THERAPEUTICS

Brands

• Nuedexta

Generic?

• No

Class

• NMDA receptor antagonist

Commonly Prescribed for

(FDA approved in bold)

• Treatment of pseudobulbar affect (PBA) in patients with underlying amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS)

• PBA in Alzheimer's disease or other dementia

• Agitation in Alzheimer's disease

• Depression

How the Drug Works

• Dextromethorphan is a serotonin transporter/norepinephrine transporter inhibitor, σ1 receptor agonist, noncompetitive NMDA receptor antagonist, and α3β4- and α4β2-nicotinic receptor antagonist. Quinidine is a specific CYP2D6 inhibitor that reduces its conversion to active metabolite dextrorphan and increases 20-fold the systemic bioavailability of dextromethorphan. The exact mechanism of action is unclear. It is possible many neurotransmitters, such as serotonin, GABA, norepinephrine, glutamate, and dopamine, participate in emotional expression involved in PBA

How Long Until It Works

• Typically less than a month

If It Works

• Continue use and monitor AEs

If It Doesn't Work

• May try increasing the dose of dextromethorphan. Evaluate the treatment efficacy for underlying disorders

Best Augmenting Combos for Partial Response or Treatment-Resistance

• There is no other drug approved for use in treating PBA

Tests

• Monitor potential QTc prolongation

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• Quinidine may cause cardiac AEs

Notable AEs

• Headache, dizziness, cough, vomiting, asthenia, urinary tract infection, flatulence, diarrhea

Life-Threatening or Dangerous AEs

• Thrombocytopenia or other hypersensitivity reactions

• Leukopenia

• Hepatitis

• QTc prolongation

• Serotonin syndrome with concomitant SSRI use

• Worsening of myasthenia gravis

Weight Gain

• Unusual

Sedation

• Unusual

What to Do About AEs

• Discontinue if severe AEs occur

Best Augmenting Agents to Reduce AEs

• Most AEs are not treatable with medications

DOSING AND USE

Usual Dosage Range

• 1 capsule every 12 hours

Dosage Forms

• Capsule: dextromethorphan 20 mg, quinidine 10 mg

How to Dose

• Start once daily for 7 days then once every 12 hours

Dosing Tips

• May take with or without food