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Review of the Triptan Drugs for Treating Migraines

Worst Pills, Best Pills Newsletter article June, 2022

Triptans are a large family of drugs commonly prescribed for treating migraines. The Food and Drug Administration (FDA) has approved seven triptans (see Table, below). All seven are approved by the FDA to temporarily relieve migraine headaches, with or without aura (sensory disturbances such as flashing light sensations, blind spots, other vision changes or tingling in the hands or face[1]), in adults;[2],[3],[4],[5],[6],[7],[8] two also are approved for treatment of migraines in children.[9],...

Triptans are a large family of drugs commonly prescribed for treating migraines. The Food and Drug Administration (FDA) has approved seven triptans (see Table, below). All seven are approved by the FDA to temporarily relieve migraine headaches, with or without aura (sensory disturbances such as flashing light sensations, blind spots, other vision changes or tingling in the hands or face[1]), in adults;[2],[3],[4],[5],[6],[7],[8] two also are approved for treatment of migraines in children.[9],[10]

Triptans, also known as serotonin receptor agonists, are thought to work by narrowing dilated blood vessels in the brain that, when over-dilated, are thought to play a role in migraine pain.[11] These drugs also block nerve pathways that are believed to play a role in the perception of migraine pain.

All seven triptans are available in oral-tablet forms, two also in nasal-spray or nasal-powder forms (sumatriptan [marketed under the brand names IMITREX, ONZETRA XSAIL and TOSYMRA] and zolmitriptan [marketed under the brand name ZOMIG]) and one in an injectable form (sumatriptan [marketed under the brand name ZEMBRACE SYMTOUCH]). Less expensive oral-tablet generic versions of each triptan are also now available.

The main differences among triptans include how fast the drug is absorbed and how long it stays in the body. Generally, the faster a triptan is absorbed, the more quickly it may relieve the migraine but the shorter the time it remains in the body. Injectable, nasal-spray and nasal-powder forms are more quickly absorbed. Some triptans are available in disintegrating tablets or wafers that dissolve quickly on the tongue, resulting in faster absorption.

FDA-Approved Triptans Available in the U.S.

Generic Name Brand Name(s) Available Forms Approved for Use in Children?
almotriptan generic only oral tablet Yes (ages 12 to 17)
eletriptan RELPAX oral tablet No
frovatriptan FROVA oral tablet No
naratriptan AMERGE oral tablet No
rizatriptan MAXALT, MAXALT-MLT oral tablet Yes (ages 6 to 17)
sumatriptan IMITREX, ONZETRA XSAIL, TOSYMRA, TREXIMET,† ZEMBRACE SYMTOUCH nasal powder, nasal spray, injectable solution, oral tablet No
zolmitriptan ZOMIG, ZOMIG ZMT nasal spray, oral tablet No

†Combination drug product containing the nonsteroidal anti-inflammatory drug naproxen

Limits on use

Triptans should be used only after a clear diagnosis of migraine has been established.[12],[13],[14],[15],[16],[17],[18] Importantly, these drugs do not prevent or cure migraines and do not reduce frequency of migraines.

Triptans should not be used in patients who have or had any of the following:

  • A type of migraine identified as basilar (brain-stem based) or hemiplegic (involves weakness on one side of the body)
  • Cluster headache
  • Ischemic heart disease, such as angina (chest pain or pressure due to decreased blood flow to the heart) or heart attack
  • Stroke or transient ischemic attack
  • Vascular disease involving the narrowing of arteries in the legs, intestines or other organs
  • Uncontrolled hypertension (high blood pressure)

Public Citizen’s Health Research Group recommends that triptans only be used after determining that acetaminophen (TYLENOL) or nonsteroidal anti-inflammatory drugs, such as ibuprofen (ADVIL, MIDOL LIQUID GELS, MOTRIN, TAB-PROFEN), fail to work or cannot be taken due to allergies or other medical reasons.

Important warnings[19],[20],[21],[22],[23],[24],[25]

Ischemic heart disease

There have been rare reports of serious adverse heart events, including heart attacks, occurring within a few hours after taking a triptan dose. Some of these events occurred in patients without known coronary artery disease. Patients not previously treated with a triptan who have multiple risk factors for heart disease (for example, increased age, diabetes, hypertension, smoking, obesity and strong family history of coronary artery disease) should undergo a heart evaluation before initiating treatment with a triptan.

