Quinidine Gluconate

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

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 All of these have appeared during the first few weeks of therapy, and most (not all) have remitted once quinidine was withdrawn.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, 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.

Read the entire FDA prescribing information for Quinidine Gluconate (Quinidine Gluconate)

Contraindications

• Patients with AV junctional or idioventricular pacemaker, including those in complete AV block.119 163 167 168 169 170

• History of quinidine- or quinine-associated thrombocytopenic purpura.119 163 167 168 169 170

• Myasthenia gravis or other conditions that might be adversely affected by anticholinergic effects.119 163 167 168 169 170

• Known hypersensitivity to quinidine.119 163 167 168 169 170

Warnings/Precautions

Warnings

Pooled analysis of data from several randomized, controlled studies in patients with ventricular arrhythmias indicates that mortality rate associated with quinidine therapy is at least as high as that associated with other antiarrhythmic agents (e.g., flecainide, mexiletine, propafenone, tocainide).b

Use quinidine only for life-threatening arrhythmias.145 Avoid use for less severe ventricular arrhythmias and treatment of asymptomatic VPCs.145

Additionally, pooled analysis of data from several randomized, controlled studies in patients with atrial flutter and fibrillation indicates that quinidine therapy may be associated with a mortality rate >3 times higher than that associated with placebo;163 167 168 169 170 consider the increased risk of death when initiating quinidine therapy.149

Use with extreme caution, if at all, in patients with incomplete AV nodal block, since complete heart block and asystole may result.b Parenteral administration is especially hazardous in the presence of AV block, in the absence of atrial activity, and in patients with extensive myocardial injury.b

The possibility that potentially serious cardiac arrhythmias, including torsades de pointes, could occur if used concomitantly with other drugs that prolong the QTc interval should be considered.119

Hypokalemia, hypoxia, and disorders of acid-base balance must be eliminated as potentiating factors in patients who require large doses of antiarrhythmic agents to control ventricular arrhythmias.b

Paradoxically, an extremely rapid ventricular rate may occur when used in the treatment of atrial flutter or fibrillation, due to a reduction in the degree of AV nodal block to a 1:1 ratio.b The anticholinergic action on the AV node also may increase the heart rate.b

This tachycardia may be prevented by prior digitalization.b

If cessation of atrial fibrillation or flutter is accompanied by depression of the normal pacemaker, an idioventricular rhythm (including ventricular tachycardia and fibrillation) may result.b

Possible marked sinus node depression and bradycardia.b

Overly rapid IV administration may cause peripheral vascular collapse and hypotension.119

Sensitivity Reactions

Idiosyncratic and hypersensitivity reactions to quinidine may occur, and the reaction to a test dose or the first dose of the drug should be observed carefully.b (See Oral Administration under Dosage and Administration.)

Observe for hypersensitivity for the first weeks of therapy.b

Symptoms of cinchonism such as tinnitus, headache, vertigo, fever, dizziness, lightheadedness, tremor, nausea, and disturbed vision may occur in sensitive patients after a single dose.b

Decrease dosage if signs of cinchonism appear.b

General Precautions

Possible syncope, probably due to ventricular tachycardia or fibrillation in usual doses.b Syncopal episodes may subside spontaneously, but occasionally are fatal.b If quinidine-induced syncope occurs, discontinue the drug.b Also may cause bradycardia.b

Severe hypotension may occur following IV administration or oral overdosage.b Vascular collapse, respiratory distress, and respiratory arrest may occur.b Reportedly related to the dose and rate of administration of the drug.102 107 119 Rapid IV injection of as little as 200 mg reportedly may cause a decrease in blood pressure of 40–50 mm Hg.119 Norepinephrine or metaraminol may be used if necessary to treat vascular collapse; artificial respiration and other supportive measures may be required.b

