Triptans Associated With Adverse Events Across Organ Systems

Adverse events associated with triptan use can occur across multiple organ systems, including the cardiac, nervous, and gastrointestinal systems, according to research published in The Journal of Headache and Pain.¹

Triptans are used to treat acute migraine and cluster headaches. | image credit: ColleenMichaels - stock.adobe.com

Advances in therapies and an increased frequency in adverse events have “prompted a shift in the way clinicians…approach drug utilization in the real world,” study authors wrote. In the current study, these investigators used the FDA Adverse Event Reporting System (FAERS) database to conduct pharmacovigilance analyses of triptans and associated adverse events, in order to provide postmarketing safety insights for triptan drugs.

For this retrospective analysis, researchers retrieved FAERS reports made between January 2018 and December 2023 associated with sumatriptan, zolmitriptan, rizatriptan, and naratriptan in patients aged 15 to 49 years. A total of 968,550 adverse event reports were identified and analyzed.

Sumatriptan was associated with the highest number of adverse event reports (1272 reports), followed by rizatriptan (162 reports), zolmitriptan (114 reports), and naratriptan (15 reports). Across all 4 medications, the ratio of men to women was approximately 3 times greater; however, investigators noted that this may be because migraine is more prevalent in women, creating a real-world population of triptan users that is predominantly made up of women. Individuals between ages 31 and 49 years were the most frequent reporters of adverse events.

READ MORE: Managing Medication Overuse Headache in Chronic Migraine

Investigators also analyzed adverse event signals for each drug, with 164 positive signals for sumatriptan, 101 positive signals for zolmitriptan, 97 positive signals for rizatriptan, and 21 positive signals for naratriptan. When analyzed at the preferred terminology level, the three most frequently reported adverse events were as follows:

• sumatriptan: dyspnea, chest discomfort, and dizziness
• zolmitriptan: nausea, fatigue, and pain
• rizatriptan: vomiting, chest discomfort, myocardial infarction
• naratriptan: terminal ileitis, nocturia, and abdominal pain.

When reviewed by proportional reporting ratio, the most common adverse events included:

• sumatriptan: migranious infarction, pityriasis lichenoides et varioliformis acuta; and subclavian artery thrombosis
• zolmitriptan: parastheisa ear, vascular malformation, and paranasal cyst
• rizatriptan: broad ligament tear, hemiataxia, and thalamic infarction

Among adverse events with the highest proportional reporting ratio, the top 3 adverse events were spinal cord infarction, terminal ileitis, and cerebral vasoconstriction.

Investigators also classified adverse event signals by system organ classification for involved organs and systems. Results of this analysis indicated that “nervous system disorders constituted the primary [system organ classification] category” for all 4 triptans within the FAERS database.

Additional analyses were conducted on the reporting odds ratio (ROR) intensity of the adverse event signal, with results as follows:

• Sumatriptan-associated adverse events: the strongest signal was coronary artery dissection (ROR, 222.69; 95% CI, 154.18-321.63). This robust cardiac signal “aligns with [the drug’s] contraindication in patients with preexisting cardiovascular disease.”
• Zolmitriptan-associated adverse events: the strongest signal was vascular malformation (ROR, 1470.28; 95% CI, 428.57-5044.00)
• Rizatriptan-associated adverse events: the strongest signal was for thalamic stroke, no infarction (ROR, 617.58; 95% CI, 187.05-2039.10), followed by coronary artery dissection (ROR, 240.14; 95% CI, 104-65-551.01), indicating that the drug can lead to a wide range of neurological disorders and possibly cardio-cerebral adverse events.
• Naratriptan-associated adverse events: the strongest signal was for spinal cord infarction (ROR, 2980.03; 95% CI, 375.50-23,649.77).

Sumatriptan exhibited the highest frequency of positive adverse events for all 4 triptans. Investigators found one common adverse event across all 4 drugs: reversible cerebral vasoconstriction syndrome, a nervous system disorder.

“The introduction of triptan medication has broadened the spectrum of potential migraine treatments, offering a greater array of options for clinicians and patients alike,” the authors wrote, adding that it is crucially important to ensure the continued safety, as well as efficacy, of these drugs.

Study limitations include the self-reporting nature of the FAERS database, which can include incomplete reporting information and uncertainty around causal relationships.

“[Adverse events are] present in a range of systems, including…cardiac, nervous, gastrointestinal, and musculoskeletal and connective tissue disorders,” the researchers concluded. “Future studies should aim to develop a new generation of highly selective analogues based on the possible mechanisms underlying the generation of these [adverse events].”

READ MORE: Pain Management Resource Center

Reference

Lui W-H, Hu H-M, Li C, et al. Real-world study of adverse events associated with triptan use in migraine treatment based on US Food and Drug Administration adverse event reporting system (FAERS) database. J Headache Pain. 2024;25(1):206. doi:10.1186/s10194-024-01913-0