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Sacubitril/Valsartan (Entresto) Pharmacology

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I cover sacubitril/valsartan (Entresto) pharmacology, adverse effects, and drug interactions.

Hey all welcome back to the real life pharmacology podcast i’m your host pharmacist eric christensen thank you so much for listening today as always go check out go subscribe and snag our free 31-page pdf on the top 200 drugs a great little resource just for brushing up on your your knowledge uh preparing for board exams um just a great

Little resource i put together personally uh with a lot of my you know clinical experience and and sharing things that you actually see out in practice as well as things that definitely show up on board exams and pharmacology exams and things like that so again go subscribe we’ll get you updates when we’ve got new podcasts available as well

All right so let’s talk about the drug of the day today and that is sacubitril valsartan brand name of this medication is intresto it is a combination medication so let’s start with the easy one first so valsartan uh if you go back through the list of podcasts i believe i have covered uh arbs specifically so i talk a little bit more about that that mechanism of

Action in there you know also you know that kind of works on the same pathway as uh ace inhibitors so definitely a lot of similarities between arbs uh and ace inhibitors uh through their adverse effects as well as kind of the mechanistic pathway there so again i’ll refer you back to those episodes uh to talk more specifically about the the details between the

Mechanism of action there now the other drug is a relatively uh newer drug to the market compared to arbs and sucubatrill is actually classified as a neprilasin inhibitor some pronounce it nepalison uh this enzyme basically breaks down uh what are called natriuretic peptides okay and so by inhibiting this enzyme that breaks down those peptides that promote fluid

Loss and things like that we’re going to end up with more of these peptides hanging around so the end result is more naturetic peptides around it’s going to promote fluid loss vasodilation and ultimately lower blood pressure now these things can definitely be helpful and have been shown to be helpful advantageous for patients with heart failure and specif more

Specifically reduced ejection fraction heart failure and that’s where you’re going to see this drug used primarily at least at this time so remembering that mechanism can definitely help you recall how it’s going to benefit a patient with heart failure who typically has you know risks from elevated blood pressure and fluid retention things like that so a drug

That you know i’ve definitely seen more and more use of over time here but there are definitely a few clinical quirks that we need to monitor there as well so let’s get into side effects a little bit so with the valsartan component we can think about some of the arb adverse effects so you’ve got hyperkalemia possible renal impairment issues uh angioedema uh

You know obviously this drug is gonna lower blood pressure so uh there is a point obviously where too low blood pressure is not a good thing for some patients so um important piece of the monitoring parameters as well as potassium and we’re going to monitor creatinine and renal function there as well so very very important things to to look out for when using this

Medication a couple other things of note angioedema is a risk you know with this combination just like it is with with aces and and arbs when they’re being used alone and arms you know valsartan in this case is contraindicated in pregnancy so that’s an important thing to to recall as well but you know patients with heart failure and reduced ejection fraction

Generally they tend to be older but there may be certain circumstances where you may see use in younger patients but by and large most patients are going to be older that are on this medication uh i wanna talk specifically this is a little clinical quirk that comes up i’ve definitely seen it in board exams and things like that so ace inhibitors are one of the

Drugs of choice in heart failure with reduced injection fraction however when we put a patient on intrestos a cubitrille valsartan we absolutely should not use or continue the ace inhibitor with this medication so this is definitely something that comes up in practice because patients will be on a beta blocker they’ll be on an ace inhibitor and you know if we

Want to try to improve mortality or whatever we’re trying to do with the intresto we want to switch them over we have to remember to manage that transition so there is a recommended 36 hour washout period with an ace inhibitor before we start succubatural valsartan so again very very important to remember that patient on an ace inhibitor a 36 hour washout period

Before we start intresto and the reason for this is the evidence has shown that there’s a significantly uh greater risk of angioedema when they are are used together so definitely an important thing to remember important thing to ask patients about if you’re you know a pharmacist or a nurse helping a provider out just making sure that everybody’s on board and the

