Narrator - Dr. Abel 00:00 Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. Speaker 1 00:11 This podcast is provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 00:17 This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified health care provider. Unknown Speaker 00:27 And now on to the show. Dr. Sean Kane 00:31 Welcome to HelixTalk. Episode 48. I'm your co-host, Dr. Kane. I'm Dr. Schuman, and Speaker 2 00:35 I'm Dr. Vital, and we once again have Dr. Lauren Angelo with us, because we're going to continue talking about some of those over-the-counter recommendations on common cold, nasal congestion, and cough products. Unknown Speaker 00:48 Wonderful to be here. Thank you for inviting me back. Dr. Sean Kane 00:51 Thank you again. So Dr. Angela, when we see a patient who's presenting to a pharmacy with symptoms of nasal congestion, what are some of the questions that should immediately come to our mind before we're recommending over the counter product therapy. Speaker 1 01:03 First and foremost, it's important to figure out what's causing the congestion. It can be a variety of things. The common cold, obviously, is the first thing we might think about. But could it also be the flu or what about allergies, which we'll talk about in a little bit, or even bacterial sinusitis, if the condition has been going on for some time, pregnancy is another option that can cause congestion. So we'd want to be careful in that regard. Dr. Sean Kane 01:25 And of course, you know, depending on, you know, are we trying to treat the symptoms, or, in the case of allergy, treat the cause, like our treatment can vary based on what the presumed causative, you know, reason is for the congestion in the first place, Speaker 1 01:39 it sure will. So if we can prevent it, let's do that. But if not, we'll be treating the symptoms. Speaker 3 01:43 So as always, one of the first things to look at is, you know, who are the patients that should not be referred for self care? Who are the ones that may actually benefit from going and seeing a provider for a workup? And so again, refer patients out to, you know, their provider for if they need a congestion due to the common cold and if they have a fever above 101.5°F, if they complain of chest pain or shortness of breath, symptoms that worsen despite treatment, if they continue to progress more and more and more, if you notice a chronic cardiopulmonary disease, so again, if they've already got asthma or COPD or even congestive heart failure or CHF, again, they're going to be more compromised if they're immunosuppressed, if they're infants less than nine months old, or frail patients of advanced ages. In these cases, it's best to not to not even mess around with trying to self treat, but to go ahead and refer back to primary care or EMT or something like that, to get it worked up. Dr. Sean Kane 02:34 And of course, these are in judgment too. So someone has mild congestion that happens to have mild COPD it doesn't mean that you always have to refer them, but if you think that they have a lot of comorbidities that would predispose them to a bad outcome, if it's actually influenza, then they probably do need to see a healthcare provider. Speaker 2 02:50 So just like discussed during the last episode as well, you know, we're talking about our pediatric patients too. The recommendation on the over the counter medications for a nasal congestion is still the same. The age limit is four, so they're not recommending to be using these products in those patients. However, some of the non-pharm measures, such as positioning them upright, using humidifiers and vaporizers, using bulb syringes to clear congestion, and using saline nasal drops or sprays, can be very effective as well. Speaker 1 03:21 And so if we're not dealing with all the patients Dr. Schuman mentioned, or our children under the age of four, we do have some options, which can be systemic or topical. So it's important to work with the patient to figure out what their preference might be. Oftentimes, we're looking at what we call decongestants, and so those are going to have vasoconstrictive properties, and those will help constrict the blood vessels, and those decrease vessel engorgement. And so it helps the patient symptomatically with the congestion he or she might be experiencing. Dr. Sean Kane 03:51 And you know, like you said, we can deliver these decongestants either systemically in the form of, typically tablet, or we can give it as a topical product. The systemic products come in two varieties. One is pseudoephedrine. The typical brand name for that is Sudafed or phenylephrine. The typical brand name is Sudafed PE and one of the problems here is this becomes very difficult for consumers who aren't well versed on these drug products, because they see a similar brand name. They see generic names that kind of look a little bit similar. They have, you know, a similar property to them, but from the medical side, they're very different, especially in terms of how the government views the dispensing of these products. Yeah. Speaker 3 04:30 So the Combat Methamphetamine Act of 2005 ended up leading to sales restrictions for pseudoephedrine products. As a result, manufacturers marketed Sudafed PE as a line extension containing phenylephrine. One clue that a product contains phenylephrine is that it is available off the shelf; if it is behind the counter (requires an ID), it's usually pseudoephedrine. Speaker 1 05:02 Phenylephrine, has been