Posts Tagged "ubrelvy"

Last updated on September 17th, 2021 at 04:53 am

WHAT ARE THE CGRP MIGRAINE MEDICATIONS AND HOW ARE THEY USED?

@Neuralgroover

What is CGRP (Calcitonin Gene Related Peptide)?

During a migraine attack, the trigeminal nerves release a variety of inflammatory proteins. One of the main proteins is called CGRP (calcitonin gene related peptide). CGRP has been studied since the early 1980s when it was discovered. It was found throughout the trigeminovascular system and trigeminal cranial nerves which transmit pain in the head and face. Therefore, a role in migraine was suspected. The trigeminal nerves are central to causing migraine as explained here. The trigeminal nerves and their associated electrical circuitry throughout the brain, brainstem, and arteries in the brain is called the trigeminovascular system. This system is the basis and an “on switch” for migraine.

In the early 1990s it was shown that CGRP was released by the trigeminal nerves and levels increased during an acute migraine attack. In 2004, a CGRP antagonist (blocks the binding of CGRP to its receptor) was shown to abort (stop) an acute migraine attack, and decrease CGRP levels. Subsequent preventive migraine studies done since 2014 with a CGRP antibody to block the effects of CGRP continued to show reduction in migraine frequency and severity.

 

CGRP causes inflammation around the brain and cerebral arteries (“sterile inflammation”) in the dural membrane surrounding the brain, intensifies pain signals, enhances transmission of pain signals through the trigeminal nerves into the brainstem and into the brain, and causes dilation of the cerebral arteries through the dural membrane. Trigeminal nerve endings surround these arteries. The dilation of these arteries triggers these trigeminal nerve endings and this leads to further increasing pain signals. Think of the process like a painful meningitis, minus the infection.

 

The result of these steps is intense migraine pain (as you are unfortunately very familiar with). So, if we can block these steps of migraine pain, the attack should be aborted quickly, and not as severe. That’s the thinking here, and that’s where the CGRP medications (gepants and CGRP monoclonal antibodies) come into play, as discussed below.

 

CGRP MEDICATIONS USED TO ABORT MIGRAINE (TAKEN AS NEEDED)

Abortive migraine medications are medications taken at the onset of the migraine with a goal of lessening the duration and severity of the migraine attack. Historically, the options have included NSAIDs, ergots, triptans, and neuromodulatory devices.

 

The gepants were the first new medicine class to emerge as new migraine abortive options (FINALLY!!!) since the triptans became available in 1992. There are currently 2 oral pill gepant abortive options available. They are Ubrelvy (Ubrogepant), and Nurtec ODT (orally dissolvable tablet) (Rimegepant). These 2 gepants are discussed and compared in much greater detail here. Zazegepant will be the 3rd abortive gepant, and will be the 1st nasal spray gepant option available. It is in ongoing clinical trials currently.

 

How does Nurtec ODT and Ubrelvy (gepants) work?

Gepants work as CGRP receptor antagonists, which means they directly block (antagonist) the CGRP receptor. This results in the medication “blocking” the CGRP inflammatory protein from sticking to the CGRP receptor to activate it, and thus prevents it from “turning on” the pathways of pain described above.

 

So, you get reversal of cerebral vasodilation, which decreases the firing off of the trigeminal nerves. Notably, the gepants do this in a way that does not cause vasconstriction, in contrast to the triptans. Thus, they are felt to be safe in those with cardiovascular or cerebrovascular disease (as opposed to the triptans).

 

By blocking the CGRP receptor, you also get reversal of the neurogenic inflammation going on through the brain and around the arteries, and you block the electrical transmission of migraine pain from traveling from the trigeminal nerves into the brainstem, and ultimately into the brain.

 

The other huge benefit of the triptans compared to all other abortive options is that they do not cause medication overuse headache (rebound headache)!

 

What are the side effects of Nurtec ODT and Ubrelvy?

The side effect profile of the gepants is minimal and similar to placebo. The most common side effects of gepants are very low risk of nausea for Nurtec ODT and low risk of nausea and mild sedation with the higher dose of Ubrelvy. Side effects are discussed in more detail here.

 

In addition, there is no interaction with using them and triptans, NSAIDs, or other acute meds in case they happen to be taken close together.

 

Compared to other abortive medications such as the triptans and NSAIDS, these medications are not associated with medication overuse headache (rebound headache), which is great! They also have no addiction potential.

 

Compared to the triptans and ergots, these medications are NOT contraindicated in patients with stable cardiovascular or peripheral vascular disease or risk factors because they do not cause vasoconstriction (narrowing) of the arteries, which is a HUGE benefit.

 

Triptans are also contraindicated in patients with visual snow, persistent migraine aura, and migrainous stroke (infarction). However, gepants are felt to be safe for these patients, as well as those with hemiplegic migraine and migraine with brainstem aura (previously called basilar migraine). There are many patients who have been stuck without safe options since they have been unable to use standard therapies such as triptans due to other medical problems such as heart disease. So, we finally have a safe alternative for them, which is a highlight of these medications.

 

Can Nurtec ODT and Ubrelvy be used in pregnancy and breastfeeding?

Safety of these medications in pregnancy or breastfeeding is unknown because they haven’t been studied, and therefore are not recommended.

 

Are there drug interactions with Nurtec ODT and Ubrelvy (gepants) and other medications?

The primary drug interactions to be aware of with these medications are when used with other medications that are metabolized by the liver enzyme system called CYP3A4. Many commonly used medications are metabolized by this system. Strong or moderate inhibitors of CYP3A4 (which slow down the metabolic drug breakdown) will cause an increase in gepant blood levels. Strong or moderate inducers of CYP3A4 (which increase the metabolic drug breakdown) will cause a decrease in gepant blood levels and possibly decreased effectiveness. These medications should be avoided in patients with severe liver disease or end stage kidney disease such as those on dialysis.

CGRP MEDICATIONS USED TO PREVENT MIGRAINE

Preventive migraine treatments are used to lessen the frequency and/or severity of migraine attacks. Preventive treatments include a variety of daily pill medications, neuromodulatory devices, herbal and natural supplements and vitamins, yoga and meditation, acupuncture and acupressure. All of the medications used for migraine prevention have always been “adopted” from other specialties. In other words, these were medicines made for other purposes (such as antidepressants, antiseizure, anti-blood pressure meds), but eventually some were also found to be useful for migraine prevention.

 

There has never been a medicine engineered and created purely and only for migraine prevention. However, that changed in 2018 when the migraine preventive landscape changed abruptly and significantly. The 1st medication class designed purely and only for migraine prevention become available, called the CGRP monoclonal antibodies (mAbs). There are currently 4 CGRP mAb treatment options. They are Aimovig (Erenumab), Emgality (Galcanezumab), Ajovy (Fremenazumab), and Vyepti (Eptinezumab).

