCG or TB infection:
• cough or bronchitis
• chest pain or shortness of breath
• sweating
• sore throat
• runny nose
• swelling of your lymph glands.

See your healthcare provider straight away if you notice any of these side effects.

The following side effects have been reported but the frequency cannot be estimated from the available information (frequency not known):

• allergic reactions that can range from mild to severe.

  Symptoms may include rash, itching, or more severe skin reactions.

• BCG infection in the blood (sepsis). Severe condition

  with multiple symptoms that may include fever, malaise, chills, sweats, weight loss and shortness of breath.

• abnormal arterial dilation for bacterial infection (infective

  aneurysm). Severe condition with symptoms that may include abdominal and/or back pain and fever.

• inflammation of the blood vessels. Severe condition with

  multiple symptoms that may include fever, headache, fatigue, weight loss, and general aches and pains.

• a serious and potentially life-threatening condition where the

  immune system becomes overactive and produces too many infection fighting cells, which can cause inflammation and damage to body’s own tissues and organs (hemophagocytic lymphohistiocytosis). Symptoms may include fever that doesn’t go away, feeling very tired or weak, looking pale, feeling lightheaded or short of breath, or easy bruising. Other side effects include:

Very common

(affects more than 1 in 10 people)

• bladder inflammation, pain when urinating, having to

  urinate often, and bloody urine. Usually this goes away within two days.

• flu-like symptoms such as fever, fatigue and feeling

  off-colour and tired (malaise). This usually happens about 4 hours after treatment and lasts for 24 to 48 hours. Common

(affects less than 1 in 10 people)

• painful joints or arthritis
• muscle pain or stiffness
• nausea and vomiting
• abdominal pain or diarrhoea
• anaemia
• problems urinating
• shivering with a high temperature (fever)
• lung inflammation
• urinary tract infection
• urge to urinate
• abnormal urine lab test

Uncommon

(affects less than 1 in 100 people)

• skin rash
• jaundice (yellow colour of your skin or eyes)
• pus in your urine
• difficulty urinating

• decreased amount of red blood cells or platelets possibly

  associated with symptoms such as fatigue and / or bruises

• decrease of white blood cells
• abnormal liver function test
• bladder constriction and blocked urine flow
• tuberculosis infections

Rare

(affects less than 1 in every 1,000 people)

• inflammation of the epididymis (tube at the back of the

  testicles)

• cough.

Very Rare

(affects less than 1 in every 10,000 people)

• headache
• back pain
• increased muscle tension

• swollen legs or arms

  • low blood pressure
  • flatulence or discomfort following meals
  • loss of appetite or weight loss
  • hair loss
  • prickling, burning, pins and needles or itching skin
  • eye infection
  • feeling confused, sleepy or dizziness (spinning sensation)
  • kidney problems
  • increased perspiration
  • bronchitis
  • shortness of breath
  • sore throat
  • runny nose
  • swelling of the lymph glands
  • granuloma (nodule in an organ)
  • inflammation of the glans
  • inflammation of the testicles
  • inflammation of the prostate
  • Reiter’s syndrome (inflammation of the eyes, joints and genitourinary system)
  • Lupus vulgaris (tuberculosis of the skin)
  • elevation of Prostatic specific antigen (PSA) (prostate laboratory test)
  • burning, itching and soreness in the female genital area
  • chest pain

In case you develop these symptoms or any new or worsening symptoms, you are advised to contact your healthcare provider, immediately.

Reporting of side effects

If you get any side effects, talk to your healthcare provider. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: 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 Oncotice

Keep Oncotice out of the reach and sight of children. Oncotice will be stored in the hospital according to the instructions given by the manufacturer on the packaging. Store at 2 °C to 8 °C (in a refrigerator). Do not use Oncotice after the expiry date which is stated on the carton and label.

6. Further information

What Oncotice contains

• The active substance is Bacillus Calmette-Guérin (BCG). It is a specially treated bacteria to be used as a medicine.

• The other ingredients are: lactose, asparagine, citric acid

  (E330), potassium phosphate, magnesium sulfate, iron ammonium citrate, glycerol (E422), ammonium hydroxide (E527), zinc formate.

What Oncotice looks like and contents of the pack

Oncotice is a freeze-dried powder, packed in 2 ml glass vials (available in packs of 1 or 3), each containing 1 dose of 12.5 mg (equivalent to 2 to 8 x 10⁸ CFU) of BCG.

Marketing Authorisation Holder:

Merck Sharp & Dohme (UK) Limited

120 Moorgate

London

EC2M 6UR

UK

Manufacturer is:

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem

The Netherlands

This leaflet was last revised in August 2025

To listen to or request a copy of this leaflet in braille, large print or audio please call, free of charge: 0800 198 5000 (UK Only) Please be ready to give the following information: Product name: Oncotice

Reference Number: PL 53095/0003

This is a service provided by the Royal National Institute for Blind People

© 2025 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. All rights reserved

II-082

Information for the patient

XXXXXXXX/XX-X

Read all of this leaflet carefully before you start using this medicine.

• Keep this leaflet. You may need to read it again.

• If you have any further questions, please ask

  your doctor or pharmacist.

• This medicine has been prescribed for you.

  Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

• If any of the side effects gets serious, or if you

  notice any side effect not listed in this leaflet, please tell your doctor or pharmacist. In this leaflet:

• What Oncotice is and what it is used for
• Before you are given Oncotice

OncoTICE^® powder for suspension

2-8 X 10⁸ CFU Tice^® BCG