Dextromethorphan hydrobromide/quinidine sulfate

What is Dextromethorphan hydrobromide/quinidine sulfate?

• Dextromethorphan hydrobromide/quinidine sulfate (NUEDEXTA) is a combination product containing dextromethorphan hydrobromide (an uncompetitive NMDA receptor antagonist and sigma-1 agonist) and quinidine sulfate (a CYP450 2D6 inhibitor) used for the treatment of pseudobulbar affect (PBA).

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Dextromethorphan skeletal

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Quinidine structure

Quinidine-3d-balls

What are the uses of this medicine?

NUEDEXTA is used for the treatment of pseudobulbar affect (PBA).

• PBA occurs secondary to a variety of otherwise unrelated neurologic conditions, and is characterized by involuntary, sudden, and frequent episodes of laughing and/or crying.
• PBA episodes typically occur out of proportion or incongruent to the underlying emotional state.
• PBA is a specific condition, distinct from other types of emotional lability that may occur in patients with neurological disease or injury.

How does this medicine work?

• Dextromethorphan (DM) is a sigma-1 receptor agonist and an uncompetitive NMDA receptor antagonist.
• Quinidine increases plasma levels of dextromethorphan by competitively inhibiting cytochrome P450 2D6, which catalyzes a major biotransformation pathway for dextromethorphan.
• The mechanism by which dextromethorphan exerts therapeutic effects in patients with pseudobulbar affect is unknown.

Who Should Not Use this medicine ?

This medicine cannot be used:

• with quinidine, quinine, or mefloquine.
• In patients with a history of quinidine, quinine or mefloquine-induced thrombocytopenia, hepatitis, or other hypersensitivity reactions.
• In patients with known hypersensitivity to dextromethorphan.
• with an MAOI or within 14 days of stopping an MAOI. Allow 14 days after stopping NUEDEXTA before starting an MAOI.
• In patients with Prolonged QT interval, congenital long QT syndrome, history suggestive of torsades de pointes, or heart failure.
• In patients with Complete atrioventricular (AV) block without implanted pacemaker, or patients at high risk of complete AV block.
• with drugs that both prolong QT interval and are metabolized by CYP2D6 (e.g., thioridazine or pimozide).

What drug interactions can this medicine cause?

• Do not use NUEDEXTA with monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days.
• Do not use with drugs that both prolong QT interval and are metabolized by CYP2D6 (e.g., thioridazine or pimozide).
• Recommend ECG in patients taking drugs with NUEDEXTA that prolong the QT interval and in patients taking concomitant moderate or strong CYP3A4 inhibitors.
• Use of NUEDEXTA with SSRIs or tricyclic antidepressants increases the risk of ‘serotonin syndrome’.
• Plasma digoxin concentrations should be closely monitored in patients taking NUEDEXTA concomitantly, and the digoxin dose reduced, as necessary.
• As with any other CNS drug, caution should be used when NUEDEXTA is taken in combination with other centrally acting drugs and alcohol.
• Desipramine exposure increases 8-fold. Reduce desipramine dose and adjust based on clinical response.
• Paroxetine exposure increases 2-fold. Reduce paroxetine dose and adjust based on clinical response.

Is this medicine FDA approved?

• Dextromethorphan/quinidine was approved for medical use in the United States in October 2010, and is marketed by Avanir Pharmaceuticals.

How should this medicine be used?

Recommended dosage: Starting dose:

• one capsule daily by mouth for 7 days.

Maintenance dose:

• After 7 days, 1 capsule every 12 hours.

Administration:

• NUEDEXTA must be taken 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 need for continued treatment should be reassessed periodically, as spontaneous improvement of PBA occurs in some patients.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Capsules: Dextromethorphan hydrobromide 20 mg/quinidine sulfate 10 mg.

This medicine is available in fallowing brand namesː

• NUEDEXTA

What side effects can this medication cause?

The most common side effects of this medicine include:

• diarrhea
• dizziness
• cough
• vomiting
• asthenia
• peripheral edema
• urinary tract infection
• influenza
• increased gamma-glutamyltransferase
• flatulence

What special precautions should I follow?

• NUEDEXTA should be discontinued immediately if thrombocytopenia occurs, unless the thrombocytopenia is clearly not drug-related, as continued use increases the risk for fatal hemorrhage.
• Hepatitis, including granulomatous hepatitis, has been reported in patients receiving quinidine, generally during the first few weeks of therapy. Discontinue if occurs.
• NUEDEXTA causes dose-dependent QTc prolongation. Monitor ECG if concomitant use of drugs that prolong QT interval cannot be avoided or if concomitant CYP3A4 inhibitors used.
• Left ventricular hypertrophy (LVH) or left ventricular dysfunction (LVD) may occur. Monitor ECG in patients with LVH or LVD.
• The quinidine in NUEDEXTA inhibits CYP2D6. Accumulation of parent drug and/or failure of metabolite formation may decrease safety and/or efficacy of concomitant CYP2D6 metabolized drugs. Adjust dose of CYP2D6 substrate or use alternative treatment when clinically indicated.
• NUEDEXTA may cause dizziness.
• Take precautions to reduce falls.
• Use of NUEDEXTA with selective serotonin reuptake inhibitor (SSRIs) or tricyclic antidepressants increases the risk of Serotonin syndrome. Discontinue if occurs.
• Monitor for worsening clinical condition in myasthenia gravis and other conditions that may be adversely affected by anticholinergic effects.

What to do in case of emergency/overdose?

Symptoms of overdosage may include: Quinidine overdose:

• ventricular arrhythmias
• hypotension
• vomiting
• diarrhea
• tinnitus
• high-frequency hearing loss
• vertigo
• blurred vision
• diplopia
• photophobia
• headache
• confusion
• delirium

Dextromethorphan overdose:

• nausea
• vomiting
• stupor
• coma
• respiratory depression
• seizures
• tachycardia
• hyperexcitability
• toxic psychosis
• ataxia
• nystagmus
• dystonia
• blurred vision
• changes in muscle reflexes
• serotonin syndrome

Treatment of overdosage:

• Treatment of dextromethorphan overdosage should be directed at symptomatic and supportive measures.
• Quinidine-induced hypotension that is not due to an arrhythmia is likely to be a consequence of quinidine-related α-blockade and vasorelaxation. Treatment of hypotension should be directed at symptomatic and supportive measures.

Can this medicine be used in pregnancy?

• There are no adequate data on the developmental risk associated with the use of NUEDEXTA in pregnant women.

Can this medicine be used in children?

• The safety and effectiveness in pediatric patients below the age of 18 have not been established.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• DEXTROMETHORPHAN HYDROBROMIDE
• QUINIDINE SULFATE

Inactive ingredients:

• CROSCARMELLOSE SODIUM
• CELLULOSE, MICROCRYSTALLINE
• SILICON DIOXIDE
• LACTOSE MONOHYDRATE
• MAGNESIUM STEARATE

Who manufactures and distributes this medicine?

Marketed by:

• Avanir Pharmaceuticals, Inc.
• Aliso Viejo, CA

• AVANIR and NUEDEXTA are trademarks or registered trademarks of Avanir Pharmaceuticals.

What should I know about storage and disposal of this medication?

• Store NUEDEXTA capsules at controlled room temperature, 25°C (77°F); excursions permitted to 15° - 30°C (59° - 86°F).

• Dailymed label info on Dextromethorphan hydrobromide/quinidine sulfate
• FDA Dextromethorphan hydrobromide/quinidine sulfate

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