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Bicalutamide

Pronunciation

Pronunciation

(bye ka LOO ta mide)

Index Terms

  • CDX
  • ICI-176334

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Casodex: 50 mg

Generic: 50 mg

Brand Names: U.S.

  • Casodex

Pharmacologic Category

  • Antineoplastic Agent, Antiandrogen

Pharmacology

Androgen receptor inhibitor; pure nonsteroidal antiandrogen that binds to androgen receptors; specifically a competitive inhibitor for the binding of dihydrotestosterone and testosterone; prevents testosterone stimulation of cell growth in prostate cancer

Absorption

Well absorbed; unaffected by food

Metabolism

Extensively hepatic; glucuronidation and oxidation of the R (active) enantiomer to inactive metabolites; the S enantiomer is inactive

Excretion

Urine and feces

Time to Peak

Active enantiomer: ~31 hours

Half-Life Elimination

Active enantiomer: ~6 days

Active enantiomer (in patients with severe liver disease): ~10 days

R-isomer (in patients with severe liver disease): Increased ~76%

Protein Binding

96%

Use: Labeled Indications

Prostate cancer, metastatic: Treatment of stage D2 metastatic prostate cancer (in combination with an LHRH agonist)

Limitation of use: Bicalutamide 150 mg daily is not approved for use alone or with other treatments

Use: Unlabeled

Monotherapy for locally-advanced prostate cancer

Contraindications

Hypersensitivity to bicalutamide or any component of the formulation; use in women, especially women who are or may become pregnant

Canadian labeling: Additional contraindications (not in U.S. labeling): Patients with localized prostate cancer undergoing watchful waiting; children

Dosing: Adult

Prostate cancer, metastatic: Oral: 50 mg once daily (in combination with an LHRH analogue)

Prostate cancer, locally-advanced, high recurrence risk (off-label use): Oral: 150 mg once daily (as monotherapy) (McLeod, 2006). Additional trials may be necessary to further define the role of bicalutamide in this condition.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment necessary.

Dosing: Hepatic Impairment

Hepatic impairment at treatment initiation: Mild, moderate, or severe impairment: No dosage adjustment is necessary. Use with caution in patients with moderate-to-severe impairment; clearance may be delayed in severe impairment (based on a limited number of patients).

Hepatic impairment during treatment: ALT >2 times ULN or jaundice develops: Discontinue immediately.

Administration

Dose should be taken at the same time each day, either in the morning or in the evening. May be administered with or without food. Treatment for metastatic cancer should be started concomitantly with an LHRH analogue.

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).

Storage

Store at room temperature of 20°C to 25°C (68°F to 77°F).

Drug Interactions

Aminolevulinic Acid: Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid. Monitor therapy

ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

Astemizole: Bicalutamide may increase the serum concentration of Astemizole. Avoid combination

Choline C 11: Antiandrogens may diminish the therapeutic effect of Choline C 11. Monitor therapy

Cisapride: Bicalutamide may increase the serum concentration of Cisapride. Avoid combination

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy

HYDROcodone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of HYDROcodone. Monitor therapy

Indium 111 Capromab Pendetide: Antiandrogens may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Avoid combination

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy

Terfenadine: Bicalutamide may increase the serum concentration of Terfenadine. Avoid combination

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Bicalutamide may increase the serum concentration of Vitamin K Antagonists. Specifically, free concentrations of the vitamin K antagonists may be increased. Monitor therapy

Adverse Reactions

Adverse reaction percentages reported as part of combination regimen with an LHRH analogue unless otherwise noted.

>10%:

Cardiovascular: Peripheral edema (13%)

Central nervous system: Pain (35%)

Endocrine & metabolic: Hot flash (53%), gynecomastia (9%; monotherapy [150 mg]: 38% to 73% [McLeod 2006])

Gastrointestinal: Constipation (22%), nausea (15%), diarrhea (12%), abdominal pain (11%)

Genitourinary: Mastalgia (6%; monotherapy [150 mg]: 39% to 85% [McLeod 2006]), pelvic pain (21%), hematuria (12%), nocturia (12%)

Hematologic & oncologic: Anemia (11%)

Infection: Infection (18%)

Neuromuscular & skeletal: Back pain (25%), weakness (22%)

Respiratory: Dyspnea (13%)

≥2% to 10%:

Cardiovascular: Chest pain (8%), hypertension (8%), angina pectoris (2% to <5%), cardiac arrest (2% to <5%), cardiac failure (2% to <5%), coronary artery disease (2% to <5%), edema (2% to <5%), myocardial infarction (2% to <5%), syncope (2% to <5%)

Central nervous system: Dizziness (10%), paresthesia (8%), headache (7%), insomnia (7%), myasthenia (7%), anxiety (5%), chills (2% to <5%), confusion (2% to <5%), drowsiness (2% to <5%), hypertonia (2% to <5%), nervousness (2% to <5%), neuropathy (2% to <5%), depression (4%)

Dermatologic: Skin rash (9%), diaphoresis (6%), alopecia (2% to <5%), pruritus (2% to <5%), xeroderma (2% to <5%)

Endocrine & metabolic: Weight loss (7%), hyperglycemia (6%), weight gain (5%), decreased libido (2% to <5%), dehydration (2% to <5%), gout (2% to <5%), hypercholesterolemia (2% to <5%)

Gastrointestinal: Dyspepsia (7%), anorexia (6%), flatulence (6%), vomiting (6%), dysphagia (2% to <5%), hernia (2% to <5%), melena (2% to <5%), periodontal abscess (2% to <5%), xerostomia (2% to <5%)

