Other Acute Migraine Headache Treatments

Ubrelvy (ubrogepant) and Nurtec (rimegepant)

Ubrelvy® (ubrogepant)  and Nurtec® (rimegepant) are two oral CGRP receptor antagonist that have been approved for acute migraine treatment.  Nurtec is also approved for migraine prevention.  This class of drugs is referred to as “Gepants”. Calcitonin Gene Related peptides (CGRP) is a protein that is found throughout the central and peripheral nervous systems.  When the CGRP is released by the trigeminal nerve cells, it finds it way to receptors on some neurons of the trigeminal nerve, blood vessels, and other glial cells in the meninges around the brain.

Ubrelvy and Nurtec block the CGRP receptors throughout the body and in the meninges, keep it from being activated by the CGRP released from the trigeminal nerves.  Ubrelvy and Nurtec have been tested in multiple clinical trials  to treat acute migraine headaches.

The initial treatment response to Ubrelvy and Nurtec is similar to triptans.  They are longer acting so many patients who do not initially respond Ubrelvy and Nurtec in 2 hours may respond later.  This is not typically seen with triptans. They have some additional advantages compared to triptans in that it will not cause arterial vasoconstriction. Ubrelvy and Nurtec block vasodilatation. Because of this, the FDA has approved Ubrelvy and Nurtec for use in patients that have a remote history of stroke or heart attack.

Ubrelvy and Nurtec do not cause triptan side effects such as chest discomfort or other abnormal sensations.  They are also effective in some patients that do not respond to triptans at all.

From a practical matter, insurance will only pay for Ubrelvy and Nurtec if you cannot have, cannot tolerate, or do not respond to less expensive triptans.  Usually patients have to first try and fail some of the triptans for insurance to cover either Nurtec or Ubrelvy. Insurance requirements vary based on the plan. Some insurances plans require as few as 1 triptan failure but I have seen an insurance payer require my patient’s to try 6 triptans before granting Ubrelvy or Nurtec.   Sometimes, the insurance payers require specific triptan failures which are typically the cheapest triptans – sumatriptan, rizatriptan, and naratriptan.

Reyvow (lasmiditan)

Reyvow® is part of a class of medications called “Ditans”.  Reyvow targets the 5-HT(1F) receptor which is a type of serotonin receptor. The triptans target a different serotonin receptor 5-HT(1B/1D). Because Reyvow does not target the 5-HT(1B) receptor  it does not cause vasoconstriction of blood vessels like the triptans. Reyvow also does not cause vasodilatation of blood vessels and does not block CGRP related vasodilatation which may be important in other parts of the body.

Reyvow does affect mental alertness. Therefore one should not drive after taking the medication for 8 hours. This was determined during the clinical studies by having participants drive in a simulator at 2 hours after taking the medication when the drug is at its maximum level. A normal person with a blood alcohol of 0.06% (not quite drunk) was used as the control. Some of those who were impaired did not feel impaired so it is important that those that use this medication not try and judge if they are safe to drive – but simply not drive for the 8 hour period as recommended by the FDA. This obviously limits the use of Reyvow.

There are also FDA warnings about serotonin syndrome and medication overuse headache but these warnings appear to be the same over blown issue that we frankly do not see in clinical practice with triptans.  These warnings seem to result in under-utilization of the triptan medications. Despite these limitations, I expect Reyvow will be very useful for those that do not respond to triptans or gepants.

Insurance coverage of Reyvow typically follows the same rules as the gepants above. You will only be able to get Reyvow if you cannot have, cannot tolerate, or do not respond to the less expensive triptans.

Dihydroergotamine – DHE-45, Trudhesa and Migranal

A very old acute migraine medication is dihydroergotamine (DHE). The brand name of DHE is DHE-45® and was released in 1946.  The injectable form of DHE  can be given IV (intravenous), SQ (subcutaneous) , or IM (intramuscular). The nasal forms of DHE are called Trudhesa® and Migranal®. While there are no head to head trials between Trudhesa® and Migranal®, the absorption data would seem to favor Trudhesa®.

DHE work well for patients who have failed multiple prior triptans. DHE works well even in patients with long duration migraine  Intravenous DHE is commonly used in office based rescue.  The only unique side effect to the nasal forms of DHE is some nasal stuffiness. Migranal causes a bad taste a high percentage of the time.  Injectable DHE is less expensive than nasal DHE but requires the patient to draw up and self-inject the medication. There is no injectable DHE auto-injector available.  There is only one maker of generic DHE so this keeps the price higher than one would expect for a generic.

NSAIDs to treat Migraine Headaches

Over the Counter NSAIDs that treat Migraines

Compounds that contain naproxen and ibuprofen are the most common over the counter nonsteroidal anti-inflammatory drugs (NSAIDs) used for migraine.  Ibuprofen doses needed are typically “prescription strength.”  The over the counter dose of Ibuprofen is 200 mg but 600-800 mg of ibuprofen is typically needed for a migraine headache.  Naproxen comes in both a faster release form (trade name Aleve) and a slower release form (like Anaprox).  For migraine, a patient would typically use 1 or 2 Aleeve type naproxen.

Cambia (diclofenac potassium)

Cambia® was the first NSAID that is FDA approved to treat migraine. It has none of the typical triptan side effects so it is also an excellent therapy for patients who cannot tolerate triptans for safety reasons.

Cambia should be avoided in those patients that cannot tolerate or are told to avoid NSAIDs. For patients with a migraine lasting 2 of 3 days, NSAIDs like Cambia can be more effective than the triptans.  Cambia is a form of the drug diclofenac potassium.  In a 3 arm blinded trial, Cambia was shown to be better than diclofenac potassium and placebo.  Diclofenac potassium was better than placebo so some insurances require the patient to try generic diclofenac potassium prior to approving Cambia.

Elyxyb (celecoxib)

Elyxyb® is the second NSAID that is FDA approved to treat migraine. It is a form of celecoxib that is mixed in such a way as to speeds it absorption.  The 120 mg liquid has been shown to cause a blood level higher than 400 mg of celecoxib tablets.  Celecoxib is felt to cause less gastric ulcers and less bleeding than other NSAIDs.

Ketorolac IM Injections

Ketorolac intramuscular injections (not the oral tablets) are very useful for patient’s to use at home.  It does require the patient learn how to draw up the medication and give it into a muscle.  Our office teaches patients how to do this.  Ketorolac IM is commonly used at urgent care and ERs.  Dr. Loftus believes it is better to teach patients who need this to self administer it to avoid the need for ER and rescue treatments.

*All NSAIDs can contribute to renal disease and ulcer.

Butalbital and Opioids

Butalbital containing products (Esgic®, Fiorecet®) and opioids should be avoided. Both of these lead to medication overuse headaches and appear to make it less likely for migraine preventatives to work.  They are studies that suggest they are not completely safe for pregnancy.