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Droxidopa (Monograph)

Brand name: Northera
Drug class: alpha- and beta-Adrenergic Agonists
Chemical name: (βR)-β,3-Dihydroxy-l-tyrosine
Molecular formula: C9H11NO5
CAS number: 23651-95-8

Warning

    Supine Hypertension
  • May cause or exacerbate supine hypertension in patients with neurogenic orthostatic hypotension (NOH). Risk of cardiovascular events may be increased in patients with uncontrolled supine hypertension.

  • Monitor supine BP prior to and during treatment and more frequently when increasing doses. To reduce the risk of supine hypertension, advise patients to elevate the head of the bed when sleeping or resting. Reduce dosage of droxidopa or discontinue drug if supine hypertension persists.

Introduction

Synthetic amino acid analog and prodrug of norepinephrine.

Uses for Droxidopa

Symptomatic Neurogenic Orthostatic Hypotension (NOH)

Management of orthostatic dizziness, lightheadedness, or the “feeling that you are about to black out” in patients with symptomatic NOH caused by primary autonomic failure (Parkinson's disease, multiple system atrophy, or pure autonomic failure), dopamine β-hydroxylase deficiency, or non-diabetic autonomic neuropathy.

Has been designated an orphan drug by FDA for treatment of symptomatic NOH in patients with primary autonomic failure, dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy.

Efficacy in symptomatic NOH beyond 2 weeks not established; reassess continued benefit periodically during therapy.

Droxidopa Dosage and Administration

General

Restricted Distribution

Administration

Oral Administration

Administer orally 3 times daily: upon arising in the morning, at midday, and in the late afternoon at least 3 hours before bedtime. Take consistently, either with food or without food. Swallow capsules whole.

Monitor supine BP prior to initiating droxidopa, periodically during treatment, and after dosage increases. (See Supine Hypertension under Cautions.)

If a dose is missed, skip the dose and take the next dose at the regularly scheduled time.

Dosage

Adults

Symptomatic NOH
Oral

Initially, 100 mg 3 times daily. May increase dosage based on symptomatic response and tolerance in increments of 100 mg 3 times daily at intervals of 24–48 hours.

Efficacy beyond 2 weeks not established; periodically reassess continued benefit.

Prescribing Limits

Adults

Symptomatic NOH
Oral

600 mg 3 times daily (1.8 g daily).

Special Populations

Renal Impairment

Mild or moderate renal impairment when GFR >30 mL/minute: Dosage adjustment not necessary.

Limited experience in patients with severe renal impairment (GFR <30 mL/minute); no dosage recommendations provided by manufacturer.

Geriatric Patients

Manufacturer makes no special dosage recommendations.

Cautions for Droxidopa

Contraindications

Warnings/Precautions

Warnings

Supine Hypertension

May cause or exacerbate supine hypertension. Risk of cardiovascular events may be increased in patients with uncontrolled supine hypertension.

Instruct patients to elevate the head of the bed when sleeping or resting to reduce risk of supine hypertension.

Monitor BP prior to initiating droxidopa, periodically during treatment, and more frequently when increasing dosage; measure BP both in the supine position and the recommended head-elevated sleeping position.

If supine hypertension persists, reduce dosage or discontinue droxidopa.

Sensitivity Reactions

Tartrazine Sensitivity

Preparations contain tartrazine (FD&C yellow No. 5), which may cause allergic reactions including bronchial asthma in susceptible individuals. Although the incidence of tartrazine sensitivity is low, it frequently occurs in aspirin-sensitive individuals.

General Precautions

Neuroleptic Malignant Syndrome (NMS)-like Reactions

Potentially life-threatening NMS-like reactions reported with droxidopa.

Symptoms may include hyperpyrexia, muscle rigidity, altered mental status (e.g., confusion), and autonomic instability. Monitor patients receiving droxidopa for the development of NMS-like symptoms; early diagnosis important for appropriate management.

Ischemic Heart Disease, Arrhythmias, and Congestive Heart Failure

May exacerbate ischemic heart disease, arrhythmias, and CHF. Consider risk in patients with these conditions when contemplating droxidopa therapy.

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Discontinue nursing or the drug.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

No overall differences in safety or efficacy in geriatric patients compared with younger adults, but increased sensitivity cannot be ruled out.

Renal Impairment

Frequency of adverse events not affected by mild or moderate renal impairment when GFR >30 mL/minute. Insufficient experience in patients with severe renal impairment (GFR <30 mL/minute).

Common Adverse Effects

Headache, dizziness, nausea, hypertension. Longer-term open label studies: falls, urinary tract infections, headache, syncope, dizziness.

Drug Interactions

Metabolized via catecholamine pathway by catechol-O-methyltransferase (COMT), aromatic L-amino acid decarboxylase, and dihydroxyphenylserine (DOPS) aldolase.

Not metabolized by CYP isoenzymes.

Drugs Affecting Hepatic Microsomal Enzymes

No formal drug interaction studies to date. No interactions expected.

Drugs that Increase Blood Pressure

Possible increased risk for supine hypertension; use concomitantly with caution.

Specific Drugs

Drug

Interaction

Comments

Amantadine derivatives

No effect on droxidopa clearance

No dosage adjustment required

Aromatic L-amino acid decarboxylase inhibitors (e.g., carbidopa)

May prevent conversion of droxidopa to norepinephrine outside the CNS

Carbidopa: Decreased clearance of droxidopa and attenuated rises in plasma norepinephrine and BP reported

Dosage adjustment of droxidopa may be required

Dopamine agonists

No effect on droxidopa clearance

No dosage adjustment required

MAO-B inhibitors

No effect on droxidopa clearance

No dosage adjustment required

Serotonin type 1 (5-HT1) receptor agonists (triptans)

Possible increased risk for supine hypertension

Use concomitantly with caution

Droxidopa Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations attained in approximately 1–4 hours (mean: about 2 hours) following oral administration. Plasma norepinephrine concentrations peak within 3–4 hours of oral administration but have no consistent relationship to droxidopa dosage.

Food

Administration with a high-fat meal delays absorption approximately 2 hours; peak plasma concentration and overall AUC decreased by 35 and 20%, respectively.

Distribution

Extent

Thought to cross the blood-brain barrier.

Distributed into milk in rats; not known whether distributed into human milk.

Plasma Protein Binding

75% plasma protein bound at 100 ng/mL and 26% at 10,000 ng/mL.

Elimination

Metabolism

Metabolized via catecholamine pathway by catechol-O-methyltransferase (COMT), dopa-decarboxylase, and DOPS aldolase.

Elimination Route

Following oral administration of radiolabeled dose in animals, approximately 75% of total radioactivity recovered in urine within 24 hours.

Half-life

Approximately 2.5 hours.

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).

Actions

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Distribution of droxidopa is restricted. (See Restricted Distribution under Dosage and Administration.)

Droxidopa

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

100 mg

Northera

Lundbeck

200 mg

Northera

Lundbeck

300 mg

Northera

Lundbeck

AHFS DI Essentials™. © Copyright 2024, Selected Revisions July 15, 2015. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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