NUEDEXTA is an innovative
combination of two well-characterized components1-4

As a CYP2D6 inhibitor, quinidine increases dextromethorphan (DM) bioavailability ~20-fold and prolongs elimination half-life of DM from ~2 hours to 13 hours1-3,5

Quinidine (10 mg) changes the exposure of dextromethorphan, which is metabolized by CYP2D6, relative to its metabolite dextromorphan1-3,5

The exact mechanism by which NUEDEXTA exerts its therapeutic effects in patients with PBA is unknown.1

  • DEXTROMETHORPHAN HBr (20 mg)1-4

    an uncompetitive NMDA receptor antagonist and sigma-1 receptor agonist, believed to modulate glutamate signaling

  • QUINIDINE SULFATE (10 mg)
    ultra-low dose6

    a metabolic inhibitor that increases DM exposure (~20 fold) and prolongs the elimination half-life of dextromethorphan by inhibiting its rapid conversion to dextrorphan

NUEDEXTA contains an ultra-low dose of quinidine (10 mg)6

The 20-mg daily dose of quinidine is 1/30 of the lowest recommended antiarrhythmic dose of quinidine (600–1600 mg/day)7

Quinidine daily dosage

Quinidine daily dosage

 

ECG data from NUEDEXTA clinical trials

Pooled data from Avanir-sponsored controlled clinical studies in patients (N=363) receiving NUEDEXTA or any DM/Q dose showed mean changes in QTc were generally smaller than ±5 msecs.8

  • In the pivotal trial, NUEDEXTA showed small changes in mean QTc interval change from baseline that were not statistically significant from placeboa,6

Normal QTc intervals range from approximately 380-440 msecs9

  • In the pivotal trial, no NUEDEXTA patients had an absolute QTc interval value >480 msecs or a QTc change from baseline >90 msecsa,6

A thorough QTc study was conducted to evaluate the effects of supra-therapeutic (adequate to represent exposure increases due to drug-drug interactions and organ dysfunctions) doses of DM/Q on QTc prolongationb,8

  • The maximum mean differences in QTc from placebo were 10.2 and 18.4 msecs following DM/Q doses of 30/30 and 60/60, respectively, showing small dose-related QTc increases8

Cardiovascular Contraindication

  • NUEDEXTA is contraindicated in patients with a prolonged QT interval, congenital long QT syndrome, history suggestive of torsades de pointes, heart failure, patients receiving drugs that both prolong QT interval and are metabolized by CYP2D6 (e.g., thioridazine and pimozide), patients with complete atrioventricular (AV) block without implanted pacemaker or at high risk of complete AV block1

aRandomized, double-blind, placebo controlled, multicenter trial in 326 PBA patients.

bRandomized, placebo-controlled, double-blind, crossover design with an additional open-label positive control (400 mg moxifloxacin) arm in 36 healthy volunteers. Supra-therapeutic doses of DM/Q (30mg/30mg and 60mg/60mg, for 7 doses) were 3-6 times the quinidine dose found in NUEDEXTA.

 

 

 

 

NUEDEXTA Pharmacology

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SEE THE PHARMACOLOGY OF NUEDEXTA (2:35)<br> <span>The exact mechanism by which NUEDEXTA exerts its therapeutic effects in patients with PBA is unknown.<sup>1</sup></span>

NUEDEXTA exhibits multifaceted pharmacology

  • NUEDEXTA is believed to modulate glutamate signaling10
  • Presynaptic inhibition of glutamate release10
  • NMDA receptor antagonism reduces postsynaptic glutamate signaling10


The exact mechanism by which NUEDEXTA exerts its therapeutic effects in patients with PBA is unknown.1

NUEDEXTA® Pharmacology