around for a long time. I think we hadn't been using it because it's just not as effective as pseudoephedrine, but now it's back on the shelves, as you mentioned. Speaker 3 05:12 Yeah, that's one of the interesting things, is that you're correct. Dr. Angela, pseudoephedrine is a lot better absorbed, about 90% bioavailability versus 38% and from a lot of the data, it seems to have better efficacy than the phenylephrine really, technically, is the preferred agent, as long as the individual has that identification, legal identification, and can meet the age requirements set by the state. So for example, in Illinois, have to be 18 years old and show that proof of ID to be able to obtain pseudoephedrine products. Speaker 2 05:40 And besides the age limitation, there is a milligram limitation on how much you can buy per month as well. This is basically put in place to prevent people from Breaking Bad. Dr. Sean Kane 05:51 So Dr. Angelo, given that it appears to have less efficacy, what kind of data do we have? More modern data to either support or refute its use in clinical practice? Sure. Speaker 1 06:01 So it looks like a lot of activity has been comparing phenylephrine to pseudoephedrine, given that we have these two options available, and we're torn as pharmacists as to what to do with these patients sometimes. And so a recent study that was published found that patients receiving seven days worth of either phenylephrine at doses up to 40 milligrams every four hours, which, mind you, is four times the amount. We'd be recommending 10 milligrams, usually for patients. But at that four times the dose, it had no significant change in the patient self reported nasal congestion. Speaker 3 06:35 And that was interesting, because that was a new way of looking at in the previous studies, which were done way back in the 1960s they had looked at something called nasal airway resistance. And so they would actually do this measurement of this number and whether or not there was a change in airway resistance that meant the drug was effective. And so instead, now they said, why don't we actually look at how patients feel about how they're doing? So they looked at these, now called nasal congestion scores. And so based upon those scores, they really didn't notice any kind of difference from the medication and placebo, again, even at four times the standard dose. Dr. Sean Kane 07:05 And this was a placebo trial, right? Yep. So given that we have a potentially negative trial with newer data of an agent, Dr. Angela, would you foresee the FDA reevaluating the role of phenylephrine as an agent that would be a decongestant for patients, Speaker 1 07:22 I'm not sure, but I would hope that they start looking more into this data as they're doing their OTC drug reviews. I know that process has been underway for many years as they're looking at the different products on the market and the safety and efficacy behind them, and so this is one product I would encourage groups to look at more closely. Since we do have a better product available, it's just harder to get. Dr. Sean Kane 07:44 And you know, in thinking about systemic versus topical therapies, at least for me, when I'm a patient, one of the things that I personally consider is the adverse effect profile of the systemic therapy versus the topical therapy. So some of the adverse effects like tachycardia, insomnia, jitteriness, dry mouth, headache, feeling nauseous, or even not for me, but if I were to be a little bit older, some prostate type symptoms of difficulty urinating. You know, all of these are fairly common side effects that we can see even among younger people who take, you know, the systemic decongestants. So for someone who doesn't want to experience some of these side effects. They can take a topical agent that has a much lower incidence of some of these problems, Speaker 2 08:26 and these topical agents can be available in the form of sprays, drops, or inhalers. Examples include phenylephrine, naphazoline, oxymetazoline, xylometazoline, and levmetamfetamine. Dr. Sean Kane 08:44 And the longest-acting agent of those is oxymetazoline. But you know, many of these agents are available over the counter that can be used, so looking at price and frequency of administration and things like that would be a consideration. And there Speaker 3 08:57 are a couple things to be careful of with these medications a child, even if they ingest even a small amount of one of these alpha one agonists, it could be life threatening, some serious adverse effects. And even beyond children, there's the idea, albeit maybe somewhat controversial, idea, about rebound congestion, which is also one of my favorite terms in pharmacy to say just rolls off the tongue, rhinitis medicamentosa. It's rebound congestion that could occur after three to five days of therapy, potentially, although some studies have not always shown it to occur. In general, there's a recommendation not to use topical decongestants for more than three to five days. Dr. Sean Kane 09:33 And on the packaging, it actually does say this, that longer than three days is not recommended because of this rebound congestion. Just know that it is controversial. Speaker 2 09:41 Yep, and then a similar product is used for red-eye relief treatment as well. We're not talking about eye products here, but it's also known to cause rebound redness of the eye, so you're using the product to get rid of it, but if you overuse it, the red eye comes back. And I think