Mixing triptans

Taking two different triptans (drugs such as Imitrex, or sumatriptan, Maxalt, or rizatriptan and other) within 24 hours of each other is contraindicated according to the FDA. However, there is no scientific reason for such prohibition. You are allowed to take a second dose of the same triptan 2 hours after the first dose, so it makes no sense why you could not take a different one. Most of the triptans (five out of seven) get washed out from the body within 2 – 3 hours, so even if there was an interaction between different triptans (and there is absolutely no evidence for that) it would be safe to give a different one 3 hours later. A report in the latest issue of the journal Headache by Dr. Rothrock studied 200 patients who “mixed triptans”, that is took a shot of sumatriptan and two hours before or after a tablet of either rizatriptan (Maxalt, zolmitriptan (Zomig), almotriptan (Axert), or eletriptan (Relpax). He found that not only there were no problems, patients were highly satisfied with this approach. I also hear from my patients that sometimes they know that one tablet of a triptan will not be enough for their severe attack and they will take two at once. Many doctors strongly advise their patients against it, but there is no evidence of any great danger from a higher dose. These dosages were arrived at by looking for an optimal dose which provides good relief and few side effects and for most people the standard dose will suffice. But some people need higher amounts. In case of eletriptan (Relpax), 20 mg and 40 mg are available in the US, but in some European countries it is available in 80 mg. It is clear that some patients benefit from a higher than recommended dose without an increase in side effects.

16 comments
  1. Mary says: 08/12/201711:25 am

    See, I just read here that there is no evidence that Triptans cause MOH, but my neurologist just reduced my Imitrex injection and Frova prescriptions because he believes that I am getting migraines daily because of MOH caused by overuse of Triptans. So he basically reduced my doses, gave me a new preventive (Namenda), which I’ve been taking for a week and still don’t notice a difference. I’ve been to the ER last Saturday, and the Urgent Care yesterday. Migraine still came back. Started a prednisone taper today. I’m celebrating my 10th wedding anniversary tonight, have one Imitrex injection left and one Frova. I took an Imitrex injection at 1:30 this morning. The Imitrex took the pain away for a few hours, but the migraine came back. Now I don’t know what to do. Take a Frova now and the Imitrex injection later? Go to the ER again? I’m so tired of being in pain.

  2. Dr. Mauskop says: 01/31/20175:32 pm

    Thank you for sharing your experience – it is very helpful to other migraine sufferers in similar circumstances. The topic of daily triptan use has generated over 200 comments under another post titled Daily Use of Triptans.

  3. Karen Cooper says: 01/31/20175:20 pm

    I know from many years of experience with triptans that they do cause rebound headaches. I have gotten into rebound many times over the years with triptan drugs and gotten myself out in various ways including a DHE 45 treatment at Duke, weight loss and magnesium supplements. However, I know the feeling very well of the daily headache creeping back up around 24 hours after I took my last dose and knowing the only way to stop it would be to take another. I have been a daily triptan user for the majority of my adult life. I’m 46 now and my migraines are better than they were in my 30s, but still almost a daily companion. Large doses of Magnesium have really helped in the past year.

  4. Dr. Mauskop says: 08/10/201410:22 pm

    We do not have any evidence that long-term use of triptans causes any lasting side effects. The first triptan, Imitrex (sumatriptan) was introduced in 1992, so we have over 20 years of experience with these drugs. On the other hand, Botox was introduced even earlier – in 1989 and it also has a very clean long-term safety profile. At least theoretically, Botox should be safer because it is used in such small amounts (nanograms) and, unlike drugs, does not appear to circulate through the liver, kidneys, and the entire body. Botox is approved for the treatment of chronic migraines for adults only. This is also true for many other migraine drugs and we have no choice but to try these drugs and Botox in children at reduce doses. My youngest patient with chronic migraines whom I treated with Botox (with very good results) was 8 years old.

    However, before we try Botox or drugs in patients with chronic migraines, especially in children, we always begin with non-drug treatments. These include regular exercise, biofeedback, magnesium, CoQ10, Boswellia, and other supplements.

  5. Jessica says: 08/10/201410:03 pm

    I am currently suffering from at least one migraine a day and have been for the last few months. As I am only 18 I am hesitant to receive the botox injections without having exhausted all my other options. This being said however, is there any lasting effects from taking triptans every day for months on end? I have tried preventatives but the side effects outweighed the benfits and am up to my 3rd triptan so far. I am also noticing a change in their effeciveness, any suggestions?

  6. Diana I've been having migraines since I was 15 now am 28 I tried everything topomax, betablockers, fioricet now currently on Imitrex and Maxalt. I don't know what to do I vomit until I dehydrate and end up in the er twice a month I get 16 to 20 migraines says: 07/21/201410:06 pm
  7. Ellen says: 07/01/20146:16 pm

    This blog is a godsend! I am on day three of an intractable migraine, and I found myself wondering if I could mix triptans. I usually take Frova, but I also have Zomig on hand. I know that Frova has a long half-life, so I am wondering if it’s a problem to take Zomig on the same day (but several hours later) as Frova. Reading this blog post makes me think it’s okay, so I will probably try it. Anything for relief!

