Dutasteride(doo TAS ter ide) | Avodart |
| Category | 5-a reductase inhibitor |
| Parameter | Effect | Result on hair growth |
| DHT |  | GOOD |
| 5a-reductases | | GOOD |
| PGD2 |  | UNKNOWN |
| PGE2 | | UNKNOWN |
| PGF2a | | UNKNOWN |
| CRTH2 | | UNKNOWN |
Information
| Description | Dutasteride is approved for the treatment of benign prostatic hyperplasia also known as an "enlarged prostate". Dutasteride provides the same effect on DHT as Finastiride to an even greater extent however at a cost of a much higher possibility and severity of side effects. Dutasteride inhibits both isoforms of 5-alpha reductase, while finasteride inhibits only one. Dutasteride will reduce DHT up to 95% Dutasteride has a half life of 5 weeks compared to a half life of 8 hours for finastiride. |
| Typical Results | Substantial regrowth of hair has been reported by many users along with side effects possibly beyond Finastiride. One study concluded that Finastiride daily and low dose Dutasteride weekly produced excellent results. |
| Typical Dosages | .5mg weekly to .5mg daily |
| Significant Side Effects | More patients exposed to dutasteride than placebo experienced impotence, decreased libido, ejaculation disorders, and gynecomastia in the course of the 24-month study. However, most of these effects were transient, and the incidence of new occurrences of each event decreased in the second year. |
| Dissolves in | Ethanol |
| Pharmacology Pharmacodynamics |
Mechanism of Action Dutasteride inhibits the conversion of testosterone to 5α-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 5α-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 5α-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. Effect on 5α-Dihydrotestosterone and Testosterone The maximum effect of daily doses of dutasteride on the reduction of DHT is dose dependent and is observed within 1 to 2 weeks. After 1 and 2 weeks of daily dosing with dutasteride 0.5 mg, median serum DHT concentrations were reduced by 85% and 90%, respectively. In patients with benign prostatic hyperplasia (BPH) treated with dutasteride 0.5 mg/day for 4 years, the median decrease in serum DHT was 94% at 1 year, 93% at 2 years, and 95% at both 3 and 4 years. The median increase in serum testosterone was 19% at both 1 and 2 years, 26% at 3 years, and 22% at 4 years, but the mean and median levels remained within the physiologic range. In patients with BPH treated with 5 mg/day of dutasteride or placebo for up to 12 weeks prior to transurethral resection of the prostate, mean DHT concentrations in prostatic tissue were significantly lower in the dutasteride group compared with placebo (784 and 5,793 pg/g, respectively, p<0.001). Mean prostatic tissue concentrations of testosterone were significantly higher in the dutasteride group compared with placebo (2,073 and 93 pg/g, respectively, p<0.001). Adult males with genetically inherited type 2 5α-reductase deficiency also have decreased DHT levels. These 5α-reductase deficient males have a small prostate gland throughout life and do not develop BPH. Except for the associated urogenital defects present at birth, no other clinical abnormalities related to 5α-reductase deficiency have been observed in these individuals. Other Effects Plasma lipid panel and bone mineral density were evaluated following 52 weeks of dutasteride 0.5 mg once daily in healthy volunteers. There was no change in bone mineral density as measured by dual energy x-ray absorptiometry (DEXA) compared with either placebo or baseline. In addition, the plasma lipid profile (i.e., total cholesterol, low density lipoproteins, high density lipoproteins, and triglycerides) was unaffected by dutasteride. No clinically significant changes in adrenal hormone responses to ACTH stimulation were observed in a subset population (n = 13) of the 1-year healthy volunteer study. Pharmacokinetics Absorption Following administration of a single 0.5-mg dose of a soft gelatin capsule, time to peak serum concentrations (Tmax) of dutasteride occurs within 2 to 3 hours. Absolute bioavailability in 5 healthy subjects is approximately 60% (range, 40% to 94%). When the drug is administered with food, the maximum serum concentrations were reduced by 10% to 15%. This reduction is of no clinical significance. Distribution Pharmacokinetic data following single and repeat oral doses show that dutasteride has a large volume of distribution (300 to 500 L). Dutasteride is highly bound to plasma albumin (99.0%) and alpha-1 acid glycoprotein (96.6%). In a study of healthy subjects (n = 26) receiving dutasteride 0.5 mg/day for 12 months, semen dutasteride concentrations averaged 3.4 ng/mL (range, 0.4 to 14 ng/mL) at 12 months and, similar to serum, achieved steady-state concentrations at 6 months. On average, at 12 months 11.5% of serum dutasteride concentrations partitioned into semen. Metabolism and Elimination Dutasteride is extensively metabolized in