Search The Medical Knowledge Base
Drug Details
OncoTICE
- Drug Class Description
BCG. - Generic Name
Mycobacterium bovis - Presentation
Powder for instillation fluid for intravesical use. - Description
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). - 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. - Adult Dosage
Dosage
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, 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.
Children
Not recommended.
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. 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).
- Child Dosage
Not recommended. - 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.
- Special Precautions
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.
- Interactions
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.
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.
- Adverse Drug Reactions
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
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 infections1 Blood and lymphatic system disorders Pancytopenia, thrombocytopenia Hepatobiliary disorders Hepatitis Skin and subcutaneous tissue disorders Rashes, eruptions and exanthems NEC1 Renal and urinary disorders Bladder constriction, pyuria, urinary retention, ureteric obstruction Table 1 Side effects reported during post-marketing surveillance (Continued)
MedDRA SOClass Preferred terms Uncommon (>1/1,000, <1/100) 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, dysaesthesia3 , hyperaesthesia3 , paraesthesia, somnolence, headache, hypertonia, neuralgia3 Eye disorders Conjunctivitis Ear and labyrinth disorders Vertigo3 Vascular disorders Hypotension Respiratory, thoracic and mediastinal disorders Bronchitis, dyspnoea, rhinitis Gastrointestinal disorders Dyspepsia3 , flatulence3 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 discomfort3 General disorders and administration site conditions Chest pain, oedema peripheral, granuloma2 Investigations 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
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 39oC 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 initially by pneumonitis, hepatitis and/or cytopenia 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.