Active substance: BCG TICE STRAIN

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36273.100 36273.BR
RA 8900 UK P6 (ref. 3.0)

RA 8900 UK S5 (ref. 3.0)

OncoTICE® powder for

OncoTICE® (Tice® BCG)
Information for the doctor

2-8 X 108 CFU Tice® BCG

1. Trade name of the medicinal product
OncoTICE® powder for instillation
fluid for intravesical use containing
2–8 x 108 CFU Tice BCG.

Information for the patient

In this leaflet:
1. What Oncotice is and what it is
used for
2. Before you are given Oncotice
3. How Oncotice is given
4. Possible side effects
5. How to store Oncotice
6. Further information
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
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). This must be treated first.
• You have blood in your urine.
• You have or think you have TB
(tuberculosis). Before you have
Oncotice, your doctor 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
doctor if any of the following apply to
❍ 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 doctor or pharmacist before being
given Oncotice.
Take special care with Oncotice
Check with your doctor or pharmacist
before being given the medicine if:
• Your bladder wall or the tube coming
into your bladder from your kidneys
(called the ‘ureter’) have been
damaged during previous treatment.

2. Qualitative and quantitative
OncoTICE® BCG 12.5 mg 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.

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 doctor or
pharmacist before being given Oncotice.
Taking other medicines
Please tell your doctor or pharmacist if
you are taking, or have recently taken
any other medicine. This includes
medicines obtained without a
prescription, including herbal medicines.

3. Pharmaceutical form
Powder for instillation fluid for
intravesical use.

Do not have Oncotice and talk to your
doctor straight away if:
• You are taking medicines for TB.

4. Clinical particulars
The following can lower the effect of
• antibiotics
• medicines which affect the immune
system (immuno-suppressants)
• medicines which affect the production
of bone marrow cells (bone marrow
• radiation treatment.
If you are having any of these medicines
or are having radiation treatment, your
doctor will probably delay giving you

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

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.

4.2 Posology and method of
For preparation of the OncoTICE
suspension see section 6.6.

Pregnancy and breast-feeding
Do not have Oncotice if you are pregnant
or breast-feeding. Ask your doctor or
pharmacist for advice before taking any
medicine if you are pregnant or

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

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

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.

Important information about some of the
ingredients of Oncotice
• Oncotice contains lactose (a type of
sugar). If you have been told by your
doctor that you cannot tolerate or
digest some sugars, talk to your
doctor before being given this
• This medicine contains a very small
amount of potassium (less than
1mmol or 39mg per dose). This means
it is essentially ‘potassium-free’.

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 every 6 months
beyond the first year of treatment
should be evaluated on the basis of
tumour classification and clinical

3. How Oncotice is given
You will always be given Oncotice by a
doctor or nurse.
Before it is given
• Do not drink any liquid the 4 hours
before Oncotice is given to you.
• You will be asked to pass water
immediately before Oncotice is given
to you.

Not recommended.

Being given your medicine
• First your genital area will be cleaned
with a sterile solution.
• A nurse will then pass a small flexible
tube into your bladder. This will
remove any urine that is still in your
• Oncotice is then run into your bladder
through this tube. This will only take a
few minutes.
• The tube will then be removed.

Intravesical instillation
Insert a catheter via the urethra into the
bladder and drain the bladder
completely. Connect the 50 ml syringe
containing the prepared OncoTICE
suspension to the catheter, and instil the
suspension into the bladder. 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

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.

suspension has sufficient contact with
the whole mucosal surface of the
bladder. Therefore the patient should
not be immobilised or, in case of a bedridden 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
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 resolved.
In patients with a positive Tuberculin
test, OncoTICE instillations are contraindicated 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
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.

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 antitumour efficacy and should therefore not
be used in combination with OncoTICE.

4.5 Interactions with other medicaments
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

4.7 Effects on ability to drive and use
Not applicable

Very common

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

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

Urinary tract infection

Blood and lymphatic system disorders

Abdominal pain, nausea, vomiting, diarrhoea

Musculoskeletal and connective tissue

Arthralgia, arthritis, myalgia

Renal and urinary disorders

Urinary incontinence, micturition urgency, urine analysis abnormal

General disorders and administration site


Infections and infestations

Tuberculous infections1

Blood and lymphatic system disorders

Pancytopenia, thrombocytopenia

Hepatobiliary disorders


Skin and subcutaneous tissue disorders

Rashes, eruptions and exanthems NEC1

Renal and urinary disorders

Bladder constriction, pyuria, urinary retention, ureteric obstruction


Hepatic enzyme increased

Respiratory, thoracic and mediastinal


Reproductive system and breast


Infections and infestations

Pharyngitis, orchitis, Reiter’s syndrome, Lupus vulgaris

Blood and lymphatic system disorders


Metabolism and nutrition disorders


Psychiatric disorders

Confusional state

Nervous system disorders

Dizziness, dysaesthesia3, hyperaesthesia3, paraesthesia, somnolence,
headache, hypertonia, neuralgia3

Eye disorders


Ear and labyrinth disorders


Vascular disorders


Respiratory, thoracic and mediastinal

Bronchitis, dyspnoea, rhinitis

Gastrointestinal disorders

Dyspepsia3, flatulence3

Skin and subcutaneous tissue disorders

Alopecia, hyperhidrosis

Musculoskeletal and connective tissue

Back pain

Renal and urinary disorders

Renal failure acute

Reproductive system and breast

Balanoposthitis, prostatitis, vulvovaginal discomfort3

General disorders and administration site

Chest pain, oedema peripheral, granuloma2


Very rare

Infections and infestations

Gastrointestinal disorders


Influenza-like illness, pyrexia, malaise, fatigue

Respiratory, thoracic and mediastinal


Cystitis, dysuria, pollakiuria, haematuria

General disorders and administration site

Renal and urinary disorders

Prostatic specific antigen increased, weight decreased

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

OncoTICE® (Tice® BCG)

OncoTICE® powder for

Information for the doctor

2-8 X 108 CFU Tice® BCG

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

5.0 Pharmacological properties
5.1 Pharmacodynamic properties
OncoTICE is an immunostimulating
agent (ATC code L 03 A).
It has anti-tumor activity, but the exact
mechanism of action is not known.
Study data suggest that an active
nonspecific 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
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.