Speaker 1 09:55 that's an important counseling point. And so that's why we need to remember side effects and all the issues with. These agents. So when we're talking to our patients, let them know that this could happen. And so they've been warned, and they know to stop use around three days to five days for these reasons. Speaker 3 10:09 And then, just to reiterate, some of the side effects, patients with enlarged prostate, high blood pressure, closed angle, glaucoma and diabetes, should avoid using these products. I remember working over the counter, working in a pharmacy, excuse me. There was some of these over the counter products that products that were, you know, supposedly, you know, safe for blood pressure, high blood pressure individuals. A lot of times they were just anti, anti histamines in that case. And also know that I've had some patients of mine that with BPH, and there's, you know, the concern about changes in urine flow. A lot of times we have to do a kind of root cause analysis to find out it was the pseudoephedrine effect. He had been taking it recently for some of his congestion symptoms, and once he stopped taking that, his urine flow improved. And so he felt a lot better. Dr. Sean Kane 10:50 Keep in mind too, that, you know, the topical agents do have this warning about their side effect profile, but this is minuscule compared to the systemic therapy that we're giving the patient. You know, it's very common with many topical agents, whether it be an eye drop or some nasal spray, that because of the drug property itself, that we carry some of these warnings with them, but you have to think about the absorption of the product and the amount of product that could potentially get in the bloodstream and things like that. Almost always it's a lot less than what you would get from a systemic product. I think Speaker 1 11:19 because of that, we have to be careful that patients don't use both. They might not realize they are both decongestants and in the same class, and so they may take one product realize, well, it's not doing the job that I wanted it to do, so I'm going to go take something else. And now they're over treating and they might run the risk of increased systemic absorption. You will see, perhaps physicians prescribing this for patients. I've seen that, especially when patients are highly congested and going on long trips in an airplane. But that's not something as pharmacists we would recommend for over the counter use. Dr. Sean Kane 11:49 And just to cover all of our bases, women who are pregnant or breastfeeding, generally should not use decongestants. Pregnant women can sometimes have the topical decongestant like oxymetazoline, because it does have a low systemic absorption. But really, this isn't under the purview of the pharmacist. This should be in conversation with the OB for the patient, for the perceived risk of decreased blood flow, because, again, this is something that is vasoconstricting, and we don't want to vasoconstrict blood to the fetus. That would be the perceived risk. Speaker 2 12:19 Yep, and a simple non-medicated saline nasal spray could be good enough for mild congestion. Dr. Sean Kane 12:28 So moving on away from decongestants, kind of, in a related field, is the symptom of runny nose, focusing mostly on runny nose caused by allergies. But there's, you know, runny nose that can be caused by the cold, and a number of other etiologies as well Speaker 1 12:42 as we talk about some of the causes. Allergens are obviously a key part of this when we talk about response to histamine in our allergic response. And so we need to consider both indoor and or outdoor allergens. Patients may be allergic to both or one or the other. And so we think of pet dander, pollen, dust mites, mold spores, cockroaches. There's a really neat website pollen.com is one that I use regularly, and this is how you can check pollen counts in your area. If they're high and you're allergic to pollen, stay indoors if you're able to and Dr. Sean Kane 13:14 of course, other things like pollution, ozone, diesel fuels, things like that, can sometimes trigger an allergic reaction using a HEPA filter can help. This, obviously would be for indoor use only. And then there's a number of nasal rinses and wetting agents and things like that that can sometimes be used mostly for symptomatic relief. And this includes things like saline nasal rinses, neti pot things like that. Generally, these are going to relieve dry mucosa in the nose that can sometimes happen, and also help with some of the irritation from that dryness. It should help with some of the stuffiness, the rhinorrhea, the sneezing. But one important counseling point, regardless of this, is you, either you know are going to get your saline solution in a bottle that has been prepared in a clean environment, or if you're going to use something like a neti pot, it's very important that you're using distilled or boiled water. There's case reports in Louisiana of patients getting infections in their nose because of contamination in the water that causes brain lesions. So using clean water is very important, Speaker 2 14:15 like those brain eating amoebas that I've heard of, yes, terrified Speaker 3 14:18 cryptosporidium and things like that. Not, not something to mess with. Yeah, just keep Dr. Sean Kane 14:22 in mind that you're shooting this water that could potentially have bacteria in it right near the brain. So it's probably a good idea to use clean