Complete Guide to Triptans
Posted on May 27 2025,
Complete Guide to Triptans
Everything you need to know about the seven FDA-approved triptan medications for migraine treatment
What Are Triptans?
Triptans target the biological mechanisms underlying migraine attacks, offering targeted relief that goes beyond pain management.
Starting with the approval of sumatriptan in the early 1990s, the development of the triptan class of medications has marked a significant advance in migraine treatment. This class of medications is migraine-specific and leads to a reduction in headache severity at 2 hours in 60% of migraine patients, with 30% having complete pain freedom.
7
Available Triptans
FDA-approved medications targeting migraine
60%
Response Rate
Patients experiencing significant pain reduction
30%
Pain Freedom
Complete headache relief at 2 hours
How Triptans Work
Triptans are selective agonists for 5-HT₁B/1D receptors located primarily in cranial blood vessels and trigeminal nerve terminals. They work by inhibiting the release of vasoactive neuropeptides at the trigeminal sensory nerve, preventing meningeal inflammation and reducing the neurogenic components of migraine pain.
Complete Triptan Dosing and Administration Guide
Comprehensive dosing information, drug interactions, and clinical considerations for all seven triptans.
| Triptan | Route & Dosing | Onset & Duration | Dosing Intervals | Key Drug Interactions | Important Notes |
|---|---|---|---|---|---|
| Sumatriptan |
Oral: 25, 50, 100 mg Subcutaneous: 3, 4, 6 mg Nasal: 5, 10, 20 mg Max Daily: 200 mg oral, 12 mg SC, 40 mg nasal |
Oral: 30 min onset, 2 hr duration SC: 10 min onset, 2 hr duration Nasal: 15 min onset, 2 hr duration |
2 hours between oral doses 1 hour between SC doses 2 hours between nasal doses |
Do not use within 24 hours of MAOIs | May cause tingling, flushing, heavy feeling in legs. Fast onset with injection. Multiple formulation options available. |
| Rizatriptan |
Oral/ODT: 5, 10 mg Max Daily: 30 mg Film: 10 mg |
Onset: 30-60 minutes Duration: 2-2.5 hours |
2 hours between doses |
Propranolol: Limit dose to 5 mg and max 15 mg/24hr Do not use within 24 hours of MAOIs |
Higher recurrence rate. Significant interaction with propranolol requiring dose reduction. |
| Zolmitriptan |
Oral: 2.5, 5 mg Nasal: 2.5, 5 mg Max Daily: 10 mg |
Oral: 45 min onset, 3 hr duration Nasal: 10-15 min onset, 3 hr duration |
2 hours between doses |
Cimetidine: Limit to 2.5 mg dose and 5 mg/day Do not use within 24 hours of MAOIs |
Only tablet has score line for lower doses. Do not break ODT. 1.25 mg commonly used. |
| Almotriptan |
Oral: 6.25, 12.5 mg Max Daily: 25 mg |
Onset: 30-120 minutes Duration: 3-4 hours |
2 hours between doses | CYP3A4 inhibitors: Dose adjustment necessary, start with 6.25 mg | Less risk of paresthesias, fatigue, nausea. First triptan FDA-approved for adolescents (12-17). |
| Eletriptan |
Oral: 20, 40 mg Max Daily: 80 mg US, 40 mg Canada |
Onset: 30-60 minutes Duration: 4 hours |
US: 2 hours (40 mg repeat not recommended) Canada: 24 hours between doses |
Do not use within 72 hours of CYP3A4 inhibitors (ketoconazole, itraconazole) | Superior efficacy to sumatriptan. Higher bioavailability but higher adverse effects. |
| Frovatriptan |
Oral: 2.5 mg Max Daily: 7.5 mg US, 5 mg Canada |
Onset: Slow, 2-4 hours Duration: 26 hours |
US: 2 hours between doses Canada: 4 hours between doses |
None | Used for menstrual migraine prevention. Less effective but fewer adverse effects. Slow onset, long duration. |
| Naratriptan |
Oral: 1, 2.5 mg Max Daily: 5 mg |
Onset: 1-4 hours Duration: 6 hours |
4 hours between doses | None | Lowest adverse effects. Longer duration, may be used for morning headaches. "Gentle" triptan option. |
Sumatriptan: The First and Most Versatile
Sumatriptan was the first triptan developed and remains the most widely prescribed. It's available in more formulations than any other triptan, making it versatile for different patient needs and attack patterns.
