Contraindications1

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 Precautions1

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.