1 00:00:00,000 --> 00:00:12,920 Hi and welcome to another episode of the Canadian Breakpoint, a Canadian infectious disease 2 00:00:12,920 --> 00:00:15,680 podcast by infectious disease physicians. 3 00:00:15,680 --> 00:00:20,800 I'm Summer Stewart, here with Dr. Rupeena Purewa, pediatric infectious disease specialist 4 00:00:20,800 --> 00:00:22,240 from Saskatoon. 5 00:00:22,240 --> 00:00:28,320 For this episode, Dr. Purewal will discuss Biloxavir in anticipation of the 2021 flu 6 00:00:28,320 --> 00:00:29,320 season. 7 00:00:29,320 --> 00:00:35,040 Hi everyone, welcome to another episode of our podcast, the Canadian Breakpoint. 8 00:00:35,040 --> 00:00:40,200 Today we'll be discussing Biloxavir, which is an antiviral that was recently approved 9 00:00:40,200 --> 00:00:46,520 by Health Canada in February 2020 for acute uncomplicated influenza infections in those 10 00:00:46,520 --> 00:00:49,880 12 years of age and older. 11 00:00:49,880 --> 00:00:54,480 I wanted to review this topic for multiple reasons, one being that our last influenza 12 00:00:54,480 --> 00:01:00,800 season was very different here in Canada and probably globally due to many factors, likely 13 00:01:00,800 --> 00:01:07,520 an increase in flu vaccine uptake versus universal masking that's been in effect. 14 00:01:07,520 --> 00:01:13,840 Now as many of us are aware, this winter season, our respiratory season, may look more similar 15 00:01:13,840 --> 00:01:19,160 to our normal respiratory season with some increased influenza cases and therefore I 16 00:01:19,160 --> 00:01:26,440 thought it was very timely for us to discuss a new antiviral that was on the market, Biloxavir. 17 00:01:26,440 --> 00:01:30,340 And therefore, that's what we'll be talking about today. 18 00:01:30,340 --> 00:01:35,160 Before I do start talking a little bit more about Biloxavir itself, I do want to mention 19 00:01:35,160 --> 00:01:38,160 this is an informational podcast. 20 00:01:38,160 --> 00:01:46,400 I do not have any financial disclosures and I'm not endorsing this product. 21 00:01:46,400 --> 00:01:52,560 So today our objective will be to learn about Biloxavir, also known as Zofluza. 22 00:01:52,560 --> 00:01:58,320 We will talk about the properties of Biloxavir, the indications, contraindications, and then 23 00:01:58,320 --> 00:02:08,100 in the end we will compare it to our conventional antiviral, also known as Tamavir or Tamiflu. 24 00:02:08,100 --> 00:02:12,520 So starting off with Biloxavir, Biloxavir marboxyl is the active ingredient, so the 25 00:02:12,520 --> 00:02:17,720 product name is Zofluza, and the route of administration is oral. 26 00:02:17,720 --> 00:02:22,800 When we will be prescribing or using this as a prescription medication, it comes in 27 00:02:22,800 --> 00:02:26,500 a 20 milligram and a 40 milligram tablet. 28 00:02:26,500 --> 00:02:32,600 So in terms of dosing for us clinicians, if your patient is between 40 to 80 kilos, then 29 00:02:32,600 --> 00:02:36,440 two 20 milligram tablets for a total dose of 40 milligrams. 30 00:02:36,440 --> 00:02:41,000 If they're greater than 80 kilos, then we're looking at two 40 milligram tablets for a 31 00:02:41,000 --> 00:02:43,840 total dose of 80 milligrams. 32 00:02:43,840 --> 00:02:50,760 Fortunately it's a single dose regimen that's given within 48 hours of symptom onset. 33 00:02:50,760 --> 00:02:56,160 Now going on to the indications, as were listed in the product's monograph, it's indicated 34 00:02:56,160 --> 00:03:01,680 for the treatment of uncomplicated influenza, as we mentioned, in patients that are 12 years 35 00:03:01,680 --> 00:03:07,520 of age and older, who have been symptomatic for no more than 48 hours and who are otherwise 36 00:03:07,520 --> 00:03:12,680 healthy or at high risk of developing influenza complications. 