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Northera (droxidopa) Prior Authorization with Quantity Limit Program Summary
Policy Number: PH-1060
This program applies to the Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.
POLICY REVIEW CYCLE
Effective Date |
Date of Origin |
07-01-2024 |
|
FDA LABELED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
Northera® (droxidopa) Capsule* |
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 should be assessed periodically. |
* Generic available |
1 |
See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm
CLINICAL RATIONALE
Orthostatic Hypotension |
Orthostatic hypotension (OH) is defined as a blood pressure decrease greater than or equal to 20mmHg systolic or greater than or equal to 10mmHg diastolic recorded within 3 minutes after that patient stands.(2-6) OH can impair perfusion to organs above the heart, resulting in symptoms of hypoperfusion in these tissues. OH is a frequent problem in the general population, especially in the elderly.(2-4,6) The overall prevalence of OH in patients greater than 65 years is approximately 20%.(2) It can result from a variety of medical conditions, such as IV volume depletion, blood pooling from varicose veins, severe anemia, medications, and physical deconditioning. In these cases, OH usually improves once the underlying cause is treated. In a minority of patients, OH occurs due to decreased norepinephrine release from sympathetic nerves, which leads to defective vasoconstriction when in the upright position. This is referred to as neurogenic orthostatic hypotension (nOH). nOH occurs frequently in patients with neurodegenerative disorders such as Parkinson’s disease, Lewy Body dementia, multiple system atrophy, and pure autonomic failure, dopamine beta-hydroxylase deficiency and nondiabetic autonomic neuropathy.(2-6) An estimated 30-50% of Parkinson’s disease patients have nOH.(2,4) When present, symptoms are similar to those observed with OH. However, in contrast to vasovagal (neutrally mediated) syncope, syncope in nOH occurs without signs of autonomic activation such as diaphoresis, tachycardia, nausea, or abdominal discomfort.(2) The goal of nOH treatment is not to normalize standing blood pressure, but to reduce symptom burden so as to improve quality of life. The steps in management include: 1) correcting aggravating factors, 2) implementing non-pharmacological measures, and 3) drug therapies. The correction of aggravating factors includes management of medications contributing to the nOH through the reduction of IV volume, induction of vasodilation, and interference with norepinephrine. The correction of anemia and vitamin deficiencies is also included. Non-pharmacological management includes insuring proper blood volume, adjusting sodium intake, physical conditioning, avoid increased core body temperature, compression garments, and head-up position while sleeping.(2) Pharmacological options include midodrine and droxidopa, as well as off-label use of fludrocortisone and pyridostigmine for nOH.(2-6) One of the challenges associated with treating nOH pharmacologically is the limited availability of clinical evidence and lack of comparative effectiveness studies. Once initial therapy has begun, symptomatic benefit, including impact on activities of daily living, and changes in blood pressure need to be assessed frequently. Little data exists to determine efficacy and safety of different combinations of therapy compared to monotherapy for nOH. Based on the experience of the consensus panel, the recommendation is to appropriately titrate to maximum tolerable dose of a single agent and then, if symptomatic benefit is not obtained, consider switching to a different therapy or adding a second agent and titrate from its lowest starting dose.(3) |
Efficacy |
Clinical studies examined the efficacy of Northera in the short-term (1-2 weeks) and over longer-term periods (8 weeks; 3 months). Studies 301 and 306B showed a treatment effect of Northera at Week 1, but none of the studies demonstrated continued efficacy beyond two weeks of treatment. Study 301: Patients with symptomatic neurogenic orthostatic hypotension (nOH) participated in this multicenter, multinational, double-blind, randomized, placebo-controlled, parallel-group study. Patients were required to have a clinical diagnosis of symptomatic nOH due to one of the following: Parkinson’s disease, pure autonomic failure, multiple system atrophy, non-diabetic autonomic neuropathy, or dopamine-beta-hydroxylase deficiency. After the initial screening, patients went through open-label dose titration period followed by a seven-day wash-out period (n=263).(1,7) Of the 263 patients who participated in dose randomization, 162 (61.6%) were identified as responders and entered the double-blind phase of the study. Responders were defined as demonstrating improvement on the Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 score by at least one point and an increase in systolic blood pressure of at least 10 mmHg upon standing. The OHSA Item #1 referred to dizziness, lightheadedness, feeling faint, and feeling like you might black out (see monograph appendix for more information). Responders were then randomized to a seven-day treatment period with droxidopa (n=82) or placebo (n=80).(1,7) Patients in the treatment period had an average age of 60 years and a primary diagnosis of Parkinson’s disease (n=60), pure autonomic failure (n=36) or multiple system atrophy (n=26). Patients were allowed to continue taking dopa-decarboxylase inhibitors (45% of patients) and fludrocortisones (29% of patients).