Prasugrel saves Clopidogrel???

You gotta love it. The other day I was talking to a pharma rep, yes I do speak with them.....and they were all excited about Effient (generic name Prasugrel).

What are these medications and why was the Pharma Rep excited?

Well, you see Plavix(generic name Clopidogrel) which is one of the top 3 selling medications in the world is given to people who have had a stroke or heart attack. This medication is given to prevent another heart attack or stroke......

Also, this medication is given to people who have received stents in their coronary arteries. This is to prevent the stents from clogging up with platelets.......sort of a Drano in a pill so to speak.

It is also given to people who are having an acute heart attack.

These 2 medications are blood thinners. How do these thinners work? They block platelets, in a way similar (but not the same) as Aspirin.

Why was the Pharma Rep excited?

1) Prasugrel is just about ready to be FDA approved for use

2) Prasugrel has a study called Triton-TIMI 38 which shows it is better than Clopidogrel with outcomes

3) 2 studies just came out last month in the New England Journal of Medicine and one in the British Journal Lancet which show that up to 1 in 3 people taking Clopidogrel(Plavix) may have little to no effect from the medication and are at 300 times more risk for ANOTHER heart attack, stroke, or stent clogging by platelets.......And another one this month in the European Heart Journal!!

4) Another study came out showing that Plavix has no effect in patients who are on proton pump inhibitors. Drug Drug interactions are a big deal.....

Why is number 3 a BIG deal? Because it is a polymorphism in CYP 2C19 which reduces proper conversion of Plavix to its active form.

This IS PERSONALIZED MEDICINE!!!!!

We can test patients, avoid a medication or perhaps increase a dose according to genotype and ultimately change the risks of being a poor metabolizer......

Why am I not so HOOO RAAAHHHH for Prasugrel?

Guess what? Prasugrel ALSO requires conversion like Plavix..........it just uses another CYP enzyme.....

What's that you say? Maybe that enzyme isn't screwed up in 1 in 3 people.....

But it is at least present in 7-10% of certain populations and as high as 83% of African Americans!!! I think 83% is pretty high.....what one in three? 33%?

Well, that enzyme is CYP 3A4. Does that sound familiar to anyone? CYP 3A4 is required for some STATINs to be metabolized as well as some immunosuppressants.......Oh and as for drug, drug interactions from CYP3A4 inhibitors....

Here's the list

amiodarone, amprenavir, cannabinoids, cimetadine, clarithromycin, clotrimazole, cyclosporin, delavirdine, diltiazem, ethinylestradiol, erythromycin, fluconazole, fluoxetine, fluvoxamine, indinavir, intraconazole, ketoconazole, metronidazole, mibefradil, miconazole, nefazodone, nelfinavir, nicardipine, norfloxacin, propafol, quinine, ritonavir, saquinavir, sertraline, troleandomycin, verapamil, zafirlukast

The ones that I bolded are medications I have prescribed in the last month......

Looks like we may have a teency Weency reason to be less exuberant......

Here's what I think. The same thing that they found with Plavix, will also be the case with Prasugrel.......

Which means.......We should stop dosing medications without knowing the patient's freaking genotype.....what the hell is wrong with these knuckleheads!!!!!!

The Sherpa Says: If Lilly was wise, they would release these "trade secrets" and let us know how many of their patients in the private trials failed therapy and were CYP3A4 poor metabolizers.....Now OFF to the PMC Clinical Science Committe meeting!