And thus it begins: Xyzal
The money being wasted on pointless research, that is. Xyzal (levocetirizine), is beginning to have some money spent on research proving that it's a good drug. I have no doubt it's a good drug. They've isolated the active isomer and decided to market it since the patent on Zyrtec (cetirizine) is running out.
Let's review, SAT-style:
Zyrtec:Xyzal::Claritin:Clarinex
Expect Zyrtec to go OTC as a means of ensuring continued profitability through marketing. (More people buy brand name Tylenol than the generic — same story for Claritin.)
Here's the bottom line: everything that Zyrtec works for, Xyzal will work for, and vice versa. Same side effects, too. And because this is so, you will never see a head-to-head study comparing Xyzal with Zyrtec, because the results will prove that it's just a waste of money. Like Clarinex. Oh sure, there will be a few isolated cases where Xyzal is 0.5% better for 0.1% of the study population, and these studies will be trumpeted, but remember that they're actually meaningless. You'll also see studies that show Xyzal is effective for some obscure condition that Zyrtec was never studied for. Just remember that this is done to make Xyzal seem like something more than a me-too drug, and that if someone bothered to spend the money, Zyrtec would work just as well.
So if you like to waste your time doing PAs or you feel an insane need to throw your patients' money away, prescribe Xyzal. Otherwise keep on using Zyrtec.
Claritin + Singulair = ???
Merck and Schering-Plough are in bed together, again. (One wonders if a merger will be the climax of their collaborations somewhere down the line?) This time it's their new combination of loratadine (Claritin) and montelukast (Singulair) which was accepted for review by the FDA on August 28. In my opinion, it's only a matter of time before the two companies are given the green light to start selling it.
This combo is not unlike their Vytorin arrangement, which is actually a pretty decent combination both therapeutically and financially: Vytorin is no more expensive than Zetia by itself, which makes it a good deal for consumers and insurers alike. (And there's also the more mundane fact that there's one less pill to take, and the fact that ezetimibe is of questionable value when prescribed alone.)
Because Claritin is now OTC, it is simultaneously more and less valuable to Schering-Plough. Less valuable because you can't charge as much for it as you could when it was Rx-only because no one would buy it — and more valuable because you've got a potential market limited only by the number of people in the United States. I know I recommend (generic) Claritin pretty regularly. It works well for most people, myself included.
If the pricing is done following in the footsteps of Vytorin — which I suspect it will be — it'll be a nice little niche drug for the two companies, and it'll save consumers money, if not insurers. I don't ever see it being a blockbuster like Vytorin, for obvious reasons.
The inobvious
One thing struck me about this deal after some thought, and it's the new reciprocity between the two companies: Vytorin is inherently more valuable to Schering-Plough because their drug ezetimibe (Zetia) is still protected by patent, whereas Merck's contribution — simvastatin — is not. With this new drug, the roles will be reversed. I don't know what this means in terms of dollars and cents, but Merck's got to be breathing a bit easier now that they're on more equal footing with their partner.
[tags]Merck, Schering-Plough, Claritin, Singulair[/tags]
Now you Europeans can waste your money on aliskiren, too
Novartis has gotten their pointless direct renin inhibitor approved by the European equivalent of the FDA.
How utterly snooze-worthy. Now you Europeans can waste your tax dollars money on the drug, too! Hooray!
Bonus Tekturna story:
Doctor writes a prescription for Tekturna for one of his patients. (One of our drug delivery guys, actually.) Gives him a free sample card, even though he doesn't have insurance and thinks he's doing him a favor. He gets 30 Tekturna for free, and the next month rolls around. That'll be $100, please, even with the employee discount I gave him because he amuses me.
He almost shit a brick.
Remember, folks: giving patients a FREE SAMPLE is great, but it's a complete WASTE OF EVERYONE'S TIME if they are without insurance or if their insurance doesn't cover it.
Mr. Delivery Guy comes back a week later with a prescription for lisinopril, after I write him a note to give to his bonehead physician.
[tags]Tekturna, aliskiren, Rasilez[/tags]
I'm still not impressed with Tekturna (aliskiren)
One of my more popular posts has been "Do we need Tekturna (aliskiren)?". The comments have been varied, but I still stand by my doubts over its usefulness. Other medbloggers have expressed their doubts as well. And I should state right now that I think Tekturna being on the market is a Good Thing™. I am not against the drug's existence.
In fact, I'm not arguing how efficacious it is. I'm sure it works. If it didn't, it wouldn't be approved. I'm merely questioning its place in current treatment paradigms. To explain what I mean, I'm going to use a crude analogy to compare angiotensin II receptor blockers (ARBs) and aliskiren, the only direct renin inhibitor (DRI).
Think of a sink. For whatever reason, you want to keep liquid from going down the drain. Does it make more sense to keep the sink turned off, or to plug the drain directly?
Well obviously if the goal is keeping the drain dry, you'd plug the drain. This is what ARBs do. They prevent specific and non-specific binding at the angiotensin II receptor sites. Tekturna just keeps the sink from turning on and does nothing to block the drain directly. This means there's still going to be non-specific binding at the angiotensin II receptor site. (Incidentally, this non-specific binding is not merely theoretical; if it were, ACEis would be more effective as a class than the ARBs, but instead they are merely comparable.)
Back to my point: Tekturna is more expensive than the ARBs, and it will be for a long time. I don't think having aliskiren as an option is a bad thing. I just question how valuable the drug truly is with less expensive ACE inhibitors and ARBs. Sitting here, it doesn't seem to have a real niche. Would I try Tekturna if nothing else worked? Of course I would. If I were targeting the RAAS, would I reach for it as first-line therapy? Hell no I wouldn't. I'd go for an ACE inhibitor in most cases.
