Dutasteride

Dutasteride is a synthetic 4-azasteroid that inhibits both type 1 and type 2 5-alpha-reductase (a 5-alpha-reductase inhibitor). It is FDA approved as Avodart 0.5 mg soft gelatin capsules and, with tamsulosin, as Jalyn. Compounded oral preparations are made pursuant to patient-specific prescriptions.

FDA-labeled indications (Avodart): 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 BPH-related surgery; and, with tamsulosin, symptomatic BPH in men with an enlarged prostate. It is not approved for prevention of prostate cancer.

Prescribers also use dutasteride off-label for male androgenetic alopecia; it has no FDA-labeled indication for hair loss.

5-alpha-reductase converts testosterone to dihydrotestosterone (DHT), the main androgen driving prostate growth and miniaturization of androgen-sensitive scalp follicles. By inhibiting both isoenzymes, dutasteride markedly lowers serum and tissue DHT, which reduces prostate volume over months. Serum testosterone rises modestly.

Oral bioavailability is about 60%, with peak concentrations 2 to 3 hours after dosing; food does not meaningfully change exposure. Dutasteride is more than 99% protein bound, and semen concentrations average about 11.5% of serum levels. It is metabolized by CYP3A4 and CYP3A5 and excreted mainly in feces. The terminal half-life is about 5 weeks at steady state, and serum levels remain detectable for 4 to 6 months after stopping.

• Pregnancy: dutasteride may cause harm to a male fetus.
• Clinically significant hypersensitivity to dutasteride or other 5-alpha-reductase inhibitors, such as serious skin reactions or angioedema.

Avodart is not indicated for use in women or in pediatric patients.

• PSA: dutasteride lowers serum PSA by about half within 3 to 6 months. Obtain a new baseline after at least 3 to 6 months of treatment and double the measured value for comparison with normal ranges; any confirmed increase from the lowest PSA on treatment warrants evaluation, even within the normal range.
• High-grade prostate cancer: 5-alpha-reductase inhibitors were associated with an increased incidence of Gleason score 8 to 10 prostate cancer in a large prevention trial.
• Evaluate for prostate cancer and other urologic conditions before starting and periodically.
• Exposure of women: dutasteride is absorbed through the skin. Women who are or may become pregnant should not handle leaking, opened or damaged capsules; wash any contact area with soap and water.
• Blood donation: men should not donate blood until at least 6 months after the last dose, to prevent exposure of a pregnant transfusion recipient.
• Semen and fertility: reductions in sperm count, semen volume and motility have been observed.
• Dutasteride is on the NIOSH list of hazardous drugs because of reproductive risk; handle under USP <800>.

• Strong CYP3A4 inhibitors (for example ritonavir, ketoconazole, itraconazole, clarithromycin) can raise dutasteride exposure; use caution with chronic coadministration.
• No clinically significant interactions were found with tamsulosin, warfarin, digoxin or cholestyramine in labeling studies.

Erectile dysfunction, decreased libido, ejaculation disorders, and breast enlargement or tenderness, which in BPH trials were most frequent in the first 6 months. Postmarketing reports include hypersensitivity reactions (rash, pruritus, urticaria, angioedema), depressed mood, testicular pain and swelling, and body hair loss or hypertrichosis.

Contraindicated in pregnancy. Dutasteride can cause abnormal development of external genitalia in a male fetus. Exposure of a pregnant partner through semen is estimated to be about 100-fold less than the level that caused abnormalities in male offspring in animal studies. Not indicated for use in women; it is not known whether dutasteride is excreted in human milk.

PSA and digital rectal examination at baseline, a new PSA baseline after 3 to 6 months, and periodic PSA thereafter; urinary symptoms in BPH; sexual adverse effects, breast changes and mood. Counsel on blood donation and on handling by women.

• Avodart (dutasteride) soft gelatin capsules Prescribing Information.
• Jalyn (dutasteride and tamsulosin hydrochloride) capsules Prescribing Information.
• NIOSH List of Hazardous Drugs in Healthcare Settings.
• USP General Chapter <800> Hazardous Drugs: Handling in Healthcare Settings.