AVODART- dutasteride capsule, liquid filled
GlaxoSmithKline LLC
DESCRIPTION
AVODART is synthetic 4-azasteroid compound that is selective inhibitor of both the type and type isoforms of steroid alpha-reductase, an intracellular enzyme that converts testosterone to DHT.
Dutasteride is chemically designated as (5?,17?)-N-{2,5 bis(trifluoromethyl)phenyl}-3-oxo-4-azaandrost-1-ene-17-carboxamide. The empirical formula of dutasteride is C27 H30 F6 N2 O2 representing molecular weight of 528.5
Dutasteride is white to pale yellow powder with melting point of 242? to 250?C. It is soluble in ethanol (44 mg/mL), methanol (64 mg/mL), and polyethylene glycol 400 g/mL), but it is insoluble in water.
Each AVODART soft gelatin capsule, administered orally, contains 0.5 mg of dutasteride dissolved in mixture of mono-di-glycerides of caprylic/capric acid and butylated hydroxytoluene. The inactive excipients in the capsule shell are ferric oxide (yellow), gelatin (from certified BSE-free bovine sources), glycerin, and titanium dioxide. The soft gelatin capsules are printed with edible red ink.
Mechanism of Action
Dutasteride inhibits the conversion of testosterone to dihydrotestosterone (DHT). DHT is the androgen primarily responsible for the initial development and subsequent enlargement of the prostate gland. Testosterone is converted to DHT by the enzyme alpha-reductase, which exists as isoforms, type and type 2. The type isoenzyme is primarily active in the reproductive tissues, while the type isoenzyme is also responsible for testosterone conversion in the skin and liver.
Dutasteride is competitive and specific inhibitor of both type and type 5 alpha-reductase isoenzymes, with which it forms stable enzyme complex. Dissociation from this complex has been evaluated under in vitro and in vivo conditions and is extremely slow. Dutasteride does not bind to the human androgen receptor.
INDICATIONS AND USAGE
1.1 Monotherapy
AVODART? (dutasteride) soft gelatin capsules are indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to:
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improve symptoms,
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reduce the risk of acute urinary retention (AUR), and
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reduce the risk of the need for BPH-related surgery.
1.2 Combination with Alpha-adrenergic Antagonist
AVODART in combination with the alpha-adrenergic antagonist, tamsulosin, is indicated for the treatment of symptomatic BPH in men with an enlarged prostate.
1.3 Limitations of Use
AVODART is not approved for the prevention of prostate cancer.
2 DOSAGE AND ADMINISTRATION
The capsules should be swallowed whole and not chewed or opened, as contact with the capsule contents may result in irritation of the oropharyngeal mucosa. AVODART may be administered with or without food.
2.1 Monotherapy
The recommended dose of AVODART is capsule (0.5 mg) taken once daily.
2.2 Combination with Alpha-adrenergic Antagonist
The recommended dose of AVODART is capsule (0.5 mg) taken once daily and tamsulosin 0.4 mg taken once daily.
3 DOSAGE FORMS AND STRENGTHS
0.5-mg, opaque, dull yellow, gelatin capsules imprinted with ?GX CE2? in red ink on one side.
4 CONTRAINDICATIONS
AVODART is contraindicated for use in:
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Pregnancy. In animal reproduction and developmental toxicity studies, dutasteride inhibited development of male fetus external genitalia. Therefore, AVODART may cause fetal harm when administered to pregnant woman. If AVODART is used during pregnancy or if the patient becomes pregnant while taking AVODART, the patient should be apprised of the potential hazard to the fetus [see Warnings and Precautions , Use in Specific Populations ].
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Women of childbearing potential [see Warnings and Precautions , Use in Specific Populations ].
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Pediatric patients [see Use in Specific Populations ].
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Patients with previously demonstrated, clinically significant hypersensitivity (e.g., serious skin reactions, angioedema) to AVODART or other alpha-reductase inhibitors [see Adverse Reactions ].
5 WARNINGS AND PRECAUTIONS
5.1 Effects on Prostate-specific Antigen (PSA) and the Use of PSA in Prostate Cancer Detection
5.2 Increased Risk of High-grade Prostate Cancer
5.3 Evaluation for Other Urological Disease
5.4 Exposure of Women?Risk to Male Fetus
5.5 Blood Donation
5.6 Effect on Semen Characteristics
Pregnancy
Pregnancy Category X.
HOW SUPPLIED/STORAGE AND HANDLING
AVODART soft gelatin capsules 0.5 mg are oblong, opaque, dull yellow, gelatin capsules imprinted with ?GX CE2? with red edible ink on one side, packaged in bottles of 30 (NDC 0173-0712-15) and 90 (NDC 0173-0712-04) with child-resistant closures.
Store at 25?C (77?F); excursions permitted to 15? to 30?C (59? to 86?F) [see USP Controlled Room Temperature].
Dutasteride is absorbed through the skin. AVODART capsules should not be handled by women who are pregnant or who could become pregnant because of the potential for absorption of dutasteride and the subsequent potential risk to developing male fetus
