TRANSCRIPT:

Voice-over: Welcome to Spotlight on Migraine, hosted by the Association of Migraine Disorders. Join us for fresh perspectives by medical experts and advocates as we explore the spectrum of migraine and dig deeper into this complex disease. This episode is brought to you, in part, by our generous sponsor, Impel Pharmaceuticals. 

Sumatriptan, a common migraine abortive treatment, is available in many forms, including a nasal powder or spray, tablet, injectable, and more. In this episode, neurologist and headache specialist, Dr. Deena Kuruvilla discusses how to use sumatriptan nasal powder, common side effects, dosage, and how it differs from other formulations. 

Deena Kuruvilla, MD: Hello, and welcome to the 2021 Migraine Symposium, hosted by the Association of Migraine Disorders. My name is Deena Kuruvilla. I am a neurologist, headache specialist, and the medical director of the Westport Headache Institute. Thank you so much for joining me today to hear about a different acute treatment option for migraine treatment, the sumatriptan nasal powder. 

Before we jump into some more details about the sumatriptan nasal powder, I thought that it would be important to start off by discussing how do we measure the success of an acute treatment? And so, there was a survey study which was done which asked patients, across the United States, what their priorities are when it comes to their acute treatments for migraine. And based on this survey study that was conducted, around 87% of participants said that they prioritized complete pain freedom; 83% of the participants reported that they wanted relief as fast as possible; and 76% of people reported that they really wanted relief from their most bothersome symptoms such as sensitivity to light, sensitivity to loud noise, and nausea. 

When I’m counseling people about how to use their acute migraine treatments, there are so many different factors that come to mind. And so these are just a couple that I’ve listed today. All patients with a confirmed diagnosis of migraine should be offered acute treatment options. I think that’s the golden rule. You know, as a headache specialist, the patients that I often see I discuss preventive treatment options to overall reduce the number of headaches that patients may experience. I recommend acute treatment options. I sometimes give patients a plan A, a plan B, a plan C to make sure that we can really get to pain freedom successfully and get folks back to living their regular lives. 

Another point that I’ve highlighted here is not to forget about lifestyle factors. You know, lifestyle triggers, lifestyle changes definitely play such a big role in triggering migraine attacks. You know, one example that comes to mind is that with the pandemic upon us, many people are having to work from home and stare at their computer screens, for example, for longer times during the day. They may be drinking more caffeine; they may have higher stress levels. And I’m seeing that this perfect storm can really produce migraine attacks for patients. 

The next point here is really finding an acute treatment that works for you individually. One thing that I have learned in treating patients now for several years is that every single person I take care of is different. Every person has a different medical history, and they may have a different tolerance to medications. And so, it’s really important to have a customized approach when you’re discussing that acute treatment option. 

The next point here is to treat early in the migraine attack. So, it’s really important that folks with migraine take their acute treatment as soon as possible early on in their attack. And the reason for this is the pain signal moves from kind of the outside of the brain is how I like to imagine it or the superficial nerves and kind of moves to the center of the brain to an area called the thalamus, which is one of the pain-producing centers of the brain. 

Once this pain signal moves from the outside to the inside, the individual migraine attack is much more difficult to treat. So I always say treat as early and as fast as possible. A lot of folks that I take care of say that they have nausea or vomiting or just can’t tolerate oral medications. There are several options out there that can really help with that issue. There are injectable treatments, acute treatments that can be considered, there are nasal sprays, nasal powders, which we’re going to discuss today. 

The next point I have here is don’t be afraid to repeat a dose of an acute treatment if you need it. I do see many times that folks take one dosage of their treatment at the onset of their headache, and they may have instructions to repeat the dose if they still have the headache, but they may forget. They may think that the headache will get better on its own. But many times, that lingering migraine that may stick around after the first dose can really produce a migraine attack later that day or on the following day. 

And the last point here is really important and something I alluded to earlier. Please make sure to have a multistep plan with your physician. It’s really important that you come up with a plan A, a plan B, and a plan C maybe because I found that each individual person may have different types of migraine attacks that respond to different treatments. You may be in a different place when you have a migraine attack. For example, a migraine attack may wake you up from sleep, or you may get it at your child’s soccer game, or you may get it at work, so you may need those different options, also, based on what scenario you’re in. 

This presentation specifically focuses on sumatriptan nasal powder and acute treatment for migraine. And so, we are going to talk a little bit about how sumatriptan nasal powder treats migraine. We will talk about some of the evidence out there, what clinical trials have been done in studying the sumatriptan nasal powder. We’ll talk about some of the potential side effects. We’ll talk about what dosages are available, and we’ll talk a little bit about how you can broach the topic of obtaining the medication with your medical provider. 

And so how does sumatriptan nasal powder actually treat migraine? So triptans have been the first-line acute treatment for migraine since the beginning of the 90s. Oral sumatriptan specifically is the most prescribed triptan in the class. The triptans work at the 5-HT1B and 1D serotonin receptor as agonist. And so they kind of activate those receptors to treat your migraine attacks. 

