Home » Drug Information » FDA Approved Drugs » 2010
Medical Areas: Neurology
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Nuedexta (dextromethorphan hydrobromide and quinidine sulfate)
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Company: Avanir Pharmaceuticals
Approval Status: Approved October 2010
Treatment Area: pseudobulbar affect
Nuedexta is an oral formulation of dextromethorphan hydrobromide (an uncompetitive NMDA receptor antagonist and sigma-1agonist) and quinidine sulfate (a CYP450 2D6 inhibitor). Dextromethorphan hydrobromide is the pharmacologically active ingredient that acts on the central nervous system while quinidine sulfate is a specific inhibitor of CYP2D6-dependent oxidative metabolism used to increase the systemic bioavailability of dextromethorphan.
Nuedexta is specifically indicated for the treatment of pseudobulbar affect. Studies to support the effectiveness of Nuedexta were performed in patients with amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). It was not shown to be safe and effective in other types of emotional lability that can commonly occur, for example, in Alzheimer’s disease and other dementias.
Nuedexta is supplied as a capsule (20 mg dextromethorphan hydrobromide and 10 mg quinidine sulfate) designed for oral administration. The recommended starting dose is one capsule daily by mouth for the initial seven days of therapy. On the eighth day of therapy and thereafter, the daily dose should be a total of two capsules a day, given as one capsule every 12 hours.
The FDA approval of Nuedexta was based on one trial in patients with underlying amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). Other trials at higher doses (dextromethorphan 30 mg/quinidine 30 mg) provided supportive evidence. The subjects were randomized to receive Nuedexta (20 mg/10 mg), dextromethorphan 30 mg/quinidine 10 mg, or placebo for 12 weeks. The primary outcome measure, laughing and crying episodes, was statistically significantly lower in each dextromethorphan/quinidine arm compared to placebo. The secondary endpoint was the Center for Neurologic Studies Lability Scale (CNS-LS). CNS-LS was analyzed based on the difference between the mean scores on day 84 and baseline, and was also statistically significantly lower in each dextromethorphan/quinidine arm compared to placebo.
Adverse events associated with the use of Nuedexta may include, but are not limited to, the following:
- Peripheral edema
- Urinary tract infection
- Increased gamma-glutamyltransferase
Mechanism of Action
Nuedexta is an oral formulation of dextromethorphan hydrobromide (an uncompetitive NMDA receptor antagonist and sigma-1agonist) and quinidine sulfate (a CYP450 2D6 inhibitor). The candidate is believed to help regulate excitatory neurotransmission in two ways: through pre-synaptic inhibition of glutamate release via sigma-1 receptor agonist activity and through postsynaptic glutamate response modulation via uncompetitive, low-affinity NMDA antagonist activity.
Pioro EP, Brooks BR, Cummings J, Schiffer R, Thisted RA, Wynn D, Hepner A, Kaye R; Safety, Tolerability, and Efficacy Results Trial of AVP-923 in PBA Investigators Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect. Annals of neurology 2010 Nov;68(5):693-702
Brooks BR, Thisted RA, Appel SH, Bradley WG, Olney RK, Berg JE, Pope LE, Smith RA; AVP-923 ALS Study Group Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial. Neurology 2004 Oct 26;63(8):1364-70
For additional information regarding Nuedexta or pseudobulbar affect, please visit the Nuedexta web page.