Nuedexta: Difference between revisions
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| bioavailability = Increased substantially via CYP2D6 inhibition<ref name="nuedexta-label" /> | | bioavailability = Increased substantially via CYP2D6 inhibition<ref name="nuedexta-label" /> | ||
| pregnancy = Limited data; quinidine has been used in pregnancy as antiarrhythmic.{{citation needed}} | | pregnancy = Limited data; quinidine has been used in pregnancy as antiarrhythmic.{{citation needed}} | ||
| legal = [[USLegal:Prescription only|Rx-only]] in US. Caution with QT-prolonging | | legal = [[USLegal:Prescription only|Rx-only]] in US. Caution with QT-prolonging medicines (quinidine itself is class IA antiarrhythmic, and the dose here, though sub-antiarrhythmic, still contributes to QT)<ref name="nuedexta-label" /> | ||
| mechanism = <vote slug="nuedexta-mech-claim">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.</vote> 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<ref name="nuedexta-label" />. | | mechanism = <vote slug="nuedexta-mech-claim">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.</vote> 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<ref name="nuedexta-label" />. | ||
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== References == | == References == | ||
<references /> | <references /> | ||
[[Category:NMDA receptor antagonists]] | |||
[[Category:Sigma-1 receptor modulators]] | |||
[[Category:CYP2D6 inhibitors]] | |||
[[Category:Fixed-dose combinations]] | |||
Latest revision as of 10:43, 23 May 2026
NMDA receptor antagonist (dextromethorphan), Sigma-1 receptor agonist (dextromethorphan), CYP2D6 inhibitor (quinidine, sub-antiarrhythmic dose), Fixed-dose combination
Dextromethorphan / Quinidine
Nuedexta
Experience
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Problems
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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)
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[1]
Bioavailability
Increased substantially via CYP2D6 inhibition[1]
Pregnancy
Limited data; quinidine has been used in pregnancy as antiarrhythmic.[citation needed]
Legal status
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[1].
References
- ↑ 1.0 1.1 1.2 1.3 FDA Prescribing Information, Nuedexta (dextromethorphan HBr / quinidine sulfate), Avanir/Otsuka, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021879s016lbl.pdf