Valacyclovir Pharmacology

Hey all, welcome back to the Real Life Pharmacology Podcast. I'm your host, Eric Christensen. Definitely go check out reallifepharmacology.com, go snag your free 31-page PDF on the top 200 drugs. Great little study guide if you're taking pharmacology classes and or just looking for a little refresher in your clinical practice as well. But yeah, go snag that for free. All along, get updates when we got new podcasts out and stuff like that too. So very kind of neat resource that you can get your hands on that no cost to you there. All right, so the drug of the day today is Val Aciclivir. Brand name of this medication is Valtrex. I have covered aciclivir in the past, which definitely has some similarities, but there are some differences here as well. First, I wanted to mention Val Aciclivir. It is in effect a pro drug where the component itself is actually converted pretty quickly by the body into aciclivir, which has anti-viral type activity. The most common indications I see this medication used for varicella, zoster infections, herpes, simplex viruses, cold sores, as well as genital herpes. Both those, it will have some activity there. It has been shown in studies to have some benefits there. I have seen it used longer term as well to prevent, not just to treat as short term therapy, but to prevent or suppress herpes infections in the longer term as well. Most commonly I would say that's going to be done in patients that don't have a great immune system. So maybe patients with HIV or something along those lines. Mechanistically, so if we think about Val Aciclivir getting converted to aciclivir, aciclivir basically gets phosphorylated to a triphosphate form, which then interrupts viral, interrupts DNA synthesis and ultimately interrupts viral replication. Now if you remember, the virus naturally wants to use deoxaguanacine triphosphate, but DNA polymerase will incorporate aciclivir triphosphate into the viral DNA, which then prevents that viral replication, basically interferes with the process of the virus replicating by interfering with that DNA polymerase. Alright so adverse effects. GI upset I would say is the most common one I've seen in clinical practice. Drug can be taken with or without food. I typically recommend just doing it with food. So we avoid the risk or at least reduce the risk of potential GI upset if we do it with food there. Rarely there can be some CNS changes, delirium type symptoms, confusion, hallucinations. This is definitely going to be more problematic or has a higher likelihood of occurring in our elderly and/or those with poor renal function, which oftentimes our renal function declines over time. So poor renal functions sometimes goes hand in hand with as a patient ages. Other adverse effects, rare increases in liver function tests. Now in the short term, a very acute course of valiciclivir, 10-day course or something, it's probably not something I'm crazy worried about. You might look at patient's past history. Do they have issues or concerns that may cause you a little hesitation, like liver toxicity in the past or something that is something to keep tabs on? Probably more likely to run into issues if we're doing a suppressive therapy. And that's really probably where we're going to more closely monitor those patients over time, making sure those LFTs are remaining okay, maybe looking out for other liver toxic medications and things of that nature. Let's touch on kinetics here a little bit, kind of tacking on to the adverse effect profile. So aciclivir is primarily eliminated in the urine. And as I mentioned, central nervous system adverse effects may be a little bit more likely in patients with poor kidney function. And as you can expect, aciclivir being primarily eliminated through the urine, as that kidney function gets worse, we basically excrete less of the drug out through the urine. And it can start to accumulate and cause some of those issues. So definitely important to think about the pharmacokinetics of aciclivir and valley aciclivir and recognizing that this drug is eliminated pretty extensively through the kidney is important because it can't accumulate for sure. Administration, so this is probably the biggest difference between valley aciclivir and aciclivir or at least the biggest clinically significant difference. Valley aciclivir of Valtrex is dosed twice a day, which is obviously much nicer than aciclivir, which is given usually in the range of three to five times per day. So keeping patients on schedule, patient adherence, so very important as we add more and more medications throughout a patient's day, the likelihood that they stay on top of those medications, take them all appropriately and on time as they should get worse as we add more and more doses to that regimen. So that's probably one of the biggest differences in clinically significant advantages of Valtrex or valley aciclivir is that it is less frequent dosing. Monitoring parameters, I mentioned the issue with LFTs potentially there. Also we're going to obviously monitor renal function particularly if we're running into issues, but oftentimes renal function, LFTs and there are some rare CBC complications that can happen. These are labs that are very routinely checked in patients over time. Now younger patients, they might not have labs on file for a significantly longer period of time. Any geriatric patient that's on a few medications for blood pressure, diabetes or just about anything, we're checking renal function and liver function and CBC on a pretty regular basis anyway. But it is important to note that particularly I get more concerned with longer term therapy. Those are something we would check out. In the shorter term, obviously if you identify issues, if there's clinical symptoms indicative of any sort of liver impairment, obviously you're going to take a peek at that and look at those labs there. All right, so let's take a quick break from our sponsor and we will wrap up with drug interactions. If you're in the market for pharmacist board certification study material like BCPS, BCGP, Amidatory Care or Board Certified Medication Therapy Management exam, definitely go check out Meded101.com/store. If you're a student, we've also got NAPLIX links there as well to content over at rxgrad.com. So definitely go follow the links at Meded101.com/store. If you're a healthcare professional, just looking to learn a little bit more about medication management. Some of the clinical common sense things that we look at when reviewing medications, monitoring medications, definitely go check out Meded101.com/store. Got a growing list of books and resources, drug interactions, also free audible books. If you've never tried an audible book, go take advantage of that. You can get an 8 to 10 hour free book on clinical pearls, case studies, drug interactions, whatever you're interested in. Your first book from audible is free. So we've got all those links to those resources. sources at metad101.com/store. All right, so finishing up on drug interactions, I would say there's not a ton of clinically significant drug interactions with Valley cyclovir. So that's definitely a nice thing there. I think about additive adverse effects. So liver toxicity, I mentioned there. Also, mild sip-1A2 inhibition can happen from Valley cyclovir. And if you remember some of those agents that are metabolized by sip-1A2, probably the two most common examples I've seen used in clinical practice, tizanidine and older skeletal muscle relaxant, and then clasoping, which is an anti-psychotic, definitely notable for agranial cytosis and other boxed warnings as well. So those two, I would say it's probably not strong, strong clinically significant, but it is there in concentrations of tizanidine or clasoping could go up. sip-1A2 also the offlin, I did want to mention, it's been a really, really long time since I've seen anyone on the offlin because there is so many drug interactions and adverse effects and risk for toxicity. And we've got a lot safer medication options in COPD and other respiratory disorders that we would use the offlin for. So again, it is broken down by sip-1A2, but the likelihood that you see a patient on that medication is pretty, pretty low. And then the last thing I did want to mention with a valet cyclover is you've got to think about live vaccines, particularly live vaccines that are viruses. So the varicella vaccine, for example, if you've got a patient taking valet cyclover, it could interfere with the response to that vaccine. You may not get quite as robust a response. So definitely important, I think, to remember that, doesn't happen incredibly often, at least in my practice, that you run into that. But think about those live vaccines, particularly with varicella, because valet cyclover can be used in that setting to help blunt that type of infection. So as you can imagine, it also might blunt the effects from a live vaccine that requires replication and all that sort of stuff. So I think that's going to wrap it up for today. If you enjoyed the podcast, do us a huge favor, help us grow the audience, share us with colleagues, friends, email lists, serves you're on. 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