water for that. Speaker 2 14:32 So we are always looking at patients, off the bat, who should not be recommended these self-care medications for treatment of allergy or allergic rhinitis, and so we're excluding pediatric patients less than 12 years of age. Again, this limitation is a little bit higher than the less than four years that we talked about common cough and cold products. Speaker 1 14:53 And the reason they added the limit of 12 for treating allergic rhinitis is to make sure we rule out asthma. And so. Long as the patient is seen, or the child is seen, and asthma is not the cause of what's going on here, then we can proceed with treatment of allergic rhinitis. Speaker 2 15:09 Pregnant or lactating females should not be using these treatments without provider input. Again, non-pharm treatments are still okay. Symptoms of nonallergic rhinitis include little to no sneezing. Their symptoms are constant, so they're not triggered by any pollutants or any kind of triggers. Nasal obstruction is present, such as polyps. If their nasal secretions are either very watery or too thick or mucopurulent, these are signs of infection; they have recurrent nosebleeds. They've got nasal polyps that they know of. They are diagnosed with deviated septums, or they have enlarged tonsils. These are all cases for the ENT doctors. So they should always almost be referred sometimes, if they can present with symptoms of otitis media, sinusitis, bronchitis or other infections. Again, if you're leaning toward a suspicion of this as an infectious base symptoms, then they should also be referred. And again, patients who have symptoms of undiagnosed or uncontrolled asthma, or they're complaining of symptoms that are more lower respiratory base, we're worried about, again, some sort of infection here. So those patients should also be referred, Speaker 3 16:22 alright, so if we do decide that it's warranted to use one of these medications, first things we got, I think one of the first ones, is our intranasal corticosteroids. And these are great things. They can work for the runny nose, for the sneezing, for the congestion, itchy nose, if the palate itch is due to allergies, maybe even with some of the itchy, watery eyes. And the thing about them is you can even get away. Even get away with using them once a day, for example, one to two sprays in each nostril, that depends, really on your age and your severity symptoms. So if I if I'm not mistaken, there's even that couple catchy little jingles you can use to really convey the message here. Let me Speaker 2 16:57 try this. How about shake it every time you take Unknown Speaker 17:01 it. My bad. Anyone else, Dr. Sean Kane 17:03 when you spray your nose, look at your toes. And how about shake and prime if it's been a long time? All right, that sounds great. So in other words, you have to shake the medication. If it's been a long time, you should prime the medication, which means that you're spraying into the air, and when you're actually administering the medication, you should look down. Look down, look at your toes when you're actually spraying it. And along Speaker 1 17:23 with administration techniques, because this medication can potentially cause nosebleeds and irritation, there's something called contralateral hand technique, which is something we would tell patients to do. And essentially, if they're spraying into their right nostril, they would use their left hand. If they're spraying into their left nostril, they would use their right hand, and that keeps the spray away from the septum, just Speaker 3 17:43 to kind of quickly go over the agents. There are three main ones that can be used: triamcinolone (Nasacort), fluticasone (Flonase), and budesonide (Rhinocort). They all have similar efficacy. And really the differences there come down to either cost or patient's patient preference. There's even some little different smells associated with the Fluticasone may smell more like roses and has a little alcohol and so that one can can sting a little bit, for example. And then there's maybe an age limitation that differs between the three different agents. You may want to be aware of that. Dr. Sean Kane 18:14 So, you know, all of these products have warning regarding slowing growth in children. You know, this is also a very common issue and the use of inhaled corticosteroids with patients with asthma. As most asthmatics are diagnosed as children, obviously they have to grow, and when they grow and they're receiving corticosteroids, we worry about their growth rate. So it's a controversial topic, at least in the asthma community, and I'm sure it is as well with the nasal corticosteroids. Speaker 1 18:40 So this is one it would be important to limit use to short term. If a child is experiencing allergies and you are finding you want to use these products long term, make sure you do have the pediatrician involved. Dr. Sean Kane 18:52 And for any patient, it's important that they're under the understanding that they're at a high risk for infection, because this is a steroid that they're applying in their nose. Vision changes, glaucoma, cataracts, all of these are potential side effects. But as you said, Dr. Angelo, minimizing the duration of use is important to minimize the risk of these more chronic side effects. Speaker 1 19:11 And then some of the other ones that are more common, we mentioned nosebleeds already, but headache, burning or irritation can cause runny nose, sore throat, and sometimes