37 00:03:12,680 --> 00:03:18,640 There's no clinical evidence for efficacy outside of influenza A and B, so not recommended 38 00:03:18,640 --> 00:03:21,280 for other viruses. 39 00:03:21,280 --> 00:03:26,080 And again, there's no efficacy or safety that's been established in those that begin therapy 40 00:03:26,080 --> 00:03:30,680 or treatment after the 48 hour mark. 41 00:03:30,680 --> 00:03:35,880 Also there's no efficacy or safety in treatment of influenza in patients requiring hospitalization, 42 00:03:35,880 --> 00:03:41,040 so those you would encounter more of your complicated influenza cases. 43 00:03:41,040 --> 00:03:47,400 And also kind of different from our also Tamifir antiviral medication, there's no efficacy 44 00:03:47,400 --> 00:03:51,900 here with Biloxavir in preventing influenza. 45 00:03:51,900 --> 00:03:58,140 Now going on to the mechanism of action, so Biloxavir merboxyl is a pro drug that's converted 46 00:03:58,140 --> 00:04:02,680 by hydrolysis to its active metabolite, Biloxavir. 47 00:04:02,680 --> 00:04:06,800 This active form exerts the anti-influenza activity. 48 00:04:06,800 --> 00:04:13,840 So it actually acts on the cap-dependent endonuclease, which is an influenza virus specific enzyme 49 00:04:13,840 --> 00:04:22,040 and actually the PA, or polymerized acidic subunit of the viral RNA polymerase complex. 50 00:04:22,040 --> 00:04:26,560 So really the way it works is it inhibits the transcription of influenza virus genomes 51 00:04:26,560 --> 00:04:33,560 resulting in inhibition of influenza virus replication. 52 00:04:33,560 --> 00:04:40,320 Looking at the pharmacokinetics of this drug, Biloxavir, the terminal elimination half-life 53 00:04:40,320 --> 00:04:48,640 of Biloxavir after your single oral administration dose is 79.1 hours and it's mainly excreted 54 00:04:48,640 --> 00:04:52,680 via the fecal route in humans in small amounts in the urine. 55 00:04:52,680 --> 00:04:57,520 So obviously as clinicians, I think it's really important for us to talk about efficacy and 56 00:04:57,520 --> 00:04:59,040 also safety. 57 00:04:59,040 --> 00:05:03,320 And so based on the monograph, they did discuss two clinical trials that we're going to talk 58 00:05:03,320 --> 00:05:10,280 about right now, but really basing it on that there was significant reduction in the time 59 00:05:10,280 --> 00:05:17,120 to alleviation or time to improvement of influenza symptoms with sofluza compared to the placebo 60 00:05:17,120 --> 00:05:19,000 group. 61 00:05:19,000 --> 00:05:24,120 So the two clinical trials, so the first trial was a phase three randomized double-blind 62 00:05:24,120 --> 00:05:30,040 multicenter placebo, an active controlled study designed to evaluate the efficacy and 63 00:05:30,040 --> 00:05:39,800 safety of Biloxavir compared with the placebo arm or also Tamavir in healthy adults or adolescents, 64 00:05:39,800 --> 00:05:47,320 that was your 12 to 64 years of age, weighing 40 kilos, all that had acute uncomplicated 65 00:05:47,320 --> 00:05:53,080 influenza, so really the eligibility for this trial was that they had to have an auxiliary 66 00:05:53,080 --> 00:05:59,880 temperature of 38 degrees Celsius or above, one respiratory symptom that was moderate or 67 00:05:59,880 --> 00:06:06,800 greater than severity and one stomach symptom like headache, fever, chills of moderate or 68 00:06:06,800 --> 00:06:09,000 greater severity. 69 00:06:09,000 --> 00:06:16,320 All patients in this study were treated within 48 hours of symptom onset as per the indications 70 00:06:16,320 --> 00:06:24,520 and dosing was 40 or 80 milligrams of sofluza or conventional dosing for Tamiflu and then 71 00:06:24,520 --> 00:06:26,920 there was the placebo arm. 72 00:06:26,920 --> 00:06:32,220 So really the design of the study was to do self-assessment which would require to assess 73 00:06:32,220 --> 00:06:39,400 their symptoms as none, mild, moderate or severe, twice daily in the first nine days 74 00:06:39,400 --> 00:06:43,220 and then once daily up to day 14. 