Now we have seven different variations of triptans, and all of those are available as oral formulations. But one of the big factors that we see in patients with migraine is that they may not be emptying contents from their stomach like people without migraine. And so because of that reason, there may be delayed absorption with oral medications. That’s kind of where this nasal powder formulation may have some benefit for those folks who have varied absorption of those oral formulations. 

A lot of the nasal spray formulations do tend to drip out of the nose when they’re being used. The liquid may build up within the nose, or a lot of patients tell me that the liquid form drips back into the throat and ends up being swallowed. And so it may not be the most efficient way to acutely treat migraine. And so the sumatriptan nasal powder was formulated to help improve drug absorption of sumatriptan and try to keep up the efficacy of the treatment since it’s not being swallowed, and we’re not really depending on the stomach or other parts of the gastrointestinal system for it to work.

And so the nasal powder formulation of sumatriptan has been FDA approved for the acute treatment of migraine in patients with aura and without aura. We know that sumatriptan itself is the oldest of the triptan family. It comes as a tablet, it comes as a liquid nasal spray, an injection, a skin patch. There’s multiple different ways to administer that sumatriptan. But what sets apart the nasal powder is the way that it’s delivered into the nose. And it’s basically this breath-powered device which one blows into, and the powder formulation kind of moves to the back of the nasal cavity. 

It’s a dry powder. 11 milligrams is administered into each nostril to equal 22 milligrams in one dose. And basically, the nasal powder can take advantage of each person’s nose and nasal passageway anatomy. And so we’re able to get away with a lower dosage of the medication because we are precisely blowing that powder straight into the nasal cavity and kind of focusing it at a very specific area. You know, sumatriptan and zolmitriptan are also available as nasal spray formulations, but we kind of talked about the liquid formulation can how that can inadvertently be swallowed. 

Since this is a powder being blown into the nose and going into the back of the nasal passageway, it’s less likely to be swallowed. So we can get away with that lower dose of the treatment. And many of the folks I see with migraine have nausea and vomiting as a very common effect of their migraine. And so, this kind of bypasses the mouth and the gastrointestinal system and goes just straight into the nose. 

This diagram, to the right here, kind of shows all the different serotonin receptor mechanisms that we have currently available for the acute treatment of migraine. And so how do you use an orally breath-powered nasal device? So this is not a nasal spray, it is not an inhaler. It basically comes with two nosepieces per treatment. So this is the device right here, and this is kind of how it’s held. So one part of the device goes into the mouth, and then each device comes with a clear disposable nosepiece, which is placed into the reusable device – it’s clicked in. 

You basically press the white button to pierce the medication capsule, so it goes into the nosepiece. So that powder goes directly into the nosepiece when you push the white button, which is right here. And then you blow with your mouth into the device – like this young lady’s doing right here – to deliver medication into each nostril. And 11 milligrams goes into each nostril to equal 22 milligrams of medication. 

How does sumatriptan nasal powder compare to other formulations? So there was this really interesting study by Obaidi and colleagues that compares the different efficacies, the different pharmacokinetic profiles, of sumatriptan the nasal powder compared with the liquid nasal spray, the tablet, and the subcutaneous injection. And it’s interesting. The first figure here looks at the plasma concentration of the nasal powder compared with the nasal spray formulations of sumatriptan. And it looks at the plasma concentrations over this 4-hour time period. And we find that the sumatriptan nasal powder kind of reaches this peak plasma concentration sooner than the liquid nasal spray formulation. 

And then the second graph that we’re taking a look at here also looks at the plasma concentration of the medication, but it’s timed over 14 hours. On this graph, we’re looking at the sumatriptan nasal powder liquid formulations, nasal spray formulation, the subcutaneous injectable treatment and the tablet. And this main figure here shows that both methods of intranasal delivery resulted in a much lower mean plasma sumatriptan concentration over that 14-hour period than we saw with the tablet or the subcutaneous injection. 

So it’s really interesting that, you know, while we reach that peak plasma concentration sooner, over time that plasma concentration is, in fact, lower than we see with the tablet and the injection. And so, I mean, then kind of the question then comes up do the sumatriptan nasal formulations have less systemic exposure? Are we having less of it absorbed throughout the whole body? The answer is probably yes, looking at this second graph here and looking at the 14-hour period. I mean this first graph here also might go on to say that the nasal powder formulation may be more efficient than the liquid nasal spray formulation. So, it’s interesting to look at how the nasal powder formulation matches up to the nasal spray and to other formulations over time and kind of how it truly works. 

The sumatriptan nasal powder was studied in the TARGET trial. This was a Phase 3, multicenter, placebo-controlled trial. They enrolled just over 200 patients to either the active drug or to a lactose formulation that lactose was the placebo that was delivered in identical breath-powered device as the active drug. 75 patients in the study had aura. And patients with hemiplegic migraine and basilar migraine were specifically excluded from the study. 

