Casodex (Bicalutamide)

Each tablet contains:

Bicalutamide В В В В В В В В  50 mg

Excipient, cbp a tablet.

Bicalutamide В В В В В В В В  150 mg

Excipient, cbp a tablet.

Casodex 50 mg is indicated for the treatment of advanced prostate cancer in combination with an LHRH analogue or surgical castration.

Casodex 150 mg is indicated as immediate therapy either alone or as adjuvant to treatment with curative intent in patients with locally advanced prostate cancer.

Casodex 150 mg is indicated as monotherapy in the treatment of cancer patients with nonmetastatic locally advanced prostate where the immediate hormonal therapy is indicated.

Casodex 150 mg can be used in patients with metastatic prostate cancer where the medical or surgical castration is not recommended or is not accepted.

Pharmacokinetics: Absorption of Casodex is good after oral administration. No evidence of a clinically important effect of food on bioavailability. The enantiomer-(S) is rapidly eliminated with respect to the enantiomer-(R), since the latter has a half life of elimination from plasma in about a week.

With daily administration of Casodex , an enantiomer-(R) builds around 10 times in the plasma due to its long half-life. During the daily administration of 50 mg dose of Casodex was observed stable plasma concentrations of the enantiomer-(R) of approximately 9 g / ml. In Casodex 150 mg, plasma concentrations of the enantiomer-(R) are approximately 22 g / ml. In stable conditions, the predominantly active enantiomer-(R), representing 99% of total circulating enantiomers.

The pharmacokinetics of the enantiomer-(R) is not affected by age, renal insufficiency or mild to moderate hepatic insufficiency. There is evidence in the case of subjects with severe hepatic insufficiency, the elimination of the enantiomer-(R) of the plasma is slower. Bicalutamide binds strongly to proteins (racemate 96% R-bicalutamide 99.6%) and extensively metabolised (oxidation and glucuronidation) and its metabolites are eliminated by renal and biliary tract in approximately equal proportions.

In a clinical study, the mean concentration of R-bicalutamide in semen of men who were given Casodex 150 mg was 4.9 g / ml. The amount of bicalutamide potentially delivered the man in your partner during intercourse is low and approximately equivalent to 0.3 g / kg, which is lower than that required to induce a change in the progeny of laboratory animals.

Pharmacodynamics: Casodex is a nonsteroidal antiandrogen that no other endocrine activity. It binds to androgen receptors without activating gene expression, thereby inhibiting androgen stimulation. This inhibition leads to regression of prostate tumors. Clinically, the suspension of Casodex can result in antiandrogen withdrawal syndrome in a subgroup of patients. Casodex is a racemate and antiandrogenic activity is found almost exclusively in the enantiomer-(R).

The efficacy of Casodex 150 mg as a treatment for patients with localized prostate cancer or locally advanced (T1-T4, any nodal status, M0) was demonstrated by a combined analysis of three placebo-controlled studies in 8.113 patients, in whom administered the drug as immediate hormonal therapy or as adjuvant to therapy with curative intent. Treatment with Casodex 150 mg was associated with a significant reduction in both the risk of disease progression and the incidence of bone metastases but no differences in survival. In addition to these primary analysis, various analysis by subgroups. These indicate that in terms of progression-free survival, there is a significant benefit in patients with locally advanced disease regardless of primary therapy received (eg, radiotherapy, radical prostatectomy, watchful waiting), but in patients with localized disease not found no benefit. In terms of survival for patients with localized disease who receive only Casodex 150 mg as immediate therapy, there was a trend to decreased survival compared with patients taking placebo, whereas in patients with locally advanced disease there was a trend improve survival with Casodex 150 mg when compared with placebo. An improvement in survival for patients with locally advanced disease who were given Casodex 150 mg as adjuvant to radiotherapy. There was no difference in survival in patients who had undergone radical prostatectomy.

