Androblok^® (Tablets) Instructions for Use

Marketing Authorization Holder

Sun Pharmaceutical Industries, Ltd. (India)

ATC Code

L02BB03 (Bicalutamide)

Active Substance

Bicalutamide (Rec.INN registered by WHO)

Dosage Form

Androblok®

Film-coated tablets, 50 mg: 10 or 28 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, round, biconvex, with an engraving “485” on one side; the cross-section is white or almost white.

Excipients: lactose monohydrate – 132 mg, sodium carboxymethyl starch – 12.5 mg, povidone K30 – 5 mg, magnesium stearate – 0.5 mg.

Shell composition Opadry II (33F28627) – 6 mg (hypromellose 2910, lactose monohydrate, titanium dioxide (E171), macrogol 3000).

14 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

Antiandrogenic drug with antitumor activity

Pharmacotherapeutic Group

Antineoplastic agent, antiandrogen

Pharmacological Action

Antineoplastic drug, nonsteroidal antiandrogen. Bicalutamide is a racemic mixture with nonsteroidal antiandrogenic activity primarily of the (R)-enantiomer. It does not possess other endocrine activity.

Bicalutamide binds to androgen receptors and, without activating gene expression, suppresses the stimulating effect of androgens. The result of this is the regression of malignant neoplasms of the prostate gland.

In some patients, discontinuation of bicalutamide may lead to the development of a clinical “antiandrogen withdrawal syndrome”.

Pharmacokinetics

Absorption and Distribution

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract. Food intake does not affect absorption.

With daily administration of bicalutamide, the plasma concentration of the (R)-enantiomer increases approximately 10-fold due to its long half-life, making once-daily administration possible.

With daily administration of bicalutamide at a dose of 50 mg, the steady-state plasma concentration (Css) of the (R)-enantiomer is about 9 µg/ml. When taking 150 mg of bicalutamide daily, the Css of the (R)-enantiomer is approximately 22 µg/ml. At steady state, about 99% of all circulating enantiomers is the active (R)-enantiomer.

Plasma protein binding is high (for the racemic mixture 96%, for the (R)-enantiomer 99.6%).

Metabolism and Excretion

Extensively metabolized in the liver (by oxidation and glucuronic acid conjugation). Metabolites are excreted in urine and bile in approximately equal proportions.

The (S)-enantiomer is eliminated from the body much faster than the (R)-enantiomer. The half-life of the latter is about 7 days.

Pharmacokinetics in Special Clinical Cases

The pharmacokinetics of the (R)-enantiomer are not influenced by age, renal impairment, or mild to moderate hepatic impairment.

There is evidence that in patients with severe hepatic impairment, the elimination of the (R)-enantiomer from plasma is slowed.

Indications

• Bicalutamide at a dose of 50 mg in combination with a GnRH (gonadotropin-releasing hormone) analogue or surgical castration is indicated for the treatment of advanced prostate cancer;
• Bicalutamide at a dose of 150 mg is indicated for the treatment of locally advanced prostate cancer (T3-T4, any N, M0; T1-T2, N+, M0) as monotherapy or adjuvant therapy in combination with radical prostatectomy or radiotherapy;
• Bicalutamide at a dose of 150 mg is also indicated for the treatment of locally advanced, non-metastatic prostate cancer in cases where surgical castration or other medical interventions are unacceptable or inapplicable.

ICD codes

Dosage Regimen

Orally, regardless of meals, preferably at the same time each day.

Adults and elderly men

For advanced prostate cancer in combination with a GnRH (gonadotropin-releasing hormone) analogue or surgical castration: orally, 50 mg once daily.

Treatment with bicalutamide should be started simultaneously with the initiation of the GnRH analogue or surgical castration.

For locally advanced prostate cancer: orally, 150 mg once daily. Bicalutamide should be taken long-term, for at least 2 years. If signs of disease progression appear, the drug should be discontinued.

Patients with renal impairment no dosage adjustment is required.

Patients with hepatic impairment: no dosage adjustment is required. Increased accumulation of the drug in the body is possible in patients with severe hepatic insufficiency.

Adverse Reactions

The pharmacological action of bicalutamide may cause the following side effects:

Very common (>10%) gynecomastia (may persist even after discontinuation of therapy, especially if the drug is taken for a long time), breast tenderness, hot flushes, decreased libido, sexual dysfunctions;

Common (>1%, but <10%) diarrhea, nausea, transient increase in liver transaminase activity, cholestasis and jaundice (the described changes in liver function were rarely assessed as serious, were transient, completely disappeared or decreased with continued therapy or after drug withdrawal), itching, asthenia; when using the drug at a daily dose of 150 mg – alopecia or hair regrowth, weight gain.

Uncommon (> 0.1%, but <1%) hypersensitivity reactions, including angioedema and urticaria, interstitial lung disease; when using the drug at a daily dose of 150 mg – abdominal pain, depression, dyspepsia, hematuria.

Rare (> 0.01%, but <0.1%) vomiting, dry skin (when using the drug at a daily dose of 150 mg, dry skin is observed frequently), liver failure (a causal relationship with bicalutamide intake has not been reliably established). When bicalutamide and GnRH analogues are used concomitantly, the following adverse events may also be observed with a frequency of > 1% (a causal relationship with drug intake has not been established, some of the noted side effects occurred in elderly patients):

Cardiovascular system heart failure, angina pectoris, conduction disorders, including prolongation of PR and QT intervals, arrhythmias, nonspecific ECG changes, increased blood pressure, myocardial infarction, syncope.

