BOX WARNING Mortality
In many trials of antiarrhythmic therapy for non-life-threatening arrhythmias, active antiarrhythmic therapy has resulted in increased mortality; the risk of active therapy is probably greatest in patients with structural heart disease.
In the case of quinidine used to prevent or defer recurrence of atrial flutter/fibrillation, the best available data come from a meta-analysis described under CLINICAL PHARMACOLOGY, Clinical Effects above. In the patients studied in the trials there analyzed, the mortality associated with the use of quinidine was more than three times as great as the mortality associated with the use of placebo.
Another meta-analysis, also described under CLINICAL PHARMACOLOGY, Clinical Effects, showed that in patients with various non-life-threatening ventricular arrhythmias, the mortality associated with the use of quinidine was consistently greater than that associated with the use of any of a variety of alternative antiarrhythmics.
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QUINIDINE SUMMARY
QUINIDINE SULFATE Extended-release TABLETS, USP
Quinidine is an antimalarial schizonticide and an antiarrhythmic agent with class 1a activity; it is the d–isomer of quinine and its molecular weight is 324.
Treatment of malaria
Quinidine gluconate injection is indicated for the treatment of life–threatening Plasmodium falciparum malaria.
Conversion of atrial fibrillation/flutter
Quinidine gluconate injection is also indicated (when rapid therapeutic effect is required, or when oral therapy is not feasible) as a means of restoring normal sinus rhythm in patients with symptomatic atrial fibrillation/flutter whose symptoms are not adequately controlled by measures that reduce the rate of ventricular response. If this use of quinidine gluconate does not restore sinus rhythm within a reasonable time, then its use should be discontinued.
Treatment of ventricular arrhythmias
Quinidine gluconate injection is also indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that in the judgement of the physician are life–threatening. Because of the proarrhythmic effects of quinidine, its use with ventricular arrhythmias of lesser severity is generally not recommended, and treatment of patients with asymptomatic ventricular premature contractions should be avoided. Where possible, therapy should be guided by the results of programmed electrical stimulation and/or Holter monitoring with exercise.
Antiarrhythmic drugs (including quinidine) have not been shown to enhance survival in patients with ventricular arrhythmias.
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NEWS HIGHLIGHTS
Published Studies Related to Quinidine
Effects of ketoconazole and quinidine on pharmacokinetics of pactimibe and its plasma metabolite, R-125528, in humans. [2008.08]
Pactimibe sulfate is a novel acyl coenzyme A:cholesterol acyltransferase inhibitor developed for the treatment of hypercholesterolemia and atherosclerotic diseases. Pactimibe has two equally dominant clearance pathways forming R-125528 by CYP3A4 and M-1 by CYP2D6 in vitro... These values were well in accordance with the values observed in this study.
Dextromethorphan and quinidine in adult patients with uncontrolled painful diabetic peripheral neuropathy: a 29-day, multicenter, open-label, dose-escalation study. [2006.10]
BACKGROUND: Pain associated with diabetic peripheral neuropathy (DPN) has a substantial negative impact on patients' quality of life. OBJECTIVES: The primary objective of this study was to evaluate the tolerability of capsules containing dextromethorphan (DM) and quinidine (Q) in patients with painful DPN. A secondary objective was to perform a preliminary assessment of the efficacy of DM/Q in this patient population... CONCLUSIONS: The results of this open-label study indicated that the combination of DMIQ (dose range, DM30/Q30-DM120/Q120) was well tolerated in patients with pain associated with DPN. Based on the preliminary efficacy results, a randomized, controlled, double-blind trial is warranted to assess the tolerability and efficacy of this combination in patients with DPN.
Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis. [2006.05]
OBJECTIVE: To evaluate the efficacy and safety of DM/Q (capsules containing dextromethorphan [DM] and quinidine [Q]) compared with placebo, taken twice daily, for the treatment of pseudobulbar affect over a 12-week period in multiple sclerosis patients... INTERPRETATION: Results in multiple sclerosis patients were similar to those of a previous study in amyotrophic lateral sclerosis, demonstrating that DM/Q may be beneficial in treating potentially disabling pseudobulbar affect in a variety of neurological disorders.
Clinical Trials Related to Quinidine
Empiric Quinidine for Asymptomatic Brugada Syndrome [Not yet recruiting]
The purpose of this study is to determine if quinidine therapy (not guided by the results of
electrophysiologic studies) will reduce the long-term risk of arrhythmic events in
asymptomatic Brugada Syndrome.
Safety and Efficacy of Dextromethorphan and Quinidine in the Treatment of the Pain of Diabetic Neuropathy [Completed]
The purpose of this study is to determine whether dextromethorphan (Neurodex) and quinidine
are effective in the treatment of pain of diabetic neuropathy.
Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS [Completed]
Safety and Efficacy of AVP-923 in PBA Patients With ALS or MS [Recruiting]
Objectives of the study are to evaluate the safety, tolerability, and efficacy of two
different doses of AVP-923 (capsules containing either 30 mg of dextromethorphan hydrobromide
and 10 mg of quinidine sulfate [AVP-923-30] or 20 mg of dextromethorphan hydrobromide and 10
mg of quinidine sulfate [AVP-923-20]) when compared to placebo, for the treatment of PBA in a
population of patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS)
over a 12-week period. An additional objective is to determine the pharmacokinetic
parameters of the two different doses of AVP-923 in a subset of the study population.
Pseudobulbar Affect (PBA) is a condition characterized by involuntary, sudden and frequent
episodes of laughing and/or crying out of proportion or incongruous to the underlying emotion
of happiness or sadness Other terms used to describe this condition include emotional
lability, emotionalism, emotional incontinence, emotional discontrol, excessive emotionalism,
and pathological laughing and crying. The outbursts can occur spontaneously or in response
to provocative stimuli such as questions or events.
A body of evidence suggests that PBA can be modulated through pharmacologic intervention.
Dextromethorphan (DM) is a low-affinity uncompetitive antagonist of the NMDA receptor,
reducing the level of excitatory activity. DM also acts at the phencyclidine-binding site,
which is part of the NMDA receptor complex. DM is a sigma receptor agonist, suppressing the
release of excitatory neurotransmitters.
Quinidine is a known potent inhibitor of cytochrome CYP2D6, that decreases the metabolism of
dextromethorphan and helps to achieve sustained and therapeutic levels of this drug.
Induction of Drug Metabolism: In Vivo Comparison of Carbamazepine and Oxcarbazepine. [Active, not recruiting]
This is a study of the possible effect of two antiepileptic drug on enzymes in the liver that
metabolizes a number of drugs. It is a well know fact that carbamazepine induces some of
these enzymes and this may reduce the effect of concomitantly administered drugs. Clinical
observations suggest that oxcarbazepine does not induce these enzymes to the same degree.
This study directly compares the ability of these two drugs to induce the cytochrome P450 3A4
enzyme, in healthy volunteers using a well defined biomarker reaction of a specific enzyme
activity.
It is the hypothesis that oxcarbazepine induces CYP3A4 to a lesser degree than
carbamazepine.
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Page last updated: 2008-11-03
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