Patient understands what they’re supposed to do and when they’re potentially supposed to start taking this new medication and when they’re supposed to stop their their ace inhibitor all right dosing or just touch on it briefly because there’s a little bit of quirky stuff there so usual initial starting dose in patients not on an acer and arb is 24 milligrams of

Sacubitril with 26 milligrams of alcohol and that’s twice a day uh and again that’s if they’re on you know very low dose acer arb or not on an acer or orb at all if they’re greater than 10 milligrams of an allopril equivalent per day then we can start at the higher dose 49 milligrams is cubitrol 51 milligrams of valsartan twice a day so dosing is kind of quirky

They don’t fall on on even numbers um so that’s that’s i think an important thing to to kind of note and remember and is definitely unusual um but from there obviously we can titrate up to the potential max of 97 milligrams and 103 again respectively to cuba trill and valsartan uh twice a day so you know it is a bit of a disadvantage having a twice daily heart

Failure medication um given the fact that many heart failure patients are already taking several medications so but again very important to remember that quirk about ace inhibitors and then also remembering that dosing um if a patient is already on an ace inhibitor because we don’t want to slam them too much with too much blood pressure lowering and they’re not

Used to that so important things to remember about dosing and starting and things like that all right let’s take a quick break from our sponsor and we’ll wrap up with drug interactions if you’re in the market for pharmacist board certification study material like bcps ambulatory care geriatrics psychiatric exam mtm exam or the naplex go check out

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To enjoy and benefit from all right so let’s take a look at drug interactions and there are definitely some things to to think about so um you know ace inhibitor and another arb on board that’s definitely one of the first things i’m i’m kind of thinking about i i talked about that already so i’m not going to go into more detail there obviously blood pressure lowering

Medications you know like cinnamon for example in in parkinson’s disease kind of comes to mind could have that additive blood pressure lowering effect on top of entresto hyperkalemia wrist so you think you’re you know trimethoprim your spironolactone adding those on top of valsartan could definitely raise potassium levels to to an unacceptable level potentially

And then you’ve got of course renal risks whenever you use an arb we got to think about you know diuretics and nsaids uh those can all kind of work together potentially in a negative way to increase the the risk of renal impairment so definitely really really important to you know minimize that risk and obviously monitor renal function uh by you know minimizing

The use or avoiding uh potential drugs so again at heart failure uh you know you probably are gonna have a patient on a loop diuretic potentially with you know succubatro valsartan and that’s something we can can monitor and follow but if somebody has issues with pain things like that you know headsets probably not going to be the safest choice that we can use

In somebody with heart failure as well as being on an arb and a diuretic for example might greatly increase their risk for uh renal impairment there and then one last one that i wanted to mention is is arbs you know valsartan here specifically can increase the risk for lithium concentrations to go up so if you know you’ve got a patient on lithium it’s always

A good one to kind of double check and look up and just run the drug interaction screen if you see somebody on lithium and sure enough you know arbs in this case or valsartan in this case can raise lithium concentrations potentially so again we’re going to keep an eye out for lithium toxicity all right so i think that’s going to wrap it up for today i hope you

Enjoyed this podcast found it helpful if you’d be so kind and leave a rating review on itunes or wherever you’re listening that’s certainly greatly appreciated new book is just out perils of poly pharmacy so you can go check that out on amazon also that link is is going to be right at store great book for anybody interested in geriatrics and how to

Reduce medications and a lot of the complications that go along with polypharmacy so that is definitely uh hot off the the presses so to speak there and then of course sign up reallife go take advantage of that free pdf and then we’ll also get you updates when we’ve got new podcasts available you can track me down met education 101 or

Linkedin is probably the social media platform i am most active on again eric christensen pharmd bcgp bcps i’m going to sign off for today thank you guys so much for listening uh take care hope you have a great rest of your day

Transcribed from video
Sacubitril/Valsartan (Entresto) Pharmacology By Eric Christianson