 

These medications either target the CGRP receptor (Aimovig), or the CGRP protein (Emgality, Ajovy, Vyepti). The result of “blocking” the CGRP protein or CGRP receptor prevents the CGRP pathways of pain from “turning on”, as discussed above and here. Clinically, some patients tend to respond better to the CGRP receptor blockade, whereas others tend to do better with binding the CGRP protein itself. There is not really any data on this in terms of who may respond to which type of CGRP mAb target, but I’m sure it will be studied further eventually.

 

Aimovig, Emgality, and Ajovy are all once monthly self-injections (push button autoinjection), although Ajovy also has the option of quarterly injections (3 injections every 3 months). Vyepti is the only IV (intravenous form) and is done by 30-minute IV treatment every 3 months. These individual CGRP mAbs are discussed and compared in much greater detail here.

 

What are the side effects of the CGRP mAbs (Aimovig, Emgality, Ajovy, Vyepti)?

Compared to most other medications used for migraine prevention historically, the side effects of the CGRP mAbs are very low. The most common side effects reported (at a very low rate) are mild upper respiratory infections and minor injection site reactions. Aimovig has a slightly increased risk of constipation and possible mild increase in high blood pressure for some patients. These have little to no drug interactions and do not affect the liver or kidneys. Data show no immunological (they do not suppress or alter the immune system because they do not have a target within the immune system), cardiovascular, or neurological safety concerns of significance.

 

Can the CGRP mAbs (Aimovig, Emgality, Ajovy, Vyepti) be used in pregnancy and breastfeeding?

There is no data to answer this question yet. However, CGRP is suspected to play a possible role in regulating uteroplacental blood flow, myometrial and uterine relaxation, and in maintaining normal gestational blood pressure. Since the mAbs have a long half-life and can last in the system for 5 months, it is recommended to stop it about 6 months prior to pregnancy planning. The CGRP mAbs are also not recommended to use during breast-feeding since we do not have enough safety data at this time.

 

Nurtec ODT and gepants for migraine prevention.

The CGRP mAbs have been a major step forward for migraine prevention. However, up to this point, we still have not had an oral pill that has been engineered and created purely and only for migraine prevention (not “adopted” from a different medicine class as mentioned above).

 

That was until now, with development of the gepants (discussed above). On 5/27/21, Nurtec ODT (Rimegepant) made history as the first and only FDA approved medication for BOTH abortive and preventive migraine treatment simultaneously, and the only option with this flexibility and is discussed in greater detail here!

 

The perspective behind this is that migraine is a fluid and variable disease, fluctuating between periods of episodic migraine (1-14 headache days per month), and other periods of chronic migraine (15 or more headache days per month). So, having a medicine that can function as both types of treatment, depending on what type of phase the migraine is in (episodic or chronic) opens up an entirely new flexible treatment paradigm and approach which we have never had up to this point.

 

So essentially, taking Nurtec ODT every other day could be used as an ongoing daily preventive strategy (the long half-life of 11 hours allows for this spread-out dosing) when the migraine is in a high frequency to chronic migraine phase. If it evolves back into a lower frequency episodic migraine pattern, it can then just be used abortively only when needed for a migraine attack.

 

This new flexible dosing option of Nurtec ODT could also be used as a “mini-prophylaxis” within the month. For example, if patients know they are approaching a predictable migraine trigger, such as menstrual migraine, barometric trigger from an airplane trip, upcoming stressful event such as an exam, etc., the medication could possibly be taken daily or every other day starting a few days before the anticipated trigger, and stopping it a day or so after the trigger is no longer present. Unlike other migraine preventive pill treatments which take 4-6 weeks to start working and 2-3 months to see full effect, the gepants work fast and this would allow this potential treatment option to begin working immediately. In fact, studies show that migraine frequency dropped by 30% within the first week alone of preventive use.

 

Atogepant is the 2nd gepant that will be used as a daily preventive pill only and is pending FDA approval, but is anticipated soon.

 

Can the preventive CGRP mAbs (Aimovig, Emgality, Ajovy, Vyepti) be used with the CGRP abortive gepant medications (Nurtec ODT, Ubrelvy)?

Can I use Aimovig with Nurtec ODT? Can I use Aimovig with Ubrelvy? Can I use Emgality with Nurtec ODT? Can I use Emgality with Ubrelvy? Can I use Ajovy with Nurtec ODT? Can I use Ajovy with Ubrelvy? Can I use Vyepti with Nurtec ODT? Can I use Vyepti with Ubrelvy? These are very common questions. Unfortunately, there aren’t many studies so far to clarify this, although I’m sure these questions will be studied and clarified in the near future. The gepants and the CGRP mAbs have much different structures, molecule sizes, and metabolism.

 

So theoretically, it would make sense that using an abortive CGRP medication (gepant) on top of a CGRP preventive medication (CGRP mAb) would give synergistic (working together) benefit. Using a CGRP preventive medication targeting the CGRP protein (Emgality, Ajovy, Vyepti) and a CGRP abortive medication targeting the CGRP receptor (Nurtec ODT, Ubrelvy) seems like a very sensible idea. Similarly, using a CGRP preventive medication targeting the CGRP receptor (Aimovig) combined with a CGRP abortive medication also targeting the CGRP receptor (Nurtec ODT, Ubrelvy) would make a lot of sense too. In fact, there are some limited studies which provide evidence that these medications used together do work better and are safe.

 

There was a publication of data from only a 2-patient cohort showing that the use of these acute and preventive CGRP migraine therapies together can be successful and safe. These two patients had been using Rimegepant (Nurtec ODT) in a long-term safety study and they had added Erenumab (Aimovig) once monthly injection as a preventive treatment. After Aimovig was added, patient 1 had 100% relief for 7 of 7 acute migraine attacks treated with Nurtec. Patient 2 had 100% relief for 9 of 9 acute migraine attacks treated with Nurtec. So, the combination of using Nurtec abortively in addition to using Aimovig preventively appeared to provide an even more effective acute migraine response. Larger studies to confirm the suspicion that they likely work together synergistically will be helpful.

