Bicadex

Bicadex

bicalutamide

Manufacturer:

Sandoz

Distributor:

Zuellig
Full Prescribing Info
Contents
Bicalutamide.
Action
Pharmacology: Pharmacodynamics: Bicalutamide is a nonsteroidal antiandrogen, devoid of other endocrine activity. It binds to androgen receptors without activating gene expression and thus, inhibits the androgen stimulus. Regression of prostatic tumors results from this inhibition. Clinically, discontinuation of bicalutamide can result in antiandrogen withdrawal syndrome in a subset of patients.
Bicalutamide is a racemate with its antiandrogenic activity being almost exclusively in the (R)-enantiomer.
Pharmacokinetics: Bicalutamide is well absorbed following oral administration. There is no evidence of any clinically relevant effect of food on bioavailability.
The (S)-enantiomer is rapidly cleared relative to the (R)-enantiomer, the latter having a plasma elimination t½ of about 1 week.
On daily administration of bicalutamide, the (R)-enantiomer accumulates about 10-fold in plasma as a consequence of its long t½.
Steady-state plasma concentrations of the (R)-enantiomer of approximately 9 mcg/mL are observed during daily administration of bicalutamide 50 mg doses. At steady state, the predominantly active (R)-enantiomer accounts for 99% of the total circulating enantiomers.
The pharmacokinetics of the (R)-enantiomer are unaffected by age, renal impairment or mild to moderate hepatic impairment. There is evidence that for subjects with severe hepatic impairment, the (R)-enantiomer is more slowly eliminated from plasma.
Bicalutamide is highly protein bound (racemate 96%, R-bicalutamide 99.6%) and extensively metabolized (via oxidation and glucuronidation). Its metabolites are eliminated via the kidneys and bile in approximately equal proportions. After excretion in the bile, hydrolysis of the glucuronides comes to existence. In the urine, scarcely altered bicalutamide is found.
Toxicology: Preclinical Safety Data: Bicalutamide is a potent antiandrogen and a mixed function oxidase enzyme inducer in animals. Target organ changes, including tumor induction in animals, are related to these activities. None of the findings in the preclinical testing is considered to have relevance to the treatment of advance prostate cancer patients.
Indications/Uses
Used alone in patients with locally advanced, nonmetastatic prostate cancer.
Dosage/Direction for Use
Adult Males Including the Elderly: 1 tablet once daily with or without food.
Treatment with bicalutamide may be started either 3 days before or at the same time as commencing treatment with luteinizing hormone-releasing hormone (LHRH) analogue or at the same time as surgical castration.
Renal Impairment: No dosage adjustment is necessary for patients with renal impairment. There is no experience with the use of bicalutamide in patients with severe renal impairment (CrCl <30 mL/min).
Hepatic Impairment: No dosage adjustment is necessary for patients with mild hepatic impairment. Increased accumulation may occur in patients with moderate to severe hepatic impairment (see Precautions).
Overdosage
There is no human experience of overdosage. There is no specific antidote; treatment should be symptomatic. Dialysis may not be helpful, since bicalutamide is highly protein bound and is not recovered unchanged in the urine. General supportive care including frequent monitoring of vital signs is indicated.
Contraindications
Hypersensitivity to bicalutamide.
Co-administration of terfenadine, astemizole or cisapride (see Interactions).
Patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption should not take Bicadex.
Use in pregnancy & lactation: Bicalutamide is contraindicated in females and must not be given to pregnant women or nursing mothers.
Use in children: Bicalutamide is contraindicated in children.
Special Precautions
Initiation of treatment should be under the direct supervision of a specialist.
Bicalutamide is extensively metabolized in the liver. Data suggest that its elimination may be slower in subjects with severe hepatic impairment and this could lead to increased accumulation of bicalutamide. Therefore, bicalutamide should be used with caution in patients with moderate to severe hepatic impairment.
Periodic liver function testing should be considered due to the possibility of hepatic changes. The majority of changes are expected to occur within the first 6 months of bicalutamide therapy.
Severe hepatic changes and hepatic failure have been observed rarely with bicalutamide (see Adverse Reactions). Bicalutamide therapy should be discontinued if changes are severe.
A reduction in glucose tolerance has been observed in males receiving LHRH agonists. This may manifest as diabetes or loss of glycemic control in those with preexisting diabetes. Consideration should therefore be given to monitoring blood glucose in patients receiving bicalutamide in combination with LHRH agonists.
Bicalutamide has been shown to inhibit cytochrome P-450 (CYP3A4), as such caution should be exercised when co-administered with drugs metabolized predominantly by CYP3A4 (see Contraindications and Interactions).
Effects on the Ability to Drive or Operate Machinery: Bicalutamide is unlikely to impair the ability of patients to drive or operate machinery. However, it should be noted that occasionally, somnolence may occur. Any affected patients should exercise caution.
Use In Pregnancy & Lactation
Bicalutamide is contraindicated in females and must not be given to pregnant women or nursing mothers.
Adverse Reactions
