Short Communication
Effects of the novel norepinephrine prodrug, droxidopa, on ambulatory blood pressure in patients with neurogenic orthostatic hypotension

https://doi.org/10.1016/j.jash.2016.07.009Get rights and content
Under a Creative Commons license
open access

Highlights

  • Twenty-four hour blood pressures (BPs) were compared on droxidopa treatment versus off drug in patients with neurogenic orthostatic hypotension.

  • Droxidopa significantly increased 24-hour and daytime BP in patients with neurogenic orthostatic hypotension.

  • Droxidopa increased nighttime BP to a lesser extent than increases in daytime, awake BP.

  • Twenty-four hour BPs can detect patients at risk of supine hypertension to adjust treatment.

Abstract

The prodrug droxidopa increases blood pressure (BP) in patients with neurogenic orthostatic hypotension. The BP profile of droxidopa in neurogenic orthostatic hypotension patients (n = 18) was investigated using ambulatory BP monitoring. Following dose optimization and a washout period, 24-hour “off-drug” data were collected. “On-drug” assessment was conducted after 4–5 weeks of droxidopa treatment (mean dose, 444 mg, three times daily). Ambulatory monitoring off drug revealed that 90% of patients already had abnormalities in the circadian BP profile and did not meet criteria for normal nocturnal BP dipping. On treatment, both overall mean 24-hour systolic and diastolic BPs were higher compared to off drug (137/81 mm Hg vs. 129/76 mm Hg; P = .017/.002). Mean daytime systolic BP was significantly higher with droxidopa (8.4 ± 3.1 mm Hg; P = .014). Although nocturnal BP was not significantly higher on droxidopa versus off treatment (P = .122), increases in nocturnal (supine) BP ≥10 mm Hg were observed in four cases (22%). Severe supine systolic hypertensive readings at night (>200 mm Hg) were captured in one case and only while on treatment. These data demonstrate that ambulatory BP monitoring is useful to evaluate the circadian BP profile after initiating treatment with a pressor agent.

Keywords

Circadian rhythm
clinical trials
supine hypertension

Cited by (0)

Conflict of interest: H.K. is a consultant for Lundbeck NA, Ltd. L.A.H. is an employee of Lundbeck. G.J.R. was an employee of Lundbeck at the time of the analysis and manuscript development. W.B.W. is a safety consultant for Lundbeck LLC.

The data were derived from clinical trials funded by Chelsea Therapeutics, now Lundbeck LLC. L.N.-K. receives research support from the National Institutes of Health (U54NS065736) and the Dysautonomia Foundation, Inc. No author received compensation in conjunction with writing or editing of this manuscript.

1

Lundbeck employee at the time of the analysis and manuscript development.