cephalexin pharmacology, adverse effects, drug interactions

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Today I'm going to cover some SSRI drug interactions, so there's plenty to pull from. I've got some specifics on specific SSRI's that have some interactions as well as kind of some general interactions I wanted to cover. So we're going to go through that here. So number one, the biggest thing that comes up in practice regarding SSRI's and serotonergic agents is the risk for serotonin syndrome. Now, serotonin syndrome, it's a very rare situation. 

You can get hyperthermia. You can get some elevations in cardiac function, such as tachycardia, for example. So this is a very, very significant drug interaction risk, but again, it's not incredibly common. But I think it is important to pay attention to. SSRI's can cause this on their own, obviously, but we can increase the risk of this happening by adding other medications to it. So I've got a list of drugs that have serotonergic activity that you definitely need to look out for and pay attention to. 

So linezolid is one that definitely comes to mind. It is an antibiotic for infection, most commonly used for MRSA, may be used for VRE as well. And this drug has MAOI activity, and it is recommended to avoid the use of linezolid with SSRI's. I also want to say Maois themselves. So these are older antidepressant type agents. In clinical practice, I don't see them used very often at all. But if you do have a patient on an MAOI, take that risk for serotonin syndrome seriously, it definitely, you know, can happen, and it is a contraindication to using Maois with SSRI's. It's recommended to discontinue an SSRI at least two weeks before starting an Maoi. 

So we really want kind of that total clearance of the drug from the body before we initiate an MaOi, or at least that's what's recommended. With that said, it's important to understand some of the kinetics of the SSRI's. And a drug like fluoxetine, you may want that washout period to be even longer. Fluoxetine's got a really long half life in the class of the SSRI's there. All right, so let's talk about some other medications in our first drug interaction with SSRI's. So drugs that have serotonergic activity that aren't in the SSRI category. 

So, obviously, you've got other antidepressant depressants like snris, tcas, tramadol tryptans are migraine medications that can have some serotonergic activity and may increase kind of that cumulative risk of serotonin syndrome. Busparone has some mild to moderate serotonergic activity. It's an anxiety medication. Some stimulants may enhance serotonergic activity. Dextromethorphan is a commonly used cough suppressant that can cause some issues, potentially, or cause some cumulative serotonergic issues. And then an herbal supplement type medication, St. John's wort, as well. So, again, not an all extensive list, but I wanted to highlight some of the ones that I have seen come up in practice. All right, let's move on and talk a little bit about QTC prolongation. So, citalopram. Escitalopram are the highest risk agents within the SSRI class. And the drug interaction that I've seen, most common is with omeprazole and or ezmeprazole. So those are prilosec and nexium. 

These drugs inhibit CyP two C 19, which can ultimately increase the concentration of citalopram, and to a lesser extent, probably escitalopram. So citalopram actually has dose limitations. As patients get older. No more than 20 milligrams is recommended with citalopram. And, of course, if they're on a PPI, we also want to recognize that that's going to increase the concentrations of that drug, and we may put a little more emphasis on that, even in those patients. 

So, definitely a common drug interaction I've seen in my geriatric patients, for sure. Omeprazole and citalopram. That's definitely a good one to remember. Third drug interaction I wanted to mention. SSRI's will flag on drug interaction. Screens as far as antiplatelet activity. So essentially, there is definitely at least a theoretical risk of increasing the chances for bleeding. That risk may increase as we use drugs that have antiplatelet or anticoagulant activity. So, you know, aspirin, clopidogrel, anticoagulants like apixaban, warfarin, nsaids have antiplatelet activity as well. So these drugs, in combination with an SSRI, may increase that risk for bleeding. So is it an absolute contraindication? You know, absolutely not. I see these drugs definitely used together quite frequently, but there are some questions that you should at least consider when considering this drug interaction.

 So, you know, are both drugs necessary? What are the dosages that we're on? Are we on multiple medications that can increase the bleed risk? What are relevant labs? So what is their hemoglobin? What are their platelets? Are those looking okay? Are they reporting bruising and bleeding? So monitoring the clinical signs and symptoms, really, really important length of time have they been on these medications? You know, they've been on baby aspirin and, you know, sertraline, 25 milligrams for 20 years, and there's never been an issue, then I'm probably less likely to be concerned about that drug interaction. And then, of course, medical history. 

