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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.
Like many other drugs (including all other Class la antiarrhythmics), quinidine prolongs the QTC interval, and this can lead to torsades de pointes, a life-threatening ventricular arrhythmia (see OVERDOSAGE). The risk of torsades'^ 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 the QTC 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 QTC interval. Estimation of the incidence of torsades'^ patients with therapeutic levels of quinidine is not possible from the available data.
Paradoxical Increase in Ventricular Heart 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 [3-receptor blocking agent.
Exacerbated Bradycardia in Sick Sinus Syndrome
Renal or hepatic dysfunction causes the elimination of quinidine to be slowed, while congestive heart failure causes a reduction in quinidine's apparent volume of distribution. Any of these conditions can lead to quinidine toxicity if dosage is not appropriately reduced. In addition, interactions with coadministered drugs can alter the serum concentration and activity of quinidine, leading either to toxicity or to lack of efficacy if the dose of quinidine is not appropriately modified. (See PRECAUTIONS—Drug and Diet Interactions.)
Because quinidine opposes the atrial and A-V nodal effects of vagal stimulation, physical or pharmacological vagal maneuvers undertaken to terminate paroxysmal supraventricular tachycardia may be ineffective in patients receiving quinidine.
All the precautions applying to regular quinidine therapy apply to this product. Hypersensitivity or anaphylactoid reactions to quinidine, although rare, should be considered, especially during the first weeks of therapy. Hospitalization for close clinical observation, electrocardiographic monitoring, and determination of serum quinidine levels are indicated when large doses of quinidine are used or with patients who present an increased risk.
Periodic blood counts and liver and kidney function tests should be performed during long-term therapy; the drug should be discontinued if blood dyscrasias or evidence of hepatic or renal dysfunction occurs.
In patients without implanted pacemakers who are at high risk of complete atrioventricular block (e.g., those with digitalis intoxication, second-degree atrioventricular block, or severe intraventricular conduction defects), quinidine should be used only with caution.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Animal studies to evaluate quinidine's carcinogenic or mutagenic potential have not been performed. Similarly, there are no animal data as to quinidine's potential to impair fertility.
Pregnancy category C
Animal reproductive studies have not been conducted with quinidine. There are no adequate and well-controlled studies in pregnant women. Quinidine should be given to a pregnant woman only if clearly needed.
In one neonate whose mother had received quinidine throughout her pregnancy, the serum level of quinidine was equal to that of the mother, with no apparent ill effect. The level of quinidine in amniotic fluid was about three times higher than that found in serum.
Labor and Delivery
Quinine is said to be oxytocic in humans, but there are no adequate data as to quinidine's effects (if any) on human labor and delivery.
Quinidine is present in human milk at levels slightly lower than those in maternal serum; a human infant ingesting such milk should (scaling directly by weight) be expected to develop serum quinidine levels at least an order of magnitude lower than those of the mother. On the other hand, the pharmacokinetics and pharmacodynamics of quinidine in human infants have not been adequately studied, and neonates' reduced protein binding of quinidine may increase their risk of toxicity at low total serum levels. Administration of quinidine should (if possible) be avoided in lactating women who continue to nurse.
In antimalarial trials, quinidine was as safe and effective in pediatric patients as in adults. Notwithstanding the known pharmacokinetic differences between the pediatric population and adults (see CLINICAL PHARMACOLOGY, Pharmacokinetics), pediatric patients in these trials received the same doses (on a mg/kg basis) as adults.
Safety and effectiveness of the antiarrhythmic use of quinidine in pediatric patients have not been established in well-controlled clinical trials.
Clinical studies of quinidine generally were not adequate to determine if significant safety or efficacy differences exist between elderly patients (65 years or older) and younger patients.
Quinidine clearance is apparently independent of age (see CLINICAL PHARMACOLOGY, Pharmacokinetics). However, renal or hepatic dysfunction causes the elimination of quinidine to be slowed (see WARNINGS, Pharmacokinetic Considerations), and since these conditions are more common in the elderly, appropriate dosing reductions should be considered in these individuals.
Last reviewed on RxList: 12/29/2008
This monograph has been modified to include the generic and brand name in many instances.
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