Dextromethorphan/quinidine

Dextromethorphan/quinidine (trade name Nuedexta) is a codrug containing dextromethorphan and the class I antiarrhythmic agent quinidine. It is the first FDA-approved drug for the treatment of pseudobulbar affect (PBA).

Dextromethorphan/quinidine
Combination of
DextromethorphanSigma-1 receptor agonist, NMDA receptor antagonist
QuinidineAntiarrhythmic agent
Clinical data
Trade namesNuedexta
Other namesAVP-786, AVP-923
MedlinePlusa611048
Pregnancy
category
  • US: C (Risk not ruled out)
    Routes of
    administration    		By mouth
    Legal status
    Legal status
    • 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

    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.[1] 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.[2]

    Nuedexta was approved in February 2011 and is marketed in the United States by Avanir Pharmaceuticals.

    Those seemingly unrelated drugs became associated so that low-dose quinidine inhibits dextromethorphan's breakdown. The latter has shown marginal efficacy in pseudobulbar syndrome due to rapid first-pass metabolism that reduces its bioavailability.

    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:[2][3][4]

    Other possible indications
    See also: List of investigational antidepressants

    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.[5] The drug is also under investigation for the treatment of major depressive disorder.[6]

    See also

    References
    1. 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.
    2. Archived 2016-03-04 at the Wayback Machine Highlights of Prescribing Information. Retrieved 2014-01-07
    3. NUEDEXTA. Avanir Pharmaceuticals. Retrieved 2013-10-28
    4. Nuedexta Official FDA information, side effects and uses. Retrieved 2014-01-07
    5. "NNuedexta Testing New Indication". CDrug Discovery and Development Magazine. June 13, 2011.
    6. 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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