75 00:06:43,220 --> 00:06:49,040 So the primary efficacy endpoint was time to alleviation of symptoms and that was defined 76 00:06:49,040 --> 00:06:54,280 when all symptoms were assessed as none or mild for a duration of at least 21 and a half 77 00:06:54,280 --> 00:06:56,160 hours. 78 00:06:56,160 --> 00:07:04,840 So this specific study had an N of 1400 patients that were randomized, the intention to treat 79 00:07:04,840 --> 00:07:10,080 infected population included over a thousand patients with PCR confirmed influenza. 80 00:07:10,080 --> 00:07:15,400 I think it's quite interesting for me to look at the predominant strains in this study and 81 00:07:15,400 --> 00:07:23,940 it was mostly influenza type A H3 subtype, that was around 80% and then coming in second 82 00:07:23,940 --> 00:07:33,200 was influenza B type at around 10% and then with the smallest number was influenza A H1 83 00:07:33,200 --> 00:07:34,200 and one. 84 00:07:34,200 --> 00:07:42,920 It was also notably mentioned in this trial that 75% of the patients enrolled did not 85 00:07:42,920 --> 00:07:46,200 receive their influenza vaccine. 86 00:07:46,200 --> 00:07:50,960 Now when looking at the primary endpoint which was that time to alleviation of symptoms, 87 00:07:50,960 --> 00:07:56,240 a statistically significant improvement was seen with the Zofluza group when compared 88 00:07:56,240 --> 00:08:03,600 to the placebo arm but there was no statistical significance that was seen in any difference 89 00:08:03,600 --> 00:08:09,640 in time to alleviation of symptoms when we compared the Zofluza group to the ulceratomavir 90 00:08:09,640 --> 00:08:11,720 group. 91 00:08:11,720 --> 00:08:16,000 As for the secondary endpoint which is time to resolution of fever was also noted that 92 00:08:16,000 --> 00:08:21,560 was faster in the Zofluza group compared to the placebo arm with a median time with the 93 00:08:21,560 --> 00:08:27,800 Zofluza group around 24 and a half hours compared to the patients that were in the placebo group 94 00:08:27,800 --> 00:08:31,220 which was up to 42 hours. 95 00:08:31,220 --> 00:08:35,640 Now as mentioned previously there was two trials that were discussing the efficacy and safety. 96 00:08:35,640 --> 00:08:41,200 So the second trial was a phase three randomized double-blinded multi-center placebo and active 97 00:08:41,200 --> 00:08:44,920 control study to evaluate efficacy and safety. 98 00:08:44,920 --> 00:08:53,040 Again of the oral dose of Zofluza compared to the placebo arm or also tamivir in adolescents 99 00:08:53,040 --> 00:08:56,900 and adult patients older than 12 years of age. 100 00:08:56,900 --> 00:09:03,640 Now with influenza who are at high risk of developing influenza related complications. 101 00:09:03,640 --> 00:09:08,760 So the patients that were included under the high risk or kind of what we see in our probably 102 00:09:08,760 --> 00:09:15,720 clinical practice but most commonly was represented in this study was underlying asthma, chronic 103 00:09:15,720 --> 00:09:22,960 lung disease at around 40%, diabetes at around 20% and then followed by heart disease and 104 00:09:22,960 --> 00:09:27,960 obesity around the 12% range. 105 00:09:27,960 --> 00:09:32,600 The patients that were excluded were if they had cancer in the last five years untreated 106 00:09:32,600 --> 00:09:40,680 HIV or treated HIV with a low CD4 count of below 350 immune suppressed patients falling 107 00:09:40,680 --> 00:09:46,160 transplant so really anybody really in your immunocompromised state. 