 

There was a larger safety study publication which evaluated the acute treatment of migraine with Rimegepant while using a CGRP monoclonal antibody for the prevention of migraine. The CGRP mAbs used were Erenumab (Aimovig) (7 patients), Fremanezumab (Ajovy) (4 patients), and Galcanezumab (Emgality) (2 patients). The study determined that Rimegepant used as an acute migraine treatment in combination with CGRP mAbs for migraine prevention was well tolerated with no safety issues identified. The researchers concluded that the probability between these 2 classes (gepants and CGRP mAbs) was low, especially because they have entirely different pathways of drug metabolism. The gepants are metabolized in the liver, while the CGRP mAbs are metabolized and cleared in the reticuloendothelial system. They also concluded that existing evidence supports the safety of combined use, although further larger research was warranted.

 

Can the CGRP mAbs (Aimovig, Emgality, Ajovy, Vyepti) be used with Botox (Onabotulinumtoxin A) for chronic migraine?

The answer is yes. Insurance companies often present various hurdles to using preferred treatment options (the bane of my existence). One common issue for patients with chronic migraine who are receiving Botox injections is that most insurance companies will now make the patient choose between Botox or the CGRP mAb. There is of course no good scientific basis for this, other than the company doesn’t want to pay for both.

 

Actually, there is evidence that using Botox with the CGRP mAbs works better together than with either individually. An abstract presented at the American Headache Society Annual Scientific meeting in June 2020 showed that in patients with chronic migraine and a baseline frequency of 25.7 days per month, the frequency dropped to 14.8 days with Botox, and 9.1 days with Botox plus a CGRP mAb.

 

Can I still use my CGRP mAb (Aimovig, Ajovy, Emgality, Vyepti) with the Covid-19 vaccine?

This hasn’t been a reported issue thus far. There is no current evidence for an interaction between the Covid-19 vaccine and CGRP mAbs, the same as any other vaccine. This has also been stated by the American Migraine Foundation. Patients receiving CGRP mAbs were not excluded from the Covid-19 vaccine trials. There is no evidence at this time that these treatments cannot be used along with receiving Covid-19 vaccination, nor do they need to be delayed or timed any differently in relation to receiving Covid-19 vaccination.

 

Most physicians feel that there should theoretically be no interaction or contraindication to receiving either of these treatments in relation to Covid-19 vaccination because they are entirely different proteins with different mechanisms of action. The Covid-19 vaccine stimulates the immune system to form antibodies against the virus, should you encounter it. The CGRP mAbs do not have any significant influence on the immune system (they do not cause immunosuppression, etc.).

 

Rarely, the immune system of some patients can form neutralizing antibodies against the CGRP mAbs, and this can weaken the effectiveness of these treatments in their ability to decrease migraine frequency and severity. However, this rarity really has nothing to do with the mechanism and how the Covid-19 vaccine works. So, it is not felt that the Covid-19 vaccine will lessen the effectiveness of these treatments, nor will these treatments lessen the effectiveness of the Covid-19 vaccine.

 

Notably, there have been just a few isolated reports of dermal fillers used in dermatology causing some facial swelling in association with Covid-19 vaccination, but not with Botox or the CGRP mAbs. These reports were with the Moderna Covid vaccine and resolved with steroids and/or antihistamines. The topic of Covid-19 headache and Covid-19 vaccination is discussed further here.

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

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Last updated on October 4th, 2021 at 01:52 pm

UBRELVY (UBROGEPANT) vs. NURTEC ODT (RIMEGEPANT) vs. REYVOW (LASMIDITAN) vs. TRIPTANS. NEW MIGRAINE ABORTIVE OPTIONS ARE FINALLY HERE, BUT WHAT ARE THE DIFFERENCES AND IS ONE BEST FOR YOU?

@Neuralgroover

BACKGROUND

Ubrelvy vs. Nurtec, Ubrelvy vs. triptans, Nurtec vs. triptans, Ubrelvy vs. Reyvow, Nurtec vs. Reyvow, Reyvow vs. triptans, Rimegepant vs. Ubrogepant, Ubrogepepant vs. triptans, Rimegepant vs. triptans, Lasmiditan vs. Ubrelvy, Nurtec vs. Lasmiditan, Lasmiditan vs. triptans, Ubrogepant vs. Lasmiditan, Rimegepant vs. Lasmiditan. How do you know which one to pick??? Let’s discuss how to pick the best one for you.

 

First off, these medications are all migraine specific abortive/acute (as needed) options. The goal of migraine abortive treatments is to stop individual migraine attacks at onset so the migraine does not reach full severity, ends quickly, and your function is restored and maintained rather than having to go lay down and miss the whole day in bed. This is in contrast to migraine preventive treatments which are a continuous treatment. Preventive treatments include a daily pill, a monthly/quarterly treatment such as CGRP monoclonal antibodies (Aimovig, Ajovy, Emgality, Vyepti), or neuromodulation devices. The goal of migraine preventive treatment is to lessen the frequency and/or severity of migraine attacks, and these options are discussed in more detail here. If you have migraine, you want to have both a good abortive and preventive treatment plan to lessen migraine’s nasty habit of interfering and disrupting life and function.

 

Since the development and availability of sumatriptan in 1992, the primary migraine specific abortive/acute (as needed) option available has been the triptans. Triptans (Imitrex, Maxalt, etc.) work great for a lot of people. However, about 30% of patients do not respond to triptans. Others cannot tolerate side effects, or they cannot use them because of medical contraindications (such as coronary artery disease, peripheral artery disease, cerebrovascular disease, stroke, etc.). Triptans are also contraindicated in patients with visual snow, persistent migraine aura, and migrainous stroke (infarction). They have been historically contraindicated in hemiplegic migraine or basilar migraine (now called migraine with brainstem aura) due to theoretical concerns of vasoconstriction potentially causing stroke. When the triptan studies were done previously, they excluded patients with these forms of migraine due to the ongoing vascular theory of migraine at that time. The vascular theory of migraine assumed that vasoconstriction and lack of blood flow was the cause of aura and neurologic features with migraine. So the thinking was that if you cause further vasoconstriction with a triptan, you may cause stroke. However, we now know that these phenomenon are primarily of an electrical basis and not a vascular basis. Therefore many specialists have gotten more liberal with the use of triptans in patients with hemiplegic or basilar migraine, and there have been a number of case series and case reports of these patients using triptans without any problems.

 

The alternatives to triptans have historically been the ergots (ergotamine, DHE) which can be complicated to use, tend to have an excess of side effects for many, and have the same medical contraindications as triptans. NSAIDs and over the counter analgesics are also commonly used, although many do not respond to or cannot take them due to other medical conditions. Even worse are opiates/opioids and butalbital medications such as fioricet, both of which (as do excess triptans, NSAIDS, OTCs) have a high risk of leading to medication overuse headache (rebound headache), as discussed here.  For close to 3 decades, these have remained the only limited options of acute/abortive migraine treatment, despite migraine being such a widespread common disorder! More recently, neuromodulation devices have also become available as abortive options.