humans. In vitro studies showed that dutasteride is metabolized by the CYP3A4 and CYP3A5 isoenzymes. Both of these isoenzymes produced the 4-hydroxydutasteride, 6-hydroxydutasteride, and the 6,4-dihydroxydutasteride metabolites. In addition, the 15-hydroxydutasteride metabolite was formed by CYP3A4. Dutasteride is not metabolized in vitro by human cytochrome P450 isoenzymes CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1. In human serum following dosing to steady state, unchanged dutasteride, 3 major metabolites (4-hydroxydutasteride, 1,2-dihydrodutasteride, and 6-hydroxydutasteride), and 2 minor metabolites (6,4-dihydroxydutasteride and 15-hydroxydutasteride), as assessed by mass spectrometric response, have been detected. The absolute stereochemistry of the hydroxyl additions in the 6 and 15 positions is not known. In vitro, the 4-hydroxydutasteride and 1,2-dihydrodutasteride metabolites are much less potent than dutasteride against both isoforms of human 5AR. The activity of 6β-hydroxydutasteride is comparable to that of dutasteride. Dutasteride and its metabolites were excreted mainly in feces. As a percent of dose, there was approximately 5% unchanged dutasteride (~1% to ~15%) and 40% as dutasteride-related metabolites (~2% to ~90%). Only trace amounts of unchanged dutasteride were found in urine (<1%). Therefore, on average, the dose unaccounted for approximated 55% (range, 5% to 97%). The terminal elimination half-life of dutasteride is approximately 5 weeks at steady state. The average steady-state serum dutasteride concentration was 40 ng/mL following 0.5 mg/day for 1 year. Following daily dosing, dutasteride serum concentrations achieve 65% of steady-state concentration after 1 month and approximately 90% after 3 months. Due to the long half-life of dutasteride, serum concentrations remain detectable (greater than 0.1 ng/mL) for up to 4 to 6 months after discontinuation of treatment. |
Clinical Studies
| Clinical Studies | Abstract |
| Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. |
Full Text PDF available Dihydrotestosterone (DHT) is the primary metabolite of testosterone in the prostate and skin. Testosterone is converted to DHT by 5alpha-reductase, which exists in two isoenzyme forms (types 1 and 2). DHT is associated with development of benign prostatic hyperplasia (BPH), and reduction in its level with 5alpha-reductase inhibitors improves the symptoms associated with BPH and reduces the risk of acute urinary retention and prostate surgery. A selective inhibitor of the type 2 isoenzyme (finasteride) has been shown to decrease serum DHT by about 70%. We hypothesized that inhibition of both isoenzymes with the dual inhibitor dutasteride would more effectively suppress serum DHT levels than selective inhibition of only the type 2 isoenzyme. A total of 399 patients with BPH were randomized to receive once-daily dosing for 24 wk of dutasteride (0.01, 0.05, 0.5, 2.5, or 5.0 mg), 5 mg finasteride, or placebo. The mean percent decrease in DHT was 98.4 +/- 1.2% with 5.0 mg dutasteride and 94.7 +/- 3.3% with 0.5 mg dutasteride, significantly lower (P < 0.001) and with less variability than the 70.8 +/- 18.3% suppression observed with 5 mg finasteride. Mean testosterone levels increased but remained in the normal range for all treatment groups. Dutasteride appeared to be well tolerated with an adverse event profile similar to placebo. |
| The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride. | BACKGROUND: Male pattern hair loss (MPHL) is a potentially reversible condition in which dihydrotestosterone is an important etiologic factor. OBJECTIVE: Our aim was to evaluate the efficacy of the type 1 and 2 5alpha-reductase inhibitor dutasteride in men with MPHL. METHODS: Four hundred sixteen men, 21 to 45 years old, were randomized to receive dutasteride 0.05, 0.1, 0.5 or 2.5 mg, finasteride 5 mg, or placebo daily for 24 weeks. RESULTS: Dutasteride increased target area hair count versus placebo in a dose-dependent fashion and dutasteride 2.5 mg was superior to finasteride at 12 and 24 weeks. Expert panel photographic review and investigator assessment of hair growth confirmed these results. Scalp and serum dihydrotestosterone levels decreased, and testosterone levels increased, in a dose-dependent fashion with dutasteride. LIMITATIONS: The study was limited to 24 weeks. CONCLUSION: Dutasteride increases scalp hair growth in men with MPHL. Type 1 and type 2 5alpha-reductase may be important in the pathogenesis and treatment of MPHL. |
