Dutasteride Info Sheet

Dutasteride 0.5mg, manufactured by GlaxoSmithKline, became available for the treatment of prostate enlargement (benign prostatic hypertrophy or BPH) in North America in January 2003 under the trade name Avodart. In 2006, Dutasteride 0.5mg became available in the United States in a generic formulation. Dutasteride 0.5mg is FDA approved for the treatment BPH, but not for hair loss.

Dutasteride is an oral medication that blocks the conversion of testosterone to dihydrotestosterone (DHT), the hormone largely responsible for prostate enlargement and for male pattern baldness. It does this by inhibiting the action of both types (Type I and II) 5-alpha reductase enzyme. In contrast, finasteride, the FDA approved medication for hair loss, inhibits only the Type II enzyme, the enzyme that is present in highest concentrations in and around the hair follicles.

Both dutasteride and finasteride produce a rapid decrease in serum DHT concentration. Lowering DHT appears to inhibit the miniaturization (shrinking) of affected hair follicles and helps restore miniaturized hair follicles to regrow visible hair.

Dutasteride (Avodart) inhibits both type I and type II, 5a-reductase. At the 0.5-mg dose, it is about 3 times as potent as finasteride at inhibiting type II, 5?-reductase enzyme and more than 100 times as potent at inhibiting the type I 5?-reductase enzyme. Type I receptors inhibited by dutasteride are present in other organs of the body besides the skin, including the liver and kidneys.

Usefulness in Male Pattern Alopecia – JAAD Study

A study published by Olsen et. al. in the Journal of the American Academy of Dermatology 2006; 55(6): 1014-1023, showed the benefit of combined type I and type II 5a-reductase inhibition in the treatment of male pattern hair loss in a randomized, placebo-controlled study of dutasteride versus finasteride.

In the study, 416 men with male pattern hair loss (MPHL) ages 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. The results of the study showed that dutasteride increased hair counts in a dose-dependent fashion and dutasteride 2.5 mg was superior to finasteride 5mg at 12 and 24 weeks.

Dutasteride caused scalp and serum dihydrotestosterone levels to decrease and testosterone levels to increase in a dose-dependent fashion. Whereas 5-mg finasteride decreases serum DHT by about 70%, dutasteride can decrease serum DHT by more than 90%.

In this phase II, dose-ranging study, 2.5-mg dutasteride was superior to 5-mg finasteride in improving scalp hair growth in men between ages 21 and 45 years with MPHL as judged by target area hair counts, expert panel assessment, and investigator assessment at 12 and 24 weeks.

In a test area at 24 weeks, results showed:

Placebo	-32.3 hairs
Finasteride 5mg	75.6 hairs
Dutasteride 0.1 mg	78.5 hairs
Dutasteride 0.5 mg	94.6 hairs
Dutasteride 2.5 mg	109.6 hairs

Both dutasteride and finasteride were well tolerated in this phase II study, and no new safety concerns have arisen in any of the phase II and phase III studies of dutasteride given at doses up to 5 mg daily (the 5-mg dose was used in a phase II study for BPH).

See the Dutasteride vs. Finasteride page for additional information on the study.

Using Avodart

Although physicians may prescribe FDA-approved medications for off-label use, it is important to keep in mind that the FDA has not approved dutasteride for the treatment of male pattern hair loss (MPHL). Therefore, when used to treat androgenetic alopecia, the beneficial effects, short- and long-term side effects and proper dosing of the medication is not known.

Avodart has been FDA approved for prostatic enlargement in a dose of 0.5mg. The recommended dose of Avodart for BPH is 1 capsule (0.5 mg) taken orally once a day. The capsules should be swallowed whole. Avodart may be administered with or without food. No dosage adjustment is necessary for subjects with renal impairment or for the elderly. Dutasteride 0.5mg is now available generically.

What to Expect in the Treatment of Hair Loss

As with finasteride, patients taking Avodart should be on the medication for one year or longer before its effects in preventing hair loss and re-growing hair can be accurately assessed. Dutasteride most likely takes up to one year or more to exert its full effects in both preventing hair loss and in re-growing hair.

During the first six months on dutasteride, one may note some thinning of one’s existing hair. This may be due to either progression of your hair loss before finasteride has had a chance to work, or some shedding of miniaturized hair that makes way for the new healthy hair to grow. It is important to be patient during this period. You should continue the medication for at least one year before you and your doctor can assess its benefits.

Duration of Effects and Blood Donation

Dutasteride has a serum half-life of approximately 5 weeks. Serum concentrations remain detectable for up to 4-6 months after discontinuation of treatment. Because of this long half-life, men being treated with dutasteride should not donate blood until at least 6 months past their last dose to prevent administration to a pregnant female transfusion recipient. In contrast, the serum half-life of finasteride is 6 to 8 hours.

Drug Interactions

Dutasteride is metabolized by human cytochrome P450 isoenzyme CYP34A.
Concentrations of dutasteride may increase in the presence of inhibitors of CYP34A such as ritonavir, ketoconazole, verapamil, diltiazem, cimetidine, and ciprofloxin.

Contraindications

Avodart is contraindicated for use in women and children and in those with known sensitivity to dutasteride or other 5-alpha reductase inhibitors.

Avodart has not been studied in women because preclinical data suggest that the suppression of circulating levels of dihydrotestosterone may inhibit the development of the external genital organs in a male fetus carried by a woman exposed to dutasteride.