a bit of a cough that gets back into the throat. Dr. Sean Kane 19:23 So if we're moving away from the topical agents, we want something more systemic. Let's say it's not just a runny nose, but more allergies in general. What are some of the options that we have more for systemic therapy? Speaker 2 19:35 We should use second-generation antihistamines: loratadine (Claritin), cetirizine (Zyrtec), or fexofenadine (Allegra). Avoid first-generation antihistamines because of sedation and anticholinergic side effects. Dr. Sean Kane 20:01 And when you say first generation and histamine, you're talking about like a diphenhydramine or a Benadryl, which is what you're saying. We're avoiding those to avoid some of the side effects associated with that current class. Speaker 1 20:12 Correct. Those are not first-line to treat allergies. The preference is to use second-generation antihistamines. And don't forget fexofenadine (Allegra). So we have three available over the counter. Speaker 3 20:22 Although not typically drying, cetirizine may be slightly more sedating than loratadine or fexofenadine because it is the active metabolite of hydroxyzine. The other agents are less sedating, but all may cause headache or fatigue. A benefit of these second-generation agents is once-daily dosing. Dr. Sean Kane 20:59 So how is it that we have diphenhydramine that works on the histamine receptor, that does produce sedation, but then we have these three other agents that tend to not be sedating? What is different about the second generation antihistamines versus our first generation antihistamines? Speaker 3 21:14 A lot of it comes down to the CNS penetration, so whether or not they can cross the blood brain barrier into the central nervous system, and so again, just just as I mentioned, something like hydroxyzine or even diphenhydramine can be used for anxiety because they cross to the brain. These other medications don't have as much penetration. You may see a little bit with cetirizine, and thus it may have some more sedating effect. The others do not, and thus are not really used for anxiety. They're not really used for sleep, but they still can have a role peripherally in getting rid of some of that rhinorrhea and some of that other nasal secretions. Dr. Sean Kane 21:47 So what do we expect the efficacy in terms of allergy symptoms to be similar between our first and second generation antihistamines? Speaker 3 21:54 Yeah, and again, because the main thing we're looking there is some of our peripheral secretions, that part is not really going to be affected by it. Speaker 1 22:00 Where we do see a little data is comparing cetirizine to loratadine and fexofenadine. Some think cetirizine may have slightly greater efficacy, possibly due to more CNS penetration, but clinically the differences are small. Patients should choose what works for them; if one agent fails, try another. Note that about 10% of patients may experience drowsiness with cetirizine; its effects last about 24 hours, so any drowsiness can persist that long. Loratadine and fexofenadine are labeled 'non-drowsy,' while cetirizine lists drowsiness as a possible side effect. Speaker 3 22:52 So like in a lot of places, one of the things we also need to consider is interactions with diet or other medications. For example, fexofenadine should not be taken with fruit juice (apple, orange, or grapefruit juice) because fruit juice can decrease absorption and reduce the effect of the medication. Dr. Sean Kane 23:09 So Dr. Schuman, you said fruit juice, not grapefruit juice, and you said it decreases absorption, not increases, radically. When we think of statins, we think of grapefruit juice increasing absorption, but you said the opposite. Speaker 3 23:21 This isn't due to liver enzymes but to OATP transporters. By interacting with these transporters, fruit juice reduces absorption and less drug is available to the body. Dr. Sean Kane 23:37 So apple juice, grapefruit juice, or orange juice — basically fruit juices — can decrease absorption and make the drug less effective. Speaker 2 23:45 And you still have to watch out for those with renal impairment; all three agents may need renal dose adjustment. Some agents, like cetirizine and loratadine, also require hepatic dose adjustment in severe liver disease. And then we focus a lot on the central versus peripheral. You know, h1 receptor blocking effect, but these agents have a little bit of inhibition of mast cell as well, so it inhibits the release of mast cell mediators. And that kind of leads us into the next category of agent, which is a topical mast cell stabilizer. The only product that's available is cromolyn sodium. It's a nasal spray, Dr. Sean Kane 24:21 and you might be familiar with cromolyn as a prescription inhaled product for asthma; cromolyn sodium is available OTC as a nasal spray and works by preventing release of histamine from mast cells. Speaker 1 24:38 The one caveat with this is the fact that you need to start using it before the symptoms begin. So it's recommended typically one to two weeks before your allergen exposure, is when you would start using this. And I would say the other hang-up that patients might have is that it is used three to six times per day, which can be cumbersome compared with an intranasal corticosteroid that is used once daily. Speaker 3 25:01 nice thing about it, just in kind of contrast, is that it's approved for patients ages two or older. Again, similar to where we talk about it with asthma, is