Northera Blue Flamingo

NORTHERA trials, data, and experience

Northera Blue Flamingo

NORTHERA trials, data, and experience

Efficacy Data

Study 306B: Primary endpoint

Patients on NORTHERA® (droxidopa) reported improvement in symptoms of orthostatic dizziness, lightheadedness, or “feeling like you might black out” at Week 11

a The error bars are the 95% confidence intervals of the mean change from baseline in OHSA Item 1 scores.1

b Nonparametric analysis of covariance was used to determine treatment difference at Week 1, and the 2-sided P-value is reported.2

aThe error bars are the 95% confidence intervals of the mean change from baseline in OHSA Item 1 scores.1

bNonparametric analysis of covariance was used to determine treatment difference at Week 1, and the 2-sided P-value is reported.2

  • At Week 1, patients on NORTHERA had a statistically significant mean decrease in symptoms vs placebo (P=0.028) as measured by OHSA Item 1 scores1
    • The mean decrease in OHSA Item 1 score for NORTHERA vs placebo was 0.9 points1
    • Statistical significance beyond Week 1 has not been demonstrated1
  • OHSA is an 11-point scale for measuring patient-reported improvement of symptomatic nOH2
  • Item 1 of the OHSA scale measures nOH symptoms of dizziness, lightheadedness, and "feeling like you might black out”2
  • When compared with placebo, patients on NORTHERA experienced a greater increase in Week 1 lowest standing SBP within 3 minutes after standing (5.6 mm Hg; P=0.032)1

CONTRAINDICATIONS

  • NORTHERA is contraindicated in patients who have a history of hypersensitivity to the drug or its ingredients.

USE IN SPECIFIC POPULATIONS

  • There are no available data on use of NORTHERA in pregnant women and risk of major birth defects or miscarriage. 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.
  • The safety and effectiveness of NORTHERA in pediatric patients have not been established. No overall differences in safety or effectiveness were observed between patients aged 75 years and older and younger patients in clinical trials, but greater sensitivity of some older individuals cannot be ruled out.
  • Clinical experience with NORTHERA in patients with severe renal function impairment (glomerular filtration rate [GFR] <30 mL/min) is limited; therefore, dosing recommendations cannot be provided for these patients.

Study 306B: Distribution by OHSA Item 1 score change

Overall, patients treated with NORTHERA improved more than those treated with placebo1

  • The mean decrease in OHSA Item 1 score of NORTHERA vs placebo was 0.9 points; some patients had a much greater improvement1

WARNINGS AND PRECAUTIONS

  • Supine Hypertension: NORTHERA therapy may cause or exacerbate supine hypertension in patients with nOH, which may increase the risk of cardiovascular events if not well managed, particularly stroke.
  • Hyperpyrexia and Confusion: Cases of a symptom complex resembling neuroleptic malignant syndrome (NMS) have been reported with NORTHERA use during post-marketing surveillance. 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 therapy may exacerbate existing ischemic heart disease, arrhythmias, and congestive heart failure. Careful consideration should be given to this potential risk prior to initiating therapy.
  • Allergic Reactions: Hypersensitivity reactions, including anaphylaxis, angioedema, bronchospasm, urticaria, and rash have been reported in post-marketing experience, with some resulting in emergency treatment. If a hypersensitivity reaction occurs, discontinue the drug and initiate appropriate therapy.

This product contains FD&C Yellow No. 5 (tartrazine), which may also 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.

Study 306B: Secondary descriptive analyses

73% of NORTHERA-treated patients vs 59% of placebo patients reported an improvement in these symptoms2

ADVERSE REACTIONS

  • The most common adverse reactions (>5% and ≥3% difference compared to placebo) were headache, dizziness, nausea, and hypertension.

