Medication Guide App

Generic Name: Bicalutamide
Class: Antineoplastic Agents
VA Class: AN900
Chemical Name: (±) - N - [4 - cyano - 3 - (trifluoromethyl)phenyl] - 3 - [(4 - fluorophenyl)sulfonyl] - 2 - hydroxy - 2 - methylpropanamide
Molecular Formula: C18H14F4N2O4S
CAS Number: 90357-06-5

Introduction

Antineoplastic agent; a nonsteroidal antiandrogen.1 3 4 14 40 43

Uses for Casodex

Prostate Cancer

Palliative treatment of metastatic (stage D2) prostate cancer; should be used in conjunction with a luteinizing hormone-releasing hormone (LHRH) analog (e.g., goserelin, leuprolide acetate).1 2 3 9 18

Slideshow: Flashback: FDA Drug Approvals 2013

Casodex Dosage and Administration

General

  • Initiate bicalutamide and LHRH analog concomitantly.1 35 43

Administration

Oral Administration

Administer orally once daily at the same time each day (morning or evening) without regard to meals.1 35 43

Dosage

Adults

Prostate Cancer
Oral

50 mg once daily.1 3 9 40 43 Duration of combined therapy with LHRH analog depends on clinical response.35

Cautions for Casodex

Contraindications

  • Known hypersensitivity to bicalutamide or any ingredient in the formulation.1

  • Should not be used in women, particularly for conditions that are not serious or life-threatening.1

  • Women who are or may become pregnant.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; contraindicated in pregnant women.1

If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.1

Hepatic Effects

Severe liver injury reported, sometimes resulting in hospitalization and/or death;1 26 manifestations generally occurred within first 3–4 months.1

Possible hepatitis or marked increases in serum concentrations of hepatic transaminases.1

Measure serum transaminase concentrations prior to initiation of therapy, at regular intervals during the first 4 months, and periodically thereafter.1

Immediately measure serum transaminase (especially ALT) concentrations if manifestations suggestive of liver dysfunction occur.1

Immediately discontinue if jaundice develops or serum ALT concentration is >2 times ULN; monitor liver function closely thereafter.1

General Precautions

PSA Monitoring

Regularly monitor serum PSA to assess response; if PSA increases, evaluate for possible disease progression.1 17

For patients with objective progression of disease and elevated serum PSA, consider temporarily withdrawing bicalutamide while continuing LHRH analog.1 35 36 37 Withdrawal of bicalutamide may be associated with PSA decrease.31 44

Possible Prescribing and Dispensing Errors

Ensure accuracy of prescription; similarity in spelling of Casodex (the trade name for bicalutamide) and Kapidex (former trade name for dexlansoprazole, a proton-pump inhibitor) may result in errors.217 218 219 223

Specific Populations

Pregnancy

Category X.1 (See Fetal/Neonatal Morbidity and Mortality and also Contraindications under Cautions.)

Lactation

Not known whether bicalutamide is distributed into milk;1 use caution.1

Pediatric Use

Safety and efficacy not established.1

Hepatic Impairment

Use with caution in patients with moderate to severe hepatic impairment.1 3

Consider periodic liver function tests in patients with hepatic impairment receiving long-term therapy.1 35

Women

Not intended for use in women, particularly for nonserious or nonlife-threatening conditions.1

Common Adverse Effects

Combined therapy with LHRH analog: hot flashes, pain (including abdominal, back, and pelvic pain), asthenia, constipation, infection, nausea, dyspnea, diarrhea.1

Gynecomastia and breast pain frequent if bicalutamide used as monotherapy.1

Interactions for Casodex

Does not induce CYP isoenzymes.1 Pharmacokinetic interaction unlikely with drugs metabolized by CYP isoenzymes.1

Specific Drugs

Drug

Interaction

Comments

Alcohol

Increased risk of facial flushing41

Avoid alcohol consumption during therapy41

LHRH analog (e.g., goserelin, leuprolide)

Pharmacokinetic interaction unlikely1

Warfarin and other coumarins

Decreased anticoagulant protein binding and increased plasma concentrations; increased anticoagulant effects1

Monitor PT; adjust anticoagulant dosage as needed1

Casodex Pharmacokinetics

Absorption

Bioavailability

Well-absorbed following oral administration; absolute bioavailability is unknown.1

Food

Food has no clinically important effect on rate or extent of absorption.1

Distribution

Plasma Protein Binding

96%.1

Elimination

Metabolism

Undergoes stereospecific metabolism in the liver.1

Active R-enantiomer is predominantly oxidized to an inactive metabolite followed by glucuronidation.1 Inactive S-enantiomer is principally metabolized by glucuronidation.1

S-enantiomer is rapidly cleared relative to the R-enantiomer; R-enantiomer accounts for about 99% of total steady-state plasma concentrations.1

Elimination Route

Both parent and metabolite glucuronides are eliminated in urine and feces.1

Half-life

Approximately 6 days.1

Special Populations

Half-life of R-enantiomer was increased approximately 76% in patients with severe hepatic impairment.1

Stability

Storage

Oral

Tablets

20–25°C.1

Actions

  • A selective antiandrogen with no androgenic or progestational activity in various animal models.12 17 43

  • Competitively blocks nuclear androgen receptors in target tissues (e.g., adrenal cortex, prostate, seminal vesicles).1 11 12 14 16 34 43

  • Blockade of androgen receptors in the hormone-sensitive tumor cells may result in growth arrest or transient tumor regression through inhibition of androgen-dependent DNA and protein synthesis.1 11 12 14 16 34 43

