Quinidine Gluonate
FDA Drug Information • Also known as: Quinidine Gluconate
- Brand Names
- Quinidine Gluconate
- Route
- ORAL
- Dosage Form
- TABLET, EXTENDED RELEASE
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
DESCRIPTION Quinidine is an antimalarial schizonticide and an antiarrhythmic agent with Class Ia activity; it is the d-isomer of quinine, and its molecular weight is 324.43. Quinidine gluconate is the gluconate salt of quinidine; its chemical name is cinchonan-9-ol, 6'-methoxy-, (9S)-, mono-D-gluconate; its structural formula is: Its empirical formula is C 20 H 24 N 2 O 2
What Is Quinidine Gluonate Used For?
INDICATIONS & USAGE Conversion of atrial fibrillation/flutter In patients with symptomatic atrial fibrillation/flutter whose symptoms are not adequately controlled by measures that reduce the rate of ventricular response, quinidine gluconate is indicated as a means of restoring normal sinus rhythm. If this use of quinidine gluconate does not restore sinus rhythm within a reasonable time (see DOSAGE AND ADMINISTRATION ), then quinidine gluconate should be discontinued. Reduction of frequency of relapse into atrial fibrillation/flutter Chronic therapy with quinidine gluconate is indicated for some patients at high risk of symptomatic atrial fibrillation/flutter, generally patients who have had previous episodes of atrial fibrillation/flutter that were so frequent and poorly tolerated as to outweigh, in the judgment of the physician and the patient, the risks of prophylactic therapy with quinidine gluconate. The increased risk of death should specifically be considered. Quinidine gluconate should be used only after alternative measures (e.g., use of other drugs to control the ventricular rate) have been found to be inadequate. In patients with histories of frequent symptomatic episodes of atrial fibrillation/flutter, the goal of therapy should be an increase in the average time between episodes. In most patients, the tachyarrhythmia will recur during therapy, and a single recurrence should not be interpreted as therapeutic failure. Suppression of ventricular arrhythmias Quinidine gluconate is also indicated for the suppression of recurrent documented ventricular arrhythmias, such as sustained ventricular tachycardia, that in the judgment 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 gluconate) have not been shown to enhance survival in patients with ventricular arrhythmias.
Dosage and Administration
DOSAGE & ADMINISTRATION The dose of quinidine delivered by quinidine gluconate extended-release tablets may be titrated by breaking a tablet in half. If tablets are crushed or chewed, their extended-release properties will be lost. The dosage of quinidine varies considerably depending upon the general condition and the cardiovascular state of the patient. Conversion of atrial fibrillation/flutter to sinus rhythm Especially in patients with known structural heart disease or other risk factors for toxicity, initiation or dose-adjustment of treatment with quinidine gluconate should generally be performed in a setting where facilities and personnel for monitoring and resuscitation are continuously available. Patients with symptomatic atrial fibrillation/flutter should be treated with quinidine gluconate only after ventricular rate control (e.g., with digitalis or β-blockers) has failed to provide satisfactory control of symptoms. Adequate trials have not identified an optimal regimen of quinidine gluconate for conversion of atrial fibrillation/flutter to sinus rhythm. In one reported regimen, the patient first receives two tablets (648 mg; 403 mg of quinidine base) of quinidine gluconate every eight hours. If this regimen has not resulted in conversion after 3 or 4 doses, then the dose is cautiously increased. If, at any point during administration, the QRS complex widens to 130% of its pre-treatment duration; the QT c interval widens to 130% of its pre-treatment duration and is then longer than 500 ms; P waves disappear; or the patient develops significant tachycardia, symptomatic bradycardia, or hypotension, then quinidine gluconate is discontinued, and other means of conversion (e.g., direct-current cardioversion) are considered. In another regimen sometimes used, the patient receives one tablet (324 mg; 202 mg of quinidine base) every eight hours for two days; then two tablets every twelve hours for two days; and finally two tablets every eight hours for up to four days. The four-day stretch may come at one of the lower doses if, in the judgment of the physician, the lower dose is the highest one that will be tolerated. The criteria for discontinuation of treatment with quinidine gluconate are the same as in the other regimen. Reduction in the frequency of relapse into atrial fibrillation/flutter In a patient with a history of frequent symptomatic episodes of atrial fibrillation/flutter, the goal of therapy with quinidine gluconate should be an increase in the average time between episodes. In most patients, the tachyarrhythmia will recur during therapy with quinidine gluconate, and a single recurrence should not be interpreted as therapeutic failure. Especially in patients with known structural heart disease or other risk factors for toxicity, initiation or dose-adjustment of treatment with quinidine gluconate should generally be performed in a setting where facilities and personnel for monitoring and resuscitation are continuously available....