Frequencies are defined as follows: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to ≤1/100); rare (≥1/10,000 to ≤1/1000); very rare (≤1/10,000); not known (cannot be estimated from the available data).
Bicalutamide 150-mg (Monotherapy): Blood and Lymphatic System Disorders: Common: Anemia.
Immune System Disorders: Uncommon: Hypersensitivity reactions (including angioneurotic edema and urticaria).
Metabolism and Nutrition Disorders: Common: Anorexia.
Psychiatric Disorders: Common: Decreased libido, depression.
Nervous System Disorders: Common: Dizziness, somnolence.
Vascular Disorders: Common: Hot flush.
Respiratory, Thoracic and Mediastinal Disorders: Uncommon: Interstitial lung disease.
Gastrointestinal Disorders: Common: Abdominal pain, constipation, dyspepsia, flatulence, nausea.
Hepatobiliary Disorders: Common: Hepatic changes (including elevated levels of transaminases, jaundice)/hepatobiliary disordersa. Rare: Hepatic failureb.
Skin and Subcutaneous Tissue Disorders: Very Common: Rash. Common: Alopecia, hirsutism/hair regrowth, dry skin, pruritus.
Renal and Urinary Disorders: Common: Hematuria.
Reproductive System and Breast Disorders: Very Common: Gynecomastia and breast tendernessc. Common: Impotence.
General Disorders and Administration Site Conditions: Very Common: Asthenia. Common: Chest pain, edema.
Investigations: Common: Weight gain.
Bicalutamide 150-mg (+ LHRH Analogue): Blood and Lymphatic System Disorders: Common: Anemia.
Immune System Disorders: Uncommon: Hypersensitivity reactions (including angioneurotic edema and urticaria).
Metabolism and Nutrition Disorders: Common: Anorexia.
Psychiatric Disorders: Common: Decreased libido, depression.
Nervous System Disorders: Very Common: Dizziness. Common: Somnolence.
Vascular Disorders: Very Common: Hot flush.
Respiratory, Thoracic and Mediastinal Disorders: Uncommon: Interstitial lung disease.
Gastrointestinal Disorders: Very Common: Abdominal pain, constipation, nausea. Common: Dyspepsia, flatulence.
Hepatobiliary Disorders: Common: Hepatic changes (including elevated levels of transaminases, jaundice)/hepatobiliary disordersa. Rare: Heart failureb.
Skin and Subcutaneous Tissue Disorders: Common: Alopecia, hirsutism/hair regrowth, dry skin, pruritus.
Renal and Urinary Disorders: Very Common: Hematuria.
Reproductive System and Breast Disorders: Very Common: Gynecomastia and breast tendernessc. Common: Impotence.
General Disorders and Administration Site Conditions: Very Common: Asthenia, chest pain, edema.
Investigations: Common: Weight gain.
aHepatic changes are rarely severe and were frequently transient, resolving or improving with continued therapy or following cessation of therapy.
bHepatic failure has occurred rarely in patients treated with bicalutamide but a causal relationship has not been established with certainty. Periodic liver function testing should be considered (see Precautions).
cThe majority of patients receiving bicalutamide 150 mg as monotherapy experience gynecomastia and/or breast pain. In studies, these symptoms were considered to be severe in up to 5% of the patients. Gynecomastia may not resolve spontaneously following cessation of therapy, particularly after prolonged treatment (≤1/10,000), not known (cannot be estimated from the available data).
In addition, cardiac failure was reported in clinical trials (as a possible adverse drug reaction in the opinion of investigating clinicians with a frequency of >1%) during treatment with bicalutamide plus an LHRH analogue. There is no evidence of a causal relationship with drug treatment.
Drug Interactions
There is no evidence of any pharmacodynamic or pharmacokinetic interactions between bicalutamide and LHRH analogues.
In vitro studies have shown that R-bicalutamide is an inhibitor of CYP3A4 with lesser inhibitory effects on CYP 2C9, 2C19 and 2D6 activity.
Although clinical studies using antipyrine as a marker of cytochrome P-450 (CYP) activity showed no evidence of a drug interactions potential with bicalutamide, mean midazolam exposure (AUC) was increased by up to 80% after co-administration of bicalutamide for 28 days. For drugs with a narrow therapeutic index eg, increase could be of relevance. As such, concomitant use of terfenadine, astemizole and cisapride is contraindicated (see Contraindications) and caution should be exercised with the co-administration of bicalutamide with compounds eg, cyclosporin and calcium-channel blockers. Dosage reduction may be required for these drugs particularly if there is evidence of enhanced or adverse drug effect. For cyclosporin, it is recommended that plasma concentrations and clinical condition are closely monitored following initiation or cessation of bicalutamide therapy.
Caution should be exercised when prescribing bicalutamide with other drugs which may inhibit drug oxidation eg, cimetidine and ketoconazole. In theory, this could result in increased plasma concentrations of bicalutamide which theoretically could lead to an increase in side effects.
In vitro studies have shown that bicalutamide can displace the coumarin anticoagulant, warfarin, from its protein-binding sites. It is therefore recommended that if bicalutamide is started in patients who are already receiving coumarin anticoagulants, prothrombin time should be closely monitored.
Storage
Store at temperatures not exceeding 25°C.
Shelf-Life: 24 months.
ATC Classification
L02BB03 - bicalutamide ; Belongs to the class of anti-androgens. Used in treatment of neoplastic diseases.
Presentation/Packing
FC tab 50 mg (white, round) x 30's.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in