FDA approves two new hrts: Endometrin and Evamist

The FDA has given new drug approval to two new prescription products that might be useful to our readership as hrts.

Endometrin


Endometrin is a 100 mg bioidentical progesterone vaginal "insert" described further as a "white to off-white oblong-shaped tablet" to be administered with a plastic applicator. Inactive Ingredients: lactose monohydrate, polyvinylpyrrolidone, adipic acid, sodium bicarbonate, sodium laurel sulfate, magnesium stearate, pregelatinized starch, and colloidal silicone dioxide.

The label indication is for fertility support, but, like Prochieve (ex-Crinone), the vaginal gel, it can presumably be used for other progesterone needs as well even though the limited data on the package insert does not discuss any use or data other than the fertility support testing done. The advantages of vaginal delivery of progesterone are mainly of interest to women taking largish doses, out of scale with their level of need, to accomplish therapeutic, rather than hormone balancing, objectives. These would include things like treating endo as well as protecting a uterus from excessive estrogen stimulation by hrt. The advantage is that more of the hormone is delivered into local circulation and systemic effects of the dose are minimized.

The 100 mg provided dose is hefty, but may not be out of line with what some women are using. Since the tablet is to be stored at normal room temp, it probably is a typical firm chalky pill. Still, it should be possible to divide it with care if some dose customization is desired. That's not likely to be entirely handy down to the 10-25 mg doses most women in surgical meno may be using to balance their hrts, however—although it could be attempted if this seems otherwise to be a good choice for a woman.

This is an approval by the US FDA; we're not aware of it being for sale in other countries, but if anyone knows differently, please let us know.

Evamist


Evamist is a transdermal spray delivery of bioidentical estradiol approved for use in menopause (that is, licensed only for hot flashes). One spray delivers 90 mcL which contains 1.53 mg estradiol; starting dose is one spray daily to the forearm but the dose may "increase to two or three sprays daily to forearm based upon clinical response" to adjacent, non-overlapping areas. "Sprays should be allowed to dry for approximately 2 minutes and the site should not be washed for 30 minutes." Inactive ingredients: octisalate (a common active ingredient in some sunscreens used to enhance skin penetration), alcohol (to dissolve the drug).

It is important to note that although the dose itself contains 1.53 mg of estradiol, that is not the amount actually delivered systemically. That delivered amount is 0.021 mg, making one spray roughly equivalent to the lowest range of patch doses and stepping up roughly at the same dose intervals as we add additional sprays. Many doctors and women don't notice this difference and mistakenly assume from the lack of response to the nominal 1.53 mg dose that a woman's dose needs are somehow much higher than typical. In fact, her response is to the 0.021 mg dose and that's the figure we need to work with in considering equivalency to other hrts.

"Application of Evamist to other skin surfaces has not been adequately studied." That means, of course, not that it won't work, but that the manufacturer didn't pay for that extra research as part of their licensing application. There is no reason to suspect that the usual other safe areas might not work although each area's absorption might vary according to the tissue and circulation present in each. The forearm typically has relatively low fat overlay and good, close-to-surface blood vessel presence, so this would provide for a faster uptake and less tissue storage than, say, the butt or belly or thighs.

The precautionary text in the package insert is pretty much standard for estrogen. Of interest in the adverse reactions table is that while nausea was sharply lower than placebo at low doses, it rose with higher doses--as one would expect in sensitive individuals using an hrt with a half-hour uptake curve. Note also that nasopharyngitis (those puzzling sinus/ear symptoms) are also present with it, especially (we don't know why) with the low dose--although that might well represent the beginning of use and the higher doses being used in women who have accommodated to estrogen use. Headaches are also seen at a higher level in the users as opposed to the control group, and we suspect that these are also the uptake-sensitive individuals. That doesn't mean, however, that this would not work for them--this was a short trial (70 days) and it could be that once stabilization occurs and normal body caching mechanisms are in place, this is less of a factor. That's no compelling reason to rule it out without trying it if it otherwise is an attractive choice for a woman.

Because the dose is delivered by a metered spray pump, dose customization would be difficult beyond the number of sprays per day. Nonetheless, a creative woman could cover some proportion of the area to be sprayed with a shield of some kind--although that's not likely to be wholly accurate (more than you'd think, though, since the sprayer is actually a bell-shaped template that fits snug against the skin to control the size of the area applied to). Trying to bypass the pump and just work with the liquid would also be tricky since the amount of spray volume would be roughly 0.135 ml and that's a very tiny amount to measure out.

One of our discussion group members has shared with us how she managed to manipulate the dose and has given us permission to share her discovery:

I did figure out how to reduce the [dose amount] from the evamist pump. The circular dispenser comes with a cover. I took an old cover or cap and cut it in half. Worked great! The "half" cover snaps right on like the full cover. There is a felt like material inside the cover and it's not securely attached so it does become loose when cut.  I'm going to take a tiny drop of glue and attach it to the inside of the cover. It needs to be there to catch and absorb the excess spray so that it doesn't drip. It might be possible to do a smaller cut or a larger cut with the cover. 
The sprays are supposed to be placed side by side but not overlapping. When using the "half cover" make sure the "open half" is placed next to the full spray or else there will be a separation between sprays. Maybe not that important but it more accurately follows the manufacturer's instructions.

No transfer of the estradiol to a partner was measured one hour after dose application, so this form is obviously more fully absorbed into the skin than gels or lotions are. "When sunscreen is applied approximately one hour after application of Evamist, estradiol absorption was decreased by 11%. When sunscreen is applied approximately one hour before the application of Evamist, no significant change in estradiol absorption was observed." The text does not distinguish between oil-based and non-oily sunscreens, but as with all transdermal hrt use, the oils used on the skin may make a difference depending upon whether they are digestible or not. Using non-oily sunscreens would probably have the lowest impact on hrt dose dynamics.

So this gives us one more retail transdermal estrogen hrt, although like all of the other retail hrts, it provides only estradiol, not the other estrogen forms that can be obtained through compounded hrts. That may or may not make any difference for a particular woman--estradiol is widely-enough tolerated that it is not necessary for most women to begin with anything else unless they have a particular philosophical preference for doing so or have prior estrogen experience to suggest a need for the less active estrogens. It is somewhat less customizable in dose than the other retail transdermal estradiols, but then, dose customization is not something that is encouraged by the FDA licensure system (because approvals are specific to the doses tested) and so manufacturers have to design packaging/delivery that thwarts dose variability and customization.