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Pharmaceutical drug
Dextromethorphan/quinidine , sold under the brand name Nuedexta , is a
fixed-dose combination medication for the treatment of
pseudobulbar affect (PBA).
[2]
[3] It contains
dextromethorphan (DXM) and the
class I antiarrhythmic agent
quinidine .
[2]
Dextromethorphan/quinidine was approved for medical use in the United States in October 2010, and is marketed by Avanir Pharmaceuticals.
[4]
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 .
[5] 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]
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]
Interactions
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 .
[6] 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.
[6]
[3] The
mechanism of action of dextromethorphan/quinidine in the treatment of PBA is unknown.
[3]
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.
[7] Another formulation,
deudextromethorphan/quinidine , is still under investigation for various indications.
[8] These include agitation,
schizophrenia , and
major depressive disorder , among others.
[8]
See also
References
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