| Effective treatment of female androgenic alopecia with dutasteride. | Dihydrotestosterone is the main molecule responsible for androgenic alopecia. Finasteride, which reduces transformation of testosterone into dihydrotestosterone and decreases dihydrotestosterone activity, is approved for treatment of androgenic alopecia in men. We describe the case of a 46-year-old woman with androgenic alopecia, non-responsive to minoxidil, who initially benefited from finasteride. Due to only limited improvement after finasteride and persisting profound psychological distress resulting from androgenic alopecia, another 5-reductase inhibitor, dutasteride, was introduced. Clinical evaluation and trichogram were applied for assessment of dutasteride efficacy in this patient. Additionally, mean hair diameter was monitored by means of computer dermoscopy. After 6 months of therapy, significant improvement was observed and after 9 months the clinical diagnosis of androgenic alopecia could no longer be made in this patient. No side effects were observed. In conclusion, theoretical data and our experience in this case show that dutasteride might develop into a true alternative in treatment of androgenic alopecia. |
| Combination therapy with finasteride and low-dose dutasteride in the treatment of androgenetic alopecia. | We report on a 47-year-old man who was initially treated with finasteride for androgenetic alopecia. Despite continuous treatment, after year 4 his hair density was not as good as at year 2, and low-dose dutasteride at 0.5 mg/week was added to the finasteride therapy. This resulted in a dramatic increase in his hair density, demonstrating that combined therapy with finasteride and dutasteride can improve hair density in patients already taking finasteride. |
| Efficacy, safety, and tolerability of dutasteride 0.5 mg once daily in male patients with male pattern hair loss: a randomized, double-blind, placebo-controlled, phase III study. | BACKGROUND: Dutasteride (Avodart) is a dual inhibitor of both type I and type II 5 alpha reductases, and thus inhibits conversion of testosterone to dihydrotestosterone, a key mediator of male pattern hair loss. OBJECTIVES: The aim of this randomized double-blind phase III study was to compare the efficacy, safety, and tolerability of dutasteride (0.5 mg) and placebo for 6 months of treatment in male patients with male pattern hair loss. METHODS: A total of 153 men, 18 to 49 years old, were randomized to receive 0.5 mg of dutasteride or placebo daily for 6 months. Efficacy was evaluated by the change of hair counts, subject assessment, and photographic assessment by investigators and panels. RESULTS: Mean change of hair counts from baseline to 6 months after treatment start was an increase of 12.2/cm(2) in dutasteride group and 4.7/cm(2) in placebo group and this difference was statistically significant (P = .0319). Dutasteride showed significantly higher efficacy than placebo group by subject self-assessment and by investigator and panel photographic assessment. There was no major difference in adverse events between two groups. LIMITATIONS: The study was limited to 6 months. CONCLUSIONS: This study clearly showed that 0.5 mg of dutasteride improved hair growth and was relatively well tolerated for the treatment of male pattern hair loss. |
| A 5-year retrospective analysis of 5α-reductase inhibitors in men with benign prostatic hyperplasia: finasteride has comparable urinary symptom efficacy and prostate volume reduction, but less sexual side effects and breast complications than dutasteride. | Objective: We evaluated 5-year safety, efficacy and prostate volume data from BPH patients treated with finasteride or dutasteride. Methods: A retrospective analysis of 378 consecutive men treated with 5α-reductase inhibitor monotherapy between January 2004 and September 2009 (197 on finasteride and 211 on dutasteride) in a single clinic was performed. Efficacy assessments included International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), postvoid residual urine volume (PVR), prostate-specific antigen (PSA) and prostate volume (PV). Safety assessments included International Index of Erectile Function (IIEF) and adverse events. Patients were evaluated at 3 months, 1 year and yearly thereafter. Results: Mean age of the group was 58.7±6.7 years. Maintenance of therapy at 5years was 57.4% and 42.5% for the finasteride and dutasteride groups respectively. Changes in IPSS, Qmax, PVR, PV and PSA were similar for both groups at 5years. The incidence of erectile dysfunction, ejaculatory dysfunction and decreased libido resulting in discontinuation from therapy was significantly (p< 0.01) higher in the dutasteride (5.1%, 2.4%, 2.7% respectively) compared with the finasteride (2.1%, 1.8%, 1.4% respectively) group. In addition, the incidence of self-reported breast tenderness and/or enlargement was significantly (p< 0.01) greater in the dutasteride (3.5%) compared with the finasteride (1.2%) group. Conclusions: In this retrospective analysis of data from consecutive patients treated at a single clinic, both finasteride and dutasteride were effective therapies for the management of lower urinary tract symptoms. However, dutasteride resulted in significantly more sexual side effects and breast complications than finasteride. |