In a separate program demonstrated the effectiveness of Casodex 150 mg for treatment in cancer patients with nonmetastatic locally advanced prostate where the immediate hormonal treatment is indicated, by a combined analysis of two studies involving 480 patients with prostate cancer metastatic (M0) without pretreatment. With a mortality of 56%, there was no statistically significant difference in survival (RR = 1.05 (IC0.81 to1.36), p = 0.699) or time to progression (RR = 1.20 (IC 0.96 to1.51), p = 0.107) between Casodex 150 mg and castration. The quality of life there was a trend
ence in favor of Casodex 150 mg compared with castration, with statistically significant benefits demonstrated in sexual interest (p = 0.029) and physical capacity (p = 0.046) in patients for which data are available.

The efficacy of Casodex 150 mg for the treatment of patients with metastatic prostate cancer was demonstrated in the combined analysis of two studies involving 805 patients with metastatic disease (M1) without prior treatment with a mortality of 43%.

Casodex 150 mg proved to be inferior to castration in terms of survival (RR 1.30, p = 0.0246), although the numerical difference in estimated time to death was only 42 days (six weeks).

The quality of life there was a trend for Casodex with daily doses of 150 mg, with statistically significant advantages in sexual interest (p = 0.041) and physical capacity (p = 0.032) in patients for which data are available data. The subjective response analysis showed a significant advantage for Casodex showing a better handle on controlling the symptoms that castration (p = 0.046).

The results of the combined analysis of two additional studies which compares Casodex 150 mg as monotherapy vs. combined androgen blockade (containing approximately 93% and 50% of M1 patients) showed a trend favoring the survival for Casodex (RR 0.858 (CI 0.61-1.20) p = 0.37).

Casodex is contraindicated in women and children.

Casodex should not be administered to any patient who has filed a hypersensitivity reaction to its use.

Casodex is extensively metabolized in the liver.

The result of research suggests that their elimination may be slower in patients with severe liver failure, which may allow some accumulation of Casodex . Therefore, Casodex should be used with caution in patients with moderate or severe hepatic impairment. Periodic liver function tests are recommended to monitor changes that may occur.

Rarely, severe liver changes were observed and liver failure with Casodex , therapy should be discontinued if changes are severe.

Effects on ability to drive or operate machinery: It is unlikely that Casodex affects the ability of patients to drive or operate machinery.

Casodex is contraindicated in women and should not be administered during pregnancy or breastfeeding.

In general, Casodex was well tolerated and there have been few withdrawals due to treatment.

Frequency of adverse reactions observed with CASODEX В® 50 mg
Frequency	System	Event
Very common ( 10%)	Reproductive system	Breast Pain 1
	disorders	Gynecomastia 1
	General disorders	Hot Flashes 1
Common ( 1% and <10%)В	Gastrointestinal Diseases	Diarrhea
		Nausea
	Hepatobiliary disorders	Hepatic changes (levels of transaminases
		high, jaundice) 2
	General disorders	Asthenia
		Pruritus
Uncommon ( 0.1% and <1%)	Immune System	Hypersensitivity reactions, including
		angioedema and urticaria
	Respiratory,	Interstitial lung disease
	thoracic and mediastinal
Few ( 0.01% and <0.1%)	Gastrointestinal disorders	Vomiting
	Hepatobiliary disorders	Liver failure
	Skin diseases and	Dry skin
	subcutaneous tissue

¹ can be decreased by concomitant castration.

² The liver changes are rarely severe and are often transient, resolving or improving with continued therapy or discontinuation of therapy (see PRECAUTIONS).

Additionally, the following adverse events have been reported in clinical trials during treatment with Casodex 50 mg plus releasing hormone analog of luteinizing hormone LHRH (as possible adverse reactions, researchers said, with a frequency 1%) .

Not established the causal relationship of these reactions to the drug and some of the reactions identified are common in elderly patients.

Cardiovascular system: Heart failure.

Gastrointestinal System: Anorexia, dry mouth, dyspepsia, constipation and flatulence.