Digestive system gastric bleeding, anorexia, dry mouth, dyspepsia, constipation, flatulence, periodontal abscess, stomach/intestinal cancer.

Nervous system dizziness, headache, insomnia, anxiety, drowsiness, neuropathy.

Respiratory system dyspnea, chest pain, cough, pharyngitis, bronchitis, pneumonia, rhinitis, bronchospasm, epistaxis.

Urinary system nocturia, dysuria, urinary retention, edema, frequent urination, hydronephrosis, infections.

Hematopoietic system anemia.

Dermatological reactions: alopecia, skin rash, increased sweating, hirsutism, dry skin, herpes infection, skin cancer.

Musculoskeletal system myasthenia, myalgia, cramps, arthritis, joint contractures, bone pain, leg cramps.

Laboratory parameters hyperglycemia, increased alkaline phosphatase activity, hypercreatininemia, hypercholesterolemia, hyperbilirubinemia.

Other diabetes mellitus, polyuria, increase or decrease in body weight, abdominal pain, chest pain, pelvic pain, sexual dysfunctions, progression of the tumor process, chills, dehydration, gout, cataract.

Contraindications

• Concomitant use with terfenadine, astemizole and cisapride;
• Bicalutamide should not be prescribed to children and women;
• Hypersensitivity to bicalutamide and auxiliary components of the drug.

Use with caution in patients with hepatic impairment, lactose intolerance, lactase deficiency or glucose/galactose malabsorption.

Use in Pregnancy and Lactation

Bicalutamide should not be prescribed during pregnancy and lactation.

The result of bicalutamide use in pregnant rats was feminization of male offspring, accompanied by anaspadia regardless of dose.

Use in Hepatic Impairment

Patients with hepatic impairment: no dosage adjustment is required. Increased accumulation of the drug in the body is possible in patients with severe hepatic insufficiency.

Use in Renal Impairment

Patients with renal impairment no dosage adjustment is required.

Geriatric Use

Adults and elderly men

For advanced prostate cancer in combination with a GnRH (gonadotropin-releasing hormone) analogue or surgical castration: orally, 50 mg once daily.

Treatment with bicalutamide should be started simultaneously with the initiation of the GnRH analogue or surgical castration.

For locally advanced prostate cancer: orally, 150 mg once daily. Bicalutamide should be taken long-term, for at least 2 years. If signs of disease progression appear, the drug should be discontinued.

Special Precautions

Rare cases of fatal outcome or hospitalization associated with bicalutamide intake have been recorded post-marketing in people with severe liver disorders. Hepatotoxicity was observed within the first 3-4 months of intake.

Hepatitis or significant increases in liver enzymes requiring drug discontinuation were observed in 1% of patients. Plasma transaminase levels should be measured before starting treatment with bicalutamide, and also regularly during the first four months of treatment and for some time thereafter.

If symptoms of liver dysfunction appear, plasma transaminase levels should be measured urgently. If jaundice appears or alanine transaminase levels increase more than two-fold, bicalutamide should be discontinued.

Patients with lactose intolerance should be informed that each 50 mg bicalutamide tablet contains 132 mg of lactose monohydrate.

In patients with disease progression against the background of an increasing concentration of prostate-specific antigen (PSA), discontinuation of treatment with the drug should be considered.

It is recommended to regularly monitor prothrombin time when prescribing bicalutamide to patients receiving indirect coumarin anticoagulants.

Decreased glucose tolerance has been observed in patients taking GnRH agonists. This effect may lead to the development of diabetes mellitus or reduced glucose tolerance in patients with diabetes.

Effect on ability to drive vehicles and operate machinery

Bicalutamide does not affect the ability of patients to drive vehicles or engage in other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions.

Overdose

There are no data on cases of drug overdose in humans.

Treatment symptomatic. There is no specific antidote. Dialysis is not very effective, as Bicalutamide is highly bound to plasma proteins and is not detected unchanged in urine. General measures are indicated, including monitoring of vital cardiac and respiratory parameters.

Drug Interactions

There are no data on pharmacokinetic or pharmacodynamic interactions between bicalutamide and GnRH (gonadotropin-releasing hormone) analogues.

In vitro studies have shown that the (R)-enantiomer of bicalutamide inhibits the CYP3A4 isoenzyme, with a lesser effect on the activity of the CYP2C9, 2C19 and 2D6 isoenzymes.

No potential for bicalutamide to interact with other drugs has been identified; however, when using bicalutamide for 28 days against the background of midazolam intake, the area under the curve (AUC) of midazolam increases by 80%.

Incompatible with terfenadine, astemizole, cisapride.

Caution should be exercised when prescribing bicalutamide simultaneously with cyclosporine or calcium channel blockers. A dose reduction of these drugs may be required, especially in case of potentiation or development of adverse events.

After initiation or discontinuation of bicalutamide, careful monitoring of cyclosporine plasma concentration and the patient’s clinical condition is recommended.

Concomitant use of bicalutamide and drugs that inhibit microsomal oxidation of drugs, for example, with cimetidine or ketoconazole, may lead to an increase in the plasma concentration of bicalutamide and possibly to an increase in the frequency of side effects.

Enhances the effect of coumarin anticoagulants, warfarin (competition for protein binding).

Storage Conditions

Store the drug in a dry, light-protected place, at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 2 years.

Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.