dextromethorphan quinidine NUEDEXTA
Class: NMDA Receptor Antagonist/Sigma-1 Receptor AgonistFDA Indications: Pseudobulbar Affect
Off-Label Use: Alzheimers Disease
Prescribing
Forms: Dextromethorphan 20 mg/Quinidine 10mg capsule mg/dayStarting: one capsule daily by mouth for 7 days then increase to 1 capsule every 12 hours
Precautions
Contraindications: Concomitant use w/ quinidine, quinine, or mefloquine; h/o quinidine, quinine or mefloquine-induced TCP, hepatitis, or other hypersensitivity rxns, or w/ known hypersensitivity to DXM; use w/ an MAOI or within 14 days of stopping an MAOI; ↑'d QT interval, congenital LQTS, h/o TdP or HF, complete AV block w/o ICDconcomitant use with drugs that both ↑ QT and are 2D6 substrates (e.g., thioridazine or pimozide)
Serious Side Effects: ↑'d risk of serotonin syndrome when coadminsitered w/ other serotonergic agents; TCP or other hypersensitivity reactions; hepatitis; QT↑; LVH or LVD
Known Risk of TdP (quinidine)
Side Effects: anticholinergic side effects, diarrhea, dizziness, cough, diarrhea, peripheral edema, flatulence
Pharmacodynamics
1° MOA: Uncompetitive NMDA receptor antagonist & σ1R agonist2° MOA: Quinidine ↑'s DXM bioavailability by competitively inhibiting CYP2D6 (which glucuronidates DXM to dextrorphan, which cannot cross the blood-brain barrier)
Target: NMDA, SERT, NET, σ1R, μ-opioid
Pharmacokinetics
t½: 13° TMAX: 3-4°Substrate of: 2D6 (DXM), 3A4 (DXM)
Inhibits: 2D6 (quinidine); Induces: ∅
Active Metabolites: ∅
DDIs
- - DO NOT CO-PRESCRIBE WITH MAOIs
- - 2D6 & 3A4 inhibitors can ↑ levels
- - 3A4 inducers can ↓ levels
- - can ↑ levels of co-prescribed 2D6 substrates
- - watch for pharmacodynamic interactions (i.e. 5HT syndrome) when co-prescribed w/ other serotonergic agents
Misc
- - PBA is manifested by involuntary labile, shallow affect with sudden and unpredictable laughing, crying, or other emotional displays that are not appropriate to the social setting and may not be congruent with the patient's prevailing mood
- - the pathophysiology of PBA may involve excessive release of glutamate by injured neurons, disrupting systems for motor control of emotional expression
- - the reported prevalence of PBA is 49% in ALS, 18-39% in Alzheimer's disease, 11-34% in CVA &10-11% in MS & TBI
Special Populations
Category Undefined.—Both quinidine & DXM are considered to be compatible with pregnancy
DXM is considered to be compatible with breastfeeding; the American Academy of Pediatrics has classified quinidine as compatible with breastfeeding
The pharmacokinetics of dextromethorphan/quinidine have not been investigated systematically in elderly subjects
Dose adjustment is not required in mild or moderate renal impairment. Has not been studied in patients with severe renal impairment.
Mild to moderate hepatic impairment had little effect on quinidine pharmacokinetics. Neither dextromethorphan alone nor NUEDEXTA has been evaluated in patients with severe hepatic impairment.
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