Abnormal heart rhythms

Life-threatening abnormal heart rhythms, including ventricular tachycardia and ventricular fibrillation leading to death, have occurred within a few hours after taking a triptan dose.

Chest pain, tightness and pressure

Sensations of pain, tightness and pressure in the chest, throat, neck or jaw commonly occur after treatment with triptans. Such symptoms usually are not due to heart problems. However, patients who are at high risk of ischemic heart disease who experience such symptoms should undergo a heart evaluation.

Serotonin syndrome

When triptans are taken in combination with any of the following types of antidepressants, a potentially fatal condition called serotonin syndrome may result:

  • Selective serotonin reuptake inhibitors (for example, fluoxetine [PROZAC])
  • Selective serotonin/norepinephrine reuptake inhibitors (for example, duloxetine [CYMBALTA, DRIZALMA SPRINKLE])
  • Tricyclic antidepressants (for example, amitriptyline [available in generic only])
  • Monoamine oxidase inhibitors (for example, phenelzine [NARDIL])

Serotonin is a neurotransmitter (a chemical messenger in the nervous system) that regulates mood, digestion and heart function, among other things.[26] Serotonin syndrome develops when the body is exposed to too much serotonin. The syndrome is characterized by agitation, confusion, hallucinations, rapid heartbeat, high blood pressure, high fever, shivering, sweating, nausea, vomiting, diarrhea and muscle rigidity. In severe cases, the syndrome can lead to seizures and coma.

Increased blood pressure

Triptans rarely have caused significant elevations in blood pressure, which in some cases has led to hypertensive crisis and organ damage. Patients using these drugs should have their blood pressure monitored periodically.

Medication overuse headache

Overuse of triptans and other drugs used to treat migraines also may lead to an exacerbation of the headaches, a condition referred to as medication overuse headache. Patients with this condition may experience more frequent, even daily, migraine headaches. Withdrawal of the triptan and treatment of withdrawal symptoms, which may include temporary worsening of headache, may be necessary to resolve medication overuse headache.

Severe allergic reactions

Life-threatening severe allergic reactions, including anaphylaxis and angioedema (swelling of the face, lips and tongue), have been reported in patients treated with several of the triptans. In general, these are more likely to occur in people who have a history of sensitivity to multiple allergens.

What You Can Do

Before taking a triptan, confirm with you doctor that you definitely have migraines (other than hemiplegic or basilar migraines) and tell your doctor about all of your other medical conditions. Also, you should carefully read the FDA-approved patient Medication Guide provided by the dispensing pharmacy.

When taking a triptan, you should seek emergency medical help if you have any of the following symptoms:

  • chest pain or chest discomfort that feels like an uncomfortable heavy pressure, squeezing, fullness or pain that lasts for more than a few minutes or that goes away and comes back;
  • pain or discomfort in your arms, back, neck, jaw or stomach;
  • shortness of breath;
  • breaking out in a cold sweat;
  • feeling light-headed;
  • mental changes such as agitation, confusion or hallucinations;
  • rapid heartbeat;
  • changes in blood pressure;
  • high fever;
  • tight muscles;
  • trouble walking;
  • nausea, vomiting or diarrhea;
  • sudden severe stomach pain;
  • stomach pain after meals;
  • bloody stools;
  • cramping or pain in your legs or hips;
  • feeling of heaviness or tightness in your leg muscles;
  • burning or aching pain in your feet or toes while resting;
  • numbness, tingling or weakness in your legs;
  • cold feeling or color changes in one or both legs or feet;
  • numbness or weakness in your face, arm or leg, especially on one side of your body;
  • problems speaking or understanding;
  • loss of vision in one or both eyes;
  • problems walking, dizziness or loss of balance or coordination;
  • severe headache with no known cause;
  • swollen face, lips, mouth, tongue or throat;
  • difficulty swallowing or breathing; or
  • an itchy rash (hives).

Finally, tell your doctor if you experience any other adverse effects that bother you or do not go away.
 


References

[1] Mayo Clinic. Migraine with aura. July 2, 2021. https://www.mayoclinic.org/diseases-conditions/migraine-with-aura/symptoms-causes/syc-20352072. Accessed April 7, 2022.

[2] Ajanta Pharma USA Inc. Label: almotriptan. November 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=6fa380c4-c885-4743-85bf-88819ae68645&type=display. Accessed April 7, 2022.

[3] Pfizer. Label: eletriptan (RELPAX). March 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/21016s029lbl.pdf. Accessed April 7, 2022.