 

Thankfully, these limited options have now expanded to 3 new migraine abortive options in adults between 2 new classes which became available commercially in 2020; the gepants and the ditans. These medications can be used SAFELY in all of the medical contraindications mentioned above! These 3 new abortive medications are compared and contrasted with one another, as well as with the triptans in the table which I constructed below.

 

GEPANTS

The gepants were the first to emerge as new migraine abortive options, first with Ubrogepant (Ubrelvy) which became available from Allergan in January 2020 and then Rimegepant (Nurtec ODT (orally dissolvable tablet)) became available by Biohaven in February 2020.

 

During a migraine attack, the trigeminal nerves release a variety of inflammatory proteins. One of the main proteins is called CGRP (calcitonin gene related peptide). CGRP causes inflammation around the brain and cerebral arteries (“sterile inflammation”) in the dural membrane surrounding the brain, intensified pain signals, enhanced transmission of pain signals through the trigeminal nerves into the brainstem and into the brain, and dilation of the cerebral arteries through the dural membrane, which in turn leads to further increasing pain signals via the trigeminal nerve endings covering the cerebral arteries. The result is intense migraine pain (as you are unfortunately very familiar with). So, if we can block these steps of migraine pain, the attack should be aborted quickly, and not as severe. That’s the thinking here, and that’s where the CGRP medications (gepants and CGRP monoclonal antibodies) come into play.

 

Gepants work as CGRP receptor antagonists, which means they directly target and block (antagonist) the CGRP receptor. This results in the medication “blocking” the CGRP inflammatory protein from sticking to the CGRP receptor to activate it, and thus prevents it from “turning on” these pathways of pain. So, you get reversal of cerebral vasodilation, which decreases the firing off of the trigeminal nerves. Notably, the gepants do this in a way that does not cause vasconstriction, in contrast to the triptans. Thus, they are felt to be safe in those with cardiovascular or cerebrovascular disease (as opposed to the triptans). By blocking the CGRP receptor, you also get reversal of the neurogenic inflammation going on through the brain and around the arteries, and you block the electrical transmission of migraine pain from traveling from the trigeminal nerves into the brainstem, and ultimately into the brain.

 

The side effect profile of the gepants is minimal and similar to placebo compared to the triptans and their alternatives.  This is really great to have new options with much less side effect potential. In addition, there is no interaction with using them and triptans, NSAIDs, or other acute meds in case they happen to be taken close together. These medications are not associated with addiction potential, and do not cause medication overuse headache (rebound), which is great! Compared to the triptans and ergots, these medications are NOT contraindicated in patients with stable cardiovascular or peripheral vascular disease or risk factors because they do not cause vasoconstriction (narrowing) of the arteries, which is a HUGE benefit. There are many patients who have been stuck in limbo unable to use standard therapies such as triptans due to other medical problems such as heart disease, so we finally have a safe alternative for them, which is another highlight of these medications. Safety of these medications in pregnancy or breastfeeding is unknown because they haven’t been studied, and therefore are not recommended. The primary drug interactions to be aware of with these medications are when used with other medications that are metabolized by the liver enzyme system called CYP3A4. Many commonly used medications are metabolized by this system. Strong or moderate inhibitors of CYP3A4 (which slow down the metabolism activity) will cause an increase in gepant exposure. Strong or moderate inducers of CYP3A4 (which increase the metabolism activity) will cause a decrease in gepant exposure and possibly decreased effectiveness. These medications should be avoided in patients with severe liver disease or end stage kidney disease such as those on dialysis.

 

Many patients use once monthly CGRP antagonist monoclonal antibody (mAbs) self-injections (autoinjection devices) which are FDA approved for migraine prevention (Aimovig (Erenumab), Ajovy (Fremanezumab), Emgality (Galcanezumab), and Vyepti (Eptinezumab), which is a once quarterly 30 minute IV infusion). The CGRP mAbs are discussed in much greater detail and compared with one another here. These have little to no drug interactions and do not affect the liver or kidneys. However, patients often ask if these medications can be used with the gepants given similar mechanisms of action (although much different structure, molecule size, and metabolism). Further confirmatory research is needed, but it is theorized that these medicines can likely be used safely together, and they are metabolized by completely different mechanisms. The gepants are metabolized in the liver, while the CGRP mAbs are metabolized and cleared in the reticuloendothelial system. Furthermore, there is limited evidence suggesting that they may even provide a synergistic effect by working together, but more evidence is needed to confirm this. An insurance battle often ensues when trying to use the large molecule preventive CGRP mAbs with the small molecule abortive gepant medications (Nurtec, Ubrelvy), which also work by a CGRP mechanism. Insurance companies will often not allow these to be used together, despite no good scientific basis. Actually, there is some limited evidence showing that these medications can work synergistically together, which would make sense when taking their mechanisms of action into account. Specifically, there was a publication of data from only a 2-patient cohort showing that the use of these acute and preventive CGRP migraine therapies together can be successful and safe. These two patients had been using rimegepant (Nurtec) in a long-term safety study and had added erenumab (Aimovig). The combination of both successfully aborted 100% of their acute migraine attacks. Certainly we need need larger studies to confirm the suspicion that they likely work together synergistically.

 

Given that Ubrelvy and Nurtec ODT are of the same gepant class, they each have their own marketing pitch to differentiate them, although the bottom line is that they are both excellent options. Although they are both very effective for most patients, I commonly see patients who may respond to one better than the other. So if one of them does not help, it is worth trying the other one as well.

 

Ubrelvy (Ubrogepant)

Allergan markets Ubrelvy as quickly relieving migraine pain within 2 hours with just one dose, and that complete elimination of migraine pain with one dose is possible. Furthermore, they highlight that they provide the option of being able to repeat a 2nd dose if needed (similar to how triptans are dosed), with a higher proportion of patients achieving pain freedom 2 hours after taking the optional second dose. They also claim effective relief whether Ubrelvy was taken right away at migraine onset or within 4 hours. The half life is 5-7 hours, so duration of effect is extended compared to many options that we had up to this point. The clinical data highlights of Ubrelvy are that at 1 hour Ubrelvy 50 mg becomes statistically superior to placebo for pain relief, and at 2 hours the 100 mg dose also becomes statistically superior to placebo for pain relief. At 2 hours, both the 50 mg and 100 mg doses become statistically superior to placebo for pain freedom as well as freedom from most bothersome migraine symptom (nausea, photophobia or phonophobia). These benefits could extend into 24 and even 48 hours. In patients who received pain relief with the 1st dose and took an optional 2nd dose of 50 mg, 55% went on to become pain free 2 hours from that point.

