Dosing & Uses
Dosage Forms & Strengths
Indicated for PBA and symptoms associated with a variety of neurological conditions (eg, MS, ALS) that result in involuntary, sudden, and frequent episodes of laughing and/or crying
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; 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
1 capsule PO qDay for 7days, THEN 1 capsule q12h
- Mild or moderate: No dose adjustment required
- Severe: Safety and effaicacy not established
- Mild or moderate: No dosage adjustment required; increase in adverse reactions possible with moderate impairment
- Severe: Safety and efficacy not established
Amyotrophic Lateral Sclerosis (Orphan)
Orphan designation for treatment of amyotrophic lateral sclerosis (ALS)
- Avanir Pharmaceuticals; 30 Enterprise, Suite 400; Aliso Viejo, California 92656
Safety and efficacy not established
Serious - Use Alternative
Significant - Monitor Closely
Peripheral edema (5%)
Increased gamma-glutamyltransferase (3%)
History of quinine, mefloquine, or quinidine-induced thrombocytopenia, hepatitis, bone marrow depression, or lupus-like syndrome
Concomitant use with drugs containing quinidine, quinine, or mefloquine
Coadministration of MAOIs or use within 14 d
Drugs that both prolong QT interval and are metabolized by CYP2D6 (eg, thioridazine, pimozide)
Complete AV block (without implanted pacemakers)
Prolonged QT interval, congenital long QT syndrome, or history of torsades de pointes or heart failure
Quinidine can cause immune-mediated thrombocytopenia (discontinue if thrombocytopenia occurs)
Hepatotoxicity reported within first few weeks following initiation of quinidine
Monitor for QTc prolongation if concomitant use of drugs taht prolong QT interval cannot be avoided or concomitant CYP3A4 used
Quinidine may cause anticholinergic effects and exacerbate certain conditions (eg, myasthenia gravis)
Monitor ECG in patients with left ventricular hypertrophy or left ventricular dysfunction
Dextromethorphan may cause serotonergic effects; monitor for worsening in myasthenia gravis and other sensitive conditions
Use caution with CYP2D6 poor metabolizers
CYP3A4 inhibitors may increase quinidine serum levels and risk for QT prolongation
Coadministration with CYP2D6 substrates other than dextromethorphan that cause accumulation of parent drug and/or failure of metabolite formation may decrease safety and/or efficacy of concomitant CYPD6 metabolized drugs; adjust dose of CYPD6 substrate or use alternative therapy when indicated
Concomitant use of dextromethorphan with serotonergic drugs (eg, SSRIs, TCAs) may increase risk for serotonin syndrome
Quinidine may increase digoxin levels (as much as double) by inhibiting P-glycoprotein
Coadministration with alcohol or other CNS depressants may cause additive effects
May cause dizziness; use precautions to reduce falls
Pregnancy & Lactation
Pregnancy Category: C
Lactation: unknown whether distributed in breast milk, caution advised
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Mechanism of Action
The mechanism by which dextromethorphan exerts therapeutic effects in patients with pseudobulbar affect is unknown
Dextromethorphan (DM) is a sigma-1 receptor agonist and an uncompetitive NMDA receptor antagonist
Quinidine increases plasma levels of dextromethorphan by competitively inhibiting cytochrome P4502D6, which catalyzes a major biotransformation pathway for dextromethorphan
Half-Life: 13 hr (dextromethorphan); 7 hr (quinidine)
Peak Plasma Time: 3-4 hr (dextromethorphan); 1-2 hr (quinidine)
Protein Bound: 60-70% ((dextromethorphan); 80-89% (quinidine)
Metabolism: dextromethorphan by CYP2D6; quinidine’s primary pharmacological action in is to competitively inhibit the metabolism of dextromethorphan catalyzed by CYP2D6 in order to increase and prolong plasma concentrations of dextromethorphan; quinidine metabolized by CYP3A4
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 7-10% of Caucasians and 3-8% of African Americans lack the capacity to metabolize CYP2D6 substrates and are classified as poor metabolizers (PMs)
The quinidine component is not expected to contribute to effectiveness 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
Genetic testing laboratories
- Genotyping tests for CYP2D6 variants are commercially available through the following companies
- Applied Biosystems (http://www.appliedbiosystems.com/)
- GenPath Diagnostics (http://www.genpathdiagnostics.com/)
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.
|1||This drug is available at the lowest co-pay. Most commonly, these are generic drugs.|
|2||This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.|
|3||This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.|
|4||This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.|
|5||This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.|
|6||This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.|
|NC||NOT COVERED – Drugs that are not covered by the plan.|
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.