A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Casodex Warnings, Precautions, Pregnancy, Nursing, Abuse - Bicalutamide
Casodex Warnings, Precautions, Pregnancy, Nursing, Abuse - Bicalutamide
WARNINGS
No information provided.
PRECAUTIONS
General
1. CASODEX should be used with caution in patients with moderate-to-severe
hepatic impairment. CASODEX is extensively metabolized by the liver. Limited
data in subjects with severe hepatic impairment suggest that excretion
of CASODEX may be delayed and could lead to further accumulation. Periodic
liver function tests should be considered for patients on long-term therapy.
2. In clinical trials with CASODEX as a single agent for prostate cancer,
gynecomastia and breast pain have been reported in up to 38% and 39% of
patients, respectively.
3. Regular assessments of serum Prostate Specific Antigen (PSA) may be
helpful in monitoring the patient’s response. If PSA levels rise during
CASODEX therapy, the patient should be evaluated for clinical progression.
For patients who have objective progression of disease together with an
elevated PSA, a treatment-free period of antiandrogen, while continuing
the LHRH analogue, may be considered.
4. Since transaminase abnormalities and, rarely, jaundice have been reported
with the use of CASODEX, periodic liver function tests should be considered.
If clinically indicated, e. g., when the patient has jaundice or laboratory
evidence of liver injury in the absence of liver metastases, CASODEX therapy
should be discontinued. If transaminases increase over 2 times the upper
limit of normal, treatment should be discontinued. Abnormalities are usually
reversible upon discontinuation.
Information for Patients
See PATIENT INFORMATION section.
Drug Interactions
See DRUG INTERACTIONS section.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Two-year oral carcinogenicity studies were conducted in both male and
female rats and mice at doses of 5, 15 or 75 mg/kg/day of bicalutamide.
A variety of tumor target organ effects were identified and were attributed
to the antiandrogenicity of bicalutamide, namely, testicular benign interstitial
(Leydig) cell tumors in male rats at all dose levels (the steady-state
plasma concentration with the 5 mg/kg/day dose is approximately 2/3 human
therapeutic concentrations*) and uterine adenocarcinoma in female rats
at 75 mg/kg/day (approximately 11/2 times the human therapeutic concentrations*).
There is no evidence of Leydig cell hyperplasia in patients; uterine tumors
are not relevant to the indicated patient population.
A small increase in the incidence of hepatocellular carcinoma in male
mice given 75 mg/kg/day of bicalutamide (approximately 4 times human therapeutic
concentrations*) and an increased incidence of benign thyroid follicular
cell adenomas in rats given 5 mg/kg/day (approximately 2/3 human therapeutic
concentrations*) and above were recorded. These neoplastic changes were
progressions of non-neoplastic changes related to hepatic enzyme induction
observed in animal toxicity studies. Enzyme induction has not been observed
following bicalutamide administration in man. There were no tumorigenic
effects suggestive of genotoxic carcinogenesis.
A comprehensive battery of both in vitro and in vivo genotoxicity
tests (yeast gene conversion, Ames, E. coli, CHO/HGPRT, human lymphocyte
cytogenetic, mouse micronucleus, and rat bone marrow cytogenetic tests)
has demonstrated that CASODEX does not have genotoxic activity.
Administration of CASODEX may lead to inhibition of spermatogenesis.
The long-term effects of CASODEX on male fertility have not been studied.
In male rats dosed at 250 mg/kg/day (approximately 2 times human therapeutic
concentrations*), the precoital interval and time to successful mating
were increased in the first pairing but no effects on fertility following
successful mating were seen. These effects were reversed by 7 weeks after
the end of an 11-week period of dosing.
No effects on female rats dosed at 10, 50 and 250 mg/kg/day (approximately
2/3, 1 and 2 times human therapeutic concentrations, respectively*) or
their female offspring were observed. Administration of bicalutamide to
pregnant females resulted in feminization of the male offspring leading
to hypospadias at all dose levels. Affected male offspring were also impotent.
*Based on a maximum dose of 50 mg/day of bicalutamide for an average
70 kg patient.
Pregnancy: Pregnancy Category X (see CONTRAINDICATIONS).
Nursing Mothers
CASODEX is not indicated for use in women. It is not known whether this
drug is excreted in human milk. Because many drugs are excreted in human
milk, caution should be exercised when CASODEX is administered to a nursing
woman.
Pediatric Use
Safety and effectiveness of CASODEX in pediatric patients have not been
established.
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