108 00:09:46,160 --> 00:09:54,000 Now most patients in this clinical trial also had not received their influenza vaccine. 109 00:09:54,000 --> 00:09:59,200 Eligibility was very similar to the previous study and the number of patients that were 110 00:09:59,200 --> 00:10:05,520 randomized were over 2100 and over 1100 of them had confirmed diagnosis of PCR at the 111 00:10:05,520 --> 00:10:07,520 study entry. 112 00:10:07,520 --> 00:10:12,600 The predominant strains here were influenza A H3 subtype very similarly but there was 113 00:10:12,600 --> 00:10:19,360 more of a 50-50 distribution here with influenza B coming in second and when looking at the 114 00:10:19,360 --> 00:10:25,840 primary endpoint here which is time to improvement of symptoms there was again statistical significance 115 00:10:25,840 --> 00:10:31,920 for the Zofluza group compared to the placebo group but again no significant improvement 116 00:10:31,920 --> 00:10:36,360 difference that was noted in the Zofluza group and comparing it to the ulceratoma beer group. 117 00:10:36,360 --> 00:10:40,680 It's very similar to our previous trial that we just discussed. 118 00:10:40,680 --> 00:10:44,920 In terms of the secondary endpoint which is resolution of fever, fever was reduced more 119 00:10:44,920 --> 00:10:49,280 rapidly in the Zofluza group compared to the placebo group. 120 00:10:49,280 --> 00:10:55,920 So I think all in all looking at both the healthy subjects in the first trial and the 121 00:10:55,920 --> 00:11:04,400 high risk subjects in the second trial as we just discussed the Zofluza group for both 122 00:11:04,400 --> 00:11:13,160 their primary and secondary endpoint did better than the placebo group I think is what mainly 123 00:11:13,160 --> 00:11:20,720 I took from this study and it was also so as we mentioned in the second trial they were 124 00:11:20,720 --> 00:11:27,760 looking at high risk patients who have a higher risk of developing or higher risk of developing 125 00:11:27,760 --> 00:11:32,820 influenza related complications and so they specifically mentioned in the monograph the 126 00:11:32,820 --> 00:11:38,560 overall incidence of influenza related complication was around three percent in the Zofluza group 127 00:11:38,560 --> 00:11:42,400 compared to the placebo group which was up to ten percent. 128 00:11:42,400 --> 00:11:48,640 So that was another important measure and really they looked at they had a lower incidence 129 00:11:48,640 --> 00:11:56,040 in these patients in the Zofluza group lower incidence of bronchitis and sinusitis. 130 00:11:56,040 --> 00:12:01,400 However there was no significant differences in some of our higher risk complications or 131 00:12:01,400 --> 00:12:10,200 more complicated presentations such as death, hospitalization, and Titus pneumonia. 132 00:12:10,200 --> 00:12:15,600 So I think that overall summed up the efficacy of Bloxivir. 133 00:12:15,600 --> 00:12:21,880 In terms of as clinicians I think it's also really important to know the safety and so 134 00:12:21,880 --> 00:12:28,000 looking at what the monograph stated safety was submitted and reviewed by Health Canada 135 00:12:28,000 --> 00:12:32,320 and safety and efficacy had been established for children that are older than 12 years 136 00:12:32,320 --> 00:12:37,440 of age and weighing greater than 40 kilos so it was not well established outside of 137 00:12:37,440 --> 00:12:42,680 that age range and outside of that weight. 