NUEDEXTA EFFICACY

Actor portrayal of a patient with PseudoBulbar Affect (PBA) without symptoms

NUEDEXTA significantly reduced PBA episode rates compared with placebo in patients with ALS or MS1,2

Pivotal trial data of 3.9 fewer PBA episodes after Nuedexta

The pivotal trial was a randomized, placebo-controlled study in 326 patients.1,2

Change in number of pseudobulbar affect (PBA) episodes per day was the primary endpoint of the pivotal trial. At Week 12, patients on NUEDEXTA experienced a mean change in daily PBA episode rate of -3.9 from a 6.8 baseline compared to -3.0 from a 4.5 baseline for placebo (P=0.005 vs placebo).1,2

Episode rate reduction from baseline in the post hoc analysis of the 12-Week Pivotal Trial3

Pivotal trial data chart of PBA episode reduction after Nuedexta

Patients received NUEDEXTA QD in Week 1 and Q12H starting at Day 8.2

Secondary outcomes showed significant improvement with NUEDEXTA vs placebo2

At Week 12, mean Center for Neurologic Study-Lability Scale (CNS-LS) score decreased by 8.2 points for patients on NUEDEXTA from a 21.0 baseline vs 5.7 points for patients on placebo from a 19.9 baseline (P=0.0113).1,2

The CNS-LS is a 7-item self-report rating scale that measures perceived frequency and control over laughing and/or crying episodes. It was validated as a PBA screening tool in amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS)  populations. CNS-LS ≥13 may suggest PBA but does not confer a PBA diagnosis.4-7

51% OF PATIENTS

Complete episode remission was achieved by 51% of patients on NUEDEXTA vs 29% placebo (P<0.005).2

Remission was defined as the absence of PBA episodes during the patient’s final 14 days of participation in the 12-week study.2

Pivotal Trial Study Design

NUEDEXTA reduced PBA symptoms in patients with stroke, dementia, or TBI8

Pivotal trial data of 7.7 point decrease PBA reduced symptoms Nuedexta

PRISM II was an open-label trial of 367 patients. Change in CNS-LS score was the primary endpoint.8

NUEDEXTA reduced PBA symptom scores (CNS-LS) and episode rates in patients with stroke, dementia, or traumatic brain injury (TBI).8

  • CNS-LS score in all cohorts combined decreased from 20.4 at baseline to 12.8 at Day 90 (P<0.001 vs baseline)8
  • CNS-LS reductions were similar across the dementia, stroke, and TBI cohorts, with a range of 7.2 to 8.5 at Day 90 (from a mean baseline of 20.4)8
Secondary endpoint: median change in number of PBA episodes per week from baseline3

Pivotal trial data chart of secondary endpoint Nuedexta

PRISM II Study Design

Age demographics of NUEDEXTA studies

  • Pivotal Trial mean age of patients taking NUEDEXTA is 50.8 years. 14% (15/107) ≥65 years of age1,2
  • PRISM II mean age of patients taking NUEDEXTA is 59.4 years. 41.4% (152/367) ≥65 years of age. 82.6% (303/367) of patients were living at home at time of study8

References: 1. NUEDEXTA [package insert]. Aliso Viejo, CA: Avanir Pharmaceuticals, Inc. 2. Pioro EP, Brooks BR, Cummings J, et al. Dextromethorphan plus ultra-low quinidine reduces pseudobulbar affect. Ann Neurol. 2010;68(5):693-702. 3. Data on file. Avanir Pharmaceuticals, Inc. 4. Brooks BR, Crumpacker D, Fellus J, Kantor D, Kaye RE. PRISM: a novel research tool to assess the prevalence of pseudobulbar affect symptoms across neurological conditions. PLoS ONE. 2013;8(8):e72232. 5. Moore SR, Gresham LS, Bromberg MB, Kasarkis EJ, Smith RA. A self report measure of affective lability. J Neurol Neurosurg Psychiatry. 1997;63(1):89-93. 6. Smith RA, Berg JE, Pope LE, Callahan JD, Wynn D, Thisted RA. Validation of the CNS emotional lability scale for pseudobulbar affect (pathological laughing and crying) in multiple sclerosis patients. Mult Scler. 2004;10(6):679-685. 7. Smith RA, Berg JE, Pope LE, Thisted RA. Measuring pseudobulbar affect in ALS. Amyotroph Lateral Scler Other Motor Neuron Disord. 2004;5(suppl 1):99-102. 8. Hammond FM, Alexander DN, Cutler AJ, et al. PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury. BMC Neurol. 2016;16:89.