Does a patient have bleeding history? Do they have peptic ulcer disease with GI bleeding risk and that sort of thing? So those are some questions that I definitely look into and ask when I'm considering this anti platelet type drug interaction. All right, number four, paroxetine inhibits Cyp two d six, as well as fluoxetine. So again, Prozac and Paxil are the brand names there. So this inhibition of Cyp two d six can increase the concentrations of numerous medications. So aripiprazole is an antipsychotic sometimes used in depression augmentation. Adamoxetine, medication used in ADHD. Metoclopramide is a drug used for gastroparesis. Concentrations of this can increase and obviously increase that risk for movement type adverse effects. Risperidone, another antipsychotic where concentrations can be increased. So lots of meds just threw out a few of the common ones I've seen in practice that can have their concentrations increased. 

Important to pay attention to toxicity risk there. Now, there is one other interaction, and I'll call this number five. And that is because proxetine and fluoxetine inhibit Cyp two d six. So tamoxifen is a pro drug, and its effectiveness ultimately can be reduced so this drug is activated by Cyp two d six. And if we're blocking that action of Cyp two, d six with paroxetine or fluoxetine, that can ultimately reduce the effectiveness of tamoxifen. So tamoxifen being an agent, obviously used for breast cancer. Very, very important drug interaction there. Alright, number six, let's talk fluvoxamine. This is a very, very important medication. If you ever have a patient on fluvoxamine, brand name luvox, you've got to run a drug interaction screen. So number six here is Cyp one, a two inhibition that fluvoxamine has. Clozapine is a good example of a drug that is broken or. Excuse me. Yeah, broken down by Cyp one, a two. So by inhibiting Cyp one, a two, we can potentially increase the risk for clozapine toxicity. Another action fluvoxamine has, number seven would be the number I'm on for drug interactions here. Cyp two c nine that can inhibit, excuse me, with inhibiting cyp two c nine that can increase warfarin concentration. So we need to monitor that INR, monitor for bleed risk with that medication. And then number eight. Eight, I wanted to mention Cyp two, C 19 and Cyp three a four. So cyp three, a four. Specifically, we can increase a medication like carbamazepine, that is a medication used in bipolar disorder, seizure disorder, sometimes used for trigeminal neuralgia. 

But we can increase the concentrations of this drug when we use fluvoxamine in combination with it. CYP two C 19. Our other one I wanted to mention is our number eight drug interaction in combination with CYP three, a four inhibition, phenytoin. So another seizure medication that has a narrow therapeutic index window. So kind of a tight balance between therapeutic dosages and toxic dosages. But anyway, fluvoxamine can increase the concentrations of phenytoin. So something you definitely need to monitor closely. Again, highly recommend if you've got a patient on fluvoxamine to run a drug interaction screen prior to starting new medications and also in reviewing a patient's medication list. All right, the last two we've got number nine, probably not as significant, but I did want to mention it. So sertraline is partly broken down by Cyp three, a four. So if you've got a Cyp three four inducer, that's going to lower concentrations potentially of sertraline, and if you've got CYp three, a four inhibitor on board, that's going to potentially raise concentrations of sertraline now, again, I mentioned that the clinical significance of this probably not as great as some of the other interactions I've mentioned previously, but I think it is important to pay attention to. So reason it's not as clinically significant is because sertraline is broken down by a bunch of different enzymes. So ultimately the drug can typically use an alternative pathway. But I think it is important to note that if you notice some clinical differences, maybe a patient's depression getting better or worse, depending up if we're using an inducer or an inhibitor, that's certainly something to look out for as well as signs and symptoms of toxicity.

 If you're using a CYP three, a four inhibitor. All right, number ten, I wanted to mention you will see bupropion, occasionally used in combination with the SSRI's and bupropion, inhibits CYp two D six. So proxetine fluoxetine, which is broken down significantly by Cyp two D six. Those concentrations can significantly go up if we add bupropion to a patient who's already taking these medications. So paying attention for signs and symptoms and toxicity is definitely a really, really important thing to do here. Alright, well, I think that's going to wrap up the podcast for today. If you want that free PDF on the top 200 drugs, go to reallifepharmacology.com dot. All it's going to take is an email for you to get access to that. Then we also get you info on when we've got new podcasts available as well. Also support meded 10 one.com store if you're taking any pharmacist board certification exams. If you're looking for study materials for Naplex and BCPs, don't hesitate to go check out met ed 10 one.com store. We've helped thousands of pharmacists pass their board exams and help them prepare for that as well. 

So go support the sponsor there. Leave us a rating review on iTunes or wherever you're listening. We greatly appreciate that helps us grow the podcast and of course, share us with friends, colleagues, anyone who may benefit from more pharmacology education. If you want to track me down or got suggestions comments, check me out at mededucation 10 one mail.com or you can connect with me on LinkedIn as well. Eric Christensen, Pharmd BCPS BCGP thank you all so much for listening. Take care and hope you have a great rest of your day.