Genitourinary: Urinary tract infection (9%), impotence (7%), difficulty in micturition (5%), urinary retention (5%), dysuria (2% to <5%), urinary urgency (2% to <5%), urinary incontinence (4%)

Hematologic & oncologic: Gastrointestinal carcinoma (2% to <5%), rectal hemorrhage (2% to <5%), skin carcinoma (2% to <5%)

Hepatic: Increased liver enzymes (7%), increased serum alkaline phosphatase (5%)

Infection: Herpes zoster (2% to <5%), sepsis (2% to <5%)

Neuromuscular & skeletal: Ostealgia (9%), arthritis (5%), leg cramps (2% to <5%), myalgia (2% to <5%), neck pain (2% to <5%), pathological fracture (4%)

Ophthalmic: Cataract (2% to <5%)

Renal: Polyuria (6%), hydronephrosis (2% to <5%), increased blood urea nitrogen (2% to <5%), increased serum creatinine (2% to <5%)

Respiratory: Cough (8%), pharyngitis (8%), flu-like symptoms (7%), bronchitis (6%), asthma (2% to <5%), epistaxis (2% to <5%), sinusitis (2% to <5%), pneumonia (4%), rhinitis (4%)

Miscellaneous: Cyst (2% to <5%), fever (2% to <5%)

<1% (Limited to important or life-threatening): Decreased glucose tolerance, decreased hemoglobin, decreased white blood cell count, hepatic failure, hepatitis, hepatotoxicity, hypersensitivity (including angioedema and urticaria), increased serum bilirubin, interstitial pneumonitis, interstitial pulmonary disease, pulmonary fibrosis

Warnings/Precautions

Concerns related to adverse effects:

• Gynecomastia: May cause gynecomastia or breast pain at higher (off-label) doses.

• Hematologic: Anemia may occur with testosterone suppression; monitor CBC periodically as indicated.

• Hepatitis: Rare cases of death or hospitalization due to hepatitis have been reported postmarketing; hepatotoxicity generally occurs within the first 3 to 4 months of use. Use with caution in moderate-to-severe hepatic dysfunction. Patients should be monitored for signs and symptoms of liver dysfunction; discontinue if patients have jaundice or ALT is >2 times the upper limit of normal.

• Interstitial lung disease: Has been reported rarely (including fatalities) although mostly at dosages greater than what is recommended; promptly evaluate any worsening of respiratory symptoms (eg, dyspnea, cough and fever).

• Spermatogenesis: May lead to spermatogenesis inhibition.

Disease-related concerns:

• Cardiovascular disease: Androgen-deprivation therapy may increase the risk for cardiovascular disease (Levine, 2010). Androgen deprivation therapy may cause prolongation of the QT/QTc interval (Garnick, 2004); evaluate risk versus benefit in patients with congenital long QT syndrome, heart failure, frequent electrolyte abnormalities, and in patients taking medication known to prolong the QT interval. Correct electrolytes prior to initiation and consider periodic electrolyte and ECG monitoring.

• Decreased bone mineral density: Prolonged use of antiandrogen therapy is associated with decreased bone mineral density and an increased risk of osteoporosis and fracture (Smith, 2003); alcohol abuse, familial history of osteoporosis, and/or chronic use of drugs capable of decreasing bone mass (eg, corticosteroids) may increase risk. Evaluate risk carefully before initiating therapy.

• Diabetes: When used in combination with LHRH agonists, a loss of glycemic control and decrease in glucose tolerance has been reported in patients with diabetes; monitor.

• Hepatic impairment: Use with caution in moderate-to-severe impairment; undergoes extensive hepatic metabolism. Limited data suggests excretion may be delayed in severe impairment leading to further drug accumulation. Consider periodic monitoring of liver function with prolonged therapy.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Anti-androgen withdrawal syndrome: Discontinue use immediately if disease worsens; decreased prostate specific antigen (PSA) levels and/or clinical improvement may be observed in some patients when antiandrogen therapy is held due to worsening of disease. The Canadian labeling recommends monitoring patients for 6 to 8 weeks after interrupting therapy to observe for withdrawal response.

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).

Monitoring Parameters

Periodically monitor CBC, ECG, echocardiograms, serum testosterone, luteinizing hormone, and prostate specific antigen (PSA). Liver function tests should be obtained at baseline and repeated regularly during the first 4 months of treatment, and periodically thereafter; monitor for signs and symptoms of liver dysfunction (discontinue if jaundice is noted or ALT is >2 times the upper limit of normal). Monitor blood glucose in patients with diabetes. If initiating bicalutamide in patients who are on warfarin, closely monitor prothrombin time.

Pregnancy Risk Factor

X

Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Bicalutamide use is contraindicated in women. Androgen receptor inhibition during pregnancy may affect fetal development.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, diarrhea, constipation, sexual dysfunction, hot flashes, sensation of warmth, sweating a lot, back pain, abdominal pain, or pelvic pain. Have patient report immediately to prescriber signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit); signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice); signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse); shortness of breath; excessive weight gain; swelling of arms or legs; bruising; bleeding; enlarged breast; breast pain; black, tarry, or bloody stools; vision changes; bone pain; urinary retention; change in amount of urine passed; angina; hematuria; severe dizziness; passing out; joint pain; joint edema; depression; muscle weakness; severe loss of strength and energy; burning or numbness feeling; or severe headache (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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