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Tice BCG Side Effects

Please note - some side effects for Tice BCG may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Tice BCG - for the Consumer

Tice BCG

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Tice BCG:

Diarrhea; increased pain or frequency of urination; loss of appetite; nausea; stomach pain.

Seek medical attention right away if any of these SEVERE side effects occur when using Tice BCG:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blood in urine; burning or pain when urinating; chills; cough; fever; flu-like symptoms; frequent or urgent urination; general feeling of discomfort; joint pain; tiredness; vomiting.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

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Tice BCG Side Effects - for the Professional

TICE BCG

Symptoms of bladder irritability, related to the inflammatory response induced, are reported in approximately 60% of patients receiving TICE® BCG. The symptoms typically begin 4 to 6 hours after instillation and last 24 to 72 hours. The irritative side effects are usually seen following the third instillation, and tend to increase in severity after each administration.

The irritative bladder adverse effects can usually be managed symptomatically with products such as pyridium, propantheline bromide, oxybutynin chloride, and acetaminophen. The mechanism of action of the irritative side effects has not been firmly established, but is most consistent with an immunological mechanism.3 There is no evidence that dose reduction or antituberculous drug therapy can prevent or lessen the irritative toxicity of TICE BCG.

"Flu-like" symptoms (malaise, fever, and chills) which may accompany the localized, irritative toxicities often reflect hypersensitivity reactions which can be treated symptomatically. Antihistamines have also been used.5

Adverse reactions to TICE BCG tend to be progressive in frequency and severity with subsequent instillation. Delay or postponement of subsequent treatment may or may not reduce the severity of a reaction during subsequent instillation.

Although uncommon, serious infectious complications of intravesical BCG have been reported.2,3,6 The most serious infectious complication of BCG is disseminated sepsis with associated mortality. In addition, M. bovis infections have been reported in lung, liver, bone, bone marrow, kidney, regional lymph nodes, and prostate in patients who have received intravesical BCG. Some male genitourinary tract infections (orchitis/epididymitis) have been resistant to multiple-drug antituberculous therapy and required orchiectomy.

If a patient develops persistent fever or experiences an acute febrile illness consistent with BCG infection, BCG treatment should be discontinued and the patient immediately evaluated and treated for systemic infection.

The local and systemic adverse reactions reported in a review of 674 patients with superficial bladder cancer, including 153 patients with carcinoma in situ, are summarized in Table V.

TABLE V: Summary of Adverse Effects Seen in 674 Patients with Superficial Bladder Cancer, Including 153 With Carcinoma in Situ
Percent of patients Percent of patients
Adverse event N Overall
(Grade ≥3)
Adverse event N Overall
(Grade ≥3)
Dysuria 401   60% (11%) Arthritis/myalgia 18 3% (<1%)
Urinary frequency 272 40% (7%) Headache/dizziness 16 2% (0)      
Flu-like syndrome 224 33% (9%) Urinary incontinence 16 2% (0)      
Hematuria 175 26% (7%) Anorexia/weight loss 15 2% (<1%)
Fever 134 20% (8%) Urinary debris 15 2% (<1%)
Malaise/fatigue   50 7% (0)   Allergy 14 2% (<1%)
Cystitis   40   6% (2%) Cardiac (unclassified) 13 2% (1%)  
Urgency   39   6% (1%) Genital inflammation/
Nocturia   30   5% (1%) abscess 12 2% (<1%)
Cramps/pain   27   4% (1%) Respiratory (unclassified) 11 2% (<1%)
Rigors   22   3% (1%) Urinary tract infection 10 2% (1%)  
Nausea/vomiting   20     3% (<1%) Abdominal pain 10 2% (1%)  

The following adverse events were reported in ≤1% of patients: anemia, BCG sepsis, coagulopathy, contracted bladder, diarrhea, epididymitis/prostatitis, hepatic granuloma, hepatitis, leukopenia, neurologic (unclassified), orchitis, pneumonitis, pyuria, rash, thrombocytopenia, urethritis, and urinary obstruction.