CNS: dizziness, insomnia, drowsiness and decreased libido.

Respiratory System: Dyspnea.

Genitourinary: Impotence and nocturia.

Hematologic: Anemia.

Skin and skin structure: Alopecia, rash, diaphoresis, and hirsutism.

Metabolic and Nutritional: diabetes mellitus, hyperglycemia, edema, weight gain and weight loss.

General: abdominal pain, chest pain, headache, pelvic pain and chills.

Casodex 150 mg may be associated with the following undesirable effects:

Very common ( 10%): In most patients receiving Casodex 150 mg as monotherapy are: Gynecomastia and / or breast pain. In clinical studies, these symptoms were considered severe by up to 5% of patients.

Gynecomastia has not resolved spontaneously after cessation of treatment, particularly after prolonged treatment.

Common ( 1% and <10%): Flushing, pruritus, asthenia, alopecia, hirsutism, dry skin, nausea, decreased libido, impotence, weight gain, nausea.

Uncommon (> 0.1% and <1%), abdominal pain, depression, dyspepsia, haematuria and interstitial lung disease.

Hypersensitivity reactions including angioedema and urticaria.

Liver abnormalities were observed (increased levels of transaminases, jaundice) which are rarely severe. Often, these changes were transient and resolved or improved despite continued treatment or after discontinuation.

Rarely (> 0.01% and <0.1%), liver failure.

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No evidence of pharmacokinetic or pharmacodynamic interaction exists between Casodex 50 mg and LHRH analogues.

Studies in vitro have shown that R-bicalutamide is an inhibitor of CYP 3A4 with minor inhibitory effects on the activity of CYP 2C9, 2C19 and 2D6.

Although studies in vitro have suggested the potential for Casodex to inhibit cytochrome 3A4, a number of clinical studies showed that the inhibition is of little clinical significance.

Studies in vitro have shown Casodex can displace the coumarin anticoagulant, warfarin from its binding sites to proteins. Therefore, to start treatment with Casodex in patients already receiving coumarin anticoagulants is recommended that patients with the prothrombin time.

In clinical trials with Casodex there have been some changes are rarely severe hepatic (increased levels of transaminases, jaundice). Often, these changes were transient and resolved or improved despite continued treatment or after discontinuation.

Should be considered for regular testing of liver function.

Casodex is a potent antiandrogen and an inducer of mixed function oxidase enzyme in animals.

Changes in target organs, including the induction of tumors in animals relate to this activity.

No enzyme induction was observed in men.

None of the findings made during preclinical testing is considered important for the treatment of patients with advanced prostate cancer.

Adults (including elderly):

Casodex 50 mg: one tablet once a day.

Treatment with Casodex should be started at the same time that treatment with an LHRH analogue or surgical castration.

Casodex 150 mg: one tablet per day including the elderly for a minimum period of two years.

Children: Casodex 50 and 150 mg is contraindicated in children.

Renal impairment: No dosage adjustment is necessary both for Casodex 50 and 150 mg.

Hepatic impairment: No dosage adjustment is necessary.

Can result in increased accumulation in liver failure patients with moderate to severe (see Precautions).

There is no experience in regard to overdosage in humans.

There is no specific antidote, treatment should be symptomatic.

Dialysis may be futile as Casodex binds strongly to proteins and not recovered intact in urine.

Indicated a general supportive treatment, including frequent measurement of vital signs.

Box with 14 and 28 tablets of 50 mg and 150 mg in blister container schedule.

Store at room temperature to no more than 30Cand dry.

Its sale requires a prescription.
Do not use during pregnancy or in the Lactanase.
This medication should be administered
only physicians
urologists and oncologists.
Keep out of reach of children.
Exclusive literature for physicians.

Made in Germany by:

AstraZeneca GmbH, Otto Hahn Strasse

Conditioning and distributed in Mexico by:

AstraZeneca , SA de CV

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HEAR-07330022090092/RM2007