NORTHERA™

Warnings

Description

Clinical pharmacology

Indications and usage

Contraindications

Precautions

Adverse reactions

Dosage and administration

How supplied

Warnings

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 NORTHERA

Description

Description:
NORTHERA capsules contain droxidopa, which is a synthetic amino acid precursor of norepinephrine, for oral administration. Chemically, droxidopa is (–)-threo-3-(3,4-Dihydroxyphenyl)-L-serine. Droxidopa is an odorless, tasteless, white to off-white crystals or crystalline powder. It is slightly soluble in water, and practically insoluble in methanol, glacial acetic acid, ethanol, acetone, ether, and chloroform. It is soluble in dilute hydrochloric acid. It has a molecular weight of 213.19 and a molecular formula of C9H11NO5.
NORTHERA capsules also contain the following inactive ingredients: mannitol, corn starch, and magnesium stearate. The capsule shell is printed with black ink.

Clinical pharmacology

Mechanism of Action:
The exact mechanism of action of NORTHERA in the treatment of neurogenic orthostatic hypotension is unknown. NORTHERA is a synthetic amino acid analog that is directly metabolized to norepinephrine by dopa-decarboxylase, which is extensively distributed throughout the body. NORTHERA is believed to exert its pharmacological effects through norepinephrine and not through the parent molecule or other metabolites. Norepinephrine increases blood pressure by inducing peripheral arterial and venous vasoconstriction. NORTHERA in humans induces small and transient rises in plasma norepinephrine.

Indications and usage

INDICATIONS AND USAGE:
NORTHERA is indicated for the treatment of orthostatic dizziness, lightheadedness, 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's disease (PD), multiple system atrophy and pure autonomic failure], dopamine beta-hydroxylase deficiency, and non-diabetic autonomic neuropathy. Effectiveness beyond 2 weeks of treatment has not been established. The continued effectiveness of NORTHERA should be assessed periodically.

Contraindications

Contraindications: None.

Precautions

WARNINGS AND PRECAUTIONS:

Supine Hypertension
NORTHERA therapy may cause or exacerbate supine hypertension in patients with NOH. Patients should be advised to elevate the head of the bed when resting or sleeping. Monitor blood pressure, both in the supine position and in the recommended head-elevated sleeping position. Reduce or discontinue NORTHERA if supine hypertension persists. If supine hypertension is not well-managed, NORTHERA may increase the risk of cardiovascular events.
Hyperpyrexia and Confusion
Postmarketing cases of a symptom complex resembling neuroleptic malignant syndrome (NMS) have been reported with NORTHERA use during post-marketing surveillance in Japan. Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics.
NMS is an uncommon but life-threatening syndrome characterized by fever or hyperthermia, muscle rigidity, involuntary movements, altered consciousness, and mental status changes. The early diagnosis of this condition is important for the appropriate management of these patients.
Ischemic Heart Disease, Arrhythmias, and Congestive Heart Failure
NORTHERA may exacerbate existing ischemic heart disease, arrhythmias and congestive heart failure. Careful consideration should be given to this potential risk prior to initiating therapy in patients with these conditions.
Allergic Reactions
This product contains FD+C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD+C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

Adverse reactions

ADVERSE REACTIONS

The following adverse reactions with NORTHERA are included in more detail in the Warnings and Precautions section of the label:

-Supine Hypertension
-Hyperpyrexia and Confusion
-May exacerbate existing ischemic heart disease, arrhythmias, and congestive heart failure

Dosage and administration

DOSAGE AND ADMINISTRATION:
Dosing Information:
The recommended starting dose of NORTHERA is 100 mg, taken orally three times daily: 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). Administer NORTHERA consistently, either with food or without food. Take NORTHERA capsule whole. Titrate to symptomatic response, in increments of 100 mg three times daily every 24-48 hours up to a maximum dose of 600 mg three times daily (i.e., a maximum total daily dose of 1800 mg).

Monitor supine blood pressure prior to initiating NORTHERA and after increasing the dose.

Patients who miss a dose of NORTHERA should take their next scheduled dose.

How supplied

DOSAGE FORMS AND STRENGTHS:

NORTHERA capsules are available in 100 mg, 200 mg, and 300 mg strengths as specified below.

100 mg: Hard gelatin capsules with “Northera” on the white body and “100” on the light blue cap
200 mg: Hard gelatin capsules with “Northera” on the white body and “200” on the light yellow cap
300 mg: Hard gelatin capsules with “Northera” on the white body and “300” on the light green cap

Reference(s)

National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
Provides access to the latest drug monographs submitted to the Food and Drug Administration (FDA). Please review the latest applicable package insert for additional information and possible updates. A local search option of this data can be found here.