, Volume 75, Issue 2, pp 197–206 | Cite as

Droxidopa: A Review of Its Use in Symptomatic Neurogenic Orthostatic Hypotension

  • Gillian M. Keating
Adis Drug Evaluation


The norepinephrine prodrug droxidopa (NORTHERA™) is approved in the US for the treatment of orthostatic dizziness, lightheadedness, or the ‘feeling that you are about to black out’ in adults with symptomatic neurogenic orthostatic hypotension associated with primary autonomic failure (e.g. Parkinson’s disease, multiple system atrophy or pure autonomic failure), dopamine β-hydroxylase deficiency or nondiabetic autonomic neuropathy. This article reviews the clinical efficacy and tolerability of droxidopa in symptomatic neurogenic orthostatic hypotension, as well as summarizing its pharmacological properties. Oral droxidopa was effective in the shorter-term treatment of patients with symptomatic neurogenic orthostatic hypotension, with improvements seen in symptoms, the impact of symptoms on daily activities and standing systolic blood pressure. More data are needed to confirm the longer-term efficacy of droxidopa. Droxidopa was generally well tolerated, although patients should be monitored for supine hypertension.


Placebo Recipient Multiple System Atrophy Midodrine Study 306a Study 306b 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The preparation of this review was not supported by any external funding. Gillian Keating is a salaried employee of Adis/Springer. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.


