Droxidopa Persistence in Neurogenic Orthostatic Hypotension May Be Affected by Titration Approach

Abstract

Droxidopa is approved for the treatment of neurogenic orthostatic hypotension (nOH) symptoms and requires patients to be titrated to individualized effective doses (100–600 mg, three times daily) based on symptomatic response. As per the product label, droxidopa should be titrated every 24–48 hours to an optimum maintenance dose (maximum daily dosage 1,800 mg). In an examination of patients with nOH treated in clinical practice settings (n=4,506) using data from the central Northera specialty-pharmacy hub, titration schedules, daily titration dosage (ie, dosage during first dispensation, the assumed titration period), and daily maintenance dosage (dosage during subsequent dispensations) were characterized. It was found that customized titration schedules (ie, different from the product-label recommendation) had been used in 53% of patients, and these patients had had an average daily titration dosage of 567 mg. In contrast, patients who were titrated as per the label schedule (48 hours, 37%; 24 hours, 10%) had daily titration dosages of 1,500–1,650 mg. A relationship between treatment persistence (measured by number of refills) and maintenance dosage was identified. Average daily maintenance doses in patients who received 2, 3–6, 7–24, and >25 dispensations were 938, 969, 1,069, and 1,167 mg, respectively ( P <0.0001). In summary, our data suggest that more than half the patients treated with droxidopa in clinical practice settings are not titrated using the schedule recommended on the product label (ie, not 24–48 hours), and as a result receive lower daily dosages of droxidopa than those treated using the recommended titration schedules. Lower daily maintenance dosages of droxidopa were associated with shorter treatment persistence (ie, fewer dispensations). Reasons for discontinuation could not be examined in this study, but further investigation of these persistence data is warranted.

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“…Droxidopa, a central and peripheral alpha and beta agonist, was recently approved by the Food and Drugs Administration for the treatment of symptomatic neurogenic OH [98,99]. The main concerns, however, remain for the durability of its benefits [100,101]. Hauser et al conducted a 12-week open-label study using droxidopa.…”

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“…With droxidopa the levels of noradrenaline are maximally elevated at 6 h and may stay elevated for up to 46 h after the last droxidopa administration. Despite this, it is recommended that droxidopa be administered at doses of 100‐600 mg three times a day 43,44 …”

“…Despite this, it is recommended that droxidopa be administered at doses of 100-600 mg three times a day. 43,44 Other drugs that may be utilized in the therapy of postural hypotension include pseudoephedrine, the noradrenaline receptor inhibitor atomoxetine, the α2-adrenergic receptor yohimbine, the cholinesterase inhibitor pyridostigmine and the somatostatin analogue octreotide. [45][46][47][48][49] In refractory subjects, combination therapies, e.g.…”