Injection Form
Subcutaneous sumatriptan offers the fastest onset of action among all triptans. Available as 3, 4, or 6 mg self-injectable devices, it achieves peak concentration in just 10-12 minutes with 97% bioavailability. This makes it ideal for severe attacks or when rapid relief is essential.
Sumatriptan Injection Benefits
Onset Time 10 minutes
Bioavailability 97%
Pain Freedom at 1 Hour 48%
Best Use Severe attacks, rapid relief needed
Oral Tablets
Most patients prefer oral sumatriptan despite its lower bioavailability of 14%. Available in 25, 50, and 100 mg tablets, the 100 mg dose provides optimal efficacy. Studies show 59% of patients experience headache relief at 2 hours, with 29% achieving complete pain freedom.
Advanced Formulations
Beyond traditional oral tablets, sumatriptan offers several innovative delivery systems. The Imitrex nasal spray provides 5, 10, and 20 mg options, with faster onset than oral forms. The Tosymra nasal spray delivers 10 mg per actuation and can be used once in each nostril. The Onzetra Xsail powder system delivers 11 mg per nostril using breath-powered technology, providing 22 mg total dose with enhanced absorption.
Injection Options and Dosing
Subcutaneous sumatriptan is available as single-dose vials, prefilled syringes, and autoinjectors in 3, 4, and 6 mg strengths. The autoinjector provides very fast onset of action and is more efficacious than oral routes, making it ideal for severe attacks or when rapid relief is essential. Maximum subcutaneous dose is 12 mg per day with at least 1 hour between injections.
Combination with Naproxen
The combination of sumatriptan 85 mg with naproxen 500 mg provides superior efficacy compared to either medication alone. Studies show 30% sustained pain-free response at 24 hours compared to 25% with sumatriptan alone and 23% with naproxen alone.
Zolmitriptan: Enhanced Brain Penetration
Zolmitriptan was specifically designed to be more lipophilic than sumatriptan, allowing for better brain penetration and potentially more effective treatment of central sensitization components of migraine.
40%
Oral Bioavailability
Nearly 3x higher than sumatriptan
2.5 mg
Optimal Dose
More effective than 1 mg dose
30%
Pain Freedom
At 2 hours with 2.5 mg dose
The higher bioavailability of 40% compared to sumatriptan's 14% means more consistent absorption and potentially more predictable effects. The 2.5 mg dose provides a 20% therapeutic gain over placebo, with a number needed to treat of 5.
Formulation Options
Zolmitriptan is available as conventional tablets, orally disintegrating tablets, and nasal spray. The nasal spray provides 102% bioavailability and reaches the bloodstream within 2-5 minutes, making it faster than the oral formulation's 10-15 minutes.
Menstrual Migraine Prevention
Zolmitriptan 2.5 mg twice daily has been shown effective for mini-prevention of menstrual migraine, reducing attacks by more than 50% when used during the perimenstrual period.
Naratriptan: The Gentle Option
Known as the "gentle" triptan, naratriptan offers the longest duration of action among oral triptans with the fewest side effects. This makes it ideal for patients who are sensitive to medication side effects or experience prolonged migraine attacks.
6h
Half-life
Longest among oral triptans
17-28%
Recurrence Rate
Lower than most other triptans
74%
Bioavailability
Higher in women than men (63%)
While naratriptan has a lower therapeutic gain at 2 hours (22%) compared to other triptans, approximately 48% of patients experience headache response. The key advantage is its excellent tolerability profile, with side effect rates similar to placebo.
Menstrual Migraine Applications
Naratriptan 1 mg twice daily has demonstrated efficacy for short-term prevention of menstrual migraine. In controlled studies, patients taking naratriptan had 50% headache-free periods compared to 25% with placebo when used 2 days prior to expected menses for 5 days over four cycles.
Morning Headache Applications
Naratriptan's longer duration of activity makes it particularly useful for morning headaches that patients experience upon waking. Its 6-hour duration and gentle profile provide sustained relief without the peaks and valleys seen with shorter-acting triptans. The 4-hour minimum interval between doses is the longest among all triptans, reflecting its extended action.
