Dextromethorphan/quinidine

Dextromethorphan/quinidine
Combination of
Dextromethorphan Sigma-1 receptor agonist, NMDA receptor antagonist
Quinidine Antiarrhythmic agent
Clinical data
Trade names Nuedexta
MedlinePlus a611048
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration
Oral
Legal status
  • (Prescription only)
Pharmacokinetic data
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
Biological half-life dextromethorphan 13h, quinidine 7h
Excretion quinidine 5-20%
Identifiers

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

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

Adverse effects

Common risks and side effects include:[3][2][4]

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

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. 1 2 3 4 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.
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