 

Side effects were similar to placebo and the most common were nausea (placebo 2%, Ubrelvy 50 mg 2%, Ubrelvy 100 mg 4%), and somnolence (sleepiness) (placebo 1%, Ubrelvy 50 mg 2%, Ubrelvy 100 mg 3%).

 

They currently have a savings card program which should work with commercial insurances for $10 per month, which works out to $1 per pill (10 pills per month). You can get a digital copy of this savings card on your phone to show to the pharmacist if you text UBRELVY to 48764.

 

Nurtec ODT (Rimegepant)

Biohaven boasts that Nurtec ODT 75 mg dissolves under or on the tongue in seconds, and starts working in minutes (15 minutes in some patients). They highlight that it does not require water or other liquids to take with the dose, so it can be taken anytime and anywhere. It is taken as a simple single strength single dose. They also point out that pain relief and pain freedom lasts up to 48 hours for many patients, which makes sense because it has the longest half-life (11 hours). The clinical data highlights of Nurtec ODT are that at 15 minutes, you get separation from placebo of both pain relief and return to normal function (but not yet statistically superior). At 1 hour, pain relief and return to normal function become statistically superior to placebo. At 1.5 hours, you get additional statistical superiority over placebo of pain freedom and freedom from most bothersome migraine symptom (nausea, photophobia or phonophobia). For the vast majority of patients, the superiority of all of these trial endpoints over placebo remain sustained through 48 hours.

 

Side effects were similar to placebo and the most common was nausea (placebo 0.4%, Nurtec 2%).

 

They currently have a savings card program which should work with commercial insurances for $0 per month (8 pills per month). You can get a digital copy of this savings card on your phone to show to the pharmacist if you text NSAVE to 26789.

 

Notably, on 5/27/21, Nurtec ODT made history as the first and only FDA approved medication for BOTH abortive and preventive migraine treatment simultaneously, and the only option with this flexibility! Nurtec ODT as a preventive migraine treatment is discussed further here. This move followed clinical trials showing that patients taking 75 mg of Rimegepant every other day experienced a 4.3 day reduction from baseline in monthly migraine days, a 30% drop of migraines within even the first week, and 49% of patients had a greater than 50% reduction in monthly migraine days.

 

Notably, on 9/28/21, Qulipta (Atogepant) became the second oral CGRP preventive gepant medication to become FDA approved for migraine prevention (not dually approved for both abortive and preventive). It is taken once daily. So, Nurtec ODT and Qulipta have become the first oral CGRP preventive medication options. They are both of the gepant medication family, which is different than the CGRP mAb family, but none the less now offer an oral alternative to once monthly CGRP monoclonal antibody injections.

 

Can I use a CGRP monoclonal antibody (mAb) (Aimovig, Ajovy, Emgality, Vyepti) with Botox injections?

Insurance companies often present various hurdles to using preferred treatment options (the bane of my existence). One common issue for patients with chronic migraine who are receiving Botox injections is that most insurance companies will now make the patient choose between Botox or the CGRP mAb. There is of course no good scientific basis for this, other than the company doesn’t want to pay for both. In fact, there is evidence that using Botox with the CGRP mAbs works better together than with either individually. An abstract presented at the American Headache Society Annual Scientific meeting in June 2020 showed that in patients with chronic migraine and a baseline frequency of 25.7 days per month, the frequency dropped to 14.8 days with Botox, and 9.1 days with Botox plus a CGRP mAb.

 

Can I use a CGRP mAb (Aimovig, Ajovy, Emgality, Vyepti) with the gepants (Nurtec, Ubrelvy)?

A similar insurance battle often ensues when trying to use the large molecule preventive CGRP mAbs with the small molecule abortive gepant medications (Nurtec, Ubrelvy), which also work by a CGRP mechanism. Insurance companies will often not allow these to be used together, but again, no good scientific basis. Actually, there is some limited evidence showing that these medications can work synergistically together, which would make sense when taking their mechanisms of action into account. Specifically, there was a publication of data from only a 2-patient cohort showing that the use of these acute and preventive CGRP migraine therapies together can be successful and safe. These two patients had been using rimegepant (Nurtec) in a long-term safety study and they had added erenumab (Aimovig) once monthly injection as a preventive treatment. After Aimovig was added, patient 1 had 100% relief for 7 of 7 acute migraine attacks treated with Nurtec. Patient 2 had 100% relief for 9 of 9 acute migraine attacks treated with Nurtec. So, the combination of using Nurtec abortively in addition to using Aimovig preventively appeared to provide an even more effective acute migraine response. Theoretically, it would make sense that benefit would be greater with both classes of medicines combined because they are entirely different types of medications targeting aspects of the same migraine pathway simultaneously (either targeting the CGRP receptor or the CGRP ligand protein). Larger studies to confirm the suspicion that they likely work together synergistically will be helpful.

 

There was a larger safety study publication which evaluated the acute treatment of migraine with Rimegepant while using a CGRP monoclonal antibody for the prevention of migraine. The CGRP mAbs used were Erenumab (Aimovig) (7 patients), Fremanezumab (Ajovy) (4 patients), and Galcanezumab (Emgality) (2 patients). The study determined that Rimegepant used as an acute migraine treatment in combination with CGRP mAbs for migraine prevention was well tolerated with no safety issues identified. The researchers concluded that the probability between these 2 classes (gepants and CGRP mAbs) was low, especially because they have entirely different pathways of drug metabolism. They also concluded that existing evidence supports the safety of combined use, although further larger research was warranted.

 

DITANS

Reyvow (Lasmiditan)

The ditans are another new class of migraine abortive, premiering with Lasmiditan (Reyvow) in January 2020 from Eli Lilly. Lasmiditan acts as a high affinity 5-HT1F (serotonin 1F) receptor agonist. The result of its action is a decrease in the release of inflammatory pain producing neurotransmitters and neuropeptides including CGRP from the trigeminal nerves during a migraine attack. These receptors are also involved in modulating other pain signals and blocking (inhibiting) other pain pathways. Notably, like the gepants, they also do not cause arterial vasoconstriction. Again, this is a tremendous benefit and another great option in patients who may not be able to use triptans due to medical contraindications such as coronary or peripheral vascular disease. Caution should be used with other serotonergic drugs given a potential for serotonin syndrome, which was reported in clinical trials.

 

Similar to the gepants, the Reyvow clinical data highlights showed superiority over placebo at trial endpoints of 2 hour pain freedom, freedom from most bothersome migraine symptom (nausea, photophobia or phonophobia), and pain relief.

