THERACYS SIDE EFFECTS
- Generic Name: bcg live (intravesical)
- Brand Name: Theracys
SIDE EFFECTS
The most common adverse reactions observed with TheraCys treatment at a rate > 10% were transient dysuria, urinary frequency and urgency, malaise, hematuria, fever, chills, cystitis, and mild nausea.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a medicinal product cannot be directly compared to rates in the clinical trials of another medicinal product and may not reflect the rates observed in practice.
Administration of TheraCys causes an inflammatory response in the bladder, thus requiring careful patient monitoring. Symptoms of bladder irritability are reported in approximately 50% of patients receiving TheraCys and typically begin 4-6 hours after instillation and last 24-72 hours. The irritative reactions usually are seen following the third instillation and tend to increase in severity after each administration. There is no evidence that dose reduction or antituberculous drug therapy can prevent or lessen the irritative symptoms of TheraCys.
In a clinical trial conducted in the United States, patients with stage Ta or T1 papillary tumor with 2 or more recurrences within the last 12 months, with carcinoma in situ (CIS), or with both of these conditions, were randomized to receive treatment with intravesical TheraCys or doxorubicin. Prior therapy with either BCG or doxorubicin was not allowed. Patients with muscle-invasive cancers or incomplete resection of papillary tumors were not eligible. Onehundred and twelve patients received TheraCys in 6 weekly instillations, followed by single instillations at 3, 6, 12, 18, and 24 months after enrollment, and were included in safety analyses. In the control group, 119 patients received doxorubicin in 5 weekly treatments, followed by 11 monthly treatments. Safety information was collected prior to each treatment dose.
Table 1 shows the frequency of adverse reactions observed in this trial. Local irritative symptoms were more common with TheraCys than with doxorubicin; however, grade ≥ 3 irritative toxicity was similar, occurring in approximately 2-7% of patients. Systemic symptoms (fever, chills, malaise, anorexia) were also more common with TheraCys. Overall, grade ≥ 3 toxicities were seen in 26 patients (23%) treated with TheraCys and 25 patients (21%) treated with doxorubicin. TheraCys treatment was discontinued in twelve patients due to toxicity.
Table 1: Adverse Reactions Reported in Patients Treated with TheraCys in a Trial Conducted in the United States
| System/Organ Class Adverse reaction | Study Arm | |||
| TheraCys (N=112) |
Doxorubicin (N=119) |
|||
| All Grades % | Grade ≥ 3 % | All Grades % | Grade ≥ 3 % | |
| Infections and Infestations | ||||
| Cystitis | 29.5 | 0 | 19.3 | 0.8 |
| Urinary tract infection | 17.9 | 0 | 17.6 | 0 |
| Pulmonary infection | 2.7 | 0 | 4.2 | 0.8 |
| Systemic infection | 2.7 | 1.8 | 0.8 | 0 |
| Infection | 0.9 | 0.9 | 0.8 | 0 |
| Blood and Lymphatic System Disorders | ||||
| Anemia | 20.5 | 0 | 24.4 | 0 |
| Leukopenia | 5.4 | 0 | 5.9 | 0 |
| Coagulopathy/ Thrombocytopenia | 0.9 | 0 | 0.8 | 0 |
| Metabolism and Nutrition Disorders | ||||
| Anorexia | 10.7 | 0 | 5.0 | 0 |
| Nervous System Disorders | ||||
| Headache | 1.8 | 0 | 3.4 | 0 |
| Dizziness | 0.9 | 0 | 0.8 | 0 |
| Cardiac Disorders | ||||
| Cardiac (unclassified) | 2.7 | 0 | 3.4 | 0.8 |
| Gastrointestinal Disorders | ||||
| Nausea/Vomiting | 16.1 | 0 | 8.4 | 0.8 |
| Diarrhea | 6.3 | 0 | 1.7 | 0 |
| Abdominal pain | 2.7 | 0 | 2.5 | 0 |
| Constipation | 0.9 | 0 | 0.8 | 0 |
| Hepatobiliary Disorders | ||||
| Liver involvement | 2.7 | 0 | 0.8 | 0 |
| Skin and Subcutaneous Tissue Disorders | ||||
| Skin rash | 1.8 | 0 | 2.5 | 0 |
| Musculoskeletal, Connective Tissue, and Bone Disorders | ||||
| Arthralgia/Myalgia/ Arthritis | 7.1 | 0.9 | 4.2 | 0 |
| Flank pain | 0.9 | 0 | 0.8 | 0 |
| Renal and Urinary Disorders | ||||
| Dysuria | 51.8 | 3.6 | 40.3 | 5.9 |
| Urinary frequency | 40.2 | 1.8 | 28.6 | 4.2 |
| Hematuria | 39.3 | 7.1 | 27.7 | 6.7 |
| Urinary urgency | 17.9 | 0.9 | 11.8 | 2.5 |
| Renal toxicity (NOS) | 9.8 | 1.8 | 9.2 | 0.8 |
| Urinary incontinence | 6.3 | 0 | 0.8 | 0.8 |
| Bladder cramps/pain | 6.3 | 0 | 5.0 | 1.7 |
| Contracted bladder | 5.4 | 0.9 | 5.0 | 0.8 |
| Tissue in urine | 0.9 | 0 | 1.7 | 0 |
| Ureteral obstruction | 0.9 | 0.9 | 0 | 0 |
| Reproductive System and Breast Disorders | ||||
| Genital pain | 9.8 | 0 | 13.4 | 1.7 |
| General Disorders and Administration Site Conditions | ||||
| Malaise | 40.2 | 1.8 | 14.3 | 0 |
| Fever ( > 38°C) | 38.4 | 2.7 | 9.2 | 0 |
| Chills | 33.9 | 2.7 | 5.9 | 0 |
| Fatigue | 0.9 | 0 | 0 | 0 |
Postmarketing Experience
The following additional adverse reactions have been identified during post-approval use of TheraCys. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Infections and Infestations
BCG Infection: BCG is capable of dissemination when administered by the intravesical route. Serious infections, including sepsis with associated mortality, have been reported. BCG infections have also been reported in eye, lung, liver, bone, bone marrow, kidney, regional lymph nodes, peritoneum, genitourinary tract (orchitis/epididymitis), and prostate (e.g., Granulomatous prostatitis). BCG infection of aneurysms and prosthetic devices (including arterial grafts, cardiac devices and artificial joints) has also been reported.
Joint symptoms (arthritis, arthralgia), ocular symptoms (including conjunctivitis, uveitis, iritis, keratitis, granulomatous choreoretinitis), urinary symptoms (including urethritis), skin rash, alone or in combination (Reiter’s syndrome), have been reported following administration of TheraCys. For the reports of Reiter’s syndrome, the risk seems to be more elevated among patients who are positive for HLA-B27.
Renal abscess
Respiratory, Thoracic and Mediastinal Disorders
Pneumonia, interstitial lung disease
Skin and Subcutaneous Tissue Disorders
Erythema nodosum
Renal and Urinary Disorders
Renal failure, pyelonephritis, nephritis (including tubulointerstitial nephritis, interstitial nephritis and glomerulonephritis)
Urinary retention (including bladder tamponade and feeling of residual urine)
General Disorders and Administration Site Conditions
Flu-like symptoms
Investigations (Laboratory Tests)
Abnormal/increased blood creatinine or blood urea nitrogen (BUN)
SRC: NLM .