Summary Of Exposure |
A) USES: Bicalutamide is used in combination with a luteinizing hormone-releasing hormone (LHRH) analogue for the treatment of advanced prostate cancer.
B) PHARMACOLOGY: Bicalutamide, a non-steroidal antiandrogen, competitively binds to cytosol androgen receptors in the target tissue to inhibit the action of androgens.
C) EPIDEMIOLOGY: Overdose is rare.
D) WITH THERAPEUTIC USE
1) In patients with advanced prostate cancer treated with bicalutamide in combination with a LHRH analogue, the predominant adverse effects were hot flashes, pain (including general, back, pelvic and abdominal), asthenia, constipation, infection, nausea, peripheral edema, dyspnea, diarrhea, hematuria, nocturia, and anemia. Other effects included chest pain, headache, flu syndrome, hypertension, elevated liver enzymes, dyspepsia, flatulence, anorexia, vomiting, hyperglycemia, elevated alkaline phosphatase, bone pain, myasthenia, arthritis, paresthesia, insomnia, anxiety, depression, cough, pharyngitis, bronchitis, pneumonia, rhinitis, rash, increased sweating, urinary tract infection, gynecomastia, and urinary frequency/retention/incontinence. Reversible fulminant hepatic failure has been reported in one patient following one dose of bicalutamide and believed to be an idiosyncratic hepatotoxicity reaction.
E) WITH POISONING/EXPOSURE
1) Overdose data are limited. Overdose effects are anticipated to be an extension of adverse effects following therapeutic doses.
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Heent |
3.4.3) EYES
A) WITH THERAPEUTIC USE 1) Bicalutamide has NOT been associated with the light adaptation problems observed during nilutamide therapy.
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Cardiovascular |
3.5.2) CLINICAL EFFECTS
A) HYPERTENSIVE EPISODE 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, hypertension was reported in 8% (34 of 401) of patients who received bicalutamide 50 mg once daily compared with 7% (29 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
B) CHEST PAIN 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, chest pain was reported in 8% (34 of 401) of patients who received bicalutamide 50 mg once daily and 8% (34 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
C) CONGESTIVE HEART FAILURE 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, congestive heart failure was reported in 2% to less than 5% of patients who received bicalutamide 50 mg once daily in combination with a luteinizing hormone-releasing hormone analog (n=401) (Prod Info CASODEX(R) oral tablets, 2015).
D) MYOCARDIAL INFARCTION 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, myocardial infarction was reported in 2% to less than 5% of patients who received bicalutamide 50 mg once daily in combination with a luteinizing hormone-releasing hormone analog (n=401) (Prod Info CASODEX(R) oral tablets, 2015).
E) PERIPHERAL EDEMA 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, peripheral edema was reported in 13% (53 of 401) of patients who received bicalutamide 50 mg once daily compared with 10% (42 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
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Respiratory |
3.6.2) CLINICAL EFFECTS
A) DYSPNEA 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, dyspnea was reported in 13% (51 of 401) of patients who received bicalutamide 50 mg once daily compared with 8% (32 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
B) COUGH 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, increased cough was reported in 8% (33 of 401) of patients who received bicalutamide 50 mg once daily compared with 6% (24 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
C) BRONCHITIS 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, bronchitis was reported in 6% (24 of 401) of patients who received bicalutamide 50 mg once daily compared with 3% (22 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
D) PHARYNGITIS 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, pharyngitis was reported in 8% (32 of 401) of patients who received bicalutamide 50 mg once daily compared with 6% (23 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
E) PNEUMONIA 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, pneumonia was reported in 4% (18 of 401) of patients who received bicalutamide 50 mg once daily compared with 5% (19 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
F) RHINITIS 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, rhinitis was reported in 4% (15 of 401) of patients who received bicalutamide 50 mg once daily compared with 5% (22 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
G) INTERSTITIAL LUNG DISEASE 1) WITH THERAPEUTIC USE a) During postmarketing surveillance, interstitial lung disease, including interstitial pneumonitis and pulmonary fibrosis, has been reported in patients who received bicalutamide therapy (Prod Info CASODEX(R) oral tablets, 2015).