 

In a driving study, 50 mg, 100 mg, or 200 mg doses of Lasmiditan significantly impaired subjects’ ability to drive, and more sleepiness was reported at 8 hours following a single dose compared to placebo. Therefore, patients should wait at least 8 hours between dosing and driving or operating machinery. This can certainly be a drawback in terms of being a treatment option for many patients as the goal of abortive therapy is partly to be able to maintain and restore function in order to not disrupt work, plans, etc. However, if you are in a position where this would not be an issue for you, it could certainly be a valid option to have in your migraine war chest. It should also be used with caution in combination with alcohol or other central nervous system depressants.

 

Notably, Lasmiditan is a Schedule V controlled substance compared to the other abortive options. Schedule V represents the lowest abuse potential category from the DEA. The reason is because in a human abuse potential study, doses of 100 mg, 200 mg, and a supratherapeutic dose of 400 mg were associated with statistically significantly higher “drug liking” scores than placebo, indicating possible abuse potential. However, it had statistically significantly lower “drug liking” scores compared to alprazolam 2 mg. Lasmiditan also produced adverse events of euphoria and hallucinations to a greater extent than placebo, although it was a low frequency (about 1% of patients). They currently have a savings card program which should work with commercial insurances for $0 per month (4 pills per month).

 

SUMMARY

The chart below compares and contrasts the treatment outcomes data between Rimegepant, Ubrogepant, Lasmiditan, and Sumatriptan (as representative of the triptan class since it was the first developed). The source of the data comes from the key trials of each medication, as well as some data obtained directly from the pharmaceutical companies. It’s important to note that the trials for each medication did not all include the same data point evaluations, so not all of the comparison data is available across the medications to compare. Also, this data is not reflective of head to head trials between these medications. The data is derived from separate independent trials, many times of which there were variations in study design and endpoints. So, they should not be thought of as head to head comparisons necessarily. In addition, the original triptan studies did not include many of the treatment outcome data points that have become more commonly used since they were developed such as 8 hour data, 2-48 hour data, most bothersome symptom, etc. Therefore, many of these data points within the columns of the different medications may be labeled by N/A (not available).

 

Overall, these are all very effective and useful medications to keep in mind for your migraine abortive war chest. They are all a welcome and much needed option for the abortive (acute) treatment of migraine. Notably, Ubrelvy, Nurtec ODT, and Reyvow were all proven to be statistically superior to placebo at 2 hours post-dose (some sooner) in terms of pain freedom, pain relief, and freedom from most bothersome migraine symptom (nausea, sensitivity to light (photophobia) or sensitivity to sound (phonophobia)). So there is no “bad” option. Many of the data points are fairly similar with some slight variations, and some data points weren’t compared. Regardless, I have highlighted some of the key differences to take note of in bold print. I hope this data can provide some guidance on some of the differences in these medications which may help to better select them based on the treatment goals, setting of use, and other patient characteristics.

 

Rimegepant Ubrogepant Lasmiditan Sumatriptan (100 mg)
Class Gepant Gepant Ditan Triptan
Mechanism of Action CGRP receptor antagonist CGRP receptor antagonist 5HT1F agonist 5HT1B and 5HT1Dagonist
Available dosing 75 mg orally dissolvable tablet 50 mg, 100 mg pill 50 mg, 100 mg, 200 mg (100 mg x 2) pill 25 mg, 50 mg, 100 mg pill; 3 mg, 4 mg, 6 mg injection; 5 mg, 10 mg, 20 mg nasal spray
Max dose per 24 hours 75 mg 200 mg 200 mg 200 mg
Pills per prescription (standard, may be more depending on insurance) 8 10 8 9
Dosing frequency 1 dose/24 hours Dose can repeated once in 2 hours; 2 doses/24 hours 1 dose/24 hours Dose can repeated once in 2 hours; 2 doses/24 hours
Suggested number of migraine attacks treated per 30 days 15 (however, currently also being studied as a daily preventive) 8 4 10
Time to reach statistically significant pain relief 60 minutes (however, there was a 15 minute measured clinical beneficial effect) 60 minutes with 50 mg or higher doses 30 minutes with 100 mg or higher doses;

60 minutes with 50 mg dose

30 minutes with 50 mg or higher doses
1 hour significant pain relief 37%

31% (placebo)

43% (50 mg)

N/A (100 mg)

36.7% (placebo)

37.3% (50 mg)

»41% (100 mg)

»46% (200 mg)

30.6% (placebo)

20-35% (100 mg)

12-21% (placebo)

Differences in pain relief at 15 minutes 8%

5% (placebo)

N/A N/A N/A
Differences in pain relief at 30 minutes 19%

17% (placebo)

19% (50 mg)

N/A (100 mg)

20% (placebo)

»15% (50 mg)

17.5% (100 mg)

19.1% (200 mg)

13.4% (placebo)

11% (100 mg)

12% (placebo)

2 hour pain relief 59%

43% (placebo)

61.7% (50 mg)

61.4% (100 mg)

48.7% (placebo)

59% (50 mg)

59.4-64.8% (100 mg)

59.5-65% (200 mg)

42.2-47.7% (placebo)

46-67% (100 mg)

18-44% (placebo)

2 hour pain freedom 21%

11% (placebo)

20.5% (50 mg)

21.2% (100 mg)

13% (placebo)

28% (50 mg)

28-31% (100 mg)

32-39% (200 mg)

15-21% (placebo)

22-33% (100 mg)

3-13% (placebo)

8 hour pain freedom with 1 dose 56%

33% (placebo)

82.3% (50 mg)

82.7% (100 mg)

69.8% (placebo)

N/A N/A
8 hour pain relief with 1 dose 74%

56% (placebo)

92% (50 mg)

N/A (100 mg)

82% (placebo)

N/A N/A
% of patients with 1st dose pain relief who achieved pain freedom after 2nddose N/A 54.7% (50 mg/50 mg)

33.3% (50 mg/placebo)

51.6% (100 mg/100 mg)

33.3% (100 mg/placebo)

N/A N/A
Sustained pain freedom 2-24 hours 15.7%

5.6% (placebo)

13.6% (50 mg)

15.4% (100 mg)

8.4% (placebo)

17.2% (50 mg)

14.8-17.9% (100 mg)

18.6-22.7% (200 mg)

7.6-13.4% (placebo)

N/A
Sustained pain relief 2-48 hours 47.8%

27.7% (placebo)

31.5% (50 mg)

34% (100 mg)

17.5% (placebo)

N/A N/A
2 hour absence of most bothersome migraine symptom 35%

27% (placebo)

38.7% (50 mg)

37.7% (100 mg)

27.6% (placebo)

41% (50 mg)

41-44% (100 mg)

41-49% (200 mg)

30-33% (placebo)

