The P2Y12 inhibitors are frequently used in the management of ACS and other coronary syndromes. They have some clinical quirks you need to be aware of and I will highlight some of my most important (not ALL inclusive) warnings for the P2Y12 inhibitors.
Clopidogrel
Clopidogrel (podcast) is one of the most cost-effective therapies in the group and it is well known that it is a prodrug. Prodrugs are administered as an inactive compound and become activated by the body’s biochemical changes. Specifically, CYP2C19 is the primary enzyme responsible for this activation. Clopidogrel carries a boxed warning for patients who are CYP2C19 poor metabolizers. (Pro tip – know this for pharmacology and board exams throughout your career!)
In addition to pharmacogenomic considerations of clopidogrel, drug interactions are a concern with regards to CYP2C19. I’ve covered the omeprazole clopidogrel interaction in a previous post if you’d like a little more background on this. In addition, I’ve also covered numerous other CYP2C19 interactions.
Ticagrelor
One critical item to consider with ticagrelor is aspirin use. Ticagrelor carries a boxed warning for dosing related to aspirin when used in combination. More specifically, the effectiveness of ticagrelor can be reduced in patients taking more than 100 mg of daily aspirin. This is a very critical patient education point because I still occasionally have patients who want to use aspirin for analgesic purposes. Be sure to always ask about OTC use!
Prasugrel
Prasugrel has specific warnings for use as well. Bleed risk is an issue with all of these agents, but prasugrel carries a specific warning with regards to age. This medication is generally not recommended in patients 75 years of age or old due to intracranial bleeding and fatal bleeding risks. It should be noted that it may be considered in higher-risk MI situations but this is going to be a risk versus benefit clinical decision.
In addition to the age considerations, be sure to assess if patients have a history of TIA or stroke. This medication should be avoided in patients who have had either of these issues.
There you have my most important warnings for P2Y12 Inhibitors. You can rest assured that you will see these medications used in practice and they will no doubt come up on exams throughout your career!
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