[4] Endo Pharmaceuticals Inc. Label: frovatriptan (FROVA). August 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021006s022lbl.pdf. Accessed April 7, 2022.

[5] GlaxoSmithKline LLC. Label: naratriptan (AMERGE). October 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=13f4a8ec-75a3-4c51-b3bc-6244f3c79e95&type=display. Accessed April 7, 2022.

[6] Organon LLC. Label: rizatriptan (MAXALT, MAXALT-MLT). June 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=007b4644-e0e7-4863-9ae3-fe09676b3f5f&type=display. Accessed April 7, 2022.

[7] GlaxoSmithKline LLC. Label: sumatriptan (IMITREX). December 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=584abe73-8290-4484-ff8e-5890831c095e&type=display. Accessed April 7, 2022.

[8] Impax Specialty Pharma. Label: zolmitriptan (ZOMIG). December 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020768s023,021231s014,021450s010lbl.pdf. Accessed April 7, 2022.

[9] Ajanta Pharma USA Inc. Label: almotriptan. November 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=6fa380c4-c885-4743-85bf-88819ae68645&type=display. Accessed April 7, 2022.

[10] Organon LLC. Label: rizatriptan (MAXALT, MAXALT-MLT). June 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=007b4644-e0e7-4863-9ae3-fe09676b3f5f&type=display. Accessed April 7, 2022.

[11] Ajanta Pharma USA Inc. Label: almotriptan. November 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=6fa380c4-c885-4743-85bf-88819ae68645&type=display. Accessed April 7, 2022.

[12] Ajanta Pharma USA Inc. Label: almotriptan. November 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=6fa380c4-c885-4743-85bf-88819ae68645&type=display. Accessed April 7, 2022.

[13] Pfizer. Label: eletriptan (RELPAX). March 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/21016s029lbl.pdf. Accessed April 7, 2022.

[14] Endo Pharmaceuticals Inc. Label: frovatriptan (FROVA). August 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021006s022lbl.pdf. Accessed April 7, 2022.

[15] GlaxoSmithKline LLC. Label: naratriptan (AMERGE). October 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=13f4a8ec-75a3-4c51-b3bc-6244f3c79e95&type=display. Accessed April 7, 2022.

[16] Organon LLC. Label: rizatriptan (MAXALT, MAXALT-MLT). June 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=007b4644-e0e7-4863-9ae3-fe09676b3f5f&type=display. Accessed April 7, 2022.

[17] GlaxoSmithKline LLC. Label: sumatriptan (IMITREX). December 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=584abe73-8290-4484-ff8e-5890831c095e&type=display. Accessed April 7, 2022.

[18] Impax Specialty Pharma. Label: zolmitriptan (ZOMIG). December 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020768s023,021231s014,021450s010lbl.pdf. Accessed April 7, 2022.

[19] Ajanta Pharma USA Inc. Label: almotriptan. November 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=6fa380c4-c885-4743-85bf-88819ae68645&type=display. Accessed April 7, 2022.

[20] Pfizer. Label: eletriptan (RELPAX). March 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/21016s029lbl.pdf. Accessed April 7, 2022.

[21] Endo Pharmaceuticals Inc. Label: frovatriptan (FROVA). August 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021006s022lbl.pdf. Accessed April 7, 2022.

[22] GlaxoSmithKline LLC. Label: naratriptan (AMERGE). October 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=13f4a8ec-75a3-4c51-b3bc-6244f3c79e95&type=display. Accessed April 7, 2022.

[23] Organon LLC. Label: rizatriptan (MAXALT, MAXALT-MLT). June 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=007b4644-e0e7-4863-9ae3-fe09676b3f5f&type=display. Accessed April 7, 2022.

[24] GlaxoSmithKline LLC. Label: sumatriptan (IMITREX). December 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=584abe73-8290-4484-ff8e-5890831c095e&type=display. Accessed April 7, 2022.

[25] Impax Specialty Pharma. Label: zolmitriptan (ZOMIG). December 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020768s023,021231s014,021450s010lbl.pdf. Accessed April 7, 2022.

[26] Berger M, Gray JA, Roth BL. The expanded biology of serotonin. Annu Rev Med. 2009;60:355-366.

Disclaimer

The information on this website is not intended to substitute for professional medical advice, diagnosis, or treatment. Consult your doctor before changing or discontinuing any medication.