I'm not going to delve into the heated debates about reactive renin production and other similar topics because I suspect that the reality lies somewhere in the middle ground, as it usually does.
In the meantime, I think don't think Tekturna has a meaningful place in current drug therapy. If ARBs do not work, it is unlikely that a DRI will, either. The only time I see it perhaps being useful is if a patient cannot tolerate ACEis or ARBs.
[tags]Medicine, pharmacy, Tekturna, aliskiren, hypertension[/tags]
How Sepracor could make a buttload of money
In 2008, CFC inhalers are going away, a topic I've covered extensively here and here. That leaves Sepracor in a position to make themselves quite a lot of money if they're willing to do one thing out of the ordinary: price the Xopenex HFA MDI at or below the same price as the other HFA albuterol products. This would set up the PBMs to be receptive to making the product a Tier 2 copay, like most of the racemic albuterol HFA formulations.*
Then send out the drug reps.
In theory, levalbuterol almost sells itself. At least they won't have to resort to underhanded marketing tactics quite as much.
Will they do it? I don't know. Probably not. That would require doing things differently — like lowering the price right off the bat — and I think we all know how much Big Pharma likes to do things Their Way. Risk is, well, risky.
If I were captain of the ship, though, I'd roll the dice. The inhaler market is huge — and only going to get more lucrative once CFCs disappear — and right now, Sepracor is not positioned to be anything more than a niche player when they could easily have most of the pie.
* Cursory research indicates that some PBMs have the Xopenex HFA MDI at Tier 2 already, but most seem to require a Prior Authorization.
[tags]Medicine, pharmacy, Asthma, Sepracor, albuterol, Xopenex[/tags]
Do we need Tekturna (aliskiren)?
Thursday saw the delivery of a new Novartis drug: Tekturna (aliskiren). None of us had any idea what it was for, so we looked it up on Facts and Comparisons, and there was next to no information whatsoever, except that it is a "direct renin inhibitor" — whatever that meant.
Now that I'm home on a non-firewalled Internet connection, I can actually get real drug information. (How sad is it that I can't do this at the pharmacy?) Aliskiren:
Aliskiren is a direct renin inhibitor, decreasing plasma renin activity (PRA) and inhibiting the conversion of angiotensinogen to Ang I. Whether aliskiren affects other RAAS components, e.g., ACE or non-ACE pathways, is not known
I'm sure you could play games targeting specific points and pathways in the renin-angiotensin-aldosterone system until the cows come home, but how many of them will be meaningful? Medscape has an article comparing, contrasting, and using Diovan and Tekturna in parallel:
Do we need Tekturna? Would not an ARB plus a diuretic do a better job? There are benefits to combining an ACEi with an ARB, that are fairly well understood. Is Tekturna going to create some sort of super trifecta?
I'm thinking not. Combining an ACEi with an ARB does a couple of things. First off, ACE inhibitors only stop the conversion of angiotensin I to angiotensin II. Blocking the pathway there does nothing to stop any non-specific binding to the angiotensin II receptor sites. ARBs block much of this non-specific binding because the receptor sites themselves are blocked. However ACEis also block the breakdown of bradkinin (which is broken down by ACE) which leads to greater vasodilation, which is why ACEis and ARBs are usually similar is study results. Bradykinins, of course, are a double-edged sword: they may contribute to vasodilation, but they are also responsible for the dry cough and angioedema associated with ACEis.
I don't see how aliskiren is going to add to this. Is there component to the RAAS that I'm not thinking of? Is it not better to attack a problem from many different angles instead of hitting the same pathway three different ways?
The NEJM on HFA inhalers
As a followup to my post the other day…
The NEJM concludes — along with the rest of the world — that HFA albuterol formulations are more expensive than their CFC counterparts. The article (subscription required) delves into some of the differences between the various HFA formulations as well as the differences between CFC and HFA albuterol.
The article doesn't talk much about ProAir HFA, which I find a bit strange, especially as it has captured 60% of the HFA albuterol market. Unrelatedly, it seems that concentrations of albuterol are slightly higher with HFA than the CFC versions, despite the smaller plume.
Here're some semi-relevant differences between Ventolin HFA and Proventil HFA, emphasis mine:
The excipients added to the propellant formulation differ according to the brand of HFA inhaler. For instance, each puff of Proventil HFA releases 4 μl of ethanol. This small amount of ethanol will not have a discernible clinical effect, but it may be of concern for patients who for religious or other reasons abstain from alcohol. Breathalcohol levels of up to 35 μg per 100 ml may be detected for up to 5 minutes after two puffs of Proventil HFA. Unlike CFC propellants, HFA propellants may cause false positive readings in anesthetic gas–monitoring systems. The infrared spectrums of HFA overlap with commonly used anesthetic gases in the range of 8 to 12 μm. One albuterol product, Ventolin HFA, contains no excipients other than the propellant, a characteristic that may improve tolerability for some patients. However, Ventolin HFA comes packaged in a moisture-resistant protective pouch containing a dessicant and has a limited shelf life once it has been removed from the pouch. Ventolin HFAs have a greater affinity for moisture than do CFCs, which means that water vapor is more likely to enter the canister around the meteringvalve gaskets. The other approved HFA inhalers are less susceptible to moisture permeation and do not require a protective pouch.
Shelf life for Ventolin HFA is 2 months after opening, so it's a mixed bag.
A breakdown:
[tags]Medicine, pharmacy, albuterol, HFA, CFC[/tags]