Rizatriptan: Fast and Effective
Rizatriptan has become one of the most commonly prescribed triptans due to its combination of high efficacy, fast onset, and affordable generic availability. It offers excellent value for both patients and healthcare systems.
42%
Bioavailability
Nearly 3x higher than sumatriptan
71%
Pain Relief
At 2 hours with 10mg dose
1.3h
Time to Peak
Faster than sumatriptan's 2.5h
In large clinical trials, rizatriptan 10 mg provided pain relief in 71% of patients versus 35% with placebo. Complete headache resolution occurred in 42% of patients, significantly better than the 10% seen with placebo.
Important Drug Interactions
Patients taking propranolol should use reduced rizatriptan dosing. Propranolol is a competitive inhibitor of monoamine oxidase A, which can increase plasma concentrations of rizatriptan, potentially leading to increased side effects. Patients taking propranolol should limit their rizatriptan dose to 5 mg and not exceed 15 mg in 24 hours.
Rizatriptan Film and ODT Options
Rizatriptan is uniquely available as RizaFilm, a thin film formulation, in addition to conventional tablets and orally disintegrating tablets (ODT). Both the ODT and film provide convenience for patients who have difficulty swallowing during migraine attacks or experience gastoparesis, though bioavailability remains similar across formulations.
The higher recurrence rate noted with rizatriptan compared to longer-acting triptans makes it important to counsel patients about the possibility of headache return and the option to take a second dose if needed, respecting the minimum 2-hour interval between doses.
Almotriptan: First Approved for Adolescents
Almotriptan holds the distinction of being the first triptan specifically FDA-approved for adolescents aged 12-17, receiving this approval in 2009. While other triptans have since received pediatric approvals, almotriptan remains an excellent choice due to its superior tolerability profile.
72.9%
Teen Pain Relief
At 2 hours with 12.5 mg in adolescents
3-3.7h
Half-life
Moderate duration of action
25 mg
Max Daily Dose
Can repeat after 2 hours
In adolescent studies, almotriptan significantly increased pain relief rates with 6.25 mg (71.8%), 12.5 mg (72.9%), and 25 mg (66.7%) compared to placebo (55.3%). Sustained pain relief at 24 hours was also significantly greater than placebo with all doses.
Safety and Metabolism
Almotriptan is metabolized primarily through monoamine oxidase-A rather than liver enzymes, which reduces the potential for drug interactions. However, dose adjustments may be needed when used with strong CYP3A4 inhibitors like ketoconazole.
Pregnancy Considerations
While most safety data for triptans in pregnancy comes from sumatriptan studies, a German prospective study of 432 women found no significant increase in preeclampsia, preterm delivery, spontaneous abortions, or major fetal effects with triptan use, including almotriptan.
Eletriptan: Superior Bioavailability
Eletriptan offers the highest bioavailability among oral triptans at 50%, leading to more consistent absorption and superior sustained pain relief. It's especially effective for patients who need reliable, long-lasting relief.
50%
Bioavailability
Highest among all oral triptans
65%
Pain Relief
At 2 hours with 80 mg dose
21%
Recurrence Rate
Lower than many other triptans
In clinical trials with over 1,000 patients, eletriptan 80 mg provided relief in 65% of attacks and complete headache resolution in 34% of attacks, compared to placebo's 19% relief rate and 3% resolution rate.
Sustained Relief Benefits
Eletriptan demonstrates superior sustained pain relief compared to other triptans. In head-to-head studies, 77% of patients treated with eletriptan 80 mg experienced relief versus 55% with sumatriptan 100 mg. The recurrence rate was also lower at 21% versus 40% with placebo.
Strict CYP3A4 Restrictions
Eletriptan has the most restrictive drug interaction profile among triptans. It should not be used within 72 hours of taking strong CYP3A4 inhibitors such as ketoconazole and itraconazole. This lengthy washout period is necessary due to eletriptan's dependence on this enzyme system for metabolism.
Regional Dosing Differences
Eletriptan dosing varies significantly between countries. In the United States, the maximum daily dose is 80 mg with the option to repeat a 40 mg dose after 2 hours (though repeating the 40 mg dose is not recommended). In Canada, the maximum daily dose is only 40 mg with 24 hours required between doses. This reflects different regulatory approaches to the same medication.