  • Inhibits initial androgenic stimulation and potential exacerbation of symptoms (e.g., bone pain, urinary obstruction, liver pain, impending spinal cord compression) associated with the first month of LHRH analog therapy.8 10 14 16 18 21 23 25 40

Advice to Patients

  • Risk of potential liver toxicity.1

  • Risk of facial flushing,1 41 particularly if used in conjunction with alcohol.41 Avoidance of alcohol recommended if flushing occurs.41

  • Importance of initiating bicalutamide concomitantly with LHRH analog and of not interrupting or discontinuing therapy without consulting a clinician.1

  • If used in women, importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Bicalutamide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film- coated

50 mg

Casodex

AstraZeneca

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Bicalutamide 50MG Tablets (APOTEX): 30/$60.99 or 90/$161.97

Casodex 50MG Tablets (ASTRAZENECA): 30/$536.99 or 90/$1,608.02

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 1, 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. AstraZeneca. Casodex (bicalutamide) tablets prescribing information. Wilmington, DE; 2002 Sep.

2. Anon. Drugs of choice for cancer chemotherapy. Med Lett Drugs Ther. 2000; 42: 83-92.

3. Blackledge G. Casodexmechanisms of action and opportunities for usage. Cancer. 1993; 72(Suppl):3830-3. [IDIS 323230] [PubMed 7504578]

4. Cockshott ID, Sotaniemi EA, Cooper KJ et al. The pharmacokinetics of Casodex enantiomers in subjects with impaired liver function. Br J Clin Pharmacol. 1993; 36:339-43. [IDIS 321958] [PubMed 12959312]

5. Wilson JD. Androgens. In: Gilman AG, Rall TW, Nies AS et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press; 1990:1413-1430.

6. Prostate cancer. From: CancerNet/PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2001 Oct.

7. Schering. Eulexin (flutamide) capsules prescribing information (dated 1994 Jul). In: Physicians’ desk reference. 49th ed. Montvale, NJ: Medical Economics Company Inc; 1995:2253-4.

8. Crawford ED, Eisenberger MA, McLeod DG et al. A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med. 1989; 321:419-24. [IDIS 258377] [PubMed 2503724]

9. Schellhammer P, Sharifi R, Block N et al et al. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Urology. 1995; 45:745-52. [PubMed 7538237]

10. Dole EJ, Holdsworth MT. Nilutamide: an anitandrogen for the treatment of prostate cancer. Ann Pharmacother. 1997; 31: 65-75.

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13. Migliari R, Muscas G, Usai E. Effect of Casodex on sleep-related erections in patients with advanced prostate cancer. J Urol. 1992; 148:338-41. [IDIS 300700] [PubMed 1378907]

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20. Brendler CB. Diseases of the prostate. In: Wyngaarden JB, Smith LH Jr, Bennett JC, eds. Cecil textbook of medicine. 19th ed. Philadelphia: WB Saunders Company; 1992:1351-5.

21. Chrisp P, Goa KL. Goserelin: a review of its pharmacodynamic and pharmacokinetic properties, and clinical use in sex hormone-related conditions. Drugs. 1991; 41:254-88. [PubMed 1709853]

22. Vogelzang NJ, Kennealey GT. Recent developments in endocrine treatment of prostate cancer. Cancer. 1992; 70:966-76. [IDIS 300575] [PubMed 1386283]

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24. Tyrrell CJ, Altwein JE, Klippel F et al et al. A multicenter randomized trial comparing the luteinizing hormone-releasing hormone analogue goserelin acetate alone and with flutamide in the treatment of advanced prostate cancer. J Urol. 1991; 146:1321-6. [IDIS 290344] [PubMed 1834864]

25. Kuhn JM, Billebaud T, Navratil H et al. Prevention of a gonadotropin-releasing hormone analogue (buserelin) in metastatic prostatic carcinoma by administration of an antiandrogen (nilutamide). N Engl J Med. 1989; 321:413-8. [IDIS 258376] [PubMed 2503723]

26. Dawson LA, Chow E, Morton G. Fulminant hepatic failure associated with bicalutamide. Urology. 1997; 49:283-4. [PubMed 9037299]

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28. Paulson DF. Management of metastatic prostatic cancer. Urology. 1985; 25:(Suppl):49-52.

29. Tolis G, Ackman D, Stellos A et al. Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists. Med Sci. 1982; 79:1658-62.

30. Elder JS, Catalona WJ. Management of newly diagnosed metastatic carcinoma of the prostate. Urol Clin North Am. 1984; 11:283-95. [PubMed 6428022]

31. Nieh PT. Withdrawal phenomenon with the antiandrogen casodex. J Urol. 1995; 153:1070-2. [IDIS 342239] [PubMed 7531785]

32. Crawford ED. Withdrawal phenomenon with the antiandrogen Casodex: editorial comments. J Urol. 1995; 153:1072.

33. Scher HI, Kelly WK. Withdrawal phenomenon with the antiandrogen Casodex: editorial comments. J Urol. 1995; 153:1072-3.

34. Kennealey GT, Furr BJA. Use of the nonsteroidal anti-androgen Casodex in advanced prostatic carcinoma. Urol Clin North Am. 1991; 18:99-110. [PubMed 1992575]

35. Zeneca Pharmaceuticals, Wilmington, DE: Personal communication.

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42. Schellhammer PF, Sharifi R, Block NL et al. Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Casodex Combination Study Group. Urology. 1997; 50:330-6. [PubMed 9301693]

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