N/A
8 hour absence of most bothersome migraine symptom N/A 90.9% (50 mg)

92.4% (100 mg)

77.7% (placebo)

N/A N/A
Time to peak plasma concentration TMAX 1.5 hours 1.5 hours 1.8 hours 1.5-2.5 hours
½ life 11 hours 5-7 hours 5.7 hours 2-2.5 hours
Time to reach pharmacologically active concentration 15 minutes Within 11 minutes N/A N/A
Time the pharmacologically active concentration is maintained 48 hours 12 hours N/A N/A
Notable side effects Nausea

2%

0.4% (placebo)

Nausea

2% (50 mg)

4% (100 mg)

2% (placebo)

 

Somnolence/Sedation

2% (50 mg)

3% (100 mg)

1% (placebo)

Nausea

3% (50 mg)

4% (100 mg)

4% (200 mg)

2% (placebo)

 

Somnolence/Sedation

6% (50 mg)

6% (100 mg)

7% (200 mg)

2% (placebo)

 

Dizziness

9% (50 mg)

15% (100 mg)

17% (200 mg)

3% (placebo)

 

Paresthesias

3% (50 mg)

7% (100 mg)

9% (200 mg)

2% (placebo)

Widely variable, most common: Dizziness, fatigue, paresthesias, sedation, nausea, palpitations, anxiety, muscle tightness sensation in chest/neck/throat

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

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Last updated on September 17th, 2021 at 06:36 am

WHAT ARE THE TRIPTAN DIFFERENCES AND WHICH IS BEST? HOW TO FINE-TUNE WHICH TRIPTAN MAY BE MOST EFFECTIVE FOR YOU.

@Neuralgroover

BACKGROUND:

Imitrex vs. Maxalt, Zomig vs. Maxalt, Amerge vs. Relpax, Frova vs. Imitrex, Maxalt vs. Relpax, Zomig vs. Imitrex, Frova vs. Amerge, Imitrex vs. Treximet. Maxalt vs. Frova. Axert vs. Imitrex. These are the triptans for migraine. There are 8 triptan types within the triptans medication class and include Imitrex (Sumatriptan) vs. Maxalt (Rizatriptan) vs. Relpax (Eletriptan) vs. Zomig (Zolmitriptan) vs. Frova (Frovatriptan) vs. Amerge (Naratriptan) vs. Axert (Almotriptan) vs. Treximet (Sumatriptan/Naproxen).

 

So what are the best triptans to use? Well let’s back up a little first. The ergot based medications such as DHE (dihydroergotamine) and cafergot (ergotamine + caffeine) have been the oldest migraine abortive medications used, which are still used today. However, they often have many side effects for patients and eventually the migraine specific triptans were developed for aborting migraine. Since 1992 (when Sumatriptan first became available), the triptans have been the first and only migraine specific abortive medications available up until 2020 when two new classes of migraine specific abortive medications have FINALLY become available with the gepants (Ubrelvy, Nurtec) and ditans (Reyvow). These new migraine abortive medications can be read about in more detail here.

 

The first triptan developed was sumatriptan in 1991 and since that time there have been a total of 8 triptan options to choose from. So how do the triptans work? They work by activating (agonist) the serotonin sub-receptor 5-HT1B. The result of activating this receptor is that it helps to constrict (narrow) the dilated inflamed pain-producing meningeal blood vessels which occurs during a migraine attack. The 5-HT1B receptors are also present in the brainstem, and likely play a role in modulating the electrical event of a migraine. Triptans also work by activating (agonist) the serotonin sub-receptor 5-HT1D. The result of activating this receptor is that they stop the trigeminal nerves from releasing a variety of inflammatory proteins around the brain and blood vessels which normally leads to pain during a migraine attack. This also interferes with normal pain processing between the brainstem and the brain (helps to block this electrical transmission), and it helps to block the nausea and vomiting centers in the brainstem. Triptans help to normalize levels of and decrease the release of a very inflammatory protein released during a migraine called CGRP (calcitonin gene related protein). Triptans also inhibit mast cell degranulation in the dural membranes, which also lessens the sterile inflammation which occurs during a migraine.

 

WHAT ARE THE SIDE EFFECTS OF TRIPTANS?

Most patients tolerate triptans very well, however, many patients have side effects and discontinue them. So let’s discuss triptans side effects. Just like any medicine, some patients may have more side effects than others. Furthermore, about 30% of patients with migraine may not respond to triptans (triptan non-responder). If side effects do occur, there is some variability between the different types of triptans. Potential side effects of the triptans include palpitations or racing heart beat, nausea, tingling, numbness or flushing in the face or extremities, drowsiness, fatigue, dizziness, and tightness or pressure in the chest, neck, or jaw. Although the chest pressure is not common, it is usually of a muscular and not a non-cardiac (heart) cause, so it can be scary if you don’t know about this potential side effect. With that said, chest pain could still potentially be a sign of heart attack (myocardial infarction) in patients with vascular risk factors and unknown coronary disease because the triptans do cause some slight vasoconstriction (narrowing) of arteries. So if there is already narrowing in an artery, increasing further narrowing could lead to lack of blood flow to the heart with subsequent heart attack in those at risk.

 

WHEN SHOULD TRIPTANS NOT BE USED?

Triptans can cause a mild degree of artery constriction (narrowing) due to its activity at the 5-HT1B receptor as discussed above. This could theoretically occur in narrowed arteries from cholesterol build up, such as in the heart. Therefore, triptans should not be used in patients who have coronary artery disease, cerebrovascular disease (stroke), peripheral arterial disease, or uncontrolled risk factors for these diseases (high blood pressure, cholesterol, diabetes, smoking, family history of early heart disease) because chest pain for them could truly represent heart attack. If there is concern for the possibility of underlying cardiovascular disease, a cardiac stress test should be performed prior to triptan prescription.

 

Triptans are also considered to be contraindicated in patients with visual snow, persistent migraine aura, and migrainous stroke (infarction) due to theoretical concerns of vasoconstriction potentially causing stroke. This contraindication has historically also included hemiplegic migraine and basilar migraine (now called migraine with brainstem aura). When the triptan studies were done previously, they excluded patients with these forms of migraine due to the ongoing vascular theory of migraine at that time. The vascular theory of migraine assumed that vasoconstriction and lack of blood flow was the cause of aura and neurologic features with migraine. So the thinking was that if you cause further vasoconstriction with a triptan, you may cause stroke. However, we now know that these phenomenon are primarily of an electrical basis and not a vascular basis. Therefore many specialists have gotten more liberal with the use of triptans in patients with hemiplegic or basilar migraine, and there have been a number of case series and case reports of these patients using triptans without any problems. However, larger confirmatory studies would be preferable.