138 00:12:42,680 --> 00:12:48,680 In terms of pregnancy and breastfeeding so definitely there are no well controlled studies 139 00:12:48,680 --> 00:12:55,640 in this population which is usually the case in most of the drugs that get released on 140 00:12:55,640 --> 00:13:02,160 our market however the current recommendations in your pregnant patients or those that are 141 00:13:02,160 --> 00:13:09,820 breastfeeding there's no kind of well controlled studies as we mentioned so the current recommendation 142 00:13:09,820 --> 00:13:14,900 is that currently should not be used during pregnancy unless there's really a potential 143 00:13:14,900 --> 00:13:19,200 benefit that justifies the risk to the fetus. 144 00:13:19,200 --> 00:13:24,880 When they did look at higher doses of Bloxivir in for instance like pregnant rabbits at six 145 00:13:24,880 --> 00:13:29,880 times higher dose than what we would be giving to humans they did see that there was maternal 146 00:13:29,880 --> 00:13:35,320 toxicity leading to miscarriages and increased incident in minor skeletal abnormalities but 147 00:13:35,320 --> 00:13:44,160 this was not obviously seen in some of the other subjects that were used and then in 148 00:13:44,160 --> 00:13:47,800 pregnancy we just don't have those studies right now. 149 00:13:47,800 --> 00:13:52,960 In terms of any contraindications so avoiding it in those that ever have any hypersensitivity 150 00:13:52,960 --> 00:14:00,040 to this drug or any ingredient in the formulation such as anaphylaxis, aorticaria, angiotema. 151 00:14:00,040 --> 00:14:05,760 I think it was important for the part of the monogram that mentioned kind of dosing considerations 152 00:14:05,760 --> 00:14:12,060 you want to avoid giving it with any calcium beverages so pretty much all in all avoid 153 00:14:12,060 --> 00:14:20,880 dairy products anything that could combine with the medication that would make it more 154 00:14:20,880 --> 00:14:22,920 or make it ineffective. 155 00:14:22,920 --> 00:14:27,640 Antacids were on the list, oral supplements like calcium, iron, magnesium, selenium or 156 00:14:27,640 --> 00:14:32,880 zinc as well and some laxatives that have polyvalent cations. 157 00:14:32,880 --> 00:14:37,960 So definitely taking that into consideration especially for our pharmacy folks that are 158 00:14:37,960 --> 00:14:41,080 helping us prescribe this medication. 159 00:14:41,080 --> 00:14:46,480 They also mentioned in the monograph that it was not well studied in renal impairment 160 00:14:46,480 --> 00:14:51,560 in patients and those with severe hepatic disease but currently there are no change 161 00:14:51,560 --> 00:15:00,200 in dose recommendations so no dose changes required for both renal and hepatic impairment. 162 00:15:00,200 --> 00:15:05,640 In terms of side effects so in the clinical trials themselves they saw some mild side 163 00:15:05,640 --> 00:15:13,200 effects the GI upset which is a really common manifestation that was seen in those patients 164 00:15:13,200 --> 00:15:20,720 including nausea and diarrhea but also developing other milder symptoms of bronchitis, sinus 165 00:15:20,720 --> 00:15:27,440 infection or headache and when looking at it more so in the post marketing adverse events 166 00:15:27,440 --> 00:15:32,960 anaphylaxis, angioedema, urticaria and rash were seen vomiting, bloody diarrhea, melanitis, 167 00:15:32,960 --> 00:15:38,000 ischemic colitis however as we're aware these are reported voluntarily from a population 168 00:15:38,000 --> 00:15:43,160 of an uncertain size so really can't reliably estimate their frequency so much that would 169 00:15:43,160 --> 00:15:46,960 be what we can do in the clinical trials and it seems like in the clinical trials really 170 00:15:46,960 --> 00:15:52,760 the milder symptoms were more predominant however with age nausea was also a predominant 171 00:15:52,760 --> 00:15:57,600 finding so that's something to consider in your patients when prescribing it and obviously 172 00:15:57,600 --> 00:16:03,240 with any other medications if there is any severe reaction should always counsel your 173 00:16:03,240 --> 00:16:08,880 patients to stop taking the medication and speak to the health care provider. 