In 2006, Dutasteride 0,5mg was marketed in the United States in a generic formula. Dutasteride 0,5 mg is approved by the FDA for the treatment of BPH, but not for baldness.
Dutasteride is an oral medication that blocks the conversion of testosterone into dihydrotestosterone (DHT). It is the hormone that is mainly responsible for the enlarged prostate and the loss of hair in men. It does this by inhibiting the activity of both types (Type I and II) of the enzyme 5-alpha reductase. By comparison, finasteride, an FDA-approved hair loss drug, inhibits only the type II enzyme. This enzyme which is present in higher concentrations in the vicinity of the hair follicles.
Both dutasteride and finasteride cause a rapid reduction in the concentration of DHT in the serum. The decrease in DHT appears to inhibit the miniaturization (shrinkage) of the hair follicles. Helps to restore miniaturized hair follicles so that visible hair can grow back.
Clinical studies by Dutasterida
At the 0,5 mg dose, it is apparent and approximately 3 times more potent than finasteride in inhibiting type II reductase enzyme; and more than a hundred times more potent in inhibiting type I.
A study printed by Olsen and others in the Journal of the American Academy of Dermatology 2006; 55 (6): 1014-1023, demonstrated the advantage of type I and type II 5-reductase inhibition in treating male pattern baldness in a randomized, placebo-controlled analysis of dutasteride versus finasteride.
In the analysis, 416 men with male pattern hair loss (MPHL) between 21 and 45 years of age 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 analysis showed that dutasteride increased the number of hairs in a dose-dependent manner and that dutasteride 2,5 mg was superior to finasteride 5 mg at 12 and 24 weeks.
While 5 mg of finasteride reduces serum DHT by 70%, dutasteride can reduce serum DHT by more than 90%.
In this stage II dose range study, 2,5 mg of dutasteride was superior to 5 mg of finasteride to improve scalp hair growth in men between the ages of 21 and 45 with MPHL, as judged by the count. of hair in the target area, the evaluation of the panel of experts and the evaluation of the researcher at 12 and 24 weeks.
In a test area at 24 weeks, the results revealed:
Both dutasteride and finasteride were well tolerated in this phase II study, and no new safety concerns have been raised in any of the phase II and phase III studies of dutasteride administered in doses up to 5 mg per day (the 5-dose mg was used in a phase II study for BPH).
Use of Dutasteride
Although doctors may prescribe injectable medications for a use not indicated on the label, it is important to note that the FDA has not approved dutasteride for the treatment of male pattern hair loss (HPM). Therefore, when used to treat androgenetic alopecia, the beneficial effects, short and long-term side effects, and the proper dosage of the drug are unknown.
The recommended dose of Avodart for BPH is 1 pill (0,5 mg) taken by mouth once daily. No dosage adjustment is required for subjects with renal impairment or for the elderly. Dutasteride 0.5mg is currently available in a generic form.
How long should Dutasteride be taken?
Like finasteride, patients taking Avodart must take the drug for a year or more before its effects in preventing hair loss and hair growth can be properly evaluated. Dutasteride probably takes up to a year or more to apply all its effects in both baldness prevention and hair growth.
During the first six months of treatment with dutasteride, a person may notice some thinning of existing hair. This can be attributed to the progression of hair loss before finasteride has had a chance to work, or to any thinning hair loss, resulting in new healthier hair growth. It is essential to be patient during this period. You must continue the medication for at least a year before your doctor can evaluate its benefits.
Dutasteride has a serum half-life of about 5 weeks. Serum concentrations remain detectable for up to 4-6 months after discontinuation of therapy. Due to this long half-life, men being treated with dutasteride should not donate blood until at least 6 months after their final dose to reduce administration to a pregnant woman receiving a transfusion.
Interactions with other medications
Dutasteride concentrations may increase in the presence of CYP34A inhibitors such as ritonavir, ketoconazole, verapamil, diltiazem, cimetidine, and ciprofloxin.
Avodart has not been studied in women because preclinical data indicates that reduced circulating levels of dihydrotestosterone may inhibit the growth of external reproductive organs in a male fetus carried by a woman exposed to dutasteride.
Therefore, women who are pregnant, or who might be, should not administer Avodart softgel capsules. This is due to the absorption potential of dutasteride and the possible risk of a fetal defect in a male fetus.
