Chemical: Drug

dextromethorphan

Annotation

NUEDEXTA is a combination of dextromethorphan and quinidine, used as a treatment for pseudobulbar affect (PBA), a condition "characterized by involuntary, sudden, and frequent episodes of laughing and/or crying." These episodes are not necessarily reflective of or proportional to the patient's underlying emotional state. The quinidine component of NUEDEXTA is a CYP2D6 inhibitor used to increase the plasma availability of dextromethorphan. Dextromethorphan is metabolized by CYP2D6, while quinidine is a CYP2D6 inhibitor that is metabolized by CYP3A4.

Excerpt from the dextromethorphan and quinidine (NUEDEXTA) label:

12.5 Pharmacogenomics

The quinidine component of NUEDEXTA is intended to inhibit CYP2D6 so that higher exposure to dextromethorphan can be achieved compared to when dextromethorphan is given alone. Approximately 7-10% of Caucasians and 3-8% of African Americans generally lack the capacity to metabolize CYP2D6 substrates and are classified as PMs. The quinidine component of NUEDEXTA is not expected to contribute to the effectiveness of NUEDEXTA in PMs, but adverse events of the quinidine are still possible. In those patients who may be at risk of significant toxicity due to quinidine, genotyping to determine if they are PMs should be considered prior to making the decision to treat with NUEDEXTA.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the dextromethorphan and quinidine (Nuedexta) drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Annotation

Quinidine is combined with dextromethorphan treatment in order to increase the bioavailability dextromethorphan. Quinidine increases dextromethorphan plasma levels by competitively inhibiting CYP2D6, an enzyme that rapidly metabolizes CYP2D6 to its primary metabolite. Variants within the CYP2D6 gene can result in lower or higher CYP2D6 activity (poor or ultra-rapid metabolizers, respectively). Ultra-rapid metabolizers may metabolize dextromethorphan more rapidly, which may result in subtherapeutic levels.

Excerpts from the dextromethorphan and quinidine (Nuedexta) EPAR:

Dose adjustment is not required in patients with a non-functional CYPD2D6 enzyme, referred to as poor metabolisers (PMs). Dose adjustment is not required in patients with increased CYP2D6 activity, referred to as ultra-rapid metabolisers (UMs), see section 5.2. In the event of inadequate clinical response, see recommended dose titration schedule.

The quinidine component is intended to inhibit CYP2D6 so that higher exposure to dextromethorphan can be achieved compared to when dextromethorphan is given alone. Approximately 7-8% of individuals of Caucasian descent, 3-6% of Black African descent, 2-3% of Arab descent and 1-2% of Asian descent generally lack the capacity to metabolize CYP2D6 substrates and are classified as Poor Metabolizer (PMs). The quinidine component is not expected to contribute to the effectiveness of NUEDEXTA in PMs, but adverse reactions of the quinidine component are still possible.

Approximately 1-10% of individuals of Caucasian descent, 5-30% of Black African descent, 12-40% of Arab descent and 1% of Asian descent exhibit increased metabolic activity for CYP2D6 substrates and are classified as Ultra-rapid Metabolizer (UMs). In such UM patients, dextromethorphan is rapidly metabolised, leading to lower, potentially subtherapeutic concentrations.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Nuedexta EMA drug label.

*Disclaimer: The contents of this page have not been endorsed by the EMA and are the sole responsibility of PharmGKB.