  1. 1.
    Freeman R, Landsberg L. The treatment of orthostatic hypotension with dihydroxyphenylserine. Clin Neuropharmacol. 1991;14(4):296–304.PubMedCrossRefGoogle Scholar
  2. 2.
    Berger MJ, Kimpinski K. A practical guide to the treatment of neurogenic orthostatic hypotension. Can J Neurol Sci. 2014;41(2):156–63.PubMedCrossRefGoogle Scholar
  3. 3.
    Schroeder C, Jordan J, Kaufmann H. Management of neurogenic orthostatic hypotension in patients with autonomic failure. Drugs. 2013;73(12):1267–79.PubMedCrossRefGoogle Scholar
  4. 4.
    Lundbeck NA Ltd. NORTHERA™ (droxidopa) capsules, for oral use: US prescribing information. 2014. Accessed 10 Dec 2014.
  5. 5.
    Goldstein DS. L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug. Cardiovasc Drug Rev. 2006;24(3–4):189–203.PubMedCrossRefGoogle Scholar
  6. 6.
    Kaufmann H. The discovery of the pressor effect of DOPS and its blunting by decarboxylase inhibitors. J Neural Transm. 2006;70(Suppl):477–84.CrossRefGoogle Scholar
  7. 7.
    Goldstein DS, Holmes C, Sewell LT, et al. Effects of carbidopa and entacapone on the metabolic fate of the norepinephrine prodrug L-DOPS. J Clin Pharmacol. 2011;51(1):66–74.PubMedCrossRefGoogle Scholar
  8. 8.
    Kaufmann H. L-dihydroxyphenylserine (droxidopa): a new therapy for neurogenic orthostatic hypotension. The US experience. Clin Auton Res. 2008;18(Suppl 1):19–24.CrossRefGoogle Scholar
  9. 9.
    Kaufmann H, Saadia D, Voustianiouk A, et al. Norepinephrine precursor therapy in neurogenic orthostatic hypotension. Circulation. 2003;108(6):724–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Goldstein DS, Holmes C, Kaufmann H, et al. Clinical pharmacokinetics of the norepinephrine precursor L-threo-DOPS in primary chronic autonomic failure. Clin Auton Res. 2004;14(6):363–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Suzuki T, Higa S, Sakoda S, et al. Pharmacokinetic studies of oral L-threo-3,4-dihydroxyphenylserine in normal subjects and patients with familial amyloid polyneuropathy. Eur J Clin Pharmacol. 1982;23(5):463–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Suzuki T, Sakoda S, Ueji M, et al. Treatment of parkinsonism with L-threo-3,4-dihydroxyphenylserine: a pharmacokinetic study. Neurology. 1984;34(11):1446–50.PubMedCrossRefGoogle Scholar
  13. 13.
    Kato T, Karai N, Katsuyama M, et al. Studies on the activity of L-threo-3,4-dihydroxyphenylserine (L-DOPS) as a catecholamine precursor in the brain: comparison with that of L-DOPA. Biochem Pharmacol. 1987;36(18):3051–7.PubMedCrossRefGoogle Scholar
  14. 14.
    US Food and Drug Administration. Droxidopa: medical review. Application number: 203202Orig1s000. 2014. Accessed 10 Dec 2014.
  15. 15.
    LeWitt P, Gorny S. Analysis of efficacy and safety outcomes in patients treated with droxidopa in combination with other drug classes [abstract no. 1294]. Mov Disord. 2012;27(Suppl 1):S425–6.Google Scholar
  16. 16.
    Kaufmann H, Oribe E, Yahr MD. Differential effect of L-threo-3,4-dihydroxyphenylserine in pure autonomic failure and multiple system atrophy with autonomic failure. J Neural Transm. 1991;3(2):143–8.CrossRefGoogle Scholar
  17. 17.
    Mathias CJ, Senard J-M, Braune S, et al. L-threo-dihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure. Clin Auton Res. 2001;11:235–42.PubMedCrossRefGoogle Scholar
  18. 18.
    Mathias CJ, Senard JM, Cortelli P. A double-blind, randomized, placebo-controlled study to determine the efficacy and safety of droxidopa in the treatment of orthostatic hypotension associated with multiple system atrophy or Parkinson’s disease [abstract]. Clin Auton Res. 2007;17:272.Google Scholar
  19. 19.
    Wikstrom L, Bjerle P, Boman K. L-threo-DOPS treatment of orthostatic hypotension in Swedish patients with familial amyloidotic polyneuropathy (TTR-met30). Amyloid J Protein Fold Disord. 1996;3:162–6.CrossRefGoogle Scholar
  20. 20.
    Kaufmann H, Freeman R, Biaggioni I, et al. Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial. Neurology. 2014;83(4):328–35.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Biaggioni I, Freeman R, Mathias CJ, et al. Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa. Hypertension. 2014. doi: 10.1161/HYPERTENSIONAHA.114.04035.
  22. 22.
    Hauser RA, Hewitt LA, Isaacson S. Droxidopa in patients with neurogenic orthostatic hypotension associated with Parkinson’s disease (NOH306A). J Parkinsons Dis. 2014;4(1):57–65.PubMedGoogle Scholar
  23. 23.
    Hauser RA, Isaacson S, Lisk JP, et al. Droxidopa for the short-term treatment of symptomatic neurogenic orthostatic hypotension in Parkinson’s disease (nOH306B). Mov Disord. 2014. doi: 10.1002/mds.26086.
  24. 24.
    Isaacson S, Shill H, Vernino S, et al. Durability of effect with long-term, open-label droxidopa treatment in patients with symptomatic neurogenic orthostatic hypotension (NOH 303) [abstract no. 1291]. Mov Disord. 2012;27(Suppl 1):S424–5.Google Scholar
  25. 25.
    Mathias C, Low P, Freeman R, et al. Integrated efficacy analysis of droxidopa in 2 double-blind, placebo-controlled phase 3 studies in patients with neurogenic orthostatic hypotension [abstract no. 1296]. Mov Disord. 2012;27(Suppl 1):S426.Google Scholar
  26. 26.
    Isaacson S, Hauser R, Szakacs C, et al. Droxidopa treatment impact on orthostatic symptoms and standing systolic blood pressure in patients with Parkinson’s disease (PD) and symptomatic neurogenic orthostatic hypotension (NOH) [abstract]. Neurology. 2013;80(19):e203.Google Scholar
  27. 27.
    Hauser RA, Jerome LP, Schwieterman WD, et al. Impact of droxidopa treatment on falls and fall related injuries in patients with Parkinson’s disease and symptomatic neurogenic orthostatic hypotension (study 306) [abstract no. 481]. Mov Disord. 2013;28(Suppl 1):S171.Google Scholar
  28. 28.
    Shill H, Vernino S, Hutchman R, et al. A multicenter, open-label study to assess the long-term safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension (NOH 304) [abstract no. 1302]. Mov Disord. 2012;27(Suppl 1):S428.Google Scholar
  29. 29.
    Lamarre-Cliche M. Drug treatment of orthostatic hypotension because of autonomic failure or neurocardiogenic syncope. Am J Cardiovasc Drugs. 2002;2(1):23–35.PubMedCrossRefGoogle Scholar
  30. 30.
    Upsher-Smith Laboratories Inc. Midodrine HCl tablets: US prescribing information. 2012. Accessed 10 Dec 2014.
  31. 31.
    Kaufmann H, Malamut R, Norcliffe-Kaufmann L, et al. The Orthostatic Hypotension Questionnaire (OHQ): validation of a novel symptom assessment scale. Clin Auton Res. 2012;22(2):79–90.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

Personalised recommendations