Απ: Και η 0.2mg δοσολογία έχει αποτελέσματα
Study of the FDA Files on PROPECIA
Sherman Frankel, April 6, 1998
Recently, the Food and Drug Administration (FDA) approved the use of the drug PROSCAR, under a new name, PROPECIA, for treatment of male pattern baldness. The medical term for the drug is finasteride but it is marketed under these two different names. The PROSCAR pill is 5 milligrams while the PROPECIA pill is 1 milligram (mg). PROSCAR is intended for older men suffering from benign prostatic hyperplasia, (BPH). It is not surprising that PROSCAR would affect hair growth since it inhibits the normal conversion of testosterone to dihydrotestosterone. It is well known that hair growth and impotence are connected to levels of dihydrotestosterone.
In the last few years it has been claimed that PROSCAR is ineffective in the treatment of BPH, both from studies of the medical literature (1), and in a more recent double blind study.(2). However there is a claim that for men with very large prostates, the incidence of choice of surgery is smaller and there is improvement in urinary retention.(3)
The double blind studies of PROPECIA do not extend beyond a few years, yet the predominant users are expected to be males in their thirties. The drug must be continued indefinitely if the new hair growth is to continue over one's lifetime.
With the announcement of the new use of PROSCAR, we recently used the Freedom of Information Act to obtain the documentation leading to the approval by the Food and Drug Administration for the use of PROPECIA.
We have examined the material and come to the conclusions that occupy the remainder of this note. The questions we address relate to dosages, side effects, and other conclusions to be drawn from the double-blind studies presented by Merck to the FDA.
A key question that needs resolution is the size of the dose of the main ingredient, finasteride, that should be used. In the PROSCAR studies it was found that, in measurements of prostate shrinkage, a 1 mg dose could not be distinguished from a 5mg dose. Yet the dosage recommended by Merck for PROSCAR was 5 mg and the effect of dosages lower than 1 mg were not studied. In the PROPECIA studies, the effects of a range of dosages were reported to the FDA. These studies examined how the drug inhibited the conversion of testosterone to dihydrotestosterone which is the significant feature affecting hair growth. This inhibition was observed to be 60-70 % in the (NDA 20-788) Merck study.
A significant result deals with the depletion of dihydrotestosterone (THD)and enhancement of testosterone (T), as measured in the scalp skin as a function of dosage.
The dose dependence appears also in the accompanying rise in T, one-onehundredth the 5 mg dose being identical in its effect on the scalp skin testosterone. See Fig. 3.
Typically, the price of 5 mg PROSCAR is $76 for 30 pills, a months supply. For 1 mg PROPECIA it is $54. Therefore a PROPECIA user would pay only $15 if he were to cut up the 5 mg pills. However the above depletion studies suggest that a dosage of 0.2 mgs would be as effective as the 1 mg dose, bringing the price down to $3. For the user willing to dissolve the PROSCAR pill, (it is soluble in ethanol), or divide it up by other means, the monthly cost would be seventy-six cents.
The data supplied to the FDA on ``efficacy parameters'', (NDA 20-788, table 8.1.2.4.2) compared .2 and 1.0 mg dosages in hair count, investigator assessment, and global photographic assessment but did not present data for other dosages above .02 mg. However the sample of participants (100) was small and the differences between the .2 and 1.0 dosages in the first two cases were not apparent and, in the photographic assessment, which showed a larger mean improvement for 1 mg, the values overlapped statistically at the 95% confidence level.
http://www.physics.upenn.edu/facultyinfo/frankel/papers/propeciafda2/index.html
