BCG CULTURE SSI freeze-dried powder for reconstitution
(and dosage form):
BCG CULTURE SSI freeze-dried powder for reconstitution
Each vial of live BCG CULTURE SSI contains a semi-dry mass of 30 mg Mycobacterium bovis BCG, Danish strain 1331 with approximately 2.5 x 108 CFU. It also contains 40 mg sodium glutamate. There is no bactericidal or bacteriostatic agent present.
A.30.1 Biologicals - Antigen
The effect of BCG against carcinoma is not completely understood. It may be related to an inflammatory response and possibly also to an immune response.
Intravesical BCG suspension produces a granulomatous response locally and in regional lymph nodes; the inflammatory response stimulates production of macrophages that have tumoricidal effects. However, the relationship of these effects to the antineoplastic effect of BCG is unknown.
BCG CULTURE SSI is intended for instillation in the urinary tract after transurethral resection, as immunoprophylaxis in primary or recurrent grade Ta or T1 superficial bladder cancer, or for immunotherapy treatment of non-invasive carcinoma in-situ of the bladder.
BCG CULTURE SSI should never be handled by or administered to persons with congenital or acquired immuno-deficiencies, including HIV-disease, or to persons who are currently in treatment with immuno-suppressive drugs, or receiving high-dose systemic corticosteroid therapy. Clinically verified or suspected active tuberculosis is also an absolute contraindication to treatment.
Immunotherapy with BCG CULTURE SSI should be postponed in patients with a urinary tract infection, or unexplained fever, until a negative urine culture is obtained, and treatment with antibiotics and/or antiseptics has ceased. Treatment with BCG CULTURE SSI should be postponed 7-14 days after a traumatised urothelium, whether due to bladder biopsy, transurethralsection, a traumatic catheterisation, or bladder lesion, as BCG treatment directly following the above invasive procedures can result in systemic BCG infection.
Local BCG infections (i.e. epididymo-orchitis or prostatitis) or systemic reactions (such as pneumonia or hepatitis) necessitate immediate cessation of immunotherapy and referral to an infectious diseases specialist for treatment with anti-tuberculosis therapy.
There is no official definition of the sensitivity of BCG strains towards antibiotics. If the definitions for Mycobacterium tuberculosis are used, the following statements can be given: BCG Danish strain 1331 is susceptible to most commonly used anti-tuberculosis drugs. However the MIC of isoniazid for the BCG Danish strain 1331 is 0.4 mg/L [as determined by Bactec 460].
There is no consensus as to whether M. bovis should be classified as susceptible, intermediately susceptible or resistant to isoniazid when the MIC is 0.4 mg/L. However, based on criteria set for Mycobacterium tuberculosis, the strain could be considered to be of intermediate susceptibility to isoniazid and fully susceptible to Streptomycin, Rifampicin and Ethambutol.
Enquiry regarding previous hypersensitivity should precede administration. Measures to treat anaphylaxis, including adrenaline, should be immediately available.
Drugs with known anti-mycobacterial action should not be co-administered with BCG CULTURE SSI. These include common anti-tuberculosis drugs as well as aminoglycosides and fluoroquinolones.
PREGNANCY AND LACTATION:
The use of BCG CULTURE SSI must be avoided in pregnancy or during lactation as no data is available regarding the effects on the foetus or excretion into human milk.
DOSAGE AND DIRECTIONS FOR USE:
FOR INTRALUMINAL URINARY TRACT USE ONLY
Must not be administered intravenously, subcutaneously or intramuscularly. The recommended dose for immunotherapy or immunoprophylaxis is 120 mg, or approximately 1x109 CFU. This dose should not be exceeded. Seven to fourteen days should elapse after a transurethral section, bladder biopsy, or traumatic catheterisation before initiating treatment with BCG CULTURE SSI.
The standard schedule of treatment consists of 6 instillations, with an interval of one week between each instillation. This treatment schedule may be repeated once if insufficient or no response is achieved after the first immunotherapy treatment. Maintenance treatment may be recommended for certain high risk patients.
The BCG CULTURE SSI should not be prepared in the same sterile area as chemotherapeutic agents due to the possible iatrogenic transmission of BCG to these agents.