Side Effects (Adverse Reactions)
ADVERSE REACTIONS Quinidine preparations have been used for many years, but there are only sparse data from which to estimate the incidence of various adverse reactions. The adverse reactions most frequently reported have consistently been gastrointestinal, including diarrhea, nausea, vomiting, and heartburn/esophagitis. In the reported study that was closest in character to the predominant approved use of quinidine gluconate, 86 adult outpatients with atrial fibrillation were followed for six months while they received slow-release quinidine bisulfate tablets, 600 mg (approximately 400 mg of quinidine base) twice daily. The incidences of adverse experiences reported more than once were as shown in the table below. The most serious quinidine-associated adverse reactions are described above under WARNINGS . ADVERSE EXPERIENCES REPORTED MORE THAN ONCE IN 86 PATIENTS WITH ATRIAL FIBRILLATION Incidence (%) diarrhea 21 (24%) fever 5 (6%) rash 5 (6%) arrythmia 3 (3%) abnormal electrocardiogram 3 (3%) nausea/vomiting 3 (3%) dizziness 3 (3%) headache 3 (3%) asthenia 2 (2%) cerebral ischemia 2 (2%) Vomiting and diarrhea can occur as isolated reactions to therapeutic levels of quinidine, but they may also be the first signs of cinchonism , a syndrome that may also include tinnitus, reversible high-frequency hearing loss, deafness, vertigo, blurred vision, diplopia, photophobia, headache, confusion, and delirium. Cinchonism is most often a sign of chronic quinidine toxicity, but it may appear in sensitive patients after a single moderate dose. A few cases of hepatotoxicity , including granulomatous hepatitis, have been reported in patients receiving quinidine. All of these have appeared during the first few weeks of therapy, and most (not all) have remitted once quinidine was withdrawn. Autoimmune and inflammatory syndromes associated with quinidine therapy have included fever, urticaria, flushing, exfoliative rash, bronchospasm, psoriasiform rash, pruritus and lymphadenopathy, hemolytic anemia, vasculitis, thrombocytopenia, thrombocytopenic purpura, uveitis, angioedema, agranulocytosis, the sicca syndrome, arthralgia, myalgia, elevation in serum levels of skeletal-muscle enzymes, a disorder resembling systemic lupus erythematosus, and pneumonitis. Convulsions, apprehension, and ataxia have been reported, but it is not clear that these were not simply the results of hypotension and consequent cerebral hypoperfusion. There are many reports of syncope. Acute psychotic reactions have been reported to follow the first dose of quinidine, but these reactions appear to be extremely rare. Other adverse reactions occasionally reported include depression, mydriasis, disturbed color perception, night blindness, scotomata, optic neuritis, visual field loss, photosensitivity, and abnormalities of pigmentation.
