Dutasteride

Dutasteride is a 5 alpha-reductase inhibitor indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to: improve symptoms, reduce the risk of acute urinary retention, and reduce the risk of the need for BPH-related surgery. Dutasteride in combination with the alpha-adrenergic antagonist, tamsulosin, is indicated for the treatment of symptomatic BPH in men with an enlarged prostate. Limitations of Use: Dutasteride is not approved for the prevention of prostate cancer.

Dutasteride inhibits the conversion of testosterone to 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 5 alpha-reductase, which exists as 2 isoforms, type 1 and type 2. The type 2 isoenzyme is primarily active in the reproductive tissues, while the type 1 isoenzyme is also responsible for testosterone conversion in the skin and liver. Dutasteride is a competitive and specific inhibitor of both type 1 and type 2 5 alpha-reductase isoenzymes, with which it forms a 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.

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. Dutasteride capsules may be administered with or without food. • Monotherapy: 0.5 mg once daily. • Combination with tamsulosin: 0.5 mg once daily and tamsulosin 0.4 mg once daily. • Dosing considerations: Swallow whole. May take with or without food.

Pregnancy. Dutasteride use is contraindicated in women who are pregnant. Patients with previously demonstrated, clinically significant hypersensitivity (e.g., serious skin reactions, angioedema) to dutasteride capsules or other 5 alpha-reductase inhibitors. Dutasteride is contraindicated for use in: Pregnancy. In animal reproduction and developmental toxicity studies, dutasteride inhibited development of male fetus external genitalia. Therefore, dutasteride may cause fetal harm when administered to a pregnant woman. Patients with previously demonstrated, clinically significant hypersensitivity (e.g., serious skin reactions, angioedema) to dutasteride or other 5 alpha-reductase inhibitors.

Dutasteride reduces serum prostate-specific antigen (PSA) concentration by approximately 50%. However, any confirmed increase in PSA while on dutasteride capsules may signal the presence of prostate cancer and should be evaluated, even if those values are still within the normal range for untreated men. Dutasteride may increase the risk of high-grade prostate cancer. Prior to initiating treatment with dutasteride capsules, consideration should be given to other urological conditions that may cause similar symptoms. Women who are pregnant or may be pregnant should not handle dutasteride capsules due to potential risk to a male fetus. Patients should not donate blood until 6 months after their last dose of dutasteride.

The most common adverse reactions, reported in ≥1% of subjects treated with dutasteride and more commonly than in subjects treated with placebo, are impotence, decreased libido, ejaculation disorders, and breast disorders.

Use with caution in patients taking potent, chronic cytochrome P450 (CYP)3A4 enzyme inhibitors (e.g., ritonavir). Cytochrome P450 3A Inhibitors Dutasteride is extensively metabolized in humans by the cytochrome P450 (CYP)3A4 and CYP3A5 isoenzymes. The effect of potent CYP3A4 inhibitors on dutasteride has not been studied. Because of the potential for drug-drug interactions, use caution when prescribing dutasteride capsules to patients taking potent, chronic CYP3A4 enzyme inhibitors (e.g., ritonavir).

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F).