Nuedexta

NMDA receptor antagonist (dextromethorphan), Sigma-1 receptor agonist (dextromethorphan), CYP2D6 inhibitor (quinidine, sub-antiarrhythmic dose), Fixed-dose combination

Dextromethorphan / Quinidine

Nuedexta

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Titration strategies

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Effects

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Pharmacy

Starting dose

1 capsule (20/10 mg dextromethorphan/quinidine) PO once daily × 7 days, then 1 capsule BID

Preparations

20 mg dextromethorphan HBr / 10 mg quinidine sulfate capsules

US FDA Max

1 capsule BID (40 mg DXM / 20 mg quinidine per day)

Common uses

Classification(s)

Classes

NMDA receptor antagonist (dextromethorphan), Sigma-1 receptor agonist (dextromethorphan), CYP2D6 inhibitor (quinidine, sub-antiarrhythmic dose), Fixed-dose combination

Pharmacology

Routes

Oral

Onset

PBA episode reduction within 1-2 weeks

Duration

12 hours

Half-life

Dextromethorphan substantially prolonged by quinidine's CYP2D6 inhibition (typical extensive metabolizers see ~10× higher AUC); quinidine ~6-8 hours

Bioavailability

Increased substantially via CYP2D6 inhibition

Pregnancy

Limited data; quinidine has been used in pregnancy as antiarrhythmic.^{[citation needed]}

Legal status

Rx-only in US. Caution with QT-prolonging drugs (quinidine itself is class IA antiarrhythmic, and the dose here, though sub-antiarrhythmic, still contributes to QT)

Purported mechanism

Like the Auvelity strategy, Nuedexta uses a CYP2D6 inhibitor (quinidine here, at sub-antiarrhythmic dose) to elevate plasma dextromethorphan; sustained DXM levels engage NMDA receptor antagonism and sigma-1 receptor agonism, which reduce the involuntary emotional outbursts characteristic of pseudobulbar affect.▲0▼ First FDA-approved treatment for PBA. The 10 mg quinidine daily dose is far below antiarrhythmic levels but sufficient to nearly fully inhibit CYP2D6, the basis of the combination's pharmacokinetic rationale.