Dextromethorphan/quinidine

Not to be confused with Deudextromethorphan/quinidine.

Dextromethorphan/quinidine

Combination of
Dextromethorphan	Sigma-1 receptor agonist, NMDA receptor antagonist, serotonin–norepinephrine reuptake inhibitor
Quinidine	Antiarrhythmic agent, CYP2D6 inhibitor
Clinical data
Trade names	Nuedexta
Other names	AVP-923; DXM/quinidine
AHFS/Drugs.com	Monograph
MedlinePlus	a611048
License data	US  DailyMed:  Nuedexta
Routes of administration	By mouth
ATC code	None
Legal status
Legal status	US: ℞-only In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	dextromethorphan 11%, quinidine 70-80%. Food has no effect on absorption.
Metabolism	Liver, extensive. Dextromethorphan is catalyzed by CYP2D6. Quinidine is metabolized by CYP3A4 and competitively inhibits the metabolism of dextromethorphan to increase and prolong plasma concentrations of dextromethorphan
Elimination half-life	dextromethorphan 13h, quinidine 7h
Excretion	quinidine 5-20%
Identifiers
CAS Number	2445595-41-3
KEGG	D10208

Dextromethorphan/quinidine, sold under the brand name Nuedexta, is a fixed-dose combination medication for the treatment of pseudobulbar affect (PBA). ^{[1] [2]} It contains dextromethorphan (DXM) and the class I antiarrhythmic agent quinidine. ^[1]

Dextromethorphan/quinidine was approved for medical use in the United States in October 2010, and is marketed by Avanir Pharmaceuticals. ^[3]

Medical uses

DXM/quinidine is used in the treatment of PBA. In a 12-week randomized, double-blind trial, amyotrophic lateral sclerosis and multiple sclerosis patients with significant PBA were given either Nuedexta 20/10 mg or placebo. In 326 randomized patients, the PBA-episode daily rate was 46.9% (p < 0.0001) lower for Nuedexta than for placebo. ^[4] The three deaths in each of the two drug treatment arms and the single death in the placebo arm of the study were believed to be due to the natural course of the disease. ^[1]

Contraindications

• Atrioventricular (AV) block, complete, without implanted pacemaker or at high risk of complete AV block
• Concomitant use with drugs containing quinidine, quinine, or mefloquine
• Concomitant use with drugs that both prolong the QT interval and are metabolized by CYP2D6 (e.g., thioridazine, pimozide); effects on QT interval may be increased
• Concomitant use with MAOIs or use of MAOIs within 14 days; risk of serious, potentially fatal, drug interactions including serotonin syndrome
• Heart failure
• Hypersensitivity to dextromethorphan
• Hypersensitivity to quinine, mefloquine, quinidine, or dextromethorphan/quinidine with a history of thrombocytopenia, hepatitis, bone marrow depression or lupus-like syndrome induced by these drugs
• QT interval, prolonged or congenital long QT syndrome or a history suggesting torsades de pointes

Adverse effects

Common risks and side effects include: ^[1]

• Abdominal pain
• Asthenia
• Cough
• Diarrhea (reported in 13% of patients)
• Dizziness
• Elevated gamma glutamyltransferase
• Flu-like symptoms
• Flatulence
• Prolonged QT interval
• Muscle spasm
• Peripheral edema
• Urinary tract infection
• Vomiting

Interactions

• Desipramine (CYP2D6 substrate) ^[1] levels increase 8-fold with co-administration
• Paroxetine (CYP2D6 inhibitor and substrate) ^[1]
• Memantine

Pharmacology

Pharmacodynamics

Dextromethorphan acts as a σ₁ receptor agonist, serotonin–norepinephrine reuptake inhibitor, and NMDA receptor antagonist, while quinidine is an antiarrhythmic agent acting as a CYP2D6 inhibitor. ^[5] Quinidine prevents the metabolism of dextromethorphan into its active metabolite dextrorphan, which is a much more potent NMDA receptor antagonist but much less potent serotonin reuptake inhibitor than dextromethorphan. ^{[5] [2]} The mechanism of action of dextromethorphan/quinidine in the treatment of PBA is unknown. ^[2]

Research

Dextromethorphan/quinidine was investigated for the treatment of agitation associated with dementia, diabetic neuropathy, drug-induced dyskinesia, migraine, and neuropathic pain, but development for these indications was discontinued. ^[6] Another formulation, deudextromethorphan/quinidine, is still under investigation for various indications. ^[7] These include agitation, schizophrenia, and major depressive disorder, among others. ^[7]

See also

• Bupropion/dextromethorphan
• Deudextromethorphan/quinidine

References

1. "Nuedexta- dextromethorphan hydrobromide and quinidine sulfate capsule, gelatin coated". DailyMed. 23 June 2019. Retrieved 23 October 2020.
2. "Highlights for prescribing information" (PDF). fda.gov. 2019. Retrieved 11 April 2023.
3. "Drug Approval Package: Nuedexta (dextromethorphan hydrobromide and quinidine sulfate) Capsules NDA #021879". U.S. Food and Drug Administration (FDA). 24 December 1999. Archived from the original on 27 February 2015. Retrieved 23 October 2020.
4. Pioro EP, Brooks BR, Cummings J, et al. (2010). "Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect". Ann Neurol. 68 (5): 693–702. doi:10.1002/ana.22093. PMID   20839238. S2CID   2824842.
5. Taylor CP, Traynelis SF, Siffert J, Pope LE, Matsumoto RR (August 2016). "Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use". Pharmacol Ther. 164: 170–82. doi: 10.1016/j.pharmthera.2016.04.010 . PMID   27139517.
6. "Dextromethorphan/quinidine - Avanir Pharmaceuticals - AdisInsight". adisinsight.springer.com. Retrieved 11 April 2023.
7. "Deudextromethorphan - Avanir Pharmaceuticals - AdisInsight".

External links

• "Dextromethorphan hydrobromide mixture with quinidine sulfate". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 28 August 2021.