Dextromethorphan/quinidine

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

Dextromethorphan/quinidine
Combination of
DextromethorphanSigma-1 receptor agonist, NMDA receptor antagonist
QuinidineAntiarrhythmic agent
Clinical data
Trade namesNuedexta
Other namesAVP-786, AVP-923
AHFS/Drugs.comMonograph
MedlinePlusa611048
License data
Routes of
administration		By mouth
ATC code
  • None
Legal status
Legal status
  • US: ℞-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailabilitydextromethorphan 11%, quinidine 70-80%. Food has no effect on absorption.
MetabolismLiver, 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-lifedextromethorphan 13h, quinidine 7h
Excretionquinidine 5-20%
Identifiers
KEGG

Dextromethorphan/quinidine was approved for medical use in the United States in October 2010, and is marketed by Avanir Pharmaceuticals.[2]

Clinical studies

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.[3] 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]

Interactions

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]

Other possible indications

In June 2012, drug discovery and development magazine reported that Avanir Pharmaceuticals plans to test the drug for the treatment of agitation associated with Alzheimer's disease.[4] The drug is also under investigation for the treatment of major depressive disorder.[5]

See also

References
  1. "Nuedexta- dextromethorphan hydrobromide and quinidine sulfate capsule, gelatin coated". DailyMed. 23 June 2019. Retrieved 23 October 2020.
  2. "Drug Approval Package: Nuedexta (dextromethorphan hydrobromide and quinidine sulfate) Capsules NDA #021879". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 23 October 2020. Lay summary (PDF).
  3. 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.
  4. "NNuedexta Testing New Indication". CDrug Discovery and Development Magazine. June 13, 2011.
  5. Nguyen, Linda; Thomas, Kelan L.; Lucke-Wold, Brandon P.; Cavendish, John Z.; Crowe, Molly S.; Matsumoto, Rae R. (2016). "Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders". Pharmacology & Therapeutics. 159: 1–22. doi:10.1016/j.pharmthera.2016.01.016. ISSN 0163-7258. PMID 26826604.
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