droxidopa

droxidopa

(drox-i-doe-pa),

Northera

(trade name)

Classification

Therapeutic: temporary class
Pharmacologic: adrenergics

Indications

Treatment of orthostatic dizziness, lightheadedness or feeling of impending blackout associated with symptomatic neurogenic orthostatic hypotension due to primary autonomic failure (Parkinson's disease, multiple system atrophy), dopamine beta-hydroxylase deficiency or non-diabetic autonomic neuropathy.

Action

Acts as a synthetic precursor that is converted by dopa decarboxylase to norepinephrine which produces peripheral arterial and venous vasocontriction. Result is increased blood pressure.

Therapeutic effects

Increased blood pressure with decreased symptoms of orthostatic dizziness.

Pharmacokinetics

Absorption: Systemic absorption follows oral administration.
Distribution: Crosses the blood-brain barrier.
Metabolism and Excretion: Metabolized via catecholamine pathway; metabolites other than norepinephrine do not contribute to activity. 75% excreted by kidneys as parent drug and metabolites.
Half-life: 2.5 hr.

Time/action profile (↑ blood pressure)

ROUTEONSETPEAKDURATION
POunknown1–4 hrunknown

Contraindications/Precautions

Contraindicated in: Hypersensitivity to droxidopa or tartrazine (FD+C No. 5 [cross sensitivity between aspirin and FD+C No. 5 may occur); CCr <30 mL/min; Lactation: Discontinue droxidopa or discontinue breastfeeding.
Use Cautiously in: Hypertension (should be controlled prior to treatment); Mild to moderate renal impairment (↑ risk of adverse reactions); History of cardiovascular disease (may exacerbate hypertension, ischemic heart disease, arrhythmias or CHF); Geriatric: Elderly patients may be more sensitive to drug effects; Obstetric: Safe use during pregnancy has not been established; Pediatric: Safe and effective use in children has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • confusion
  • dizziness
  • fatigue
  • headache

Cardiovascular

  • arrhythmias (life-threatening)
  • CHF (life-threatening)
  • myocardial ischemia (life-threatening)
  • supine hypertension

Gastrointestinal

  • nausea

Miscellaneous

  • hyperpyrexia

Interactions

Drug-Drug interaction

↑ risk of supine hypertension with other agents that ↑ blood pressure including ephedrine, norepinephrine, midodrine, pseudoephedrine, and triptans.Concurrent use of DOPA decarboxylase inhibitors may require dose adjustments.

Route/Dosage

Oral (Adults) 100 mg three times daily, may be ↑ by 100 mg three times daily up to 600 mg three times daily (last dose should be given at least 3 hr prior to bedtime).

Availability

Capsules (contain tartrazine): 100 mg, 200 mg, 300 mg

Nursing implications

Nursing assessment

  • Monitor blood pressure prior to and during therapy; more frequently during dose increases. Measure blood pressure in supine position and while head of bed is elevated; lessens risks of supine hypertension. If supine hypertension cannot be managed by elevating head of bed, reduce or discontinue droxidopa. Poorly managed supine hypertension may increase risk for cardiovascular events.
  • Monitor for symptom complex resembling neuroleptic malignant syndrome (fever, muscle rigidity, involuntary movements, altered consciousness, mental status changes) when dose is changed or when concomitant levodopa is abruptly reduced or discontinued, especially if patient is receiving neuroleptics. Syndrome is rare but potentially fatal.

Potential Nursing Diagnoses

Deficient knowledge, related to disease process and medication regimen (Patient/Family Teaching)

Implementation

  • Oral: Administer upon arising in the morning, midday, and in late afternoon at least 3 hr prior to bedtime to reduce risk of supine hypertension during sleep. Swallow capsule whole; do not open, crush or chew.
    • May be administered without regard to food, but should be consistent each dose.

Patient/Family Teaching

  • Instruct patient to take droxidopa as directed. If dose is missed, omit and take next dose at scheduled time; do not double doses.
  • Advise patient to raise head of bed when resting or sleeping.
  • Instruct patient how to take blood pressure and manage elevations.
  • Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

  • Increased blood pressure with decreased symptoms of orthostatic dizziness.
References in periodicals archive ?
Droxidopa (Northera) is given orally and is indicated for symptomatic neurogenic orthostatic hypotension.
Reported positive interim analysis of Phase II study of droxidopa in fibromyalgia by an independent data monitoring committee supporting the efficacy and safety of a novel droxidopa/carbidopa combination therapy; and
Just as L-3,4-dihydroxyphenylalanine (levodopa) is converted to dopamine via L-aromatic-amino-acid decarboxylase, droxidopa is converted to NE.
Chelsea is developing the drug, Droxidopa, as a treatment for symptomatic neurogenic orthostatic hypotension (NOH)--a neurological disorder that causes blood pressure to drop when the afflicted person assumes a standing position.
In addition to its autoimmune pipeline, Chelsea has received approval for the designation of Droxidopa in the US as an Orphan Drug.
has announced that the FDA has granted Orphan Drug designation to its drug candidate Droxidopa for the treatment of symptomatic neurogenic orthostatic hypotension (NOH) in patients with Primary Autonomic Failure, a group of diseases that includes Parkinson's Disease, Pure Autonomic Failure (PAF) and Multiple Systems Atrophy (MSA).
FDA's Complete Response Letter for droxidopa as a possible orthostatic hypotension treatment highlights importance of Shire's commitment to complete additional trials to verify and describe the clinical benefit of midodrine
Droxidopa is a synthetic catecholamine that is directly converted to norepinephrine (NE) via decarboxylation, resulting in increased levels of NE in the nervous system, both centrally and peripherally.
The complaint alleges that during the Class Period, defendants issued materially false and misleading statements regarding the safety and efficacy of Droxidopa for patients with NOH, the results of the Phase III testing of Droxidopa for patients with NOH, the post-marketing events in Japan (where Droxidopa has been approved for the same indication at lower doses) and the likelihood of FDA approval of Droxidopa for patients with NOH in light of the known adverse material facts concerning Droxidopa for patients with NOH.
has announced top-line results from Study 302, the first of two Phase III trials of Droxidopa for the treatment of symptomatic neurogenic orthostatic hypotension (NOH).
The complaint alleges that during the Class Period, defendants made material misstatements and omissions concerning (i) the safety and efficacy of Droxidopa for patients with NOH; (ii) the results of the Phase III testing of Droxidopa for patients with NOH; and (iii) the post-marketing events in Japan and the likelihood of FDA approval of Droxidopa for patients with NOH in light of the known adverse material facts concerning Droxidopa for patients with NOH.
Currently approved and marketed in Japan for the treatment of symptomatic orthostatic hypotension, freezing gait in Parkinson's disease and intradialytic hypotension, Droxidopa has accumulated over 15 years of proven safety and efficacy, historically generating annual revenues of approximately $50 million in Japan.