INDICATION AND USAGE

NUEDEXTA® (dextromethorphan HBr and quinidine sulfate) is indicated for the treatment of pseudobulbar affect (PBA). PBA occurs secondary to a variety of otherwise unrelated neurologic conditions, and is characterized by involuntary, sudden, and frequent episodes of laughing and/or crying. PBA episodes typically occur out of proportion or incongruent to the underlying emotional state. PBA is a specific condition, distinct from other types of emotional lability that may occur in patients with neurologic disease or injury.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Quinidine and Related Drugs: NUEDEXTA contains quinidine, and should not be used concomitantly with other drugs containing quinidine, quinine, or mefloquine.

Hypersensitivity: NUEDEXTA is contraindicated in patients with a history of NUEDEXTA-, quinine-, mefloquine-, or quinidine-induced thrombocytopenia, hepatitis, bone-marrow depression, lupus-like syndrome, or known hypersensitivity to dextromethorphan (eg, rash, hives).

MAOIs: NUEDEXTA is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs), or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping NUEDEXTA before starting an MAOI.

Cardiovascular: NUEDEXTA is contraindicated in patients with a prolonged QT interval, congenital long QT syndrome, history suggestive of torsades de pointes, heart failure, patients receiving drugs that both prolong QT interval and are metabolized by CYP2D6 (eg, thioridazine and pimozide), patients with complete atrioventricular (AV) block without implanted pacemaker, or at high risk of complete AV block.

WARNINGS AND PRECAUTIONS

Thrombocytopenia and Other Hypersensitivity Reactions: Quinidine can cause immune-mediated thrombocytopenia that can be severe or fatal. Non-specific symptoms, such as lightheadedness, chills, fever, nausea, and vomiting, can precede or occur with thrombocytopenia. NUEDEXTA should be discontinued immediately if thrombocytopenia occurs.

Hepatotoxicity: Hepatitis, including granulomatous hepatitis, has been reported in patients receiving quinidine, generally during the first few weeks of therapy. Discontinue immediately if this occurs.

Cardiac Effects: NUEDEXTA causes dose-dependent QTc prolongation. QT prolongation can cause torsades de pointes–type ventricular tachycardia, with the risk increasing as the degree of prolongation increases. When initiating NUEDEXTA in patients at risk for QT prolongation and torsades de pointes, electrocardiographic (ECG) evaluation of QT interval should be conducted at baseline and 3 to 4 hours after the first dose. Some risk factors include use with CYP3A4 inhibitors or drugs that prolong QT interval, electrolyte abnormalities, bradycardia, or left ventricular hypertrophy or dysfunction. If patients taking NUEDEXTA experience symptoms that could indicate the occurrence of cardiac arrhythmias (eg, syncope or palpitations), NUEDEXTA should be discontinued, and the patient further evaluated.

Concomitant Use of CYP2D6 Substrates: NUEDEXTA inhibits CYP2D6 and may interact with other drugs metabolized by CYP2D6. Adjust dose of CYP2D6 substrates as needed.

Dizziness: NUEDEXTA may cause dizziness. Take precautions to reduce the risk of falls.

Serotonin Syndrome: Use of NUEDEXTA with selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants increases the risk of “serotonin syndrome.”

Anticholinergic Effects of Quinidine: Monitor for worsening in myasthenia gravis.

ADVERSE REACTIONS

The most common adverse reactions (incidence of ≥3% and two-fold greater than placebo) in patients taking NUEDEXTA are diarrhea, dizziness, cough, vomiting, asthenia, peripheral edema, urinary tract infection, influenza, increased gamma-glutamyltransferase, and flatulence.

These are not all the risks for use of NUEDEXTA. Please see Full Prescribing Information.

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