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Neurologic |
3.7.2) CLINICAL EFFECTS
A) HEADACHE 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, headache was reported in 7% (29 of 401) of patients who received bicalutamide 50 mg once daily and 7% (27 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
b) Dizziness, headache, fatigue or tiredness, and confusion have been reported occasionally during bicalutamide therapy (7% or less) (Kennealey & Furr, 1991; Newling, 1990).
B) CLOUDED CONSCIOUSNESS 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, confusion was reported in 2% to less than 5% of patients who received bicalutamide 50 mg once daily in combination with a luteinizing hormone-releasing hormone analog (n=401) (Prod Info CASODEX(R) oral tablets, 2015).
C) DIZZINESS 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, dizziness was reported in 10% (41 of 401) of patients who received bicalutamide 50 mg once daily compared with 9% (35 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
D) INSOMNIA 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, insomnia was reported in 7% (27 of 401) of patients who received bicalutamide 50 mg once daily compared with 10% (39 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
E) PARESTHESIA 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, paresthesia was reported in 8% (31 of 401) of patients who received bicalutamide 50 mg once daily compared with 10% (40 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
F) ASTHENIA 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, asthenia was reported in 22% (89 of 401) of patients who received bicalutamide 50 mg once daily compared with 21% (87 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
G) ANXIETY 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, anxiety was reported in 5% (20 of 401) of patients who received bicalutamide 50 mg once daily compared with 2% (9 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
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Gastrointestinal |
3.8.2) CLINICAL EFFECTS
A) NAUSEA AND VOMITING 1) WITH THERAPEUTIC USE a) Nausea (3% to 8%) and vomiting (4% to 7%) have been reported during monotherapy of prostate cancer with bicalutamide. No dose dependency was noted at doses exceeding 30 milligrams daily (Kennealey & Furr, 1991; Kaisary, 1994; Newling, 1990).
b) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, vomiting was reported in 6% (24 of 401) of patients who received bicalutamide 50 mg once daily compared with 8% (32 of 407) of patients who received flutamide 250 mg 3 times daily. Nausea was reported in 15% (62 of 401) of patients who received bicalutamide 50 mg once daily compared with 14% (58 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
B) CONSTIPATION 1) WITH THERAPEUTIC USE a) Constipation (0% to 7%) and diarrhea (2% to 3%) have been reported during monotherapy of prostate cancer with bicalutamide. No dose dependency was noted at doses exceeding 30 milligrams daily (Kennealey & Furr, 1991; Kaisary, 1994; Newling, 1990).
b) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, constipation was reported in 22% (87 of 401) of patients who received bicalutamide 50 mg once daily compared with 17% (69 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
C) INDIGESTION 1) WITH THERAPEUTIC USE a) Dyspepsia was reported in up to 2% of patients during monotherapy of prostate cancer (Kennealey & Furr, 1991).
b) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, dyspepsia was reported in 7% (30 of 401) of patients who received bicalutamide 50 mg once daily compared with 6% (23 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
D) ABDOMINAL PAIN 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, abdominal pain was reported in 11% (46 of 401) of patients who received bicalutamide 50 mg once daily and 11% (46 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
E) DIARRHEA 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, diarrhea was reported in 12% (49 of 401) of patients who received bicalutamide 50 mg once daily compared with 26% (107 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
F) FLATULENCE/WIND 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, flatulence was reported in 6% (26 of 401) of patients who received bicalutamide 50 mg once daily compared with 5% (22 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
G) LOSS OF APPETITE 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, anorexia was reported in 6% (25 of 401) of patients who received bicalutamide 50 mg once daily compared with 7% (29 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
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Hepatic |
3.9.2) CLINICAL EFFECTS
A) LIVER ENZYMES ABNORMAL 1) WITH THERAPEUTIC USE a) In controlled clinical trials, hepatitis or marked increases in liver enzymes resulting in therapy discontinuation were reported in approximately 1% of patients who received bicalutamide (Prod Info CASODEX(R) oral tablets, 2015).
b) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, an increased liver enzyme test was reported in 7% (30 of 401) of patients who received bicalutamide 50 mg once daily compared with 11% (46 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
B) SERUM ALKALINE PHOSPHATASE RAISED 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, increased alkaline phosphatase was reported in 5% (22 of 401) of patients receiving bicalutamide 50 mg once daily compared with 6% (24 of 407) of patients receiving flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
C) HEPATIC FAILURE 1) WITH THERAPEUTIC USE a) CASE REPORT: A 59-year-old man with prostate cancer developed fulminant hepatic failure following 4 doses of daily bicalutamide and subsequently died from multiorgan failure 8 days after bicalutamide initiation. The patient was diagnosed with stage IV adenocarcinoma of the prostate with neuroendocrine and small cell histologic features. He was successfully treated with leuprolide acetate and concomitant bicalutamide as well as a chemotherapy regimen consisting of cisplatin and etoposide, and radiation therapy. Multiple metastasis were found 5 months after completion of radiotherapy. Bicalutamide was restarted along with cisplatin and etoposide chemotherapy. Upon treatment initiation, hepatic transaminases, total bilirubin, and abdominal computer tomographic (CT) scan were verified as normal. The patient presented to the emergency department 4 days later with complaints of right lower quadrant pain, abdominal distension, and diffuse abdominal tenderness. The patient was admitted to the hospital and bicalutamide was discontinued. Other concurrent medications included: oxycodone-acetaminophen, olmesartan, leuprolide acetate, oxybutynin, and docusate sodium. Acetaminophen levels were undetectable. Liver function panel revealed an AST level of 166 units/L and an ALT level of 111 units/L. The patient's condition continued to worsen despite discontinuation of bicalutamide (AST, 2026 units/L; ALT, 1400 units/L on hospital day 3). The patient died of multiorgan failure on hospital day 4 (8 days after bicalutamide initiation) (O'Bryant et al, 2008). b) CASE REPORT: A 60-year-old male with prostate cancer developed fulminant hepatic failure following two doses (50 mg/daily) of bicalutamide. Bilirubin was 333 mmol/L (normal less than 20), AST 1527 IU/L, ALT 2690 IU/L, alkaline phosphatase 181 IU/L, and GGT 121 IU/L. Following supportive therapy the patient improved; hepatic enzymes returned to normal within 2 months. Its suggested that the effects may have been due to an idiosyncratic hepatotoxicity reaction (Dawson et al, 1997). 1) Schellhammer (1997) refuted the conclusions of this report; the patient had received one month of cyproterone acetate and three months of flutamide therapy prior to beginning bicalutamide. Flutamide is known to cause severe hepatotoxicity and is a more likely etiology of this patients fulminant hepatic failure.
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Genitourinary |
3.10.2) CLINICAL EFFECTS
A) URINARY TRACT INFECTIOUS DISEASE 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, urinary tract infection was reported in 9% (35 of 401) of patients who received bicalutamide 50 mg once daily and 9% (36 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
B) URINARY INCONTINENCE 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, urinary incontinence was reported in 4% (15 of 401) of patients who received bicalutamide 50 mg once daily compared with 8% (32 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
C) RETENTION OF URINE 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, urinary retention was reported in 5% (20 of 401) of patients who received bicalutamide 50 mg once daily compared with 3% (14 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
D) INCREASED FREQUENCY OF URINATION 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, urinary frequency was reported in 6% (23 of 401) of patients who received bicalutamide 50 mg once daily compared with 7% (29 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
E) DYSFUNCTIONAL VOIDING OF URINE 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, impaired urinary function was reported in 5% (19 of 401) of patients who received bicalutamide 50 mg once daily compared with 4% (15 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
F) NOCTURIA 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, nocturia was reported in 12% (49 of 401) of patients who received bicalutamide 50 mg once daily compared with 14% (55 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
G) BLOOD IN URINE 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, hematuria was reported in 12% (48 of 401) of patients who received bicalutamide 50 mg once daily compared with 6% (26 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
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Hematologic |
3.13.2) CLINICAL EFFECTS
A) ANEMIA 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, anemia was reported in 11% (45 of 401) of patients who received bicalutamide 50 mg once daily compared with 13% (53 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
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Dermatologic |
3.14.2) CLINICAL EFFECTS
A) ERUPTION 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, rash was reported in 9% (35 of 401) of patients who received bicalutamide 50 mg once daily compared with 7% (30 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
b) Skin rash and/or pruritus have been reported during bicalutamide therapy in up to 6% of prostate cancer patients (Kennealey & Furr, 1991).