Despite higher adverse effects compared to some other triptans, eletriptan's superior efficacy and sustained relief make it an excellent choice for patients who need reliable, long-lasting headache relief and can tolerate the side effect profile.
Frovatriptan: The Long-Acting Prevention Option
Frovatriptan has the longest half-life of all triptans at 26 hours, making it unique for both acute treatment and short-term prevention of predictable migraine attacks, particularly menstrual migraine.
26h
Half-life
Longest duration among all triptans
2.5 mg
Standard Dose
Can repeat after 2 hours if needed
52%
Menstrual Reduction
Decrease in menstrual migraine frequency
Menstrual Migraine Prevention
Frovatriptan is especially effective for menstrual migraine prevention. Studies show that taking frovatriptan 2.5 mg twice daily for 6 days (starting 2 days before expected menstruation) reduces menstrual migraine frequency by 52% compared to placebo.
For women who can accurately predict their menstrual cycles, this "mini-prevention" approach provides significant relief from predictable menstrual migraine attacks without the need for daily preventive medication.
Regional Dosing Variations
Frovatriptan dosing schedules differ between the United States and Canada. In the US, doses can be repeated every 2 hours with a maximum daily dose of 7.5 mg. In Canada, a longer 4-hour interval is required between doses with a maximum daily dose of 5 mg.
Evidence-Based Menstrual Prevention
Frovatriptan has Class A evidence from the International Headache Society for mini-prevention of menstrual migraine. The slow onset and long duration make it less effective for acute treatment but ideal for predictable migraine patterns. It causes fewer adverse effects overall and has a uniquely long duration of action among all triptans.
Safety and Contraindications
While triptans are generally safe and well-tolerated, they have important contraindications that must be considered before prescribing. Understanding these limitations helps ensure safe and effective treatment.
Absolute Contraindications
Coronary Artery Disease Contraindicated
Uncontrolled Hypertension Contraindicated
Recent Stroke or TIA Contraindicated
Peripheral Vascular Disease Contraindicated
Recent Ergot Use 24-hour washout required
Common Side Effects
Most triptan side effects are mild to moderate and resolve within hours. The most common include chest sensations (2-20%), dizziness (1-7%), and injection site reactions with subcutaneous forms (5-15%). Taste disturbance occurs in 15-40% of patients using nasal spray formulations.
Cardiovascular Considerations
Chest tightness symptoms have been reported with most triptans, affecting 1-9% of patients. However, studies consistently show that triptans have very little effect on coronary artery diameter. The contractile effects appear to be primarily mediated by 5-HT₂ receptors rather than the 5-HT₁ receptors that triptans target.
Serotonin Syndrome Risk
The FDA issued an advisory in 2006 about potential serotonin syndrome with combined triptan and SSRI/SNRI use. However, subsequent analysis suggests this risk is mainly theoretical. Studies show at least 20% of triptan users are co-prescribed SSRIs or SNRIs without significant problems.
Pregnancy and Breastfeeding
Sumatriptan has the most extensive pregnancy data. The Sumatriptan Pregnancy Registry, which followed over 600 pregnancies, found a 4.2% rate of major birth defects with first-trimester exposure, which falls within the general population baseline risk of 1-3%.
For breastfeeding, studies show that infants receive a maximum of 3.5% of the maternal dose through breast milk when mothers use subcutaneous sumatriptan. This is well below the 10% threshold considered safe for breastfeeding.
Choosing the Right Triptan
Selecting the most appropriate triptan depends on several factors including attack characteristics, patient preferences, tolerability concerns, and response to previous treatments. There's often an element of trial and error in finding the optimal choice for each individual.
Key Selection Factors
Cost is frequently a major factor, making sumatriptan and rizatriptan popular first choices due to generic availability. For headaches that are slow to develop and linger throughout the day, longer-acting options like naratriptan or frovatriptan may work better. Patients concerned about side effects should consider naratriptan or almotriptan.
