DESCRIPTION
Mechanism of Action
• Nonsteroidal antiandrogen agent that binds to androgen receptor
and inhibits androgen uptake as well as inhibiting androgen binding
in the nuclei of androgen-sensitive prostate cancer cells.
• Affinity to androgen receptor is four-fold greater than flutamide.
Mechanism of Resistance
• Decreased expression of androgen receptor.
• Mutation in androgen receptor leading to decreased binding affinity
to bicalutamide.
Absorption
Well absorbed by the GI tract. Peak plasma levels observed 1–2 hours after
oral administration. Absorption is not affected by food.
Distribution
Distribution is not well characterized. Extensively bound to plasma proteins
(96%).
Metabolism
Extensive metabolism occurs in the liver via oxidation and glucuronidation
by cytochrome P450 enzymes to inactive metabolites. Both parent drug
and its metabolites are cleared in urine and feces. The elimination half-life
is long, on the order of several days.
Indications
Stage D2 metastatic prostate cancer.
Dosage Range
Recommended dose is 50 mg PO once daily, either alone or in combination
with a luteinizing hormone–releasing hormone (LHRH) analog.
Drug Interactions
Warfarin—Bicalutamide can displace warfarin from its protein-binding
sites, leading to increased anticoagulant effect. Coagulation parameters
(PT and INR) must be followed closely, and dose adjustments may be
needed.
Special Considerations
1. Use with caution in patients with abnormal liver function. Monitor
LFTs at baseline and during therapy.
2. Caution patients about the potential for hot flashes. Consider the use
of clonidine 0.1–0.2 mg PO daily, megestrol acetate 20 mg PO bid,
or soy tablets one tablet PO tid for prevention and/or treatment.
3. Instruct patients on the potential risk of altered sexual function and
impotence.
4. Pregnancy category D. Breastfeeding should be avoided.
Toxicity 1
Hot flashes, decreased libido, impotence, gynecomastia, nipple pain, and
galactorrhea. Occur in 50% of patients.
Toxicity 2
Constipation observed in 10% of patients. Nausea, vomiting, and diarrhea
occur rarely.
Toxicity 3
Transient elevations in serum transaminases are rare.
SPECIFICATION
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