174 00:16:08,880 --> 00:16:15,720 So there was an interesting part of the monograph that was brought up in terms of resistance 175 00:16:15,720 --> 00:16:21,960 or development of resistance and treatment emergent amino acid substitution resistance 176 00:16:21,960 --> 00:16:27,840 that have something they've been noticing in the US so it since FDA approval in the 177 00:16:27,840 --> 00:16:34,200 US which is back in 2018 they are seeing that now more so in vitro in clinical isolates 178 00:16:34,200 --> 00:16:39,400 really it's the treatment emergent amino acid substitution and the PA protein which 179 00:16:39,400 --> 00:16:45,560 showed mainly for influenza A virus isolates that there's a tenfold reduced susceptibility 180 00:16:45,560 --> 00:16:50,960 but not so much or not as high in the influenza B group but still representing a fivefold 181 00:16:50,960 --> 00:16:54,080 reduced susceptibility to block severe. 182 00:16:54,080 --> 00:17:00,480 In the clinical trials and the healthy subjects this mutation at this amino acid substitution 183 00:17:00,480 --> 00:17:06,080 position was seen in about 10% of the Zoflouza group and the high risk patients about 5% 184 00:17:06,080 --> 00:17:11,640 of the patients that were seen had this mutation detected so just something to consider when 185 00:17:11,640 --> 00:17:17,560 we are looking into prescribing so kind of the evidence or the supporting recommendations 186 00:17:17,560 --> 00:17:21,720 that were given in regards to that was that health professionals should consider available 187 00:17:21,720 --> 00:17:26,400 information on the influence of virus drug susceptibility patterns and treatment effects 188 00:17:26,400 --> 00:17:32,240 when deciding whether to use Zoflouza if that's an option. 189 00:17:32,240 --> 00:17:40,880 And so I'm kind of pretty much wanted to sum up this episode by comparing Tamiflu to Bloxivir 190 00:17:40,880 --> 00:17:48,360 because I think most of us are quite aware of the properties of Tamiflu or also Tamivir 191 00:17:48,360 --> 00:17:53,960 versus Bloxivir but really doing a side by side comparison can sometimes help especially 192 00:17:53,960 --> 00:17:57,480 because these are the two antivirals that are on the market. 193 00:17:57,480 --> 00:18:03,240 Most of us may not be familiar with Bloxivir because it was just released prior to the 194 00:18:03,240 --> 00:18:08,920 COVID pandemic and since we didn't see much influenza activity in our last respiratory 195 00:18:08,920 --> 00:18:16,120 season a lot of us probably did not prescribe this medication however we may be seeing a 196 00:18:16,120 --> 00:18:20,800 different respiratory season coming forward in these winter months and so we'll just end 197 00:18:20,800 --> 00:18:25,560 this podcast by talking a little bit about Tamiflu versus Bloxivir some of the properties 198 00:18:25,560 --> 00:18:30,000 that stood out to me and will help me as well in my clinical practice. 199 00:18:30,000 --> 00:18:36,360 So when we talk about cost I think it's always an important topic to bring up when we're 200 00:18:36,360 --> 00:18:40,320 comparing medications and when we're prescribing medications so both of them are prescription 201 00:18:40,320 --> 00:18:47,600 drugs Tamiflu is less costly whereas Bloxivir is more expensive so that's something to consider. 