Clinical Decision Framework
Triptan Selection Guide
Cost-Conscious Patients Sumatriptan or Rizatriptan
Fast Onset Needed Sumatriptan injection or Rizatriptan ODT
Side Effect Sensitivity Naratriptan or Almotriptan
Long-Duration Attacks Naratriptan or Eletriptan
Severe Nausea/Vomiting Nasal spray or injection forms
Menstrual Migraine Frovatriptan for prevention
Adolescent/Pediatric Patients Almotriptan (12-17), Rizatriptan (6-17), Zolmitriptan nasal (12+)
Optimization Strategies
Early treatment during the mild pain phase consistently shows better outcomes than waiting until pain becomes severe. One study found that taking sumatriptan when pain is mild resulted in 50% pain-free rates versus only 18% when taken during severe pain.
If one triptan doesn't provide adequate relief, it's important to try at least 2-3 different options before concluding that triptan therapy is ineffective. Lack of response to one triptan doesn't predict response to another, as individual patients may respond differently to various agents.
Medication Overuse/Adaptation Prevention
Triptans should be limited to no more than 10 days per month to prevent medication overuse/adaptation headache. Patients using triptans frequently should be optimize their preventive medications.
Clinical Efficacy Comparison
Head-to-head comparison of pain freedom and relief rates across the most common triptans based on clinical trial data.
| Outcome | Sumatriptan 100 mg | Rizatriptan 10 mg | Eletriptan 80 mg | Naratriptan 2.5 mg |
|---|---|---|---|---|
| Pain Freedom at 2h | 29% (range 18-50%) | 37% (range 32-43%) | 40% (range 32-65%) | 22% (range 17-26%) |
| Pain Relief at 2h | 59% (range 56-69%) | 67% (range 66-77%) | 65% (range 54-77%) | 52% (range 43-60%) |
| Sustained Relief 2-24h | 18% (range 8-29%) | 32% (range 18-46%) | 33% (range 23-44%) | 14% (range 11-17%) |
| Headache Recurrence | 38% (range 25-46%) | 31% (range 25-40%) | 20% (range 15-32%) | 28% (range 20-35%) |
| Side Effect Profile | Chest symptoms, dizziness Well-tolerated overall | Dizziness, fatigue Generally mild | Chest symptoms, dizziness Similar to others | Minimal side effects "Gentle" profile |
Future Developments
While triptans remain the gold standard for acute migraine treatment, ongoing research continues to refine their use and develop new formulations. Recent innovations focus on improved delivery methods and reduced side effects.
Advanced Delivery Systems
New delivery technologies continue to emerge, including breath-powered nasal devices that provide more consistent absorption and intranasal formulations with permeation enhancers that improve bioavailability while reducing the required dose.
Personalized Medicine Future
Research into pharmacogenomics may eventually allow for personalized triptan selection based on individual genetic profiles, potentially improving response rates and reducing side effects. Current research focuses on genetic variants affecting drug metabolism and receptor sensitivity.
Final Points
Triptans represent one of the most successful classes of medications in neurology, providing targeted relief for millions of migraine sufferers worldwide. Understanding the unique characteristics of each triptan allows for personalized treatment approaches that can significantly improve patient outcomes.
2-3
Trial Different Triptans
Before concluding triptan therapy ineffective
Early
Treatment Timing
Most effective when taken during mild pain
≤10
Days per Month
Usage limit to prevent overuse/adaptation headache
"Choosing the right triptan depends on several factors. Sumatriptan and rizatriptan are popular choices because they're more affordable. If your headaches build up slowly and last all day, longer-lasting options like naratriptan or frovatriptan might work better for you." - Cerebral Torque
The key to successful triptan therapy lies in matching the right medication to the individual patient's needs, attack characteristics, and preferences. With seven different options available, most patients can find an effective triptan that provides meaningful relief from their migraine attacks.
Disclaimer
This article is for educational purposes only and is not intended to replace professional medical advice, diagnosis, or treatment. Always consult with qualified healthcare providers regarding your specific medical conditions and treatment options. Do not stop, start, or change any medications without first discussing with your healthcare provider.
References
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- Teall J, Tuchman M, Cutler N, et al. Rizatriptan (MAXALT) for the acute treatment of migraine and migraine recurrence. A placebo-controlled, outpatient study. Headache. 1998;38(4):281-287.
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- Clinical Practice Guidelines: Headaches in Pregnancy and Postpartum. American College of Obstetricians and Gynecologists; 2022.
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- Evans RW. The FDA alert on serotonin syndrome with combined use of SSRIs or SNRIs and triptans: an analysis of the 29 case reports. MedGenMed. 2007;9(3):48.
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