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Droxidopa


General


Pronunciation

(drox i DOE pa)


Brand Names: U.S.

  • Northera

Indications


Use: Labeled Indications

Neurogenic orthostatic hypotension: Treatment of orthostatic dizziness, light-headedness, or the "feeling that you are about to black out " � in adult patients with symptomatic neurogenic orthostatic hypotension (NOH) caused by primary autonomic failure (Parkinson disease [PD], multiple system atrophy [MSA], and pure autonomic failure [PAF]), dopamine beta-hydroxylase deficiency, and nondiabetic autonomic neuropathy.


Contraindications


There are no contraindications listed in the manufacturers labeling.


ALERT: U.S. Boxed Warning

Supine hypertension:

Monitor supine blood pressure prior to and during treatment and more frequently when increasing doses. Elevating the head of the bed lessens the risk of supine hypertension, and blood pressure should be measured in this position. If supine hypertension cannot be managed by elevation of the head of the bed, reduce or discontinue droxidopa.


Dosing and Administration


Dosing: Adult

Neurogenic orthostatic hypotension: Oral: Initial: 100 mg 3 times daily; titrate in increments of 100 mg 3 times daily every 24 to 48 hours to symptomatic response (maximum total daily dose: 1800 mg).


Dosing: Geriatric

Refer to adult dosing.


Dosing: Renal Impairment

No dose adjustments are required in patients with mild to moderate renal impairment; dose adjustments for severe renal impairment have not been studied.


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturers labeling.


Administration

Administer capsule whole, consistently with or without food, upon arising in the morning, at midday, and in the late afternoon at least 3 hours prior to bedtime (to reduce the potential for supine hypertension during sleep).


Storage

Store at 20 � �C to 25 � �C (68 � �F to 77 � �F); excursions permitted to 15 � �C to 30 � �C (59 � �F to 86 � �F)


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Northera: 100 mg, 200 mg [contains fd&c blue #2 (indigotine)]

Northera: 300 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40, tartrazine (fd&c yellow #5)]


Drug Interactions

Carbidopa: May diminish the therapeutic effect of Droxidopa. Carbidopa may decrease serum concentrations of the active metabolite(s) of Droxidopa. Carbidopa may increase the serum concentration of Droxidopa. Monitor therapy

Ephedra: May enhance the hypertensive effect of Droxidopa. Monitor therapy

EPHEDrine (Systemic): May enhance the hypertensive effect of Droxidopa. Monitor therapy

Midodrine: May enhance the hypertensive effect of Droxidopa. Monitor therapy

Norepinephrine: May enhance the hypertensive effect of Droxidopa. Monitor therapy

Serotonin 5-HT1D Receptor Agonists: May enhance the hypertensive effect of Droxidopa. Monitor therapy


Monitoring Parameters

Monitor supine blood pressure prior to and during treatment and more frequently when increasing the dose.


Adverse Reactions


>10%:

Cardiovascular: Syncope (13%)

Central nervous system: Falling (24%), headache (6% to 13%)

Genitourinary: Urinary tract infection (15%)

1% to 10%:

Cardiovascular: Hypertension (2% to 7%)

Central nervous system: Dizziness (4% to 10%)

Gastrointestinal: Nausea (9%)

Postmarketing and/or case reports: Confusion, hyperpyrexia


Warnings/Precautions


Concerns related to adverse effects:

- Hypertension: [U.S.Boxed Warning]: Droxidopa may cause or exacerbate supine hypertension. Advise patients to elevate the head of bed when resting or sleeping. Monitor blood pressure in supine position and in recommended head-elevated sleeping position. Reduce or discontinue droxidopa if supine hypertension persists. Risk of cardiovascular events may be increased if supine hypertension is not well managed.

- Neuroleptic malignant syndrome: A symptom complex resembling neuroleptic malignant syndrome has been reported; symptoms have included hyperpyrexia and confusion. Observe patients carefully with dose changes or when concomitant levodopa is reduced abruptly or discontinued, especially if patient is receiving neuroleptics.

Disease-related concerns:

- Cardiovascular disease: Droxidopa may exacerbate existing ischemic heart disease, arrhythmias, and congestive heart failure; consider potential risk prior to initiating therapy.

Dosage form specific issues:

- Tartrazine: May contain FD+C Yellow No. 5 (tartrazine), which may cause allergic reactions, including bronchial asthma in susceptible individuals, especially in patients with aspirin hypersensitivity.


Pregnancy Risk Factor

C


Pregnancy Considerations

Adverse events were observed in some animal reproduction studies.


Actions


Pharmacology

A synthetic amino acid analog that is directly metabolized to norepinephrine by dopadecarboxylase. Droxidopa is believed to exert its pharmacological effects through norepinephrine. Norepinephrine increases blood pressure by inducing peripheral arterial and venous vasoconstriction.


Absorption

High-fat meals reduce the Cmax and area under the plasma concentration-time curve (AUC) by 35% and 20%, respectively, and delay the Cmax by approximately 2 hours.


Distribution

Vd: ~200 L


Metabolism

The metabolism of droxidopa is mediated by catecholamine pathway. Droxidopa is initially converted to methoxylated dihydroxyphenylserine (3-OM-DOPS), a major metabolite, by catechol-O-methyltransferase (COMT), to norepinephrine by DOPA decarboxylase (DDC), or to protocatechualdehyde by DOPS aldolase.


Excretion

Urine (~75%)


Time to Peak

Plasma: 1 to 4 hours


Half-Life Elimination

~2.5 hours


Protein Binding

26% to 75%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience nausea. Have patient report immediately to prescriber severe headache, severe dizziness, passing out, vision changes, or signs of neuroleptic malignant syndrome (fever, muscle cramps or stiffness, dizziness, very bad headache, confusion, change in thinking, fast heartbeat, abnormal heartbeat, or sweating a lot) (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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