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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