Information for the patient

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

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 all of
your bladder.
• Do not drink any liquid for 2 hours
after you have been given Oncotice.
• After 2 hours you will be asked to pass
water, to empty your bladder. You
should do this while sitting down to
avoid splashing your urine around the
During the next 6 hours
• If you need to pass water again, also
do this while sitting down.
• Every time you pass water, add two
cups of household bleach to the toilet.
• Leave the bleach and urine to stand in
the toilet for 15 minutes before

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 Instruction for use/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

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 doctor will
talk to you about this.

Transfer 50 ml of the diluent into a
sterile container and add 1 ml from the
sterile container to the vial. Allow to
stand for a few minutes then gently
swirl until a homogenous suspension is
obtained. Forceful agitation should be

Having sex in the week after having
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.

6. Pharmaceutical particulars
6.1 List of excipients
Citric Acid (E330)
Dibasic Potassium Phosphate
Magnesium Sulfate
Ammonium Citrate
Glycerol (E422)
Zinc formate
Ammonium Hydroxide (E527)

Preparation of the solution for
Transfer the reconstituted contents of
the vial back into the container. Rinse
the vial by transfering 1 ml from the
container back into the vial, then add
back to the container. Mix the
suspension carefully.
The suspension, with a total volume of
50 ml is now ready for instillation; it
contains a total of 2–8 x 108 CFU of
Tice BCG.

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

7. Marketing authorisation holder
N.V. Organon, Kloosterstraat 6,
PO Box 20, 5340 BH, Oss,
The Netherlands

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

If you have more Oncotice than you should
Oncotice is made up from a standard
bottle by your doctor, pharmacist or
nurse. It is unlikely that you will receive
too much Oncotice. If you do have too
much, your doctor will check carefully to
see whether you have BCG infection.
If necessary you will need to have
treatment for TB.

9. Date of first authorisation/renewal of
4 August 2000/19 March 2004

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

8. Marketing authorisation number
PL 05003/0046

If you notice the following side effects,
see your doctor 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 tightness
❍ sweating
❍ sore throat
❍ cold in the nose
❍ swelling of your lymph glands.
See your doctor straight away if you
notice any of these side effects.

10. Date of (partial) revision of the text
June 2004
REF: USoncviV5.2

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.
Also commonly observed are malaise, a
low to medium grade fever and/or
influenza-like symptoms (fever, rigors,
malaise and myalgia). 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
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 initially by pneumonitis,
hepatitis and/or cytopenia after a period
of fever and malaise during which
symptoms progressively increase.
Patients with symptoms of therapyinduced 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

Other side effects include:
Very common
(affects more than 1 in 10 people)
• bladder infection, pain when passing
water, having to pass water often,
feeling the need to pass water and
bloody urine. Usually this goes away
within two days.
• flu-like symptoms such as fever and
feeling off-colour and tired (malaise).
This usually happens about 4 hours
after treatment and last for 24 to
48 hours.
(affects less than 1 in 10 people)
• painful joints or arthritis
• muscle pain or stiffness
• feeling sick (nausea) and being sick

36273.BRA 36273.A

abdominal pain or diarrhoea
chest infection
problems with passing water or having
a large amount of blood in your urine
• shivering with a high temperature
(affects less than 1 in 100 people)
• skin rash
• jaundice (yellow colour of your skin or
• pus in your urine
• difficulty passing water
• low blood count (shown in blood tests)
(affects less than 1 in every 1,000 people)
• inflammation of the genitals or prostate.
Very Rare
(affects less than 1 in every 10,000 people)
• headache
• back pain
• increased muscle tension
• swollen legs or arms
• low blood pressure
• blood problems (shown in blood tests)
• flatulence or discomfort following meals
• loss of appetite or weight loss
• hair loss
• prickling or itching skin
• open sores on your skin
• eye infection
• feeling confused, sleepy or dizzy
• kidney problems
Tell your doctor if any side effect is severe
or lasts longer than 48 hours.
If you notice any side effects not listed in
this leaflet, tell your doctor or pharmacist.
5. How to store Oncotice
Keep Oncotice out of the reach and sight of
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
• The other ingredients are: lactose,
asparagine, citric acid (E330), potassium
phosphate, magnesium sulfate, iron
ammonium citrate, glycerol (E422),
ammonium hydroxide (E527), zinc
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),
each containing 1 dose of 12.5 mg
(equivalent to 2 to 8 x 108 CFU) of BCG.
The Marketing authorisation holder is:
N.V. Organon
PO Box 20, 5340 BH, Oss
The Netherlands
The Manufacturer is:
Organon Teknika Corporation
100 Rodolphe Street
Building 1300, Durham, NC27712
This leaflet was last updated in December
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
Product name: Oncotice
Reference Number: PL 05003/0046
This is a service provided by the Royal
National Institute for Blind People

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.