In SWOG study 8795, toxicity evaluations were available on a total of 222 TICE BCG-treated patients and 220 MMC-treated patients. Direct bladder toxicity (cramps, dysuria, frequency, urgency, hematuria, hemorrhagic cystitis, or incontinence) was seen more often with TICE BCG with 356 events, compared to 234 events for MMC. Grade ≤2 toxicity was seen significantly more frequently following TICE BCG treatment (P=0.003). No life-threatening toxicity was seen in either arm. Systemic toxicity with TICE BCG was markedly increased compared to that of MMC, with 181 events for TICE BCG compared to 80 for MMC. The frequency of toxicity was increased in all grades, particularly for grades 2 and 3. The most common complaints were malaise, fatigue and lethargy, fever, and abdominal pain. Thirty-two TICE BCG patients were reported to have been treated with isoniazid. Five TICE BCG patients had liver enzyme elevation, including 2 with grade 3 elevations. Eighteen of the 222 (8.1%) TICE BCG patients failed to complete the prescribed protocol compared to 6.2% in the MMC group. Table VI summarizes the most common adverse reactions reported in this trial.7

TABLE VI: Most Common Adverse Reactions in SWOG Study 8795*
Study arm
TICE BCG (N=222) MMC (N=220)
Adverse event All Grades Grade ≥3 All Grades Grade ≥3
*
The adverse reaction profile of TICE BCG was similar in the Nijmegen study.8
Dysuria 115 (52%) 6 (3%) 77 (35%) 5 (2%)
Urgency/frequency 112 (50%) 5 (2%) 63 (29%) 7 (3%)
Hematuria   85 (38%) 6 (3%) 56 (25%) 5 (2%)
Flu-like symptoms   54 (24%)   1 (<1%) 29 (13%) 0         
Fever   37 (17%)   1 (<1%) 7 (3%) 0         
Pain (not specified)   37 (17%) 4 (2%) 22 (10%)   1 (<1%)
Hemorrhagic cystitis 19 (9%) 3 (1%) 10 (5%)   0         
Chills 19 (9%) 0         2 (1%) 0         
Bladder cramps 18 (8%) 0         9 (4%) 0         
Nausea 16 (7%) 0         12 (5%)   0         
Incontinence   8 (4%) 0         3 (1%) 0         
Myalgia/arthralgia   7 (3%) 0         0         0         
Diaphoresis   7 (3%) 0            1 (<1%) 0         
Rash   6 (3%)    1 (<1%) 16 (7%)   2 (1%)
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Side Effects by Body System - for Healthcare Professionals

Genitourinary

Genitourinary side effects including dysuria (54%), urinary frequency (40%), hematuria (39%), cystitis (29%), urinary tract infection (18%), urgency (18%), genital pain (10%), urinary incontinence (6%), cramps (6%), and contracted bladder (5%) were most commonly reported.

Nervous system

Nervous system side effects including malaise (40%) and arthralgia/myalgia (7%) have been reported.

Hematologic

Hematologic side effects including anemia (21%), leukopenia (5%), and coagulopathy (3%) have been reported.

Gastrointestinal

Gastrointestinal side effects including nausea/vomiting (16%), anorexia (11%), diarrhea (6%), and abdominal pain (3%) have been reported.

General

General side effects including fever (38%), chills (34%), and headache (2%) have been reported.

Immunologic

Immunologic side effects including systemic infection (3%) and pulmonary infection (3%) have been reported. Four cases of immune reconstitution syndrome have also been reported.

Renal

Renal side effects including renal toxicity (10%) have been reported.

Dermatologic

Dermatologic side effects including skin rash (2%) have been rarely reported.

Cardiovascular

Unclassified cardiovascular side effects were infrequently reported (3%).

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