Plavix allergy… can I use prasurgel?
I mean, your first reaction would be no, right? This question was posed by a cardiovascular physician as I was staffing in the heart center one day. I gave him a quick, “can I call you back?” and hurriedly looked up the information.
Going back to pharmacy school, we all know- prasurgel is part of the thienopyridine class, more the P2Y12 receptor antagonists that irreversibly inhibits ADP from activating platelet formation. Clopidogrel is most often used as well due its documentation in clinical trials and ticlopidine is also approved, although it can cause neutropenia. Cangrelor and ticagrelor were in phase III trials when I studied them.
When I was in pharmacy school, prasurgel was in its “investigational stages” when I learned it- the Triton TIMI-38 trial had just been done, showing that prasurgel had less ischemic effects but also more significant amount of fatal bleeding in patients with acute coronary syndrome (UA, NSTEMI, STEMI) with scheduled percutaneous coronary intervention.
The Triton TIMI-38 trial showed that prasurgel’s inhibition of platelet aggregations was significantly greater than that of clopidogrel. But it led to more significant amounts of bleeding- specifically with those individuals with a prior stroke. The use of prasurgel over clopidogrel for those over 75 showed no difference. And the other difference I was interested in? The study did not mention the use of prasurgel in those with clopidogrel allergies.
You would think, allergy to clopidogrel, thus, allergy to prasurgel. Yes, same class….but totally different metabolisms. Clopidogrel is much more reliant on CYP2C19 for its activation from inactive parent drug to active metabolite, while prasurgel is less reliant on CYP2C19 and more on CYP3A4 and 2B6….
And then there’s the question, is prasurgel even that efficient or does it even cause significant hemorrhaging? Or was an incorrect dose given? After the Triton TIMI-38 trial was released, one of the patent holders of prasurgel released a FDA warning letter, stating that the dose used in the trial was 2.5 times more potent than that of clopidogrel used (60mg LD/10mg MD versus 300mg LD/75mg MD, respectively), that metastatic tumors were seen, and that the timing of the doses being given were off and so on (read more here).
So back to the question. Currently, there are no studies out that test the use of prasurgel in those with clopidogrel allergy. And that’s what I told the physician- no studies have been done, it’s a newer drug, and they are part of the same class, although their mechanisms to their active metabolites are different (which yields the question- could clopidogrel allergies only effect certain ethnic groups?).
As pharmacists, we try our best to answer questions like that posed above. I wish I could have given him a definite answer..but with no data out there (or is there? And I just do not know about it?), I just presented the facts. We present the facts and hope that the physician and staff make the right decision in the future……