Warnings: Exposure of Women – Risk to Male Fetus

Dutasteride is absorbed through the skin. Therefore, women who are pregnant, or may be pregnant, should not handle Avodart soft gelatin capsules because of the possibility of absorption of dutasteride and the potential risk of a fetal defect to a male fetus. If contact is made with leaking capsules, the contact area should be washed immediately with soap and water.

Use in Hepatic Impairment

Because dutasteride is extensively metabolized and has a half-life of approximately 5 weeks at steady state, caution should be used in the administration of dutasteride to patients with liver disease.

Use with Potent CYP3A4 Inhibitors

Because of the potential for drug-drug interactions, care should be taken when administering dutasteride to patients taking potent, chronic CYP3A4 enzyme inhibitors (e.g., ritonavir).

Effects on PSA and Prostate Cancer Detection

Digital rectal examinations, as well as other evaluations for prostate cancer, should be performed on patients with BPH prior to initiating therapy with Avodart and periodically thereafter. Dutasteride reduces total serum Prostate-Specific Antigen (PSA) concentration by approximately 50% after 6 months. For the interpretation of serial PSAs in a man taking Avodart, a new baseline PSA concentration should be established after 3 to 6 months of treatment, and this new value should be used to assess potentially cancer-related changes in PSA. To interpret an isolated PSA value in a man treated with Avodart for 6 months or more, the PSA value should be doubled for comparison with normal values in untreated men.

The free-to-total PSA ratio (percent free PSA) remains constant at Month 12, even under the influence of Avodart. If clinicians elect to use percent free PSA as an aid in the detection of prostate cancer in men receiving Avodart, no adjustment to its value appears necessary.

Hormone Levels

Statistically significant, baseline-adjusted mean increases compared with placebo were observed for total testosterone and thyroid-stimulating hormone (TSH). After stopping dutasteride for 24 weeks, the mean levels of testosterone and TSH had returned to baseline in the group of subjects with available data at the visit. In patients with BPH treated with dutasteride 0.5 mg/day for 4 years, the median decrease in serum DHT was approximately 95%. The median increase in serum testosterone was 22% at 4 years, but the mean and median levels remained within the physiologic range.

Fertility

Sperm concentration and sperm morphology were unaffected. After 24 weeks of follow-up, the mean percent change in total sperm count in the dutasteride group remained 23% lower than baseline. While mean values for all semen parameters at all time points remained within the normal ranges and did not meet predefined criteria for a clinically significant change (30%), two subjects in the dutasteride group had decreases in sperm count of greater than 90% from baseline at 52 weeks, with partial recovery at the 24-week follow-up. The clinical significance of dutasteride’s effect on semen characteristics for an individual patient’s fertility is not known.

Sexual Function

Ejaculate volume might be decreased in some patients during treatment with Avodart. This decrease does not appear to interfere with normal sexual function. In clinical trials, impotence and decreased libido, considered by the investigator to be drug-related, occurred in a small number of patients treated with Avodart or placebo.

Adverse Reactions

Most adverse reactions were mild or moderate and generally resolved while on treatment in both the Avodart and placebo groups. The most common adverse events leading to withdrawal in both treatment groups were associated with the reproductive system.

Dutasteride was investigated in controlled multi-center studies involving 4,325 men aged 50 and above with prostate enlargement. Drug-related side effects during the first six months were as follows: impotence (4.7 percent vs. 1.7 percent for placebo), decreased libido (3 percent vs. 1.4 percent), breast tenderness and breast enlargement (gynecomastia; 0.5 percent vs. 0.2 percent) and ejaculation disorders (1.4 percent vs. 0.5 percent). Z

Long-Term Treatment (Up to 4 Years)

There is no evidence of increased drug-related sexual adverse events (impotence, decreased libido and ejaculation disorder) or gynecomastia (breast enlargement) with increased duration of treatment. The relationship between long-term use of dutasteride and male breast neoplasia is currently unknown.

A congenital deficiency of the type 2 5a-reductase enzyme has been identified in some men. These men neither went bald nor suffered any long-term consequences of this deficiency. This supports that idea that there are no long-term consequences with taking Finasteride (which blocks this type 2 enzyme). Unfortunately, there is no known natural deficiency to the type I enzyme that might support the long-term safety of dutasteride.

Patient Monitoring

It is recommended that men aged 50, or over, should inform their regular physicians or urologists that they are taking Avodart (dutasteride 0.5 mg). It is also recommended that all men aged 50 or over have a routine annual evaluation for prostate disease, regardless of whether or not Avodart is used. For those patients who are black and/or who have a family history of prostate disease, these recommendations would apply beginning at age 40. An evaluation may include a rectal examination, a baseline PSA, and other tests that your examining physician feels are appropriate. Specific recommendations for each patient should be based upon the judgment of his own physician.

Summary Comments on Using Dutasteride for Hair Loss

• The approved dose of dutasteride for treatment of BPH is 0.5 mg daily and that limited data is available on the safety of higher doses.
• The prescribing information for Avodart is in a population of patients with BPH. The short- and long-term side effects of this medication, when used for the treatment of androgenetic hair loss, are not known.
• Dutasteride is not approved for treatment of male pattern hair loss, and the beneficial effects of dutasteride in male pattern hair loss must be weighed against the possible adverse effects reported during use in BPH, including, but not limited to:
• sexual dysfunction
• gynecomastia (breast enlargement)
• reduced sperm count (prolonged decreased sperm counts have been seen with dutasteride at 5 months)
• There have been some cases where the DHT levels were still only 25% of the baseline at 12 months after discontinuing the drug.

Patients should read the Patient Information leaflet before starting therapy with Avodart and reread it upon prescription renewal for new information regarding the use of this medication.