 

Patients that can not use triptans due to side effects, or if they have any of these medical contraindications noted above, should consider one of the newer types of migraine abortive medications available with either the gepants (Ubrelvy, Nurtec), ditans (Reyvow) or neuromodulatory devices. Ubrelvy, Nurtec, and Reyvow are not triptans. These newer options often have a much lower side effect profile, can be taken in the setting of these medical contraindications to triptans mentioned above, and work by an entirely different mechanism of action.

 

It is also important to know that triptans can cause medication overuse headache (rebound headache) if used consistently greater than 10 days per month on average. The result is that the headache continues to worsen in frequency and/or severity. This also happens with NSAIDs, over the counter pain meds, and other types of as-needed pain medications. The phenomenon of rebound headache is discussed in much greater detail here. Notably, the gepants (Ubrelvy, Nurtec) do not cause rebound headache. If triptans, or any migraine abortive medication, is having to be used at this high frequency, a preventive migraine treatment should be used until the migraine and headache frequency is significantly improved consistently for several months. This can be done with a variety of medications which may also include the CGRP monoclonal antibody (mAb) treatments (Aimovig, Ajovy, Emgality, Vyepti), Botox, natural supplements, herbals and vitamins, or neuromodulatory devices.

 

WHAT IS THE BEST TRIPTAN TO USE?

Triptans are all similar in mechanism of action in how they work. So, it is not necessarily that one is better than another and some people may respond better to one versus another. However, there are many differences between the triptans drugs which allow them to be tailored and fine-tuned towards different types of migraine characteristics, as discussed below. This is a very important clinical point that is almost always overlooked by most physicians prescribing these medications if they are not headache specialists. Tailoring triptans to specific migraine characteristics can make a dramatic difference in its effectiveness since triptans are not all one in the same medication. The information below can be discussed with your doctor to hopefully get a better response to your triptan therapy.

 

LIST OF TRIPTANS:

-Sumatriptan: oral, subcutaneous injection, needle-less subcutaneous injection, nasal spray, breath-powered intranasal delivery system
-Zolmitriptan: oral, orally dissolvable tablet, nasal spray
-Rizatriptan: oral, orally dissolvable tablet
-Almotriptan: oral
-Eletriptan: oral
-Sumatriptan/Naproxen: oral
-Frovatriptan: oral
-Naratriptan: oral

GROUP 1 TRIPTANS:

-Faster onset of action, higher potency (thus can have higher side effect potential), tend to have a higher 24-hour migraine recurrence
-Sumatriptan, Sumatriptan/Naproxen, Zolmitriptan, Rizatriptan, Almotriptan, Eletriptan

 

GROUP 2 TRIPTANS:

-Slower onset of action, lower potency (thus often have lower side effect potential), lower 24-hour migraine recurrence since the duration of action is longer:
-Frovatriptan, Naratriptan

 

FINE-TUNING YOUR TRIPTAN CHOICE: (Remember the mnemonic CORN, and this will help to narrow down the best triptan to consider):

Contraindications
Onset to peak pain
Recurrence of migraine after treatment
Nausea and vomiting severity

Contraindications: This is not an exhaustive list, but are the most common. Your doctor should be well aware of when triptans should not be used.
-Known vascular disease (coronary artery disease, peripheral vascular disease, history of stroke)
-Vascular risk factors (poorly controlled hypertension, hyperlipidemia, diabetes, smoking, premature family history of coronary artery disease (men less than age 55, women less than age 65), postmenopausal women, etc.
-Kidney or liver failure
-Prinz-Metal angina

 

Onset to migraine peak pain:
-Group 1 triptan (quicker onset) is generally much more useful than a Group 2 triptan (slower onset).
-A subcutaneous injection or nasal spray triptan will typically be most helpful if:
-Patient wakes with migraine already ongoing (waking migraine)
-Migraine hits its peak pain level within 30 minutes or so

 

Return of migraine after treatment:
-If migraine recurrence occurs within 24 hours (for example it goes away with the triptan, but keeps returning later in the day or the next day), or the migraine is usually multiple consecutive days long (such as menstrual migraine):
-Combine the 1st dose of the triptan with an NSAID (such as Naproxen)
-Use a group 2 triptan (Naratriptan vs. Frovatriptan)

 

Nausea and vomiting severity:
-If nausea and vomiting occur early in the attack, or are severe to where it is hard to keep a pill down without vomiting it back up:
-A subcutaneous injection or nasal spray triptan should be used.
-Of note, dissolvable triptan tablets are still absorbed by the gastrointestinal tract, not sublingually. So, vomiting will still make this route ineffective, similar to a regular pill.

 

TRIPTAN PEARLS IN FURTHER FINE-TUNING TRIPTAN CHOICES:

Sumatriptan:
-Highest potency (in subcutaneous form) and quickest onset (subcutaneous > nasal spray) of triptans
-Greatest flexibility is dosing route options

Rizatriptan:
-Fastest onset of oral triptans
-Greatest likelihood of 2h pain-free and sustained pain-free response
-Propranolol increases its serum concentration, so 5mg per dose should be if used together

Zolmitriptan:
-Most likely to treat persistent headache when 1st dose fails

Almotriptan:
-The group 1 triptan with the least side effects

Eletriptan:
-Highest potential for drug interactions. Decrease dosage with CYP3A4 drugs such as macrolides, fungal, HIV, etc.

Naratriptan:
-The “gentle triptan” with the least side effects given its slower onset of action
-Low 24 hour migraine recurrence rate
-Good choice to give shortly prior to an expected and known migraine trigger (menstruation, air travel, etc.)
-Does not have monoamine oxidase metabolism, so it can be given with MAOI (as can Eletriptan and Frovatriptan)

Frovatriptan:
-Low side effect potential given its slower onset of action
-Longest half life
-Low 24 hour migraine recurrence rate
-Good choice to give shortly prior to an expected and known migraine trigger (menstruation, air travel, etc.)

 

CONCLUSIONS:

The triptans were and have been a game changer for millions of migraine patients in aborting migraine attacks. Using the highest available triptan dose is also generally recommended to see the full effect. We see many patients who have “failed triptans”, but on further history they were put on very low doses (such as 25 mg sumatriptan, when 100 mg is the standard dose). Even so, about 30% of migraineurs do not respond to triptans, only 1/3rd are pain-free at 2 hours, and only 17-25% remain pain-free at 24 hours. Therefore, although the majority respond well to triptans, not everyone does. Luckily, there are other medication options including two brand new classes of migraine abortive medications (gepants, ditans), and these are detailed here.

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

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