Since dutasteride is extensively metabolized and has a half-life of about 5 weeks at steady state, caution should be exercised in the administration of dutasteride to patients with liver disease.
Due to the potential for drug interactions, caution should be exercised when dutasteride is administered to patients taking chronic and potent inhibitors of the CYP3A4 enzyme.
Digital rectal examinations should be performed in patients with BPH prior to initiation of Avodart and occasionally thereafter. As well as other screenings for prostate cancer. Dutasteride reduces the total serum prostate specific antigen (PSA) concentration by approximately 50% after 6 weeks. For interpretation of serial PSA in a type taking Avodart, a new baseline PSA level should be established after 3 to 6 weeks of therapy; This new value should be used to assess changes in PSA potentially related to cancer. To translate an isolated PSA value in a person treated with Avodart for 6 weeks or longer, the PSA value must be doubled to compare with normal values in untreated men.
The ratio of free to total PSA (percentage of free PSA) remains constant at month 12, even under the influence of Avodart.
Statistically significant increases in mean adjusted to baseline compared to placebo were observed for total testosterone and thyroid stimulating hormone (TSH). After stopping dutasteride for 24 weeks, mean testosterone and TSH levels had returned to baseline in the group of subjects with data available at the visit. In BPH patients treated with dutasteride 0,5 mg / day for 4 decades, the mean reduction in serum DHT was approximately 95%. The median increase in serum testosterone was 22% at 4 years. The median and mean levels were within the physiological range.
Sperm concentration and morphology were not affected. After 24 months of follow-up, the mean percentage change in total sperm count in the dutasteride group remained 23% lower compared to baseline. While the mean values of all semen parameters at all time points remained within normal ranges and did not meet the predefined criteria for a clinically significant change (30%), two subjects in the dutasteride group had decreases in count. sperm count greater than 90% from baseline at 52 weeks, with partial recovery at 24 weeks follow-up. The clinical importance of the impact of dutasteride on semen characteristics for the fertility of a single patient is unknown.
Ejaculation volume may decrease 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 some of the patients treated with Avodart or placebo.
Adverse reactions of the Dutasuterida
Most adverse reactions were mild or moderate and generally resolved during therapy in both the Avodart and placebo groups. The most frequent adverse reactions leading to withdrawal of both treatment groups were related to the reproductive system.
Dutasteride has been investigated in multicenter controlled studies involving 4.325 men over 50 years of age with an enlarged prostate.
Medication-related side effects for 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 enlargement (gynecomastia; 0,5 percent vs. 0,2 percent)
- Ejaculation disorders (1,4 percent vs. 0,5 percent).
Long-term treatment (up to 4 years)
There is absolutely no evidence of an increase in drug-related sexual adverse events (impotence, decreased libido, and ejaculation disorder) or gynecomastia (increased breast) with longer duration of therapy. The association between long-term use of dutasteride and male breast neoplasia is currently unknown.
A congenital deficiency of the enzyme 5a-reductase type 2 was identified in certain men. These men did not go bald or suffer any long-term effects from this deficiency. This supports the notion that there are no long-term effects from taking Finasteride (which blocks this type 2 enzyme). Unfortunately, there is absolutely no known natural deficiency of the type I enzyme that can promote dutasteride's long-term safety.
Patient monitoring with Dutasteride
It is suggested that men 50 years of age and older should notify their regular doctors or urologists that they are taking Avodart (Dutasteride 0,5 mg). In addition, all men age 50 and older are advised to undergo a regular annual evaluation for prostate disorders, 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 starting at age 40. The evaluation may include a rectal exam, a baseline PSA, along with other tests that your examining physician deems appropriate. Specific recommendations for each individual should be based on the judgment of their own physician.
Summary of comments on the use of Dutasteride for hair loss
- The approved dose of dutasteride for the treatment of BPH is 0,5 mg per day. Limited data are available on the safety of high doses.
- The information and prescription indication for Avodart is found in a population of BPH patients.
- 100% of the drug's short and long-term side effects, when used to treat androgenetic hair loss, are unknown.
- Although Dutasteride is accepted for the treatment of male pattern baldness, the beneficial effects of dutasteride in male pattern baldness must be weighed against the potential adverse effects reported during its use in BPH, including, but not limited to:
- Sexual dysfunction-gynecomastia (breast enlargement)
- Reduced sperm count (prolonged decreased sperm counts are seen with dutasteride in 5 weeks).