The paperwork concerning Dutasteride is now publicly available at the FDA’s web site. Upon review of the documents, Regrowth has the following comments and notes regarding Dutasteride that may be of interest to its readers.
It has been reported that Glaxo is awaiting approval of a secondary New Drug Application before releasing the new medication. It can take up to 6 months for the new application to be approved, however Glaxo is not required to wait for this approval. They can release Dutasteride as soon as they are ready. The new application will give them more leeway in the claims they can make as it includes two year data. The pill will be available in a 0.5 mg soft gel for Benign Prostatic Hyperplasia. Since it will be a soft gel, dividing it into smaller doses as was done with Proscar will be much harder.
It is unknown at this time whether the hairloss version will be the same dosage. It has been rumored that a new drug application for Dutasteride for hairloss was submitted around the time of approval for BPH. How this affects the timeline for approval specifically for hairloss is not yet known.
A few concerns were listed by the investigators of the medication. One was that caution should be used in the use of the drug for those with hepatic (liver) impairment or those taking CYP3A4 inhibitors. Nizoral / Ketoconazole is a CYP3A4 inhibitor which is commonly used for hairloss. The documents were not specific about what forms should not be used so it is unknown at this time whether using the topical shampoo would require any precaution or if the caution only applies to the oral form of the medication.
The drug was tested in its large scale Phase III tests in 3 separate trials lasting 2 years each all with the same clinical specifications and methods — 2 held in the United States and one outside the United States that was conducted in 19 countries. The documents available at the FDA’s web site included only results from the first year of those studies. The subsequent years were/are to be reported later (it is unknown if this data has been submitted and was unavailable or has not been submitted yet).
The studies included 4,324 men with 2,158 given a placebo and 2,166 given Dutasteride. Of these, 3,522 men completed the first year of study (1,750 on placebo, 1,772 on Dutasteride). The studies measured factors for the evaluation of BPH, so the study results were not particularly applicable in terms of hairloss. However, as with all studies, safety and side effects were evaluated and this information will be important to the many men who will try the drug prior to its approval for hairloss.
The safety data was evaluated using the results of several studies including the Phase III studies. Altogether 5,305 men were studied for safety concerns, including over 400 men who had completed two years of study. The side effects studied are listed in the table below.
|
Placebo (2,158 patients)
|
Dutasteride (2,166 patients)
|
|
| Decreased Libido |
2% (49)
|
4% (88)
|
| Impotence |
4% (76)
|
7% (141)
|
| Ejaculation Disorder |
< 1% (18)
|
2% (53)
|
| Sexual Function Disorder |
< 1% (2)
|
<1% (7)
|
| Gynecomastia |
< 1% (11)
|
1% (32)
|
| Prostate Cancer |
< 1% (12)
|
<1% (11)
|
When measuring side effects reported by medication users compared to placebo this indicates a real rate of side effects of 2% reporting decreased libido, 3% reporting impotence, 1-2% reporting ejaculation disorder, <1% reporting sexual function disorder, <1% reporting Gynecomastia, and no higher incidence of prostate cancer compared to placebo. Some may see Prostate Cancer listed and take an alarmist position — however it should be noted that this is a study of men with enlarged prostates which is often a precondition to prostate cancer. As the study shows, a certain percentage would go on to develop the condition regardless of the medication, and since it did not occur in more men on the medication than those taking placebo, it is a result of their prostatic condition rather than Dutasteride. All in all the side effects seem surprisingly low and compare favorably to Propecia.
Another concern for all 5-alpha reductase inhibitors such as Dutasteride is exposure in pregnant women. Dutasteride will carry the same prohibitive labeling for women not to handle or take the medication if the are or may become pregnant. An analysis of the amount of Dutasteride found in the semen found it was far below the required levels to have any effect on a woman through sexual intercourse, so no warning will be included in the label regarding this. Studies showed that the amount of Dutasteride required in the semen to have an effect on a woman would be over a hundred times the level that was found to be present in semen. All pregnancies which occurred in patients participating in the studies produced healthy babies.
Prostate Specific Antigen (PSA) levels were reduced 50% when taking the medication (the same as use of Propecia/Proscar/Finasteride). Men having their PSA levels checked will need to let the doctor know this and to double the results obtained by the test to evaluate the test results properly. PSA tests are routinely done to evaluate prostatic enlargement and other prostate conditions.
Other Notes:
Serum testosterone increased 20% on average, an amount which is not considered clinically significant. Some weightlifters and athletes have considered this a bonus of the medication when using Propecia — an increase in Testosterone and protection from hairloss.
In studies of the effects on sperm, no significant changes were noticed in sperm morphology, sperm concentration, or sperm motility. Ejaculate volume decreased 25%, similar to Propecia, but stayed within the normal range. Two patients experienced a significant decrease in sperm count after the 52-week trial which reversed itself by the 26 week evaluation after the trial had ended.
No toxic effects were found from the use of the medication.
Although their studies indicated the amount passed in blood probably would not affect a pregnant female receiving a blood transfusion, it is recommended that men taking the medication not donate blood until they have stopped taking the medication for 6 months.
Dutasteride at this dosage reduced DHT by 93.1-93.6% after 12-months on the medication.
Contrary to previous reports, the medications trade name will NOT be Duagen. The FDA documents state that the names Duagen and Zygara were rejected and that no name has yet been approved for the medication.
Glaxo initially requested a 5 year drug exclusivity for Dutasteride before generics can be made or the exclusivity can be renewed.