  8. Dr. Mauskop says: 03/24/20148:19 pm

    I would recommend that the readers of this blog challenge their doctors to explain the reason for not mixing triptans. Yes, it says so in the package insert approved by the FDA, but there is no theoretical or practical reason behind it. And in 20 years there have been no reports of any problems from mixing triptans. You can also refer your doctors to this blog. It does not make sense for the doctor to prescribe three drugs such as verapamil, Savella and diclofenac, all three of which have potentially serious side effects, instead of prescribing a safer category of drugs, such as triptans. Unfortunately, if the second Botox treatment did not help, it is not likely that the third will work and the fourth one is even less likely.

  9. Bev says: 03/24/20146:29 pm

    I have had two Botox treatments (about 40 injections in my head and back of neck) and have seen a little improvement. I have at least 15 migraine days a month, sometimes my Imitrex works, sometimes it doesn’t. I started taking Maxalt too but my regular doctor doesn’t like me mixing them. I even told her I would alternate months but she WOULD NOT write two scripts! I still have some of both for now but I will soon run out of Imitrex. I am having my 3rd Botox treatment next month so I hope it will finally kick in. My neurologist told me to give it a year (4 Botox Treatments). My neurologist also doesn’t want me to take any triptans if possible, but as most of you reading this know when you have a migraine you will do almost anything to get relief. She also has me taking a med for blood pressure, Verapamil, an antidepressant,Savella, and an arthritis med called diclofenac-misoprost that’s supposed to help the triptans work better.I just started the verapamil and D-M two weeks ago. I have yet to see improvent (just had a five day migraine taking at least six triptans), but I will continue to try anything for a year. After that I don’t know.
    I hope this might help someone. By the way I believe my migraines are mostly triggered by hormone fluctuation. As I near menapause they are worse because my hormones are crazy…

  10. Steve says: 01/11/20136:32 pm

    This is interesting in that my neurologist has prescribed mixed triptans as the mainstay for treating acute episodes (I’m an episodic migraineur with ~7 headache days a month) for a few years now: one tablet of Maxalt 10 mg at symptom onset followed by one tablet of naratriptan 2.5 mg two hours later regardless of whether or not pain persisted. The rationale evidently is to maintain triptan blood levels at a high enough level to minimize next-day recurrence, which I am troubled with. I take valproate as a prophylactic measure as I have Wolff-Parkinson-White syndrome that prevents me from being able to use beta-blockers and the like.

  11. Dr. Mauskop says: 01/10/201311:34 pm

    Compared with preventive medications, Botox has fewer and milder side effects, although some side effects are possible. Your doctor will discuss the potential side effects with you before injecting you with Botox.

  12. Sigma says: 01/10/20132:37 pm

    Really interested in the botox as I am dealing with serious debilitation (ER visits) due to migraine degree and frequency. My neurologist is also now sending me to a specialist and I will be evaluated for botox. While I dislike taking any of these meds, I do not know what else to do and still be a functioning human being. What are the side-effects of the botox? What are long term issues? Is there any hope in the future for this incapacitating problem?

  13. Sharon says: 08/06/20129:41 pm

    I’ve had migraines since I was 12 (49 now) and have taken almost everything from caffergot through Trexemet. Finally, after 17 migraines a month, I’d had it. My neurologist suggested Botox which I had read about but was leary about. I was not only migraine free but headache free for four weeks. It was absolutely amazing. Unfortunately due to some serious family issues, I then had three in a row but am back on a four day stretch of no headaches – even four days is amazing!

  14. Ny71 says: 02/07/20113:35 pm

    Thank you for the reply, and for the Informative site

  15. Dr. Mauskop says: 02/06/20119:31 pm

    There is no evidence that triptans cause rebound headaches (the official name is MOH – medication overuse headaches). We have good evidence from large epidemiological studies that caffeine, butalbital (Fioricet, Fiorinal) and opioids (narcotics, such as codeine, Percocet, Vicodin, etc) cause MOH. Non-steroidal anti-inflammatory drugs also do not cause MOH, and if fact aspirin seems to prevent it. This was one of the reasons for including aspirin (with magnesium) in Migralex.
    Regarding beta blockers, Bystolic (nebivolol) does cause fewer side effects and works for the prevention of migraines, but we’ve been having hard time getting it covered by many insurance companies because it is a lot more expensive than the generic propranolol or atenolol.

  16. Ny71 says: 02/06/20115:50 pm

    Your blog is very insightful, thank you for sharing it.

    Interesting, as I have always been told not to mix triptans within 24 h, and to use them no more than 3x per week to a avoid transformation and or rebound.
    I have a friend who routinely uses Frova and relpax in combination because of the longer duration of the Frova.

    Off topic, but related to an older entry: do you have success treating patients with newer beta blockers such as bystolic compared to non-selectives like propanolol? I ask because I have taken propanolol for 1 yr now. I would like to try one with potential for less side effects.

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