ONCOTICE

PATIENT PACKAGE INSERT IN ACCORDANCE WITH THE

PHARMACISTS REGULATIONS (PREPARATIONS) 1986

This medicine is marketed upon physician’s prescription only

OncoTICE

®

Powder for solution for instillation

Each vial contains:

2-8 x 10

CFU Tice BCG.

For a list of inactive ingredients see section 6.1 “What OncoTICE contains?”. See also section 2.7

“Important information about some of the ingredients of OncoTICE”.

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

This leaflet contains concise information about the medicine. If you have any further questions, refer

to the doctor or pharmacist.

This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their

medical condition seems similar to yours.

1. WHAT ONCOTICE IS INTENDED FOR?

OncoTICE is used to:

treat bladder cancer

prevent bladder cancer from coming back after bladder surgery

Therapeutic group: immunostimulating agent

2. BEFORE USING OncoTICE

2.1 Do not use OncoTICE 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 tuberculosis. Before you have OncoTICE, your doctor may do a skin

reaction test, to see if you have tuberculosis. 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.

Are pregnant or breast-feeding.

Tell your doctor 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 doctor or

pharmacist before being given OncoTICE.

2.2 Special warnings regarding use of OncoTICE

Check with your doctor or pharmacist 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 doctor or pharmacist before being given

OncoTICE.

2.3 Interactions with other medicines

If you are taking, or have recently taken, other medicines including non-prescription medicines and

nutritional supplements, tell the doctor or pharmacist. Especially if you are taking:

Medicines for tuberculosis - do not have OncoTICE and talk to your doctor straight away.

Antibiotics; medicines which affect the immune system (immuno-suppressants); medicines which

affect the production of bone marrow cells (bone marrow suppressants); radiation treatment- these

can lower the effect of OncoTICE. If you are having any of these medicines or are having radiation

treatment, your doctor will probably delay giving you OncoTICE.

2.4 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.

2.5 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 breast-feeding.

2.6 Driving and using machines

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

2.7 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 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?

Dosage is according to doctor's instructions only.

Treatment usually includes one instillation a week for 6 weeks. Afterwards, one instillation a week for 3

weeks at months 3, 6 and 12 after initiation of OncoTICE treatment. If necessary treatment can be

repeated every 6 months with one instillation a week for 3 weeks.

Attention: Do not swallow! This medicine is intended for instillation into the urinary bladder only.

Directions for use:

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 nurse 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.

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.

Do not exceed the recommended dose.

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 tuberculosis.

If you or if a child has accidentally swallowed the medicine, proceed immediately to a doctor or to a hospital

emergency room and bring the package of the medicine with you.

Treatment should be completed as recommended by the doctor.

Even if there is an improvement in your health, do not discontinue use of this medicine before consulting your

doctor.

Do not take medicines in the dark! Check the label and the dose each time you take a medicine. Wear

glasses if you need them.

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

4. SIDE EFFECTS

As with any medicine, OncoTICE may cause side effects in some users. Do not be alarmed by reading the

list of side effects, you may not suffer from any of them.

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 tuberculosis infection:

cough or bronchitis

chest pain or shortness of breath

sweating

sore throat

runny nose

swelling of your lymph glands.

See your doctor 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.

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 these

go away within two days.

flu-like symptoms such as fever, fatigue and feeling off-colour and tired (malaise). These usually

happen 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

Tell your doctor if any side effect is severe or lasts longer than 48 hours. If a side effect appears, if

any of the side effects worsens or if you suffer from a side effect not mentioned in this leaflet,

consult with the doctor.

Side effects can be reported to the Ministry of Health by using the link "Adverse Drug Reactions Report" at

the home page of the Ministry of Health's web site (www.health.gov.il) which refers to the online side effects

reporting form, or by using the link:

https://sideeffects.health.gov.il

5. HOW TO STORE OncoTICE?

Avoid Poisoning! This medicine and any other medicine must be stored in a safe place out of the reach

and sight of children and/or infants, in order to avoid poisoning. Do not induce vomiting unless explicitly

instructed to do so by a doctor.