202 00:18:47,600 --> 00:18:52,640 In terms of the mechanism of action Tamiflu as we're all aware stops the viral copies 203 00:18:52,640 --> 00:18:58,120 from leading your cells to preventing you from becoming more sick whereas Bloxivir as 204 00:18:58,120 --> 00:19:02,600 we just learned stops the influenza virus itself from actually making copies of itself 205 00:19:02,600 --> 00:19:07,800 so the viral replication now both of them it's advised to take within 48 hours of feeling 206 00:19:07,800 --> 00:19:13,360 sick and I think as a pediatrician it was actually quite important to me to know that 207 00:19:13,360 --> 00:19:20,560 Bloxivir is only approved in those older than 12 years of age and greater than 40 kilos 208 00:19:20,560 --> 00:19:25,600 whereas Tamiflu and what I see in my clinical practice as well as we can give it as young 209 00:19:25,600 --> 00:19:31,520 as two weeks old and not only that but we can use Tamiflu or also Tamivir as a treatment 210 00:19:31,520 --> 00:19:39,120 and prevention agent whereas Bloxivir as we just learned is only indicated for treatment 211 00:19:39,120 --> 00:19:45,040 and just kind of remembering that Tamiflu can be given for your complicated patients 212 00:19:45,040 --> 00:19:50,080 and is recommended whereas Bloxivir is more probably in your outpatient setting where you 213 00:19:50,080 --> 00:19:56,960 have an acute uncomplicated influenza positive patient maybe somebody who is higher risk 214 00:19:56,960 --> 00:20:01,880 for developing complications or even in our pediatric populations in that adolescent group 215 00:20:01,880 --> 00:20:06,420 if you have a patient where you can detect them within the first 48 hours of feeling 216 00:20:06,420 --> 00:20:11,320 sick and can give them a single dose probably helps with compliance that it's a single dose 217 00:20:11,320 --> 00:20:17,240 as opposed to Tamiflu where you're taking it for five days twice a day dosing that's 218 00:20:17,240 --> 00:20:22,920 probably the conventional dosing. Now I did want to kind of touch on the topic of antiviral 219 00:20:22,920 --> 00:20:32,640 use in general because in the pediatric population we often kind of shy away from giving antivirals 220 00:20:32,640 --> 00:20:38,800 especially Tamiflu which has been on the market for a long time and recently in the pediatric 221 00:20:38,800 --> 00:20:45,560 journal there was a study that was released by Impact Network which is a pediatric hospital 222 00:20:45,560 --> 00:20:51,200 national active surveillance network which is actually a really good paper that sums 223 00:20:51,200 --> 00:20:56,440 up kind of the antiviral use in the pediatric population so it's only looking at from zero 224 00:20:56,440 --> 00:21:05,920 to 16 years of age and was comparing our use in 2010 to 2011 compared to 2018 to 2019. 225 00:21:05,920 --> 00:21:11,920 Now overall our use of antivirals despite the current recommendations from Canadian 226 00:21:11,920 --> 00:21:18,200 Pediatric Society and the American Academy of Pediatrics stating that antiviral agents 227 00:21:18,200 --> 00:21:22,820 are recommended for influenza especially in patients that are hospitalized patients even 228 00:21:22,820 --> 00:21:30,440 if they've are past that 48 hour mark however overall use in our pediatric patients when 229 00:21:30,440 --> 00:21:41,720 looking at the over 7500 cases we were only at around a use rate of about 41 percent so 230 00:21:41,720 --> 00:21:47,560 definitely could be variable among centers different centers have different abilities 231 00:21:47,560 --> 00:21:54,320 for testing and those that can test sooner obviously had higher rates so something to 232 00:21:54,320 --> 00:22:01,460 consider so just coming into this respiratory season and likely our influenza season that's 233 00:22:01,460 --> 00:22:07,720 something to consider and when they looked at the antiviral use rate in these pediatric 234 00:22:07,720 --> 00:22:15,200 hospitals comparing it from the 2010 to the 2018-2019 data we did see that the overall 235 00:22:15,200 --> 00:22:22,200 use had increased now whether that's