(1) Efficacy was measured utilizing the Orthostatic Hypotension Questionnaire (OHQ, see monograph appendix for more information), which measures the symptoms of nOH and their impact on the patient’s daily activities. The OHQ was administered at baseline, randomization, and at the end of the study. The pre-specified primary efficacy endpoint was the change in overall composite score from randomization to end of study. Secondary endpoints were individual OHQ items and changes in symptom and symptom impact scores. Blood pressure was also measured throughout the study.(1,7) Results revealed a statistically significant improvement in the OHQ composite score from randomization to the end of the study (p=0.003). Several symptom items revealed differences between droxidopa and placebo including dizziness/lightheadedness (item 1 for randomization), vision disturbance, weakness, and fatigue. Differences from placebo were also observed on all symptom-impact items. Standing systolic blood pressures increased an average of 11.2 mmHg in patients receiving droxidopa versus 3.9 mmHg with placebo.(7) The mean baseline dizziness score on OHSA Item #1 (“dizziness, lightheadedness, feeling faint, and feeling like you might black out”) was 5.2 units on an 11-point scale. At week one of treatment, patients showed a mean 0.7 unit decrease in dizziness with NORTHERA versus placebo (P=0.06).(1) Study 306B: Study 306B was a multi-center, double-blind, randomized, placebo-controlled, parallel-group study that consisted of an initial dose titration period followed by an 8-week treatment period. Patients (n=171) in the study had symptomatic nOH and Parkinson’s disease, and were required to have a decrease of at least 20 mmHg or 10 mmHg, respectively, in systolic or diastolic blood pressure within three minutes after standing. Dosing was titrated to patient response and ranged from 100 mg to 600 mg three times daily. Data was collected throughout an eight-week treatment period. At week one, patients demonstrated a statistically significant decrease (0.9-unit) in dizziness as reported on the OHSA Item #1 11-point scale (p=0.028). This effect did not continue beyond week one.(1) |
Safety |
Northera has a Boxed Warning for supine hypertension. Supine blood pressure should be monitored 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.(1) |
REFERENCES
Number |
Reference |
1 |
Northera prescribing information. Lundbeck LLC. July 2019. |
2 |
Palma JA, Kaufmann H. Epidemiology, Diagnosis, and Management of Neurogenic Orthostatic Hypotension. Mov Disord Clin Pract. 2017 May-Jun;4(3):298-308. |
3 |
Gibbons CH, Schmidt P, Biaggioni I, et al. The Recommendations of a Consensus Panel for the Screening, Diagnosis, and Treatment of Neurogenic Orthostatic Hypotension and Associated Supine Hypertension. J Neurol. 2017;264(8):1567-1582. |
4 |
2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients with Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. J Am Coll Cardiol. 2017 Aug;70(5):e39-e110. |
5 |
Brignole M, Moya A, de Lange FJ, et al. 2018 European Society of Cardiology (ESC) Guidelines for the Diagnosis and Management of Syncope. Eur Heart J. 2018 June;39(21):1883-1948. |
6 |
Kalra DK, Raina A, Sohal S. Neurogenic Orthostatic Hypotension: State of the Art and Therapeutic Strategies. Clin Med Insights Cardiol. 2020;14:1-12. |
7 |
A Clinical Study for Patients With Neurogenic Orthostatic Hypotension (NOH) Using Droxidopa (NOH301). Chelsea Therapeutics. https://clinicaltrials.gov/study/NCT00782340?term=northera&page=4&rank=36&a=12. September 2010. |
POLICY AGENT SUMMARY PRIOR AUTHORIZATION
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Targeted MSC |
Available MSC |
Final Age Limit |
Preferred Status |
|
||||||
Northera |
droxidopa cap |
100 MG ; 200 MG ; 300 MG |
M ; N ; O ; Y |
O ; Y |
|
|
POLICY AGENT SUMMARY QUANTITY LIMIT
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
QL Amount |
Dose Form |
Day Supply |
Duration |
Addtl QL Info |
Allowed Exceptions |
Targeted NDCs When Exclusions Exist |
|
|||||||||
Northera |
Droxidopa Cap 100 MG |
100 MG |
450 |
Capsules |
30 |
DAYS |
|
|
|
Northera |
Droxidopa Cap 200 MG |
200 MG |
180 |
Capsules |
30 |
DAYS |
|
|
|
Northera |
Droxidopa Cap 300 MG |
300 MG |
180 |
Capsules |
30 |
DAYS |
|
|
|
CLIENT SUMMARY – PRIOR AUTHORIZATION
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Northera |
droxidopa cap |
100 MG ; 200 MG ; 300 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
CLIENT SUMMARY – QUANTITY LIMITS
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Northera |
Droxidopa Cap 100 MG |
100 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Northera |
Droxidopa Cap 200 MG |
200 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Northera |
Droxidopa Cap 300 MG |
300 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
||||||||
|
Initial Evaluation Target Agent(s) will be approved when ALL of the following are met:
Length of Approval: 1 month NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. *Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.
Renewal Evaluation Target Agent(s) will be approved when ALL of the following are met:
Length of Approval: 3 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. |
QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
|
Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:
Length of Approval: Initial - Up to 1 month; Renewal - Up to 3 months |
This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.
The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.
Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.
ALBP _ Commercial _ CSReg _ Northera_PAQL _ProgSum_ 07-01-2024 _ © Copyright Prime Therapeutics LLC. May 2024 All Rights Reserved