NUEDEXTA SAFETY PROFILE

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

Most common adverse reactions in the pivotal trial1

Adverse events with NUEDEXTA were generally mild to moderate in nature.1,a

 
NUEDEXTA (n=107)
Placebo (n=109)
Diarrhea
13%
6%
Dizziness
10%
5%
Cough
5%
2%
Vomiting
5%
1%
Asthenia
5%
2%
Peripheral edema
5%
1%


aAdverse reactions occurring in ≥5% of patients on NUEDEXTA and ≥2x placebo rate.

Pivotal Trial Study Design

Adverse reactions leading to discontinuation1

The most commonly reported adverse reactions (incidence ≥2% and greater than placebo) that led to discontinuation of NUEDEXTA were muscle spasticity (3%), respiratory failure (1%), abdominal pain (2%), asthenia (2%), dizziness (2%), fall (1%), and muscle spasm (2%).

Risk of falls1,2

  • The incidence of falls with NUEDEXTA was similar to placebo; however, NUEDEXTA may cause dizziness
  • Precautions to reduce the risk of falls should be taken, particularly for patients with motor impairment affecting gait or a history of falls
These are not all the risks from use of NUEDEXTA.

Important Safety Information Full Prescribing Information

Adverse events in the PRISM II open-label trial3

Reported adverse events (AEs) were generally consistent with the NUEDEXTA safety profile observed in the placebo-controlled pivotal trial.3

AEs (N=367)b
n (%)
Diarrhea
20 (5.4)
Headache
15 (4.1)
Urinary tract infection
10 (2.7)
Dizziness
9 (2.5)
Nausea
6 (1.6)
Fall
6 (1.6)
Fatigue
5 (1.4)
Somnolence
5 (1.4)


bAEs occurring in >1% of patients.

PRISM II Study Design

Serious AEs and AEs leading to study withdrawal3

  • Serious AEs were reported in 6.3% of patients; none were considered treatment related by investigators
  • 2 deaths were reported during the course of the study (2 males aged 91 and 83 with dementia). Both deaths were deemed not related to study drug
  • In total, 36 (9.8%) participants had AEs that led to study withdrawal, most commonly for diarrhea (8 [2.2%]), dizziness, affective lability, and agitation (3 [0.8%] each)
These are not all the risks from use of NUEDEXTA 

Important Safety Information Full Prescribing Information

NUEDEXTA contains an ultra-low dose of quinidine1

The 20-mg daily dose (at Q12H dosing) of quinidine in NUEDEXTA is about 3% of the lowest recommended antiarrhythmic dose.4

Data chart that illustrates Nuedexta has an ultra-low dose of quinidine

CARDIOVASCULAR CONTRAINDICATION1

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.

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. 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. 4. Grace AA, Camm AJ. Quinidine. N Engl J Med. 1998;338(1):35-45. 5. Data on file. Avanir Pharmaceuticals, Inc. 6. 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. 7. 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. 8. 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. 9. 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.

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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