In this particular TARGET trial, just about 68% of people in the active group compared to 45.2 in the placebo group reported pain relief at two hours, and that was statistically significant. This graph kind of shows well a lot of patients ask me when can I expect to see some relief from my acute treatment? Well with the sumatriptan nasal powder, we see the 30-minute mark is really where the active drug becomes superior to the placebo dose. Headache relief was more likely at that 30-minute mark with the active drug than compared with the placebo drug. 

We also saw, in this trial, that patients in the active arm were twice as likely to have pain freedom at two hours, and that was 34% in the active group compared to 17% in the placebo group. We also see that, you know, we really want our acute treatments to last. We want them to give sustained pain freedom at 24 hours and at 48 hours after that acute treatment was taken. We found that people who took the active drug were more likely to have sustained pain freedom at 24 hours – around 23% versus 11% in the placebo arm. 

The people who took active drug in the study were also more likely to have sustained pain freedom at 48 hours. That was 20% of folks in the active group had sustained pain freedom at 48 hours compared to around 8 to 9% in the placebo arm. So the clinical trial did end up showing us that the active drug with sumatriptan nasal powder was superior to placebo in providing headache freedom at 2 hours, headache relief at 2 hours, sustained pain freedom at 24 hours, sustained pain freedom at 48 hours, and they did measure disability in this study too. And folks had more reduced disability in the active arm compared to the placebo arm. 

The next most common question that I receive from patients is the adverse reactions. So what were the side effects to this treatment in the study? I want to take you through some of the adverse reactions now, and I promise we’ll also go through some warnings and precautions. Some scenarios where you should definitely discontinue the medication if you experience these issues. 

So the most common reported adverse effects in the study were abnormal taste in the mouth. Around 22% of folks who received the active drug reported abnormal taste; that was compared to 4% in the placebo. 13% of folks in the active arm said that they had some type of nasal discomfort compared to 2% in the placebo arm. 5% reported a runny nose compared to 3% in the placebo. And 3% reported irritation or inflammation in the nose compared to no patients who reported that in the placebo arm. 

One patient using active drug reported dizziness, and another one reported paraesthesias or tingling in the body. But interestingly, there were no reports of chest pain or chest pressure in the study of sumatriptan nasal powder. And so for some cautionary things to look out for, some contraindications. So, if any of these factors exist, sumatriptan nasal powder is not a treatment that really should be considered for the person with migraine. It really, really takes a conversation with your provider to see if sumatriptan nasal powder is the right option for you given your individual tolerances to medications and given your own individual medical history. 

People with coronary artery disease or coronary vasospasm; people with arrythmias of the heart or one variation of that is Wolff-Parkinson-White syndrome, which is a heart conduction issue; people with a history of stroke, TIA, hemiplegic migraine, basilar migraine, peripheral vascular disease, ischemic bowel disease, uncontrolled hypertension, liver issues, anybody that’s had an allergic reaction to sumatriptan in the past sumatriptan nasal powder should be avoided in those folks. 

And so I promised you some warnings and precautions. So please remember to discontinue sumatriptan nasal powder, Onzetra Xsail, if any of these occur. Heart attack or lack of blood flow to the heart causing ischemia or infarction, angina, arrhythmias, any abnormal heart rhythms – if you experience chest, throat, neck, jaw pain, tightness in these areas, pressure/heaviness, you know – do not continue this medication. Your provider, your physician should really work you up for a heart issue if you experience any of these symptoms. 

Any bleeding in the brain, any history of any stroke, any lack of blood flow to the gastrointestinal system, or any spasm of the blood vessels that supply any part of your body you should completely avoid Onzetra. Serotonin syndrome, this rare syndrome that occurs from using medications that activate serotonin receptors that can result in changes in thinking, muscle tightness or pain, changes in your blood pressure, you know, serotonin syndrome can mean many things. But the drug should be discontinued immediately. 

And, you know, I really try to avoid using this treatment in people with epilepsy or somebody that may be likely to have a seizure. These are really important precautions and contraindications to using this treatment. So dosage and administration – we talked a little bit about this earlier, but with the nosepiece, you can administer 11 milligrams in each nostril; that’s a total of 22 milligrams total. You basically take 22 milligrams at the very onset of your migraine attack, and you may repeat the dose in 2 hours if you’re still having that same lingering migraine attack. 

So the maximum dose in a 24-hour period is 44 milligrams. So please try your best do not exceed 44 milligrams in a 24-hour period. You know, triptans, ergotamines, opiate medications, nonsteroidal inflammatories if overused can result in medication overuse headache. So, you know, it’s always a good idea to discuss a preventive treatment with your physician if you find that you may be using your as-needed medications too much. 

I really appreciate you attending this session today. 

Voice-over: Thank you for tuning into Spotlight on Migraine. For more information on migraine disease, please visit MigraineDisorders.org.

*The contents of this podcast are intended for general informational purposes only and do not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. The speaker does not recommend or endorse any specific course of treatment, products, procedures, opinions, or other information that may be mentioned. Reliance on any information provided by this content is solely at your own risk.