Warnings and Precautions
WARNINGS 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. Proarrhythmic effects Like many other drugs (including all other Class Ia antiarrhythmics), quinidine prolongs the QT c interval, and this can lead to torsades de pointes , a life-threatening ventricular arrhythmia (see OVERDOSAGE ). The risk of torsades is increased by bradycardia, hypokalemia, hypomagnesemia or high serum levels of quinidine, but it may appear in the absence of any of these risk factors. The best predictor of this arrhythmia appears to be the length of QT c interval, and quinidine should be used with extreme care in patients who have preexisting long-QT syndromes, who have histories of torsades de pointes of any cause, or who have previously responded to quinidine (or other drugs that prolong ventricular repolarization) with marked lengthening of the QT c interval. Estimation of the incidence of torsades in patients with therapeutic levels of quinidine is not possible from the available data. Other ventricular arrhythmias that have been reported with quinidine include frequent extrasystoles,ventricular tachycardia, ventricular flutter, and ventricular fibrillation. Paradoxical increase in ventricular rate in atrial flutter/fibrillation When quinidine is administered to patients with atrial flutter/fibrillation, the desired pharmacologic reversion to sinus rhythm may (rarely) be preceded by a slowing of the atrial rate with a consequent increase in the rate of beats conducted to the ventricles. The resulting ventricular rate may be very high (greater than 200 beats per minute) and poorly tolerated. This hazard may be decreased if partial atrioventricular block is achieved prior to initiation of quinidine therapy, using conduction-reducing drugs such as digitalis, verapamil, diltiazem, or a β-receptor blocking agent. Exacerbated bradycardia in sick sinus syndrome In patients with the sick sinus syndrome, quinidine has been associated with marked sinus node depression and bradycardia. Pharmacokinetic considerations Renal or hepatic dysfunction causes the...
Contraindications
CONTRAINDICATIONS Quinidine is contraindicated in patients who are known to be allergic to it, or who have a history of immune thrombocytopenia or have developed thrombocytopenic purpura during prior therapy with quinidine or quinine (see WARNINGS ). In the absence of a functioning artificial pacemaker, quinidine is also contraindicated in any patient whose cardiac rhythm is dependent upon a junctional or idioventricular pacemaker, including patients in complete atrioventricular block. Quinidine is also contraindicated in patients who, like those with myasthenia gravis, might be adversely affected by an anticholinergic agent.
Overdosage
OVERDOSAGE Overdoses with various oral formulations of quinidine have been well described. Death has been described after a 5-gram ingestion by a toddler, while an adolescent was reported to survive after ingesting 8 grams of quinidine. The most important ill effects of acute quinidine overdoses 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. Arrhythmias Serum quinidine levels can be conveniently assayed and monitored, but the electrocardiographic QT c interval is a better predictor of quinidine-induced ventricular arrhythmias. The necessary treatment of hemodynamically unstable polymorphic ventricular tachycardia (including torsades de pointes ) is withdrawal of treatment with quinidine and either immediate cardioversion or, if a cardiac pacemaker is in place or immediately available, immediate over drive pacing. After pacing or cardioversion, further management must be guided by the length of the QT c interval. Quinidine-associated ventricular tachyarrhythmias with normal underlying QT c intervals have not been adequately studied. Because of the theoretical possibility of QT-prolonging effects that might be additive to those of quinidine, other antiarrhythmics with Class I (disopyramide, procainamide) or Class III activities should (if possible) be avoided. Similarly, although the use of bretylium in quinidine overdose has not been reported, it is reasonable to expect that the α-blocking properties of bretylium might be additive to those of quinidine, resulting in problematic hypotension. If the post-cardioversion QT c interval is prolonged, then the pre-cardioversion polymorphic ventricular tachycardia was (by definition) torsades de pointes . In this case, lidocaine and bretyliumare unlikely to be of value, and other Class I antiarrhythmics (disopyramide, procainamide) are...
How Supplied
HOW SUPPLIED Quinidine gluconate extended-release tablets, 324 mg are round white tablets, debossed “E27” on one side. Bottles of 100 NDC 71930-016-12 Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature]. DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER AS DEFINED IN THE USP.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.