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Dextromethorphan / Quinidine sulfate (Nudexta)

Class

NMDA receptor antagonist / sigma-1 receptor agonist combination

Mechanism

Dextromethorphan modulates glutamate signaling via NMDA and sigma‑1 receptors to stabilize emotional expression, while quinidine slows its breakdown via CYP2D6 inhibition, maintaining therapeutic levels .

FDA-Approved Use

Pseudobulbar affect (PBA)

Off-Label Use

None with sufficient evidence

Formulation

Oral capsules (20mg/10mg)

Titration

1 capsule in the morning for one week, then increase to 1 capsule BID

Dose Range

40 mg dextromethorphan / 20 mg quinidine per day

Kinetics

Hepatic metabolism; maximal plasma concentrations of dextromethorphan reached ~ 3–4 hours after dosing and quinidine at 1–2 hours. Quinidine inhibits CYP2D6, resulting in an approximately 20-fold increase in dextromethorphan exposure compared to dextromethorphan alone.

Common AEs

Diarrhea, dizziness, cough, vomiting, weakness, lower extremity edema

Serious/Rare AEs

Dose-dependent QTc prolongation, immune-mediated thrombocytopenia, hepatitis, and serotonin syndrome. Quinidine can also cause other hypersensitivity reactions, lupus-like syndrome, agranulocytosis, and anticholinergic effects.

Monitoring

Monitoring with ECG is recommended in patients at risk for QT prolongation or those on interacting medications.

Black Box Warning

None

Considerations

Dextromethorphan / Quinidine sulfate can help manage emotional dysregulation in neurologic conditions but should be used with caution in older adults or those with heart disease. It is important to distinguish pseudobulbar affect from mood disorders, as the symptoms may overlap but require different treatments. Emotional lability in neuropsychiatric conditions is often multifactorial, and not all cases will respond to this medication.