pharmacopeia
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/api/v1/drug/quinidine

Mechanism of action

Sourced from openFDA

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.

Cytochrome P450 2D6

Indications

Sourced from openFDA
  • NUEDEXTA is indicated 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.

Contraindications

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  • Concomitant use with quinidine, quinine, or mefloquine. ( 4.1 ) Patients with a history of quinidine, quinine or mefloquine-induced thrombocytopenia, hepatitis, or other hypersensitivity reactions.contraindicated

Dosage & administration

Sourced from openFDA

Starting dose: one capsule daily by mouth for 7 days. ( 2.1 ) Maintenance dose: After 7 days, 1 capsule every 12 hours. ( 2.1 ) 2.1 Recommended Dose The recommended starting dose of NUEDEXTA is 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.

Warnings & precautions

Sourced from openFDA

Thrombocytopenia or other hypersensitivity reactions: Discontinue if occurs. ( 5.1 ) Hepatitis: Discontinue if occurs. ( 5.2 ) QT Prolongation: Monitor ECG if concomitant use of drugs that prolong QT interval cannot be avoided or if concomitant CYP3A4 inhibitors used. ( 5.3 ) Left ventricular hypertrophy (LVH) or left ventricular dysfunction (LVD): Monitor ECG in patients with LVH or LVD. ( 5.3 ) CYP2D6 substrate: 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. ( 5.4 , 12.4 ) Dizziness: Take precautions to reduce falls. ( 5.5 ) Serotonin syndrome: Use of NUEDEXTA with selective serotonin reuptake inhibitor (SSRIs) or tricyclic antidepressants increases the risk. Discontinue if occurs. ( 5.6 , 7.4 ) Anticholinergic effects of quinidine: Monitor for worsening in myasthenia gravis and other sensitive conditions. ( 5.7 ) 5.1 Thrombocytopenia and Other Hypersensitivity Reactions Quinidine can cause immune-mediated thrombocytopenia that can be severe or fatal. Non-specific symptoms, such as lightheadedness, chills, fever, nausea, and vomiting, can precede or occur with thrombocytopenia. 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.

Adverse reactions

Sourced from openFDA

A total of 946 patients participated in four Phase 3 controlled and uncontrolled PBA studies and received at least one dose of the combination product of dextromethorphan/quinidine in various strengths at the recommended or higher than the recommended dose. Of those patients, 393 patients were exposed for at least 180 days and 294 patients were exposed for at least one year. Median exposure was 168 days. Controlled trials enrolled only patients with either ALS or MS. Uncontrolled studies enrolled 136 patients with PBA secondary to a wide variety of underlying neurological conditions including stroke (45 patients) and traumatic brain injury (23 patients). Consequently, patients with other underlying neurologic diseases may experience other adverse reactions not described below. The most common adverse reactions (incidence of ≥ 3% and two-fold greater than placebo) in patients taking NUEDEXTA are diarrhea, dizziness, cough, vomiting, asthenia, peripheral edema, urinary tract infection, influenza, increased gamma-glutamyltransferase, and flatulence. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Avanir Pharmaceuticals, Inc. at 1-855-4NUEDEX (468-3339) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience A 12-week, placebo-controlled study evaluated NUEDEXTA (dextromethorphan 20 mg/quinidine 10 mg) (N=107) and a 30 mg dextromethorphan/10 mg quinidine combination (N=110) compared to placebo (N=109). Approximately 60% of patients had ALS and 40% had MS. Patients were 25 to 80 years of age, with a mean age of approximately 51 years.

Use in specific populations

Sourced from openFDA

Pregnancy: Based on animal data, may cause fetal harm. ( 8.1 ) 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of NUEDEXTA in pregnant women. In oral studies conducted in rats and rabbits, a combination of dextromethorphan/quinidine demonstrated developmental toxicity, including teratogenicity (rabbits) and embryolethality, when given to pregnant animals (see Data) . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data When dextromethorphan/quinidine was administered orally (0/0, 5/100, 15/100, and 50/100 mg/kg/day) to pregnant rats during the period of organogenesis, embryo-fetal deaths were observed at the highest dose tested and reduced skeletal ossification was observed at all doses. The lowest dose tested (5/100 mg/kg/day) is approximately 1/50 times the recommended human dose (RHD) of 40/20 mg/day on a mg/m 2 basis. Oral administration to pregnant rabbits during organogenesis in two separate studies (0/0, 5/60, 15/60, and 30/60 mg/kg/day; 0/0, 5/100, 15/100, and 50/100 mg/kg/day) resulted in an increased incidence of fetal malformations at all but the lowest dose tested.

