Nuedexta

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE NUEDEXTA 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 neurological disease or injury. NUEDEXTA is a combination product containing dextromethorphan hydrobromide (an uncompetitive NMDA receptor antagonist and sigma-1 agonist) and quinidine sulfate (a CYP450 2D6 inhibitor) indicated for the treatment of pseudobulbar affect (PBA). ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION Starting dose: one capsule daily by mouth for 7 days. ( 2.1 ) Maintenance dose: After 7 days, 1 capsule every 12 hours. ( 2.1 ) 2.1 Recommended Dose The recommended starting dose of NUEDEXTA is one capsule daily by mouth for the initial seven days of therapy. On the eighth day of therapy and thereafter, the daily dose should be a total of two capsules a day, given as one capsule every 12 hours. The need for continued treatment should be reassessed periodically, as spontaneous improvement of PBA occurs in some patients. Warnings and cautions 5 WARNINGS AND PRECAUTIONS Thrombocytopenia or other hypersensitivity reactions: Discontinue if occurs. ( 5.1 ) Hepatitis: Discontinue if occurs. ( 5.2 ) QT Prolongation: Monitor ECG if concomitant use of drugs that prolong QT interval cannot be avoided or if concomitant CYP3A4 inhibitors used. ( 5.3 ) Left ventricular hypertrophy (LVH) or left ventricular dysfunction (LVD): Monitor ECG in patients with LVH or LVD. ( 5.3 ) CYP2D6 substrate: Nuedexta inhibits CYP2D6. Accumulation of parent drug and/or failure of metabolite formation may decrease safety and/or efficacy of concomitant CYP2D6 metabolized drugs. Adjust dose of CYP2D6 substrate or use alternative treatment when clinically indicated. ( 5.4 , 12.4 ) Dizziness: Take precautions to reduce falls. ( 5.5 ) Serotonin syndrome: Use of NUEDEXTA with selective serotonin reuptake inhibitor (SSRIs) or tricyclic antidepressants increases the risk. Discontinue if occurs. ( 5.6 , 7.4 ) Anticholinergic effects of quinidine: Monitor for worsening in myasthenia gravis and other sensitive conditions. ( 5.7 ) 5.1 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, unless the thrombocytopenia is clearly not drug-related, as continued use increases the risk for fatal hemorrhage. Likewise, NUEDEXTA should not be restarted in sensitized patients, because more rapid and more severe thrombocytopenia than the original episode can occur. NUEDEXTA should not be used if immune-mediated thrombocytopenia from structurally related drugs, including quinine and mefloquine is suspected, as cross-sensitivity can occur. Quinidine-associated thrombocytopenia usually, but not always, resolves within a few days of discontinuation of the sensitizing drug. Quinidine has also been associated with a lupus-like syndrome involving polyarthritis, sometimes with a positive antinuclear antibody test. Other associations include rash, bronchospasm, lymphadenopathy, hemolytic anemia, vasculitis, uveitis, angioedema, agranulocytosis, the sicca syndrome, myalgia, elevation in serum levels of skeletal-muscle enzymes, and pneumonitis. 5.2 Hepatotoxicity Hepatitis, including granulomatous hepatitis, has been reported in patients receiving quinidine, generally during the first few weeks of therapy. Fever may be a presenting symptom, and thrombocytopenia or other signs of hypersensitivity may also occur. Most cases remit when quinidine is withdrawn. 5.3 Cardiac Effects NUEDEXTA causes dose-dependent QTc prolongation [ see Clinical Pharmacology ( 12.2 ) ] . 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 of 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. This includes patients concomitantly taking/initiating drugs that prolong the QT interval or that are strong or moderate CYP3A4 inhibitors, and patients with left ventricular hypertrophy (LVH) or left ventricular dysfunction (LVD). LVH and LVD are more likely to be present in patients with chronic hypertension, known coronary artery disease, or history of stroke. LVH and LVD can be diagnosed utilizing echocardiography or another suitable cardiac imaging modality. Strong an