BICALUTAMIDE tablet, film coated

Ország: Egyesült Államok

Nyelv: angol

Forrás: NLM (National Library of Medicine)

Aktív összetevők:

BICALUTAMIDE (UNII: A0Z3NAU9DP) (BICALUTAMIDE - UNII:A0Z3NAU9DP)

Beszerezhető a:

Proficient Rx LP

Az alkalmazás módja:

ORAL

Recept típusa:

PRESCRIPTION DRUG

Terápiás javallatok:

Bicalutamide tablets, USP 50 mg daily are indicated for use in combination therapy with a luteinizing hormone-releasing hormone (LHRH) analog for the treatment of Stage D2 metastatic carcinoma of the prostate. Bicalutamide tablets, USP 150 mg daily are not approved for use alone or with other treatments [see Clinical Studies (14.2)]. Bicalutamide is contraindicated in: Bicalutamide is contraindicated in any patient who has shown a hypersensitivity reaction to the drug or any of the tablet’s components. Hypersensitivity reactions including angioneurotic edema and urticaria have been reported. Bicalutamide has no indication for women, and should not be used in this population. Bicalutamide can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Risk Summary Bicalutamide is contraindicated for use in pregnant women because it can cause fetal harm. Bicalutamide is not indicated for use in females. There are no human data on the use of bicalutamide in pregnant women. In animal reproduction studies, oral administration of bicalutamide to pregnant rats during organogenesis caused abnormal development of reproductive organs in male fetuses at exposures approximately 0.7 to 2 times the human exposure at the recommended dose (see Data). Data Animal Data In an embryo-fetal development study in pregnant rats dosed during the period of organogenesis from gestation days 6-15, male fetuses had reduced anogenital distance at doses of 10 mg/kg/day and above (approximately 0.7 to 2 times the human exposure at the recommended dose). In a pre- and post-natal development study, female rats were dosed from gestation day 7-16 and allowed to litter and rear their offspring to weaning. Male offspring of rats receiving doses of 10 mg/kg/day (approximately 0.7 times the human exposure at the recommended dose) and above, were observed to have reduced anogenital distance. In a peri- and post-natal development study, female rats were dosed from gestation day 16 to lactation day 22 and allowed to litter and rear their offspring to weaning. Survival and weights of offspring during lactation were reduced for litters from maternal rats receiving doses of 250 mg/kg/day (approximately 2 times the human exposure at the recommended dose). Male offspring of rats receiving doses of 10 mg/kg/day (approximately 0.7 times the human exposure at the recommended dose) and above, were observed to have reduced anogenital distance, smaller secondary sex organs, cryptorchidism and hypospadias resulting in an inability to mate and impregnate their female partners. Female offspring of rats receiving doses of 10 mg/kg/day (approximately 0.7 times the human exposure at the recommended dose) and above had reduced pregnancy rates. Risk Summary Bicalutamide is not indicated for use in pregnant women. There is no information available on the presence of bicalutamide in human milk, or on the effects on the breastfed infant or on milk production. Bicalutamide has been detected in rat milk. Contraception Males Antiandrogen therapy may cause morphological changes in spermatozoa [see Nonclinical Toxicology (13.1)]. Based on findings in animal reproduction studies and its mechanism of action, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 130 days after the final dose of bicalutamide [see Use in Specific Populations (8.1) and Clinical Pharmacology (12.1)]. Infertility Males Based on animal studies, bicalutamide can lead to inhibition of spermatogenesis and may impair fertility in males of reproductive potential. The long-term effects of bicalutamide on male fertility have not been studied [see Nonclinical Toxicology (13.1)] . The safety and effectiveness of bicalutamide in pediatric patients have not been established. Bicalutamide orodispersible tablet was studied in combination with Arimidex# (anastrozole) orodispersible tablet in an open-label, non-comparative, multi-center study that assessed the efficacy and safety of this combination regimen over 12 months in the treatment of gonadotropin-independent precocious puberty in boys with familial male-limited precocious puberty, also known as testotoxicosis. Patients were enrolled in the study if they had a baseline age ≥2 years and a diagnosis of testotoxicosis based on clinical features of progressive precocious puberty, symmetrical testicular enlargement, advanced bone age, pubertal levels of serum testosterone, prepubertal pattern of gonadotropin secretion following a GnRH stimulation test, and absence of other clinical and biochemical causes of testosterone excess. Thirteen out of the 14 patients enrolled completed 12 months of combination treatment (one patient was lost to follow-up). If central precocious puberty (CPP) developed, an LHRH analog was to be added. Four patients were diagnosed with CPP during the 12-month study and received LHRH analog treatment and 2 additional patients were diagnosed at the end of the 12 months and received treatment subsequently. Mean ± SD characteristics at baseline were as follows: chronological age: 3.9±1.9 years; bone age 8.8±2.5; bone age/chronological age ratio: 2.06±0.51; growth rate (cm/yr): 10.81±4.22; growth rate standard deviation score (SDS): 0.41±1.36. The starting bicalutamide dose was 12.5 mg. Bicalutamide was titrated in each patient until steady-state R-bicalutamide (the active isomer of bicalutamide) trough plasma concentration reached 5 mcg/mL to 15 mcg/mL, which is the range of therapeutic concentrations achieved in adults with prostate cancer following the administration of the currently approved bicalutamide dose of 50 mg. The starting daily dose of anastrozole was 0.5 mg. Anastrozole was independently titrated in each patient until it reached at steady-state a serum estradiol concentration of <10 pmol/L (2.7 pg/mL). The following ascending doses were used for bicalutamide: 12.5 mg, 25 mg, 50 mg, and 100 mg. For anastrozole there were two ascending doses: 0.5 mg and 1 mg. At the end of the titration phase, 1 patient was on 12.5 mg bicalutamide, 8 patients were on 50 mg bicalutamide, and 4 patients were on 100 mg bicalutamide; 10 patients were on 0.5 mg anastrozole and 3 patients were on 1 mg anastrozole. In the majority of patients, steady-state trough concentrations of R-bicalutamide appeared to be attained by Day 21 with once daily dosing. Steady-state trough plasma anastrozole concentrations appeared to be attained by Day 8. The primary efficacy analysis of the study was to assess the change in growth rate after 12 months of treatment, relative to the growth rate during the ≥6 months prior to entering the study. Pre-study growth rates were obtained retrospectively. There was no statistical evidence that the growth rate was reduced during treatment. During bicalutamide / Arimidex# treatment the mean growth rate (cm/yr) decreased by 1.6 cm/year, 95% CI (-4.7 to 1.5) p=0.28; the mean growth rate SDS decreased by 0.1 SD, 95% CI (–1.2 to 1.0) p=0.88. Table 2 shows descriptive data for growth rates for the overall population and for subgroups defined by history of previous treatment for testotoxicosis with ketoconazole, spironolactone, anastrozole or other aromatase inhibitors. Endpoint   Analysis Population Pre-study Mean   Change from pre-study to 12 months % patients with growth reduction*  Mean  Median  (Min, Max)  Growth rate (cm/yr)  All treated (n=13)  10.8  -1.6  -2.8  (-7.4, 8.4)  9/13 (69%)  PT† (n=6)  10.3  -0.2  -2.6‡  (-7.2, 8.4)  4/6 (67%)  NPT§ (n=7)  11.2  -2.8  -2.8  (-7.4, 1.1)  5/7 (71%)  Growth rate (SD units)  All treated (n=13)  0.4  -0.1  -0.4  (-2.7, 3.5)  9/13 (69%)  PT† (n=6)  -0.1  +0.7  -0.2‡  (-1.6, 3.5)  4/6 (67%)  NPT§ (n=7)  0.8  -0.7  -0.4  (-2.7, 0.5)  5/7 (71%) Total testosterone concentrations increased by a mean of 5 mmol/L over the 12 months of treatment from a baseline mean of 10 mmol/L. Estradiol concentrations were at or below the level of quantification (9.81 pmol/L) for 11 of 12 patients after 12 months of treatment. Six of the 12 patients started treatment at an estradiol concentration below the level of quantification. There were no deaths, serious adverse events, or discontinuations due to adverse events during the study. Of the 14 patients exposed to study treatment, 13 (92.9%) experienced at least one adverse event. The most frequently reported (>3 patients) adverse events were gynecomastia (7/14, 50%), central precocious puberty (6/14, 43%), vomiting (5/14, 36%), headache (3/14, 21%), pyrexia (3/14, 21%), and upper respiratory tract infection (3/14, 21%). Adverse reactions considered possibly related to bicalutamide by investigators included gynecomastia (6/14, 43%), central precocious puberty (2/14, 14%), breast tenderness (2/14, 14%), breast pain (1/14, 7%), asthenia (1/14, 7%), increased alanine aminotransferase [ALT] (1/14, 7%), increased aspartate aminotransferase [AST] (1/14, 7%), and musculoskeletal chest pain (1/14, 7%). Headache was the only adverse reaction considered possibly related to anastrozole by investigators. For the patient who developed elevated ALT and AST, the elevation was <3X ULN, and returned to normal without stopping treatment; there was no concomitant elevation in total bilirubin. In two studies in patients given 50 mg or 150 mg daily, no significant relationship between age and steady-state levels of total bicalutamide or the active R-enantiomer has been shown. Bicalutamide should be used with caution in patients with moderate-to-severe hepatic impairment. Bicalutamide is extensively metabolized by the liver. Limited data in subjects with severe hepatic impairment suggest that excretion of bicalutamide may be delayed and could lead to further accumulation. Periodic liver function tests should be considered for hepatic-impaired patients on long-term therapy [see Warnings and Precautions (5.1)]. No clinically significant difference in the pharmacokinetics of either enantiomer of bicalutamide was noted in patients with mild-to-moderate hepatic disease as compared to healthy controls. However, the half-life of the R-enantiomer was increased approximately 76% (5.9 and 10.4 days for normal and impaired patients, respectively) in patients with severe liver disease (n=4). Renal impairment (as measured by creatinine clearance) had no significant effect on the elimination of total bicalutamide or the active R-enantiomer.

