What are the potential side effects of Elitriptan (a triptan medication) in patients, particularly those with a history of cardiovascular disease?

Eletriptan Side Effects

Eletriptan is generally well tolerated with most side effects being mild and transient, but carries important cardiovascular contraindications and warnings that must be carefully considered, particularly in patients with cardiovascular disease or risk factors. 1

Common Side Effects

The most frequently reported side effects of eletriptan include:

• Dizziness, nausea, weakness, and tiredness are the most common adverse effects 1
• Chest pressure or heaviness and paresthesias (abnormal sensations) are common sensory disturbances associated with triptan use 2
• The adverse event profile of eletriptan 20 mg is similar to placebo, while eletriptan 40 mg (the most commonly used dose) has an adverse event profile only marginally higher than placebo 3
• These side effects are typically mild and do not last long 1

Serious Cardiovascular Side Effects

Absolute Contraindications

Eletriptan should NOT be given to patients with: 1

• Documented ischemic or vasospastic coronary artery disease (CAD)
• Uncontrolled hypertension
• Hemiplegic or basilar migraine
• History of stroke or cerebrovascular disease
• Serious liver problems
• Peripheral vascular ischemia

Cardiovascular Warnings in High-Risk Patients

For patients with cardiovascular risk factors (hypertension, hypercholesterolemia, smoking, obesity, diabetes, strong family history of CAD, postmenopausal women, or men over 40), it is strongly recommended that eletriptan NOT be given unless a cardiovascular evaluation provides satisfactory evidence that the patient is reasonably free of coronary artery disease. 1

• If cardiovascular evaluation is satisfactory, the first dose should be administered in a physician's office or similar medically staffed facility 1
• Consider obtaining an ECG during the interval immediately following first administration in patients with risk factors 1
• Patients who are long-term users with cardiovascular risk factors should undergo periodic cardiovascular evaluation 1

Recent Cardiovascular Safety Data

A 2024 study found that triptans likely increase the risk of major adverse cardiovascular events (MACE) in patients with cardiovascular disease or elevated cardiovascular risk, though the absolute incidence remains low (1.48% at 60 days). 4

• The relative risk of MACE was 4.00 (95% CI, 2.24 to 7.14) compared to nontriptan treatments 4
• Increased risk of nonfatal myocardial infarction, heart failure, and nonfatal stroke was observed 4
• However, earlier large-scale observational data from general practice showed no increased risk of stroke, MI, or cardiovascular death with triptan use 5

This creates a clinical dilemma: the most recent high-quality study 4 suggests increased cardiovascular risk, while earlier consensus statements 6 and observational data 5 found the cardiovascular risk-benefit profile favorable. Given this contradiction, extreme caution is warranted in patients with established cardiovascular disease or multiple risk factors.

Other Serious Adverse Effects

Serotonin Syndrome

Serotonin syndrome is a potentially life-threatening condition that may occur with eletriptan, particularly during combined use with SSRIs or SNRIs. 1

• Symptoms include: mental status changes (agitation, hallucinations, coma), autonomic instability (tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (hyperreflexia, incoordination), and gastrointestinal symptoms (nausea, vomiting, diarrhea) 1
• If concomitant treatment with SSRIs or SNRIs is clinically warranted, careful observation is advised, particularly during treatment initiation and dose increases 1
• However, the actual risk appears low, as one large prospective study failed to document a single case 7

Cerebrovascular Events

• Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported with 5-HT1 agonists, some resulting in fatalities 1
• Patients with migraine may be at increased baseline risk of certain cerebrovascular events 1

Other Vasospastic Reactions

• Peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea have been reported with 5-HT1 agonists 1

Blood Pressure Elevation

• Significant elevation in blood pressure, including hypertensive crisis, has been reported on rare occasions 1
• Oral eletriptan (at doses of 60 mg or more) causes small, transient dose-related increases in blood pressure, predominantly diastolic 1
• The effect is more pronounced in renally impaired and elderly subjects 1

Drug Interactions

Eletriptan should NOT be used within at least 72 hours of treatment with potent CYP3A4 inhibitors: 1

• Ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir
• These medications may cause an increase in eletriptan blood levels 1

Eletriptan should NOT be taken within 24 hours of other triptans or ergotamine derivatives due to similar side effects and additive vasoconstrictive effects 1

Special Populations

Pediatric Patients

It is reasonable to avoid triptan agents in children with hemiplegic migraine, basilar migraine, known vascular risk factors, or prior cardiac or cerebral ischemia. 8

• The stroke risk from triptans in children is unknown 8
• Triptans should also be avoided in individuals with renal or hepatic disease and in adolescents who are pregnant or lactating 8

Perioperative Management

Triptans should be taken preoperatively but held on the day of operation. 8, 2

• There are theoretical concerns regarding drug-drug interactions with triptans and commonly used perioperative medications 8
• Risk of serotonin syndrome with combining triptans and SSRIs or SNRIs exists, though it is low 8

Clinical Pearls

• If a patient experiences unpleasant sensory disturbances with one triptan, trying a different triptan may be beneficial 2
• Patients should try a medication for 2-3 headache episodes before abandoning that line of therapy 8, 2
• The incidence of serious cardiovascular events with triptans in clinical trials and clinical practice appears extremely low in appropriately selected patients 1, 6
• Eletriptan is safe and well tolerated for both short- and long-term treatment in patients without contraindications 3
• Relatively large changes in dose and plasma concentration result in minimal changes in tolerability 3