Can frovatriptan increase blood pressure, particularly in patients with pre-existing hypertension (high blood pressure) or cardiovascular disease?

Frovatriptan and Blood Pressure Effects

Frovatriptan can cause transient increases in blood pressure, but these effects are generally small, dose-dependent, and clinically insignificant at the recommended 2.5 mg dose, though the drug is contraindicated in patients with uncontrolled hypertension. 1

Blood Pressure Effects at Therapeutic Doses

At the recommended 2.5 mg dose, frovatriptan produces only transient, small changes in systolic blood pressure that resolve spontaneously and remain within the normal range. 1 The FDA label specifically notes that in young healthy subjects, statistically significant increases in systolic and diastolic blood pressure occurred only after single doses of 80 mg (32 times the clinical dose) and above. 1 In elderly subjects (65-77 years), transient changes in systolic blood pressure were recorded at the 2.5 mg dose, but any increases were generally small, resolved spontaneously, and blood pressure remained within the normal range. 1

Cardiovascular Safety Profile

Frovatriptan demonstrates a favorable cardiovascular safety profile compared to other triptans, with no clinically significant effects on heart rate or blood pressure in controlled studies. 2, 3 In a 12-month open-label study involving 496 patients treating 13,878 migraine attacks, no effects of frovatriptan on heart rate or blood pressure were observed. 2

Critically, in a randomized, double-blind study of 75 migraineurs with documented coronary artery disease or at high risk (Framingham score ≥14), frovatriptan 2.5 mg was not associated with clinically significant changes in heart rate or blood pressure. 3 This high-risk population study provides reassuring evidence that frovatriptan does not cause problematic blood pressure elevations even in vulnerable patients. 3

Use in Hypertensive Patients

Frovatriptan appears to have a sustained antimigraine effect in both hypertensive and normotensive patients, with no blood pressure or heart rate increment observed during treatment in hypertensive subjects. 4 In a pooled analysis of three randomized, double-blind, crossover Italian studies involving 60 subjects with treated or untreated essential arterial hypertension and 286 normotensive subjects, no blood pressure or heart rate increment was observed during the study in hypertensive subjects. 4

The relapse rate at 48 hours was similarly low in hypertensive and normotensive patients with frovatriptan (29% vs. 31%), while comparator triptans showed significantly higher relapse rates in hypertensive patients (62% vs. 44% in normotensive patients, p<0.05). 4 This suggests frovatriptan may actually be preferable in hypertensive migraineurs due to its sustained effect and lack of blood pressure elevation. 4

Absolute Contraindications

Frovatriptan is absolutely contraindicated in patients with uncontrolled hypertension. 1 The FDA label explicitly states this contraindication, though it does not define specific blood pressure thresholds for "uncontrolled." 1

Frovatriptan should not be given to patients with ischemic heart disease, cerebrovascular syndromes, peripheral vascular disease, or other significant underlying cardiovascular disease. 1 For patients with cardiovascular risk factors, the FDA recommends that the first dose be administered in a physician's office or similar medically staffed facility, with consideration given to obtaining an ECG during the interval immediately following administration. 1

Mechanism of Blood Pressure Effects

The blood pressure effects of frovatriptan stem from its agonism at serotonin 5-HT₁B and 5-HT₁D receptors, which can cause vasoconstriction. 5 However, frovatriptan appears to be functionally selective for 5-HT receptors in human basilar arteries over coronary arteries, which translates into a low cardiovascular risk profile. 5, 6

An 18% increase in mean pulmonary artery pressure was documented with another 5-HT₁ agonist in subjects undergoing cardiac catheterization, highlighting the class effect on vascular tone. 1

Comparative Tolerability

Frovatriptan demonstrates superior tolerability compared to other triptans, with significantly fewer adverse events than sumatriptan 100 mg (36% vs. 43%, p=0.03) and fewer cardiovascular symptoms. 2 In short-term studies, only 1% of patients withdrew due to lack of tolerability with frovatriptan 2.5 mg, compared to 5% in long-term studies. 2

Clinical Recommendations for Hypertensive Patients

• Verify blood pressure control status before prescribing frovatriptan—avoid entirely if hypertension is uncontrolled. 1
• For patients with controlled hypertension, frovatriptan 2.5 mg can be used safely with appropriate monitoring. 4, 3
• Consider frovatriptan as a preferred triptan option in hypertensive migraineurs due to its sustained effect and lack of blood pressure elevation. 4
• Monitor blood pressure during initial therapy, particularly in patients with cardiovascular risk factors or pre-existing hypertension. 1
• Ensure patients with cardiovascular risk factors undergo periodic cardiovascular evaluation when using frovatriptan long-term. 1

Critical Pitfalls to Avoid

• Do not confuse "controlled" with "uncontrolled" hypertension—only uncontrolled hypertension is a contraindication, but the threshold is not precisely defined in the FDA label. 1
• Do not assume all triptans have equivalent cardiovascular safety—frovatriptan has a more favorable profile than sumatriptan in head-to-head comparisons. 2
• Do not withhold frovatriptan from well-controlled hypertensive patients based solely on their hypertension diagnosis—evidence supports safe use in this population. 4, 3
• Do not administer frovatriptan within 24 hours of another 5-HT₁ agonist or ergot-type medication, as this increases cardiovascular risk. 1