1. Clinical Overview
Dutasteride is a synthetic 4-azasteroid compound that acts as a potent, selective, and irreversible inhibitor of both type I and type II 5α-reductase isoenzymes. It is used primarily 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 need for BPH-related surgery. It is not indicated for use in women or children.
| Onset | Duration | Bioavailability |
|---|---|---|
| Clinical improvement in urinary symptoms may be observed within 3-6 months of continuous therapy, though maximum therapeutic effect on prostate volume reduction (approx. 25-30%) is typically seen after 6-12 months. | Long-lasting due to its long half-life. Serum DHT levels remain suppressed for up to 4-6 months after discontinuation of therapy. | Approximately 60% (range 40-94%). Absolute bioavailability is not established due to poor aqueous solubility. |
2. Mechanism of Action
Dutasteride inhibits the conversion of testosterone to the more potent androgen, dihydrotestosterone (DHT), by irreversibly binding to and inhibiting both type I and type II isoforms of the enzyme 5α-reductase. Type I isoenzyme is predominant in the skin, liver, and sebaceous glands, while type II is predominant in the prostate, seminal vesicles, epididymides, and hair follicles. By suppressing intraprostatic and serum DHT levels by >90%, it induces apoptosis of prostate epithelial cells, leading to a reduction in prostate gland volume.
3. Indications & Uses
- Symptomatic Benign Prostatic Hyperplasia (BPH) in men with an enlarged prostate to improve urinary symptoms (hesitancy, weak stream, frequency, urgency, nocturia)
- To reduce the risk of Acute Urinary Retention (AUR) in men with BPH
- To reduce the risk of the need for BPH-related surgery (e.g., Transurethral Resection of the Prostate - TURP)
4. Dosage & Administration
Adult Dosage: 0.5 mg orally once daily, with or without food. Must be taken consistently.
Administration: Swallow the soft gelatin capsule whole. Do not crush, chew, or open the capsule. If a dose is missed, it should be taken as soon as remembered unless it is almost time for the next dose. Do not double the dose. Can be taken at any time of day, but preferably at the same time each day.
5. Side Effects
Common side effects may include:
- Decreased libido (3-6%)
- Erectile dysfunction (4-7%)
- Ejaculation disorders (1-4%)
- Breast enlargement (gynecomastia) (1-2%)
- Breast tenderness
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Tamsulosin, Alfuzosin, Silodosin (Alpha-1 blockers) | Increased risk of orthostatic hypotension, dizziness. Combination therapy (e.g., Dutasteride + Tamsulosin) is a common and approved regimen for BPH. | Moderate |
| Cimetidine | Cimetidine (a non-specific CYP inhibitor) may decrease the metabolism of dutasteride, potentially increasing its plasma concentration. Clinical significance is likely minimal due to wide therapeutic index. | Minor |
| Rifampicin, Carbamazepine, Phenytoin (Potent CYP3A4 Inducers) | May increase the metabolism of dutasteride, potentially reducing its plasma concentration and efficacy. | Moderate |
| Ketoconazole, Itraconazole, Ritonavir (Potent CYP3A4 Inhibitors) | May decrease the metabolism of dutasteride, potentially increasing its plasma concentration. Clinical significance is likely minimal. | Minor |
| Warfarin | No clinically significant interaction observed in studies. | None |
7. Patient Counselling
- DO take the capsule whole, once daily, as prescribed. Do not stop without consulting your doctor.
- DO inform all your doctors and surgeons that you are taking dutasteride, especially prior to any surgery or PSA test.
- DO NOT donate blood while taking dutasteride and for at least 6 months after stopping it to prevent potential administration to a pregnant woman.
- DO NOT allow women who are pregnant or may become pregnant to handle crushed or broken capsules.
- DO report any new breast lumps, breast pain, nipple discharge, or changes in breast tissue to your doctor.
8. Toxicology & Storage
Overdose: Single doses up to 40 mg have been administered without significant adverse effects. In clinical trials, daily doses up to 5 mg for 6 months were well-tolerated. Expected symptoms in overdose would be an extension of its pharmacological effects and may include dizziness, headache, and potentially more pronounced sexual side effects.
Storage: Store at room temperature (15°C to 30°C). Protect from light and moisture. Keep in the original blister pack or container. Keep out of reach and sight of children. Do not use after the expiry date printed on the pack.