B) ITCHING OF SKIN 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, pruritus was reported in 2% to less than 5% of patients who received bicalutamide 50 mg once daily in combination with a luteinizing hormone-releasing hormone analog (n=401) (Prod Info CASODEX(R) oral tablets, 2015).
C) FLUSHING 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, hot flashes were reported in 53% (211 of 401) of patients who received bicalutamide 50 mg once daily compared with 53% (217 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
D) SWEATING 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, sweating was reported in 6% (25 of 401) of patients who received bicalutamide 50 mg once daily compared with 5% (20 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
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Musculoskeletal |
3.15.2) CLINICAL EFFECTS
A) PAIN IN PELVIS 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, pelvic pain was reported in 21% (85 of 401) of patients who received bicalutamide 50 mg once daily compared with 17% (70 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
b) Pelvic or back pain has been reported in 3.4% to 8.5% of prostate cancer patients during monotherapy with oral bicalutamide versus 17.6% of castration patients (Kaisary, 1994) Tyrrell, 1992).
B) BACKACHE 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, back pain was reported in 25% (102 of 401) of patients who received bicalutamide 50 mg once daily compared with 26% (105 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
C) BONE PAIN 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, bone pain was reported in 9% (37 of 401) of patients who received bicalutamide 50 mg once daily compared with 11% (43 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
D) ARTHRITIS 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, arthritis was reported in 5% (21 of 401) of patients who received bicalutamide 50 mg once daily compared with 7% (29 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
E) MUSCLE WEAKNESS 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, myasthenia was reported in 7% (27 of 401) of patients who received bicalutamide 50 mg once daily compared with 5% (19 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
F) PATHOLOGICAL FRACTURE 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, pathological fracture was reported in 4% (17 of 401) of patients who received bicalutamide 50 mg once daily compared with 8% (32 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
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Endocrine |
3.16.2) CLINICAL EFFECTS
A) DISORDER OF ENDOCRINE SYSTEM 1) WITH THERAPEUTIC USE a) Breast tenderness (25 to 64%), gynecomastia (23 to 62%) and hot flashes (9 to 24%) were reported during monotherapy with bicalutamide in prostate cancer or benign prostatic hypertrophy patients (Kaisary, 1994; Kennealey & Furr, 1991) Tyrrell, 1992). These effects have, however, only rarely necessitated discontinuation of treatment.
b) Testosterone and LH serum levels are elevated during monotherapy studies (Kennealey & Furr, 1991).
B) GYNECOMASTIA 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, gynecomastia was reported in 9% (36 of 401) of patients who received bicalutamide 50 mg once daily compared with 7% (30 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
b) In clinical trials, gynecomastia has been reported in up to 38% of patients receiving bicalutamide 150 mg as a single agent for prostate cancer (unapproved use) (Prod Info CASODEX(R) oral tablets, 2015).
C) HYPERGLYCEMIA 1) WITH THERAPEUTIC USE a) In a multicenter, double-blind, controlled clinical trial in patients with previously untreated advanced prostate cancer, hyperglycemia was reported in 6% (26 of 401) of patients who received bicalutamide 50 mg once daily compared with 7% (27 of 407) of patients who received flutamide 250 mg 3 times daily. Both bicalutamide and flutamide were given in combination with a luteinizing hormone-releasing hormone analog (Prod Info CASODEX(R) oral tablets, 2015).
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Immunologic |
3.19.2) CLINICAL EFFECTS
A) HYPERSENSITIVITY REACTION 1) WITH THERAPEUTIC USE a) During postmarketing surveillance, hypersensitivity reactions, including angioneurotic edema and urticaria, have been uncommonly reported in patients who received bicalutamide therapy (Prod Info CASODEX(R) oral tablets, 2015).
