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Black Box Warning
WARNING:
See full prescribing information for complete Boxed Warning.
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
Overview
Droxidopa is a Sympathomimetic that is FDA approved for the treatment of neurogenic orthostatic hypotension. There is a Black Box Warning for this drug as shown here. Common adverse reactions include Headache, dizziness, nausea, hypertension, and fatigue.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indications
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.
Dosage
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 to 48 hours up to a maximum dose of 600 mg three times daily (i.e., a maximum total daily dose of 1,800 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.
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
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Droxidopa in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Droxidopa in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Droxidopa in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Droxidopa in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Droxidopa in pediatric patients.
Contraindications
None
Warnings
WARNING:
See full prescribing information for complete Boxed Warning.
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
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.
5.2 Hyperpyrexia and Confusion
Post-marketing 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.
5.3 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.
5.4 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
Clinical Trials Experience
The following adverse reactions with NORTHERA are included in more detail in the Warnings and Precautions section of the label:
Supine Hypertension [see Warnings and Precautions (5.1)]
Hyperpyrexia and Confusion [see Warnings and Precautions (5.2)]
May exacerbate existing ischemic heart disease, arrhythmias, and congestive heart failure [see Warnings and Precautions (5.3)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety evaluation of NORTHERA is based on two placebo-controlled studies 1 to 2 weeks in duration (Studies 301 and 302), one 8-week placebo-controlled study (Study 306), and two long-term, open-label extension studies (Studies 303 and 304). In the placebo-controlled studies, a total of 485 patients with Parkinson's disease, multiple system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency, or non-diabetic autonomic neuropathy were randomized and treated, 245 with NORTHERA and 240 with placebo [see Clinical Studies (14)].
Placebo-Controlled Experience
The most commonly observed adverse reactions (those occurring at an incidence of greater than 5% in the NORTHERA group and with at least a 3% greater incidence in the NORTHERA group than in the placebo group) in NORTHERA-treated patients during the three placebo-controlled trials were headache, dizziness, nausea, hypertension. The most common adverse reactions leading to discontinuation from NORTHERA were hypertension or increased blood pressure and nausea.
Note: n=number of patients. Table displays adverse reactions that were reported in greater than 5% of patients in the NORTHERA group and with at least a 3% greater incidence in the NORTHERA group than in the placebo group.
Long-Term, Open-Label Trials with NORTHERA
In the long-term, open-label extension studies, a total of 422 patients, mean age 65 years, were treated with NORTHERA for a mean total exposure of approximately one year. The commonly reported adverse events were falls (24%), urinary tract infections (15%), headache (13%), syncope (13%), and dizziness (10%).
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Droxidopa in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Drug Interactions
Drugs that Increase Blood Pressure
Administering NORTHERA in combination with other agents that increase blood pressure (e.g., norepinephrine, ephedrine, midodrine, and triptans) would be expected to increase the risk for supine hypertension.
7.2 Parkinson's Medications
Dopa-decarboxylase inhibitors may require dose adjustments for NORTHERA.
There are no adequate and well-controlled trials in pregnant women.
Following consecutive oral administration at doses of 60, 200, and 600 mg/kg/day to pregnant Sprague Dawley rats, increased incidences of lower body weight and occurrence of undulant rib were noted in fetuses, but they were slight and spontaneously reversed after birth. Based on dose per unit body surface area, these three doses correspond to approximately 0.3, 1, and 3 times, respectively, the maximum recommended total daily dose of 1,800 mg in a 60 kg patient. Shortening of the gestation period was observed in rats at 600 mg/kg/day. Low incidences of renal lesions (cysts, indentations, or renal pelvic dilation) were observed on the surface of the kidneys of female rats treated with droxidopa during the period of fetal organogenesis. No other potentially teratogenic effects have been observed in rats or rabbits.
Pregnancy Category (AUS):
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Droxidopa in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Droxidopa during labor and delivery.
Nursing Mothers
Choose nursing or NORTHERA. In rats, droxidopa is excreted in breast milk, and when the drug was administered to the nursing dams during the period of lactation, reduced weight gain and reduced survival were observed in the offspring.
Pediatric Use
The safety and effectiveness of NORTHERA in pediatric patients have not been established.
Geriatic Use
A total of 197 patients with symptomatic NOH aged 75 years or above were included in the NORTHERA clinical program. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Gender
There is no FDA guidance on the use of Droxidopa with respect to specific gender populations.
Race
There is no FDA guidance on the use of Droxidopa with respect to specific racial populations.
Renal Impairment
NORTHERA and its metabolites are primarily cleared renally. Patients with mild or moderate renal impairment (GFR greater than 30 mL/min) were included in clinical trials and did not have a higher frequency of adverse reactions. Clinical experience with NORTHERA in patients with severe renal function impairment (GFR less than 30 mL/min) is limited.
Hepatic Impairment
There is no FDA guidance on the use of Droxidopa in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Droxidopa in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Droxidopa in patients who are immunocompromised.
Administration and Monitoring
Administration
Oral
Monitoring
Monitor supine blood pressure prior to and during treatment and more frequently when increasing doses.
IV Compatibility
There is limited information regarding IV Compatibility of Droxidopa in the drug label.
Overdosage
Symptoms
There was one case of overdose reported during post-marketing surveillance in Japan. The patient ingested 7,700 mg of NORTHERA and experienced a hypertensive crisis that resolved promptly with treatment.
10.2 Treatment
There is no known antidote for NORTHERA overdosage. In case of an overdose that may result in an excessively high blood pressure, discontinue NORTHERA and treat with appropriate symptomatic and supportive therapy. Counsel patients to remain in a standing or seated position until their blood pressure drops below an acceptable limit.
Pharmacology
There is limited information regarding Droxidopa Pharmacology in the drug label.
