NORTHERA- droxidopa capsule

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

DROXIDOPA (UNII: J7A92W69L7) (DROXIDOPA - UNII:J7A92W69L7)

Available from:

Lundbeck Pharmaceuticals LLC

INN (International Name):

DROXIDOPA

Composition:

DROXIDOPA 100 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic 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. NORTHERA is contraindicated in patients who have a history of hypersensitivity to the drug or its ingredients [see Warnings and Precautions (5.4)]. Risk Summary There are no available data on use of NORTHERA in pregnant women and risk of major birth defects or miscarriage. NORTHERA did not produce significant reproductive toxicity in pregnant female rats or rabbits or in their fetuses. However, when pregnant female rats were dosed during days 7-17 of gestation (the period of fetal organogenesis) with doses of NORTHERA corresponding to 0.3, 1 and 3 times the maximum recommended daily dose of 1,800 mg in a 60 kg patient, based on body surface area, and when their male and female offspring (who were exposed only during fetal life) were subsequently bred, the female offspring exhibited a dose-dependent reduction in the number of live fetuses across all three doses and an increased number of embryonic/fetal deaths at the two higher doses (see Data ). The estimated background risk of major birth defects and miscarriage in the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data During a multigenerational reproductive toxicity study in rats, pregnant females were dosed during days 7-17 of gestation (the period of fetal organogenesis) with doses of NORTHERA corresponding to 0.3, 1 and 3 times the maximum recommended daily dose of 1,800 mg in a 60 kg patient. Reduced weight gain, renal lesions, and a small number of deaths were observed in females treated with the two higher doses. When their male and female offspring (who were exposed to NORTHERA only during fetal life) were subsequently bred, the female offspring exhibited a dose-dependent reduction in the number of live fetuses across all three doses and an increased number of embryonic/fetal deaths at the two higher doses. Risk Summary There is no information regarding the presence of NORTHERA or its active metabolite(s) in human milk, the effects of NORTHERA on the breastfed child, nor the effects of NORTHERA on milk production/excretion. Droxidopa is present in rat milk with peak concentrations seen 4 hours after oral drug administration and drug excretion into milk still occurring 48 hours after administration (see Data ). However, due to species-specific differences in lactation physiology, animal lactation data typically do not reliably predict levels in humans. Because of the potential for serious adverse reactions, including reduced weight gain in breastfed infants, advise a woman not to breastfeed during treatment with NORTHERA. Data Animal Data In rats, oral administration of droxidopa resulted in excretion into breast milk with peak concentrations seen 4 hours after administration, and excretion still occurring 48 hours after administration. When the drug was administered to nursing dams during the period of lactation at a dose corresponding to 3 times the maximum recommended daily dose of 1,800 mg in a 60 kg patient when based on body surface area, reduced weight gain and reduced survival were observed in the offspring. Despite the observed decreased weight gain, physical development was normal (with respect to timing and organ morphology).   The safety and effectiveness of NORTHERA in pediatric patients have not been established. 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 patients and younger patients, 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. 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.

Product summary:

NORTHERA capsules are supplied in the following dosage strengths: 100 mg:  Hard gelatin, size 3 capsule, with an opaque light blue cap and an opaque white body, printed with “Northera” on body and “100” on cap, filled with a white to light brown powder. 200 mg:  Hard gelatin, size 2 capsule, with an opaque light yellow cap and an opaque white body, printed with “Northera” on body and “200” on cap, filled with a white to light brown powder. 300 mg:  Hard gelatin, size 1 capsule, with an opaque light green cap and an opaque white body, printed with “Northera” on body and “300” on cap, filled with a white to light brown powder. 100 mg 90-count bottle (NDC code# 67386-820-19) 200 mg 90-count bottle (NDC code# 67386-821-19) 300 mg 90-count bottle (NDC code# 67386-822-19) NORTHERA capsules should be stored at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature ].

Authorization status:

New Drug Application

Summary of Product characteristics

NORTHERA- DROXIDOPA CAPSULE
LUNDBECK PHARMACEUTICALS LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
NORTHERA® SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR NORTHERA.
NORTHERA® (DROXIDOPA) CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 2014
WARNING: SUPINE HYPERTENSION
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
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 _[SEE WARNINGS AND PRECAUTIONS (5.1)]._
RECENT MAJOR CHANGES
Indications and Usage (1) X/202X
INDICATIONS AND USAGE
NORTHERA is an adrenergic agonist 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 effectiveness of
NORTHERA should be assessed periodically. Use beyond 2 weeks or
repeated intermittent use can be
considered based on individual benefit and tolerability (1).
DOSAGE AND ADMINISTRATION
Starting dose is 100 mg three times during the day (2.1)
Titrate by 100 mg three times daily, up to a maximum dose of 600 mg
three times daily (2.1)
Take consistently with or without food (2.1)
To reduce the potential for supine hypertension, elevate the head of
the bed and give the last dose at
least 3 hours prior to bedtime (2.1)
Take NORTHERA capsule whole (2.1)
DOSAGE FORMS AND STRENGTHS
100 mg, 200 mg, and 300 mg capsules (3)
CONTRAINDICATIONS
History of hypersen