At Week 1, more than half of NORTHERA-treated patients showed ≥50% improvement in OHSA Item 1 scores2

NORTHERA was approved by the FDA under the Subpart H accelerated approval pathway2
  • Subpart H applies to certain therapies that treat a serious condition and provide meaningful therapeutic benefit to patients over existing treatments3
  • Marketing approval under Subpart H may be granted on the basis of adequate and well-controlled clinical trials establishing that the drug product has an effect on a clinical endpoint that is reasonably likely to predict a clinical benefit3
  • Approval under this pathway requires that NORTHERA be studied further to verify and describe its clinical benefit2
    • The RESTORE clinical study to assess the sustained effects of NORTHERA therapy in adult patients with symptomatic nOH is ongoing4

DRUG INTERACTIONS

  • 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.
  • Dopa-decarboxylase inhibitors may require dose adjustments for NORTHERA.
  • The concomitant use of selective MAO-B inhibitors, such as rasagiline or selegiline, was permitted in the NORTHERA clinical trials. However, based on mechanism of action, the use of non-selective MAO inhibitors and linezolid should be avoided as there is a potential for increased blood pressure when taken with NORTHERA.
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Find out more about adverse reactions reported during clinical trials and other safety considerations.1

SEE SAFETY CONSIDERATIONS
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Find out how NORTHERA is metabolized in the body.

SEE PHARMACOLOGY

References:

1. NORTHERA [package insert]. Deerfield, IL: Lundbeck. 2. Data on file. Deerfield, lL: Lundbeck. 3. CFR – Code of Federal Regulations Title 21. U.S. Department of Health & Human Services; U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=314&showFR=1&subpartNode=21:5.0.1.1.4.8. Updated September 4, 2018. Accessed July 21 2020. 4. U.S. National Library of Medicine. Clinical Trials website. https://clinicaltrials.gov/ct2/show/results/NCT02586623. Accessed July 21 2020.

Please see Important Safety Information, including Boxed Warning for supine hypertension.

For more information, see the full Prescribing Information.

Indications and Usage

NORTHERA (droxidopa) 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.

Important Safety Information

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.

CONTRAINDICATIONS

  • NORTHERA is contraindicated in patients who have a history of hypersensitivity to the drug or its ingredients.

WARNINGS AND PRECAUTIONS

  • Supine Hypertension: NORTHERA therapy may cause or exacerbate supine hypertension in patients with nOH, which may increase the risk of cardiovascular events if not well managed, particularly stroke.
  • Hyperpyrexia and Confusion: Cases of a symptom complex resembling neuroleptic malignant syndrome (NMS) have been reported with NORTHERA use during post-marketing surveillance. 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 therapy may exacerbate existing ischemic heart disease, arrhythmias, and congestive heart failure. Careful consideration should be given to this potential risk prior to initiating therapy.
  • Allergic Reactions: Hypersensitivity reactions, including anaphylaxis, angioedema, bronchospasm, urticaria, and rash have been reported in post-marketing experience, with some resulting in emergency treatment. If a hypersensitivity reaction occurs, discontinue the drug and initiate appropriate therapy.
  • This product contains FD&C Yellow No. 5 (tartrazine), which may also 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

  • The most common adverse reactions (>5% and ≥3% difference compared to placebo) were headache, dizziness, nausea, and hypertension.

DRUG INTERACTIONS

  • 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.
  • Dopa-decarboxylase inhibitors may require dose adjustments for NORTHERA.
  • The concomitant use of selective MAO-B inhibitors, such as rasagiline or selegiline, was permitted in the NORTHERA clinical trials. However, based on mechanism of action, the use of non-selective MAO inhibitors and linezolid should be avoided as there is a potential for increased blood pressure when taken with NORTHERA.

USE IN SPECIFIC POPULATIONS

  • There are no available data on use of NORTHERA in pregnant women and risk of major birth defects or miscarriage. 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.
  • The safety and effectiveness of NORTHERA in pediatric patients have not been established. No overall differences in safety or effectiveness were observed between patients aged 75 years and older and younger patients in clinical trials, but greater sensitivity of some older individuals cannot be ruled out.
  • Clinical experience with NORTHERA in patients with severe renal function impairment (GFR <30 mL/min) is limited; therefore, dosing recommendations cannot be provided for these patients.

For more information, please see the full Prescribing Information, including Boxed Warning for supine hypertension.