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Reproductive |
3.20.1) SUMMARY
A) Bicalutamide is classified as FDA pregnancy category X and is not indicated for use in women. Embryo-fetal toxicity (ie, reduced anogenital distance and hypospadias) in male offspring has been reported in animal studies. Because bicalutamide is a nonsteroidal antiandrogen and has the potential for causing feminization of a male fetus, pregnant women should be warned of the possible risk to the male fetus.
3.20.2) TERATOGENICITY
A) ANIMAL STUDIES 1) In reproductive toxicology studies, male offspring of rats receiving doses of bicalutamide of 10 mg/kg/day (plasma concentrations in rats equal to approximately 2/3 human therapeutic concentrations) and above were observed to have reduced anogenital distances and hypospadias (Prod Info CASODEX(R) oral tablets, 2015).
2) There were no other teratogenic effects observed in rabbits receiving doses up to 200 mg/kg/day (approximately 1/3 human therapeutic concentrations) or rats receiving doses up to 250 mg/kg/day (approximately 2 times human therapeutic concentrations) (Prod Info CASODEX(R) oral tablets, 2015).
3.20.3) EFFECTS IN PREGNANCY
A) PREGNANCY CATEGORY 1) The manufacturer has classified bicalutamide as FDA Pregnancy Category X (Prod Info CASODEX(R) oral tablets, 2015).
2) Bicalutamide is not indicated for use in women and may cause fetal harm if administered to a pregnant woman. Animal studies have demonstrated reduced anogenital distance and hypospadias in male offspring when administered during the gestational period. If bicalutamide is used during pregnancy or if the patient becomes pregnant while taking bicalutamide, she should be apprised of the potential hazard to the fetus (Prod Info CASODEX(R) oral tablets, 2015).
3.20.4) EFFECTS DURING BREAST-FEEDING
A) BREAST MILK 1) No human or animal studies of bicalutamide use during lactation have been published, and there are no reports of inadvertent exposure during breastfeeding. Since bicalutamide has no indication for use in women (Prod Info CASODEX(R) oral tablets, 2015), well-controlled studies are not expected.
3.20.5) FERTILITY
A) SPERMATOGENESIS 1) The long-term effects of bicalutamide on male fertility have not been studied. The manufacturer states that there is the potential for inhibition of spermatogenesis with bicalutamide administration (Prod Info CASODEX(R) oral tablets, 2015).
B) ANIMAL STUDIES 1) LACK OF EFFECT: In male rats administered bicalutamide 250 mg/kg/day (approximately 2 times human therapeutic concentrations), precoital interval and time to successful mating were increased in the first pairing, but there were no effects on fertility reported following successful mating. By 7 weeks after discontinuation of an 11-week bicalutamide dosing period, the effects were reversed (Prod Info CASODEX(R) oral tablets, 2015).
2) In female rats administered bicalutamide 10, 50 and 250 mg/kg/day (approximately 2/3, 1, and 2 times human therapeutic concentrations, respectively), no effects on the pregnant females or their female offspring were observed. However, at all dose levels of bicalutamide administered to the pregnant female rats resulted in feminization of the male offspring leading to hypospadias and impotence (Prod Info CASODEX(R) oral tablets, 2015)
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Carcinogenicity |
3.21.3) HUMAN STUDIES
A) NEOPLASM 1) Leydig cell hyperplasia has been identified in 5 prostate cancer patients following prolonged administration of bicalutamide (50 milligrams once daily for at least 7 months). The ultrastructural appearance of the Leydig cells, however, in these patients were normal (Bjerklund Johansen et al, 1994).
3.21.4) ANIMAL STUDIES
A) NEOPLASM 1) Two-year oral carcinogenicity studies were conducted in both male and female rats and mice at doses of 5, 15 or 75 milligrams/kilogram/day of bicalutamide (Prod Info Casodex(R), bicalutamide, 1998). a) A variety of tumor target organ effects were identified and attributed to the antiandrogenicity of bicalutamide, namely, testicular benign interstitial (Leydig) cell tumors in male rats at all dose levels and uterine adenocarcinoma in female rats at 75 milligrams/kilogram/day (Prod Info Casodex(R), bicalutamide, 1998).
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