Dextromethorphan Hydrobromide And Quinidine Sulfate

Dextromethorphan hydrobromide and quinidine sulfate capsules are 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. PBA 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.

• Starting dose: one capsule daily by mouth for 7 days. (
  
  
  2.1 Recommended Dose

  The recommended starting dose of dextromethorphan hydrobromide and quinidine sulfate capsules are 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.
  )
  
• Maintenance dose: After 7 days, 1 capsule every 12 hours. (
  
  
  2.1 Recommended Dose

  The recommended starting dose of dextromethorphan hydrobromide and quinidine sulfate capsules are 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.
  )
  

Dextromethorphan hydrobromide and quinidine sulfate capsules contain 20 mg dextromethorphan hydrobromide and 10 mg quinidine sulfate in a white to off-white colored opaque hard gelatin capsule imprinted with 'H' on cap with black ink and 'D22' on body with black ink filled with white to off-white powder.

• Pregnancy: Based on animal data, may cause fetal harm. (
  
  8.1)
  

• Thrombocytopenia or other hypersensitivity reactions: Discontinue if occurs. (
  
  
  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. Dextromethorphan hydrobromide and quinidine sulfate should be discontinued immediately if thrombocytopenia occurs, unless the thrombocytopenia is clearly not drug-related, as continued use increases the risk for fatal hemorrhage. Likewise, dextromethorphan hydrobromide and quinidine sulfate should not be restarted in sensitized patients, because more rapid and more severe thrombocytopenia than the original episode can occur. Dextromethorphan hydrobromide and quinidine sulfate should not be used if immune-mediated thrombocytopenia from structurally related drugs, including quinine and mefloquine is suspected, as cross-sensitivity can occur. Quinidine-associated thrombocytopenia usually, but not always, resolves within a few days of discontinuation of the sensitizing drug.

  Quinidine has also been associated with a lupus-like syndrome involving polyarthritis, sometimes with a positive antinuclear antibody test. Other associations include rash, bronchospasm, lymphadenopathy, hemolytic anemia, vasculitis, uveitis, angioedema, agranulocytosis, the sicca syndrome, myalgia, elevation in serum levels of skeletal-muscle enzymes, and pneumonitis.
  ) 
  
• Hepatitis: Discontinue if occurs. (
  
  
  5.2 Hepatotoxicity

  Hepatitis, including granulomatous hepatitis, has been reported in patients receiving quinidine, generally during the first few weeks of therapy. Fever may be a presenting symptom, and thrombocytopenia or other signs of hypersensitivity may also occur. Most cases remit when quinidine is withdrawn.
  )
  
• QT Prolongation: Monitor ECG if concomitant use of drugs that prolong QT interval cannot be avoided or if concomitant CYP3A4 inhibitors used. (
  
  
  5.3 Cardiac Effects

  Dextromethorphan hydrobromide and quinidine sulfate causes dose-dependent QTc prolongation

  [see Clinical Pharmacology ]

  . QT prolongation can cause torsades de pointes-type ventricular tachycardia, with the risk increasing as the degree of prolongation increases. When initiating dextromethorphan hydrobromide and quinidine sulfate in patients at risk of QT prolongation and torsades de pointes, electrocardiographic (ECG) evaluation of QT interval should be conducted at baseline and 3 to 4 hours after the first dose. This includes patients concomitantly taking/initiating drugs that prolong the QT interval or that are strong or moderate CYP3A4 inhibitors, and patients with left ventricular hypertrophy (LVH) or left ventricular dysfunction (LVD). LVH and LVD are more likely to be present in patients with chronic hypertension, known coronary artery disease, or history of stroke. LVH and LVD can be diagnosed utilizing echocardiography or another suitable cardiac imaging modality.
  
  Strong and moderate CYP3A inhibitors include, but are not limited to, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, and verapamil.
  
  Reevaluate ECG if risk factors for arrhythmia change during the course of treatment with dextromethorphan hydrobromide and quinidine sulfate. Risk factors include concomitant use of drugs associated with QT prolongation, electrolyte abnormality (hypokalemia, hypomagnesemia), bradycardia, and family history of QT abnormality. Hypokalemia and hypomagnesemia should be corrected prior to initiation of therapy with dextromethorphan hydrobromide and quinidine sulfate, and should be monitored during treatment.
  
  If patients taking dextromethorphan hydrobromide and quinidine sulfate experience symptoms that could indicate the occurrence of cardiac arrhythmias, e.g., syncope or palpitations, dextromethorphan hydrobromide and quinidine sulfate should be discontinued and the patient further evaluated.
  ) 
  

• Left ventricular hypertrophy (LVH) or left ventricular dysfunction (LVD): Monitor ECG in patients with LVH or LVD. (
  
  5.3)
  
• CYP2D6 substrate: Dextromethorphan hydrobromide and quinidine sulfate 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 dextromethorphan hydrobromide and quinidine sulfate 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)