OncoTICE will be stored in the hospital according to the instructions given by the manufacturer on the

packaging.

Do not use the medicine after the expiry date (exp. date) which is stated on the pack. The expiry date

refers to the last day of the indicated month.

Storage conditions:

Store at 2-8ºC, protect from light.

Medicines should not be disposed of via wastewater or household waste. Ask the pharmacist how to

dispose of medicines you no longer use. These measures will help to protect the environment.

6. FURTHER INFORMATION

6.1 What OncoTICE contains?

In addition to the active ingredient, OncoTICE also contains:

Lactose monohydrate, L-Asparagine monohydrate, citric acid monohydrate, potassium phosphatephosphate

dibasic, magnesium sulfatesulfate heptahydrate, iron ammonium citrate, glycerin, zinc formate, ammonium

hydroxide

6.2 What OncoTICE looks like and contents of the pack

OncoTICE is a white to off-white cake or powder, packed in 2 ml glass vial (packs of 1 or 3 vials).

Not all pack sizes are marketed.

6.3 Marketing authorization holder

Merck Sharp & Dohme (Israel-1996) Company Ltd., P.O.Box 7121, Petah-Tikva 49170

6.4 Manufacturer

Organon, N.V., Oss, The Netherlands

Revised in August 2020

Drug registration no. listed in the official registry of the Ministry of Health: 103-18-28561

OncoTICE

®

Powder for solution for instillation

1.

NAME OF THE MEDICINAL PRODUCT

OncoTICE

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

OncoTICE BCG containing 2-8 x 10

CFU Tice BCG per vial.

After reconstitution in 50 ml saline the suspension contains 0.4-1.6 x 10

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.

PHARMACEUTICAL FORM

Powder for solution for instillation

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

OncoTICE is used as a treatment of flat urothelial cell carcinoma in situ (CIS) of the bladder

and as an adjuvant therapy after transurethral resection (TUR) of a primary or relapsing

superficial papillary urothelial cell carcinoma of the bladder stage Ta (grade 2 or 3) or T1 (grade

1 2 or 3).

OncoTICE is only recommended for stage Ta grade 1 papillary tumors when there is judged to

be a high risk of tumor recurrence.

4.2 Posology and method of administration

For preparation of the OncoTICE suspension see section 6.6.

Posology

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. Delay in treatment should be considered in cases of major bladder irritability.

Maintenance treatment

Maintenance 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.

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 instill 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

catheter.

instilled

OncoTICE

suspension

must

remain in the bladder for a period of

2 hours. During this period care should be taken

that

instilled

OncoTICE suspension

sufficient

contact

with

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:

patient

must

ingest

fluid

period

starting

hours

prior

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

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.

OncoTICE

sensitise

patients

tuberculin

resulting

positive

reaction to PPD.

Reconstitution

preparation

OncoTICE

suspension

instillation

administration should be performed under aseptic conditions.

Spillage

OncoTICE

suspension

cause

Tice

contamination.

spilled

OncoTICE

suspension

should

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

Tice

could

occur

through

self-inoculation,

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

sensitive

most

antibiotics

particular

routinely used anti-

tuberculosis

drugs

like

streptomycin,

para-amino

salicylic

acid

(PAS),

isoniazid

(INH),

rifampicin

ethambutol.

Therefore

anti-tumour

activity

OncoTICE

may be

influenced by concomitant therapy with antibiotics. If a patient is being treated

with

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

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

side

effects

intravesical

OncoTICE

therapy

generally

mild

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

present,

isoniazid

(300

daily)

analgesics can be given until disappearance of symptoms.