Termék összefoglaló:

White to off white, circular, biconvex, film-coated tablets debossed with “485” on one side and plain on other side. Bottles of 90…..…….…..…….…..…….…..…….…..…….NDC 82804-082-90 Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F) [see USP Controlled Room Temperature].

Engedélyezési státusz:

Abbreviated New Drug Application

Termékjellemzők

BICALUTAMIDE- BICALUTAMIDE TABLET, FILM COATED
PROFICIENT RX LP
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HIGHLIGHTS OF PRESCRIBING INFORMATION
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
BICALUTAMIDE TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
BICALUTAMIDE TABLETS .
BICALUTAMIDE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 1995
INDICATIONS AND USAGE
•
•
DOSAGE AND ADMINISTRATION
The recommended dose for bicalutamide tablets therapy in combination
with an LHRH analog is one 50
mg tablet once daily (morning or evening). (2) (2)
DOSAGE FORMS AND STRENGTHS
50 mg tablets (3) (3)
CONTRAINDICATIONS
•
•
•
WARNINGS AND PRECAUTIONS
•
•
•
•
•
ADVERSE REACTIONS
Adverse reactions that occurred in more than 10% of patients receiving
bicalutamide plus an LHRH-A
were: hot flashes, pain (including general, back, pelvic and
abdominal), asthenia, constipation, infection,
nausea, peripheral edema, dyspnea, diarrhea, hematuria, nocturia, and
anemia. (6.1)
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT SUN PHARMACEUTICAL
INDUSTRIES, INC. AT
1-800-818-4555 OR FDA AT 1-800-FDA-1088 OR WWW.FDA.GOV/MEDWATCH.
DRUG INTERACTIONS
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•
USE IN SPECIFIC POPULATIONS
•
Bicalutamide tablet 50 mg is an androgen receptor inhibitor indicated
for use in combination therapy
with a luteinizing hormone-releasing hormone (LHRH) analog for the
treatment of Stage D
metastatic carcinoma of the prostate. (1)
2
Bicalutamide tablet 150 mg daily is not approved for use alone or with
other treatments. (1)
Hypersensitivity (4)
Women (4)
Pregnancy (4,8.1)
Severe hepatic injury and fatal hepatic failure have been observed.
Monitor serum transaminase
levels prior to starting treatment with bicalutamide, at regular
intervals for the first four months of
treatment and periodically thereafter, and for symptoms or signs
suggestive of hepatic dysfunction.
Use bicalutamide with caution in patients with hepatic impairment.
(5.1)
Hemorrhage with Concomitant Use of Coumarin Anticoagulant. Closely
m