again because of more testing or more complicated 236 00:22:22,200 --> 00:22:29,600 patients for many reasons so it went from 20 up to 60 but I just wanted to kind of bring 237 00:22:29,600 --> 00:22:35,120 that up because definitely there are benefits and a lot of observational studies that have 238 00:22:35,120 --> 00:22:39,000 been seen in children and adults that are hospitalized that suggest clinical benefit 239 00:22:39,000 --> 00:22:43,740 of antiviral use now whether that's decrease in length of stay decrease in health care 240 00:22:43,740 --> 00:22:53,000 costs and decrease in our ICU and overall mortality morbidity so something to consider 241 00:22:53,000 --> 00:23:00,360 for us as clinicians as well and and knowing of the indications for each of the antivirals 242 00:23:00,360 --> 00:23:05,880 that are available to us on the market I think was one of the first steps for me just knowing 243 00:23:05,880 --> 00:23:13,360 and learning about blocks of year because it was something that I definitely have not 244 00:23:13,360 --> 00:23:17,880 encountered in my clinical practice just kind of remembering that now obviously we detoured 245 00:23:17,880 --> 00:23:22,440 a little bit more of talking about hospitalized patients whereas Tamiflu would be the indication 246 00:23:22,440 --> 00:23:28,760 there in blocks of year is only used in acute uncomplicated setting now finally just what 247 00:23:28,760 --> 00:23:34,760 we have on formulary so in Tamiflu with Tamiflu it's a liquid and tablet that's available 248 00:23:34,760 --> 00:23:39,320 and that's probably more beneficial for us pediatricians out there in terms of blocks 249 00:23:39,320 --> 00:23:44,800 of year there's no liquid formulation that's available but they do have a tablet form unfortunately 250 00:23:44,800 --> 00:23:53,440 cannot be crushed so considering that in your acute outpatient setting might be an important 251 00:23:53,440 --> 00:23:59,360 me way in your decision when prescribing either of these antiviral agents definitely with 252 00:23:59,360 --> 00:24:04,760 Tamiflu there was less side effects as we're quite aware with pretty safe drug less side 253 00:24:04,760 --> 00:24:08,360 effects usually the side effects are nausea vomiting which get better with foods always 254 00:24:08,360 --> 00:24:12,480 counsel your patients regarding that and then in the blocks of your group we discussed some 255 00:24:12,480 --> 00:24:20,160 of the side effects again nausea gi upset were predominant but we're likely maybe encountering 256 00:24:20,160 --> 00:24:28,520 more side effects in that with that agent compared to Tamiflu so that is basically what 257 00:24:28,520 --> 00:24:37,180 I wanted to discuss today and as usual we are very grateful to have this podcast up 258 00:24:37,180 --> 00:24:44,560 and running definitely would like everyone to reach out to us via email and let us know 259 00:24:44,560 --> 00:24:51,080 what you're interested in listening to I would love to hear your thoughts your comments on 260 00:24:51,080 --> 00:24:55,600 any of the episodes or any future episodes if you would personally like to come on to 261 00:24:55,600 --> 00:25:02,160 the podcast and discuss an important infectious disease microbiology topic please do let us 262 00:25:02,160 --> 00:25:06,640 know and thank you thanks for listening. 263 00:25:06,640 --> 00:25:11,480 Thank you Dr. Purwall as well as Verity Pharmaceuticals for the generous sponsorship follow us on 264 00:25:11,480 --> 00:25:18,720 Twitter at CA Breakpoint and email us at thecanadianbreakpoint at gmail.com to suggest infectious disease 265 00:25:18,720 --> 00:25:24,040 topics or discussions you'd like to hear we look forward to seeing you again at the Canadian 266 00:25:24,040 --> 00:25:37,680 Breakpoint.