Section 08 · Monograph

Dextromethorphan-quinidine

Reviewed Nov 2026FDA label

NuedextaSigma-1/NMDA agonist + CYP2D6 inhibitor

Indications

Treatment of pseudobulbar affect (PBA) — involuntary, sudden episodes of laughing and/or crying in patients with underlying neurologic conditions including ALS and multiple sclerosisFDA-labeled

Investigated for agitation associated with Alzheimer's disease dementia (studied and later separately developed as a distinct product, AVP-786, for this indication)Off-label
Explored for neuropathic pain given dextromethorphan's NMDA antagonist activityOff-label

Dextromethorphan is an NMDA receptor antagonist and sigma-1 receptor agonist thought to modulate glutamatergic neurotransmission implicated in PBA
Quinidine is a strong CYP2D6 inhibitor included at a sub-antiarrhythmic dose solely to inhibit dextromethorphan's rapid first-pass metabolism, increasing dextromethorphan bioavailability and plasma half-life
Combination allows sustained dextromethorphan exposure at doses that would otherwise be rapidly metabolized

Initial: one capsule (dextromethorphan 20 mg/quinidine 10 mg) orally once daily for 7 days
Maintenance: one capsule orally every 12 hours starting on day 8
Reassess need for continued treatment periodically

Not studied in renal or hepatic impairment beyond labeling precautions; avoid in severe hepatic impairment

Concurrent use with quinidine, quinine, or mefloquine
Use with MAO inhibitors or within 14 days of discontinuing an MAOI
Prolonged QT interval, congenital long QT syndrome, or history of torsades de pointes
Heart failure
Complete AV block without implanted pacemaker, or high risk of complete AV block
Concomitant use of drugs that both prolong QT interval AND are metabolized by CYP2D6 (e.g., thioridazine, pimozide)
History of quinidine-, quinine-, or mefloquine-induced thrombocytopenia, hepatitis, or other hypersensitivity reactions

Strong CYP2D6 inhibitor (quinidine component) — increases levels of CYP2D6 substrates (e.g., many antidepressants, antipsychotics, beta-blockers)
QT-prolonging drugs — increased risk of serious arrhythmia
Serotonergic drugs (SSRIs, SNRIs, MAOIs, triptans) — risk of serotonin syndrome
P-glycoprotein substrates (e.g., digoxin) — quinidine increases digoxin levels
CYP3A4 inhibitors — may increase quinidine levels and QT prolongation risk

Baseline and periodic ECG in patients at risk for QT prolongation, especially with interacting drugs
Signs of serotonin syndrome if combined with serotonergic agents
Liver function periodically
Clinical response and continued need for PBA treatment

Limited human data; animal studies did not show adverse developmental effects at clinically relevant exposures for dextromethorphan, but quinidine component data are limited — use only if clearly needed
Quinidine is present in human milk; caution advised, monitor breastfed infant for adverse effects or consider alternative feeding during use