Key result
Lasmiditan plus propranolol reduces maximum heart rate by ~7 bpm and transiently increases blood pressure.
Why the study?
Although lasmiditan is not known to induce vasoconstriction, its cardiovascular effects required evaluation because it is likely to be coadministered with beta-blockers like propranolol used for migraine prophylaxis.
Does coadministration of lasmiditan and propranolol affect cardiovascular parameters or pharmacokinetics in healthy subjects?
Does coadministration of lasmiditan and propranolol affect cardiovascular parameters or pharmacokinetics in healthy subjects?
Coadministration of lasmiditan and propranolol in healthy subjects is generally well tolerated with only transient, mild effects on heart rate and blood pressure and no pharmacokinetic interactions.
Answers are grounded in this paper and cite their sources.
Transient HR/BP shifts support monitoring on coadministration; extends early safety data but leaves open effects in patients.
receptor agonist currently under investigation for acute treatment of migraine. Although lasmiditan is not known to induce vasoconstriction, it remains important to understand its effect on cardiovascular parameters because it is likely to be coadministered with β-adrenergic receptor antagonists used for migraine prophylaxis, such as propranolol. This phase 1, single-center, open-label, fixed-sequence study evaluated the cardiovascular and pharmacokinetic effects of 200 mg lasmiditan in 44 healthy subjects receiving repeated oral doses of twice-daily 80 mg propranolol under fasting conditions. Coadministration caused statistically significant decreases in mean hourly heart rate relative to propranolol alone, but the maximum magnitude of this effect was -6.5 bpm and recovered to predose levels by 3 to 4 hours before stabilizing. Additionally, short-lived (≤2.5 hours) statistically significant increases in systolic blood pressure (8.3 mm Hg) and diastolic blood pressure (6.4 mm Hg) were observed following coadministration. Consistent with the largely nonoverlapping metabolic pathways of lasmiditan and propranolol, exposure to either drug was not affected by coadministration. Overall, compared with administration of either drug alone, coadministration was generally well tolerated.
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Tsai et al. (2020) studied Healthy subjects (n=44). Lasmiditan vs. Propranolol alone was evaluated on Mean hourly heart rate (MD -6.5 bpm). Coadministration of 200 mg lasmiditan with propranolol caused a maximum decrease in heart rate of 6.5 bpm and transient increases in blood pressure, but was generally well tolerated.
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