Prostate cancer, metastasized

Prostate cancer metastasized in association with castration, medical or surgical

Prostate cancer locally advanced

BICALUTAMIDE PHR LAB 50 mg film-coated tablet is indicated in patients with locally advanced prostate cancer at high risk of progression of the disease either alone or in adjuvant therapy with radical prostatectomy or Radiotherapy (see section on pharmacodynamic properties).

Prostate cancer, metastasized

· In adult men, including the elderly, one 50 mg tablet per day, to start with medical or surgical castration. Code>
Cancer of the prostate locally advanced

· In adult men, including the elderly, three tablets of 50 mg per day.

It is currently recommended to treat 5 years.

In patients with renal insufficiency or mild hepatic impairment, no dosage adjustment is necessary. In cases of moderate to severe hepatic impairment, accumulation may be observed (see sections 4.3 and 4.4). >
Tablet, white to white, broken, round, biconvex, engraved, "93" on one side and "220" on the other side

ANTIANDROGENES, ATC code, L 02 BB03

(L: Antineoplastic and Immunomodulators)

BICALUTAMIDE PHR LAB 50 mg film-coated tablet is an anti-androgenic, non-steroidal, receptor-specific, androgenic, devoid of any other endocrine activity
It induces a regression of prostatic cancer by blocking the activity of androgens in the receptors. Clinically, discontinuation of BICALUTAMIDE PHR LAB 50 mg film-coated tablets may lead to withdrawal symptoms in some patients.
Bicalutamide 150 mg has been studied in patients with non-metastatic prostate cancer, localized (T1-T2, N0 or NX, M0) or locally advanced (T3-T4, all N, M0, T1-T2 , N +, Mo). It was the subject of a combined analysis of 3 controlled, placebo-controlled, double-blind studies involving 8113 patients. In these studies, bicalutamide 150 mg was given as immediate hormone therapy or adjunctive therapy to radical prostatectomy or radiotherapy (mainly irradiation, external). At 7.4 years of median follow-up, 27.4% of patients treated with bicalutamide and 30.7% of patients treated with placebo showed an objective progression of their disease
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A reduction in the risk of progression of the objective disease was observed in most groups of patients but was more pronounced in patients with a high risk of progression of the disease. Therefore, clinicians may decide that the optimal medical strategy for a patient at low risk of disease progression, particularly in adjuvant therapy, to radical prostatectomy, or delaying hormone therapy at onset of Signs of progression of the disease.

No difference in overall survival was observed at 7.4 years of follow-up, median with 22.9% mortality (HR '= 0.99, 95% CI 0.91, 1.09). However, trends are visible in the exploratory analyzes of subgroups.

The progression-free survival and overall survival data of patients at the locally advanced stage are summarized in the tables below
Table 1: Progression-free progression at the locally advanced stage according to the treatment

Events (%)

Events (%)

Hazard Ratio

Population analyzed

Among the patients

Among the patients

(95% CI)

Bicalutamide

Under placebo

Abstention, monitoring

193/335; (57,6)

222/322; (68,9)

0.60 (0.49) to 0.73

Radiotherapy

66/161; (41,0)

86/144; (59,7)

0.56 (0.40 to 0.78)

Radical prostatectomy

179/870 (20,6)

213/849 (25,1)

0.75 (0.61 to 0.91)

Table 2: Overall survival at the locally advanced stage according to the treatment

Deaths (%) among the

Deaths (%) among the

Hazard Ratio

Population, analyzed

Patients under

Patients under placebo

(95% CI)

Bicalutamide

Abstention surveillance

164/335 (49,0)

183/322 (56,8)

0.81 (0.66 to 1.01)

Radiotherapy

49/161 (30,4)

61/144 (42,4)

0.65 (0.44 to 0.95)

Radical prostatectomy

137/870 (15,7)

122/849 (14,4)

1.09 (0.85 to 1.39)

For patients, at the localized stage treated with bicalutamide alone, there is no significant difference in progression-free survival. In these patients, there is also a tendency for a decrease in survival compared to patients treated with placebo (HR '= 1.16, 95% IC 0.99 to 1.37). Based on these results, the benefit / risk ratio of a BICALUTAMIDE PHR; LAB 50 mg film-coated tablet is not considered favorable in this group of patients.

Bicalutamide is a racemic whose anti-androgenic activity almost exclusively belongs to the (R) -enantiomer.
· Women.

· Children

· Patients who have responded to hypersensitivity to bicalutamide.

· History of liver disease associated with taking bicalutamide

· Hepatic impairment, severe

Warnings

·;This medicine contains lactose. Its use is not recommended in patients with galactose intolerance, Lapp lactase deficiency or malabsorption syndrome, glucose or galactose (hereditary or rare diseases).
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A transaminase control should be performed prior to initiation of therapy. The patient will be informed of the need to immediately notify the attending physician of any symptoms or signs suggestive of liver damage (see Precautions, Specific Uses).

This check must be repeated periodically, in subsequent check-ups. An elevation of serum transaminase activity beyond 3 times the upper limit of normal should cause treatment to stop.

Special precautions for use

In case of clinical signs suggestive of hepatitis (nausea or vomiting, pain, abdominal pain, jaundice or dark urine, pruritus, asthenia, anorexia), transaminases should be assayed immediately. An elevation of transaminases greater than 3 times the upper limit of normal should make definitively stop treatment.

· Bicalutamide is essentially metabolized by the liver. Its elimination is slowed in case of severe hepatic insufficiency. Therefore, it is recommended to use BICALUTAMIDE PHR LAB 50 mg film-coated tablet cautiously in case of moderate hepatic insufficiency
· In vitro studies showed that the (R) enantiomer of bicalutamide was an inhibitor of cytochrome CYP 3A4 and to a lesser degree of cytochrome CYP 2C9, 2C19 and 2D6.

· Coumarin Anticoagulants: Because of the strong plasma protein binding, a competitive type interaction was observed in vitro with warfarin.

It is recommended to regularly check the coagulation tests and reduce, if necessary, the dosage of the anticoagulant during treatment with BICALUTAMIDE PHR LAB 50 mg tablet, film-coated. >

Not applicable.

No cases of overdose have been reported to date. In the absence of an antidote, the treatment should be symptomatic. Due to the strong binding of bicalutamide to plasma proteins and its metabolism, dialysis is not appropriate.
Effects observed during treatment in patients with prostate cancer, locally advanced, at high risk of disease progression, either in treatment alone or in adjuvant therapy, to radical prostatectomy or to; Radiotherapy.

The pharmacological properties of bicalutamide are responsible for certain adverse effects observed. Among these

· Very frequently (> 10%)

Gynecomastia and breast tenderness: The majority of patients receiving bicalutamide (150 mg / day) was concerned with this problem. Clinical experience shows that these effects were found to be severe in 5% of patients. Gynecomastia may stop treatment in some patients in particular after prolonged treatment

· Frequently (> 1%)

Alopecia, hair regrowth, dryness of the skin, decreased libido, impotence and weight gain

Other effects

· Frequently (> 1%)

Nausea.
· Little Frequently (

Prostate cancer metastasized prostate cancer metastasized in combination with castration medical or surgical treatment prostate cancer locally advanced BICALUTAMIDE PHR LAB 50 mg film - coated tablet is indicated in patients with prostate cancer, Prostate cancer locally advanced, at high risk of progression of the disease, either as a treatment alone or as adjunctive therapy to radical prostatectomy or radiotherapy (see section on Pharmacodynamic properties)
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