Pharmacokinetics

Sourced from openFDA
Metabolism
NUEDEXTA contains dextromethorphan and quinidine, both of which are metabolized primarily by liver enzymes. Quinidine’s primary pharmacological action in NUEDEXTA is to competitively inhibit the metabolism of dextromethorphan catalyzed by CYP2D6 in order to increase and prolong plasma concentrations of dextromethorphan [ see Warnings and Precautions ( 5.4 ), ( 5.8 ), and Clinical Pharmacology ( 12.5 ) ] .

Overdosage

Sourced from openFDA

Evaluation and treatment of NUEDEXTA overdose is based on experience with the individual components, dextromethorphan and quinidine. Metabolism of the dextromethorphan component of NUEDEXTA is inhibited by the quinidine component, such that adverse effects of overdose due to NUEDEXTA might be more severe or more persistent compared to overdose of dextromethorphan alone. During development of NUEDEXTA, dose combinations of dextromethorphan/quinidine containing up to 6-times higher dextromethorphan dose and 12-times higher quinidine dose were studied. The most common adverse events were mild to moderate nausea, dizziness, and headache. The most important adverse effects of acute quinidine overdose are ventricular arrhythmias and hypotension. Other signs and symptoms of overdose may include vomiting, diarrhea, tinnitus, high-frequency hearing loss, vertigo, blurred vision, diplopia, photophobia, headache, confusion, and delirium.

Approval history

Sourced from openFDA
  • Sep 26, 1983ANDAANDA088072Epic Pharma Llc
  • Feb 11, 1987ANDAANDA089338Sun Pharm Industries
  • Oct 29, 2010NDANDA021879Avanir Pharms
  • Sep 17, 2021ANDAANDA212589Hibrow Hlthcare
  • Aug 28, 2024ANDAANDA218426Hetero Labs Ltd Iii

FAERS reports

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Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
3,805 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Fall2125.6%
  2. 2Off Label Use2085.5%
  3. 3Drug Ineffective2005.3%
  4. 4Product Use In Unapproved Indication1955.1%
  5. 5Death1905.0%
  6. 6Dizziness1784.7%
  7. 7Fatigue1664.4%
  8. 8Therapy Interrupted1614.2%
  9. 9Diarrhoea1423.7%
  10. 10Nausea1203.2%
  11. 11Dysphagia1052.8%
  12. 12Somnolence1042.7%
  13. 13Depression1032.7%
  14. 14Gait Disturbance1022.7%
  15. 15Inability To Afford Medication1012.7%

Literature

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Recent PubMed references pinned to Quinidine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 69 ClinicalTrials.gov registrations naming Quinidine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Pharmacogenomics

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CPIC-curated drug–gene pairs for Quinidine. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

  • CYP2D6CPIC C (provisional)

Frequently asked questions

How does Quinidine 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.
What is Quinidine used for?
According to FDA labeling, Quinidine carries indications including: NUEDEXTA is indicated 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Quinidine?
Quinidine is classified as Antiarrhythmics, class Ia, Antiarrhythmic, Cytochrome P450 2D6 Inhibitor, Calcium Channel Interactions, Cytochrome P450 2D6 Inhibitors, Potassium Channel Interactions, Sodium Channel Interactions, Cardiac Rhythm Alteration.
What are the brand names for Quinidine?
Quinidine is marketed under brand names including Nuedexta.
What are the contraindications for Quinidine?
Quinidine labeling lists contraindications including: Concomitant use with quinidine, quinine, or mefloquine. ( 4.1 ) Patients with a history of quinidine, quinine or mefloquine-induced thrombocytopenia, hepatitis, or other hypersensitivity reactions.. Always consult the full prescribing information and a clinician.
Note. Data for quinidine is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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