that it's one that's kind of more pediatric friendly. Speaker 2 25:11 And if you want to educate the patient, how fast it's going to start taking the effect, like Dr. Angelo said, you know, needs to be used before the symptom starts. If they're using it, it takes about three to seven days for the effect to appear, and about two to four weeks of continued therapy may be needed to see clinical benefit. Dr. Sean Kane 25:32 benefit, and we do see some adverse effects. So sneezing is actually more common with this even though sneezing is often one of the symptoms that we worry about with allergic rhinitis, nasal stinging and burning, which is somewhat common with any anything you spray up your nose, is something that we could consider as well, kind of as a side note, from my perspective, you know, we have a once daily intranasal spray that is a corticosteroid available. We have a once daily oral tablet antihistamine, even some of which are non sedating. And then we have cromolyn, which is given three to six times per day and may take three to seven days to produce benefit. From my perspective, I have a really hard time unless you're very afraid of the potential for reduced adult height among pediatric patients, or if you are very sensitive to the systemic antihistamines, terms of a sedating property, I see very little role for this in the arena of, you know, any allergy type symptoms. Speaker 1 26:29 And I think when we look at the literature, the two populations that we may see this being used would be those who are pregnant and those who are breastfeeding, because it is a safe agent. And so sometimes that is considered the drug of choice depending on the obstetricians preference. Speaker 3 26:45 So as always in pregnancy, for example, you want to make sure to rule out other causes of it, such as pregnancy-related nonallergic rhinitis. If the PCP is okay with it, cromolyn sodium is often first-line for pregnancy. Speaker 2 27:11 If they must use a once-daily antihistamine, then chlorpheniramine is the first-line agent used in pregnancy, versus loratadine or cetirizine that we talked about. Speaker 1 27:22 I just, I think there's not a lot of data on using these agents in pregnancy, so we may still see some older drugs recommended because we have more historical data on them. Speaker 3 27:33 To clarify, chlorpheniramine is a sedating, first-generation antihistamine; you can get it in a short-acting formulation. Speaker 1 27:38 that in a short-acting formulation. So you can get a product that's only four hours, which might be good if you are helping a pregnant patient. Dr. Sean Kane 27:46 It turns out that pregnant women with allergic rhinitis aren't lining up to engage in clinical studies, so it's unlikely that we're going to see a lot of new data, which is why sometimes we see some of these older products being recommended as a first line agent, simply due to a lack of data, not because of lack of safety or efficacy with our newer agents. Speaker 3 28:04 Well, is there any information anyone on the use of some of those corticosteroid nasal sprays? Speaker 2 28:09 So we do know that orally taken triamcinolone can cause cleft palate in the developing fetus. If you compare available corticosteroid nasal sprays, fluticasone propionate has the most data available because systemic absorption after intranasal use is minimal. Dr. Sean Kane 28:33 In terms of lactation, cromolyn sodium would be one of the preferred options due to minimal systemic absorption and low infant exposure. Generally, antihistamines are not preferred because of adverse effects to the infant. It also reduces breast milk production. So you know, if lactating patient must have an antihistamine, they can, of course, take a dose, preferably the shortest acting agent that they're comfortable taking, preferably at the end of the day. If they're not continuously breastfeeding, that it would be kind of at the end of the day after the baby is asleep and doesn't plan to feed overnight. And generally, we try to avoid the first generation antihistamines if possible, because of their sedating effects. So loratadine or fexofenadine would generally be preferred among second-generation antihistamines. Speaker 3 29:19 And then, regarding the nasal corticosteroids, we do know that they can pass into breast milk, but adverse event data in infants have not been reported up to this point. Speaker 1 29:31 And I think for children, we talked about referring them less than 12 initially to make sure it's not asthma, but we do have some great products for children to treat even down to the age of two. So loratadine is approved for that age group. We also have the inhaled nasal corticosteroids we talked about available down at the age of two. It depends on the product, so you definitely want to check package labeling before making a recommendation. Speaker 2 29:54 For elderly patients, the drug of choice should be a non-drowsy agent such as loratadine, or cromolyn sodium if tolerated; cromolyn can be cumbersome to use. Speaker 1 30:09 you'll definitely see first-generation antihistamines on the Beers Criteria, so we'll avoid those in the elderly; second-generation agents might be worth a shot. Dr. Sean Kane 30:17 So you know, many patients often seek complementary and alternative medicine, therapy for cough and cold and congestion and things like that. What are some of the agents that are available that actually have some data, or are popular that have no data, that our patients