dextromethorphan/quinidine

{{Infobox drug

| type = combo

| image =

| width =

| alt =

| caption =

| component1 = Dextromethorphan

| class1 = Sigma-1 receptor agonist, NMDA receptor antagonist, serotonin–norepinephrine reuptake inhibitor

| component2 = Quinidine

| class2 = Antiarrhythmic agent, CYP2D6 inhibitor

| tradename = Nuedexta

| Drugs.com = {{drugs.com|monograph|dextromethorphan-hydrobromide-and-quinidine-sulfate}}

| MedlinePlus = a611048

| DailyMedID = Nuedexta

| pregnancy_AU =

| pregnancy_US = C

| pregnancy_US_comment = {{cite web | title=Dextromethorphan / quinidine (Nuedexta) Use During Pregnancy | website=Drugs.com | date=21 August 2019 | url=https://www.drugs.com/pregnancy/dextromethorphan-quinidine.html | access-date=13 September 2020}}

| legal_AU =

| legal_CA =

| legal_UK =

| legal_US = Rx-only

| legal_status = Rx-only

| routes_of_administration = By mouth

| ATC_prefix = None

| ATC_suffix =

| CAS_number = 2445595-41-3

| ATCvet =

| PubChem =

| DrugBank =

| synonyms = AVP-923; DXM/quinidine

| KEGG = D10208

| 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%

}}

Dextromethorphan/quinidine, sold under the brand name Nuedexta, is a fixed-dose combination medication for the treatment of pseudobulbar affect (PBA).{{cite web | title=Nuedexta- dextromethorphan hydrobromide and quinidine sulfate capsule, gelatin coated | website=DailyMed | date=23 June 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=484e0918-3442-49dc-8ccf-177f1f3ee9f3 | access-date=23 October 2020}}{{cite web|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021879s014lbl.pdf|title=Highlights for prescribing information|website=fda.gov|access-date=11 April 2023|year=2019}} It contains dextromethorphan (DXM) and the class I antiarrhythmic agent quinidine.

Dextromethorphan/quinidine was approved for medical use in the United States in October 2010, and is marketed by Avanir Pharmaceuticals.{{cite web | title=Drug Approval Package: Nuedexta (dextromethorphan hydrobromide and quinidine sulfate) Capsules NDA #021879 | website=U.S. Food and Drug Administration (FDA) | date=24 December 1999 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/021879Orig1s000TOC.cfm | archive-url=https://web.archive.org/web/20150227211325/http://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/021879Orig1s000TOC.cfm | url-status=dead | archive-date=27 February 2015 | access-date=23 October 2020}}

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.{{cite journal |vauthors=Pioro EP, Brooks BR, Cummings J |title=Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect |journal=Ann Neurol |volume=68 |issue=5 |pages=693–702 |year=2010 |pmid=20839238 |doi=10.1002/ana.22093|s2cid=2824842 |display-authors=etal}} 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.

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:

Interactions

Desipramine (CYP2D6 substrate) levels increase 8-fold with co-administration
Paroxetine (CYP2D6 inhibitor and substrate)
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.{{cite journal | vauthors = Taylor CP, Traynelis SF, Siffert J, Pope LE, Matsumoto RR | title = Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use | journal = Pharmacol Ther | volume = 164 | issue = | pages = 170–82 | date = August 2016 | pmid = 27139517 | doi = 10.1016/j.pharmthera.2016.04.010 | url = | doi-access = free }} 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. The mechanism of action of dextromethorphan/quinidine in the treatment of PBA is unknown.

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.{{Cite web|url=https://adisinsight.springer.com/drugs/800015120|title=Dextromethorphan/quinidine - Avanir Pharmaceuticals - AdisInsight|website=adisinsight.springer.com|accessdate=11 April 2023}} Another formulation, deudextromethorphan/quinidine, is still under investigation for various indications.{{Cite web|url=http://adisinsight.springer.com/drugs/800035704|title = Deudextromethorphan - Avanir Pharmaceuticals - AdisInsight}} These include agitation, schizophrenia, and major depressive disorder, among others.

References

External links

{{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/dextromethorphan%20hydrobromide%20mixture%20with%20quinidine%20sulfate | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Dextromethorphan hydrobromide mixture with quinidine sulfate }}

Category:Combination psychiatric drugs

Category:Otsuka Pharmaceutical