Intravesical dosage: The required dosage of BCG CULTURE SSI, (normal dose = 120 mg = 4 reconstituted vials) is resuspended in 50 mL sterile saline (preservative free 0.9% sodium chloride).
Aseptic conditions are necessary and care must be taken in order to properly resuspend clusters of freeze-dried bacteria. Using a disposable syringe add approximately 2-3 mL sterile saline to the first vial.
GENTLY release/push back the plunger to thoroughly resuspend the living BCG CULTURE. Each vial must be carefully inverted a few times, then gently swirled (AVOID VIGOROUS SHAKING) before being transferred to a syringe. Transfer the contents of the vial to a 50 mL syringe. Repeat for vials 2, 3 and 4. Add a further volume of the sterile saline, until the total volume is 50 mL. The suspension should be homogenous, and slightly cloudy. The suspension must be prepared shortly before use (less than 4 hours) and should not be exposed to light. Aseptic insertion of a urethral catheter must be performed atraumatically to avoid damage to the surface of the urethra and bladder. Treatment with BCG CULTURE SSI must be postponed if the urothelium becomes traumatised during catherterisation, as a lesion in the urothelium increases the risk of systemic BCG infection. Only small quantities of lubricants should be used during catheterisation as large quantities may inhibit BCG viability. The 50 mL BCG CULTURE is slowly instilled into the empty bladder, taking care never to force the flow. At the end of instillation, the catheter is removed, and the patient is instructed to retain the suspension in the bladder for 2 hours, if possible. (Restrictions of fluid intake 3 6 hours prior to and during the instillation may be recommended for patients with a limited bladder capacity). As BCG CULTURE SSI is not a biohazardous material, the suspension may be voided in a normal manner, and no special precautions are necessary.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
More frequent: Mild-to-moderate reactions: The reactions described below are generally mild to moderate, normally last no longer than 2 days, and are believed to be the result of a positive response to BCG.
Local side effects, such as, increased urinary frequency, cystitis and hematuria are common. Mild systemic influenza - like reactions such as fever or chills occur in a significant number of cases, and malaise or myalgia may also occur. Antipyretics, liquids, and/or mild analgesics may be used to manage these symptoms.
Less frequent: The complications listed in this section are seldom seen, most often in connection with a maintenance regimen. Fever over 39ºC, which does not disappear within 24 48 hours after the patient receives liquids and antipyretics, and/or a period with malaise and fever, during which the symptoms increase, can indicate a systemic infection. BCG immunotherapy should be discontinued until a systemic infection has been ruled out. Immunotherapy may be reinstituted with caution if deemed necessary.
Rare: Allergic reactions, arthralgia, myalgia or rash, occur in some patients. Macroscopic hematuria, bladder contraction or temporary urethral obstructions are also complications.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
BCG CULTURE SSI must only be prescribed and administered by doctors with special knowledge of cancerous diseases and their treatments.
Overdosage occurs if more than four (4) vials of BCG CULTURE SSI are administered per instillation. If overdosage occurs, the patient should be closely monitored for signs of active local or systemic BCG infection.
For acute local or systemic reactions suggesting active infection, management should be in accordance with procedures listed under WARNINGS above.
Brown glass vials containing a white to off-white freeze-dried powder.
Reconstituted product: slightly opaque and colourless suspension.
Packs of four 4 mL brown glass vials closed with grey rubber stoppers capped with an aluminium overseal, each containing 30 mg of BCG CULTURE SSI.
Store the vials of freeze-dried BCG CULTURE SSI in a refrigerator (+2 +8°C). Do not expose to light unnecessarily. The resuspended solution may be kept for 4 hours at room temperature, protected from light. BCG CULTURE SSI will deteriorate when exposed even for short periods to direct sunlight and diffuse daylight (also indoors).
Keep out of reach of children.
NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION:
Litha Vaccines (Pty) Ltd
23 Herman Road
DATE OF PUBLICATION OF THE PACKAGE INSERT:
15 May 2006
STATENS SERUM INSTITUT
2300 Copenhagen S
10-499-01 en Rev. 09-2011
New addition to this site: May 2014
Source: Pharmaceutical Industry
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