might be approaching us with? Speaker 1 30:33 The one I always shake my head at is zinc. We see a lot of patients using zinc for hopefully treating their cold symptoms, or preventing cold symptoms, if they think of colds coming on. I don't know if some of you might remember this, but the Zicam nasal swabs that were on the market several years ago then also disappeared. Well, what was happening? There was a link between these zinc nasal swabs and permanent loss of smell, or the ability to smell. And so the company removed those, and then, lo and behold, a month or two ago, or maybe a little bit longer, they're back on the shelves. And so looking into, well, what's going on with these looks like it's a homeopathic agent that they've converted the product over to. Speaker 2 31:16 And I'm sure they've done safety studies on this homeopathic product, making sure that there's no further side effects of anosmia, which is the permanent loss of smell. Dr. Sean Kane 31:25 Be great if they did, but they didn't. So what we have right now is, if you look at the packaging, they claim a 45% reduction in symptoms. And being the evidence-based medicine person that I am, I actually contacted the company that produces Zicam and asked them what the data was for that claim. So for the Zicam cold remedy nasal spray, they said that the publication of a clinical trial is ongoing, but the study results are proprietary. For the Zicam rapid melts, they said they had unpublished data with no plans to publish. For Zicam Allergy Relief spray, the citation they provided was in a small report in the Journal of Family Practice (Volume 1, Issue 1) that included 32 patients — one of the larger Zicam studies available. So I would say that to have that claim bothers me a lot as a pharmacist, knowing that a, it's a homeopathic product, which we had already discussed in a previous episode, but then B, to make that claim with this level of data, that is quote, unquote proprietary or secret in some way, I don't think is supportive of the fact that this does or doesn't work. Speaker 2 32:38 So then I'm pretty sure that the high dose vitamin C got pretty solid data for us to Speaker 3 32:43 refer well. The nice thing about it is that we do have more data than we have with our zinc or Zicam products. So with vitamin C, they again consider high dose, usually around two grams or more a day. And there was a really nice review Cochrane Database looked in 2013 and they looked at 29 different trials, and they analyzed them, and the end result they said, it's not beneficial for prevention in healthy individuals. They did note that the few studies that did show benefit were in some interesting populations. They were either very small studies or highly specialized populations, marathon runners. They looked at Ski schools in the Alps. They looked at soldiers, literally on sub Arctic exercises, for example. And they did find some benefit in prevention of cold symptoms in those populations, but again, in the average populations that are more likely to be the consumers of these especially in the general American market, no benefit. And furthermore, they noticed the risk of kidney stones in men with regular use Speaker 1 33:40 so next time I'm out skiing in the Alps, probably bring this along. Speaker 3 33:44 Yeah. Again, if you're if that's, if that's your thing and your high intensity athlete, which I am not, but if you are wonderful, then that may work. Speaker 2 33:52 And you might want to take some Imodium with you too, because high doses of vitamin C can easily cause diarrhea as well. So that's delightful. Speaker 1 34:00 What about kidney stones? Is that a possibility? I remember hearing about that some time ago. Speaker 3 34:04 Yeah, again, that can be potentially something that, if it is with a regular, routine use. So then the other interesting thing is we can also look at the data as it relates to duration of cold. Other part of that 2013 Cochrane Review, they looked at 17 trials in adults and 14 in children. And what they did find is that there was a reduced cold duration in adults, but only if you took these tablets all year long. Dr. Sean Kane 34:28 And of course, the actual magnitude of benefit was not very impressive at all. So among adults who did have a cold, regular supplementation of vitamin C decreased the cold duration by 8% which means that if your cold was three days in duration. It turned out to be 2.76 days in duration, and then 14% in children. But again, this is if you're taking vitamin C all day long, for the entire year with the anticipation of having a cold come at some point. And it's interesting to note that most studies used at least a gram a day, if not more, for these kind of preventative cold studies. Interestingly, within the Cochrane Review, they had one of the dumbest statements that you can have in a meta analysis, which is that overall, the results were negative. But they said, quote, it may be worthwhile for common cold patients to test on an individual basis whether therapeutic Vitamin C is beneficial for them. The entire point of doing an evidence based medicine randomized controlled trial is to determine whether given therapy is effective or not. A single patient taking a single medication isn't going to have a control group to know whether a medication is effective or not. They're going to have confirmation bias if their cold doesn't prove quicker than normal, even if the vitamin C had no role in that, despite Cochrane Review, having