Table 1 Side effects reported during post-marketing surveillance

Occurrence

MedDRA SOClass

Preferred terms

Very common

(>1/10)

Renal and urinary disorders

Cystitis, dysuria, pollakiuria, haematuria

General disorders and

administration site conditions

Influenza-like illness, pyrexia, malaise, fatigue

Common

(>1/100,<1/10)

Infections and infestations

Urinary tract infection

Blood and lymphatic system

disorders

Anaemia

Respiratory, thoracic and

mediastinal disorders

Pneumonitis

Gastrointestinal disorders

Abdominal pain, nausea, vomiting, diarrhoea

Musculoskeletal and connective

tissue disorders

Arthralgia, arthritis, myalgia

Renal and urinary disorders

Urinary incontinence, micturition urgency, urine analysis

abnormal

General disorders and

administration site conditions

Rigors

Uncommon

(>1/1,000, <1/100)

Infections and infestations

Tuberculous infections

Blood and lymphatic system

disorders

Pancytopenia, thrombocytopenia

Hepatobiliary disorders

Hepatitis

Skin and subcutaneous tissue

disorders

Rashes, eruptions and exanthems NEC

Renal and urinary disorders

Bladder constriction, pyuria, urinary retention, ureteric

obstruction

Investigations

Hepatic enzyme increased

Rare

(>1/10,000, <1/1,000)

Respiratory, thoracic and

mediastinal disorders

Cough

Reproductive system and breast

disorders

Epididymitis

Very rare

(<1/10,000)

Infections and infestations

Pharyngitis, orchitis, Reiter’s syndrome, Lupus vulgaris

Blood and lymphatic system

disorders

Lymphadenopathy

Metabolism and nutrition

disorders

Anorexia

Psychiatric disorders

Confusional state

Nervous system disorders

Dizziness, dysaesthesia

, hyperaesthesia

paraesthesia,somnolence, headache, hypertonia,

neuralgia

Eye disorders

Conjunctivitis

Ear and labyrinth disorders

Vertigo

Vascular disorders

Hypotension

Respiratory, thoracic and

mediastinal disorders

Bronchitis, dyspnoea, rhinitis

Gastrointestinal disorders

Dyspepsia

, flatulence

Skin and subcutaneous tissue

disorders

Alopecia, hyperhidrosis

Musculoskeletal and connective

tissue disorders

Back pain

Renal and urinary disorders

Renal failure acute

Reproductive system and breast

disorders

Balanoposthitis, prostatitis, vulvovaginal discomfort

General disorders and

administration site conditions

Chest pain, oedema peripheral, granuloma

Investigations

Prostatic specific antigen increased, weight decreased

NEC = not elsewhere classified

High Level Term instead of Preferred Term

Granuloma NOS has been observed in various organs including the aorta, bladder, epididymis, gastrointestinal

tract, kidney, liver, lungs, lymphnodes, peritoneum, prostate

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

toxicicities

that

often

reflect

hypersensitivity

reactions

treated

symptomatically.

These symptoms usually appear within 4 hours after instillation

last

hours. Fever higher than 39ºC 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

indicated. Fever

above

that

does

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

manifested

pneumonitis,

hepatitis,

cytopenia,

vasculitis, infective aneurysm and/or sepsis after a period of fever and malaise during which

symptoms

progressively increase.

Patients

with

symptoms

therapy-induced

systemic

infection

should

adequately

treated

with

anti-tuberculosis

drugs

according

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.

Any suspected adverse events should be reported to the Ministry of Health according to the

National Regulation by using an online form: https://sideeffects.health.gov.il

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.

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

active

non-specific

immune

response

takes

place.

invokes

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.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Lactose monohydrate

L-Asparagine monohydrate

Citric acid monohydrate

Potassium phosphate dibasic

Magnesium sulfate heptahydrate

Iron ammonium citrate

Glycerin

Zinc formate

Ammonium hydroxide

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

The expiry date of the product is indicated on the packaging materials. 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 2-8ºC, protect from light.

6.5

Nature and contents of containers

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

Not all pack sizes may be marketed.

6.6

Special precautions for disposal and other handling

OncoTICE

contains

live,

attenuated

mycobacteria.

Because

potential

risk

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

stand

minutes

then

gently

swirl

until

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 10

CFU of Tice BCG.

7 MANUFACTURER

Organon N.V., Oss, The Netherlands.

8 MARKETING AUTHORIZATION HOLDER

Merck Sharp & Dohme (Israel-1996) Company Ltd, P.O.Box 7121, Petah-Tikva 49170

9 REGISTRATION NUMBER

103-18-28561

Revised in 08/2020