generally very good evidence based reviews. This conclusion just baffles me that they put that in there. Speaker 4 35:47 So it's basically saying, spend the money if they want to exactly Dr. Sean Kane 35:51 there is one other supplement that I know is very common. It's called airborne. This is a combination of vitamins and herbs. I know this is a very common product. When I was in high school and early college, I took it. What is the evidence for airborne I know is produced by a teacher or a high school teacher, or something like that. Speaker 1 36:09 When this first came out, it got a lot of attention, but I think the few studies that we have around this really haven't shown this to be an efficacious product. So again, it's patient spending money, but really without any benefit. Dr. Sean Kane 36:22 So, Dr. Angelo, what you're saying is that patients should try this on an individual basis to see whether therapeutic airborne is beneficial for them or not. Not. Speaker 1 36:31 My words, however, if we want to support, I guess, the product market, we could recommend they do that. Dr. Sean Kane 36:40 And this is honestly a fairly common theme among these, you know, complementary and alternative medicine therapies, is that we generally don't have a wealth of data, because there's no requirement by the FDA that they run a safety and an efficacy study for these herbal based products or homeopathic based products. Speaker 1 36:56 You often wonder if it's simply a placebo effect when patients do come back and tell you, hey, this worked great. You really don't have the data to support that other than anecdotal reports, and Speaker 2 37:07 that usually drives the market. You know, I have a friend who's flying long distance and scared of getting infection on a closed face, and they're getting airborne, and that's where the name drives too, right? If you're getting airborne, take airborne so you don't get sick. But there's little to no benefit of taking that. Dr. Sean Kane 37:26 And this really reminds me of Oscillococcinum for flu that we talked about in a previous episode. This is a homeopathic product marketed to prevent the flu. When you begin to feel the onset of flu taking hold, there is essentially no evidence of efficacy. The product is an extract of goose heart and liver, diluted to 200C, so there is virtually no active material left in the final preparation. But despite that, it has a five star review on Amazon with more than 800 reviews. So the power of this anecdotal evidence is a real thing in the market, which is one of the reasons why sales of some of these products are really driven not by evidence, but based on anecdotal reports. So just as a brief review looking at Sudafed PE versus Sudafed, what can you tell us, Dr. Angelo, as kind of good take-home points about the comparison of those two products? Speaker 1 38:18 Sure, as we break down the active ingredients, Sudafed is pseudoephedrine, and Sudafed PE is the phenylephrine product that came about when pseudoephedrine was put behind the shelves due to the methamphetamine issues. And when we look at those two products, I think it's important to consider the efficacy. The data tells us that pseudoephedrine is far more efficacious than phenylephrine, but it is harder to get. So as pharmacists, we definitely want to encourage our patients to come see us in the pharmacy, show us their ID, do the paperwork or whatever we need to do to log the sales and make sure they are getting a product that works for them. Speaker 3 38:53 So I want to focus on antihistamines. First-generation (sedating) antihistamines that cross the blood-brain barrier include chlorpheniramine, diphenhydramine, and hydroxyzine. Second-generation (non-sedating) antihistamines include fexofenadine (Allegra), loratadine (Claritin), and cetirizine (Zyrtec). Cetirizine is the metabolite of hydroxyzine, so it can cause some sedation in a minority of patients. The nice thing about these second-generation agents is they can each be taken once daily. Dr. Sean Kane 39:34 symptoms, and my take home point relates to the nasal corticosteroids. One of the adverse effects that patients should definitely know about is the risk of nosebleeds with these agents, and one way to kind of reduce the risk is the contralateral technique, where you're using your left hand to spray your right nostril and vice versa. Although there's still a risk of nosebleed, I think it's important that patients know the technique and also know that the adverse effect exists. Speaker 2 39:59 And the take home point. I would like to cover is that try not to recommend any of these products, such as zinc or high dose vitamin C or airborne because we don't have good evidence available for their use in common cold and allergies. Dr. Sean Kane 40:13 So with that, if you haven't done so already, check us out at HelixTalk.com. We're also on Twitter at HelixTalk, where you can get new episode alerts and other things relevant to the podcast. So with that, I'm Dr. Kane, I'm Dr. Schuman, I'm Dr. Vital, and I'm the guest, Dr. Angelo. Speaker 2 40:30 Thank you once again, Dr. Angelo, for joining us. And with that, I'm going to say, study hard. Narrator - Dr. Abel 40:35 If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five star review in the iTunes Store, search for HelixTalk and place your review there Narrator - ? 40:46 to suggest an episode or contact us. We're online at HelixTalk.com. Thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.