While substantial cardiovascular toxicity generally has not occurred, ECG changes, including prolonged QT interval, widened QRS complex, and flattened T waves (without dysrhythmia), have occurred frequently and hypotension and ventricular tachycardia have occurred occasionally in patients receiving IV quinidine gluconate for the treatment of Plasmodium falciparum malaria.102 104 108 124

Use with caution in patients without implanted pacemakers at high risk of complete atrioventricular block (e.g., digitalis intoxication, second-degree atrioventricular block, severe intraventricular conduction defects).163 167 168 169 170

Because of potentially fatal consequences of delays in initiating treatment of severe malaria, institutional pharmacy services should be aware of the essential role of ready availability of IV quinidine gluconate.b 142 143 148 153

If IV quinidine gluconate is not readily available for a patient with severe P. falciparum malaria (e.g., in hospitals where the drug is not maintained on formulary or otherwise available), health-care professionals should contact a nearby healthcare facility that stocks the drug.143 If a local source cannot be found, contact local or regional distributor or manufacturer of the drug.143

If IV quinidine gluconate is unavailable locally and cannot be obtained quickly or cannot be used because of adverse effects or contraindications or if parasitemia is high and has not responded to quinidine gluconate, IV artesunate is available from CDC under an IND protocol for initial treatment of severe malaria.143 144 171 172 (See Malaria under Uses.)

Specific Populations

Category C.119 163 166 167 168 169 170

Generally considered relatively safe at usual dosages, but may exhibit oxytocic effect (possible abortion) at high dosages.166

Distributed into milk.119 163 166 167 168 169 170 Avoid, if possible, in nursing women.119 163 167 168 169 170

Safety and efficacy as an antiarrhythmic agent in children not established.119 163 167 168 169 170 Has been used in children with arrhythmias†.165 b

Study and experience in children with malaria suggest that safety and efficacy of IV quinidine gluconate are similar to those in adults.119

Safety and efficacy not systematically studied in geriatric patients.119 167 168 169 170 Clinical studies did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently than younger adults;119 other reported clinical experience has not identified differences in responses between geriatric adults and younger patients.119

When used in geriatric patients, select dosage with caution, usually initiating therapy at the low end of dosage range, and consider the greater frequency of decreased hepatic, renal, and/or cardiac function and concomitant disease and drug therapy in this age group.119

Decreased clearance;119 163 167 168 169 170 may result in quinidine toxicity if dosage is not reduced.119 167 168 169 170

Decreased clearance;119 163 167 168 169 170 may result in quinidine toxicity if dosage is not reduced.119 163 167 168 169 170 (See Special Populations under Dosage and Administration.)

Common Adverse Effects

GI effects (diarrhea, nausea, vomiting, heartburn/esophagitis, upper GI distress),119 163 167 168 169 170 lightheadedness.119 163 167 168 169 170

Absorption

Bioavailability

Quinidine sulfate conventional tablets: Absolute bioavailability is about 70% (range 45–100%) and peak serum concentrations are attained in about 2 hours.167 170

Quinidine gluconate or quinidine sulfate extended-release tablets: Absolute bioavailability is 70–80% and peak serum concentrations are attained within 3–6 hours.163 168 169

Onset

After oral administration of 400–600 mg of quinidine sulfate, onset of cardiovascular effects usually occurs in 1–3 hours.b

Duration

Therapeutic cardiovascular effects of an oral 400- to 600-mg dose of quinidine sulfate persist for 6–8 hours.b

Food

Quinidine sulfate conventional tablets: Food slows the rate of absorption, but does not affect the extent of absorption.167 170

Quinidine gluconate extended-release tablets: Food increases the rate (by 27%) and extent (by 17%) of absorption.168 169

Grapefruit juice may delay absorption156 157 163 168 169 and inhibit GI metabolism.156 157

Distribution

Extent

Rapidly distributed into all body tissues except the brain.b

Crosses the placenta.163 166 167 168 169 170

Distributed into breast milk.119 163 166 167 168 169 170

Plasma Protein Binding

About 80–88% bound to plasma proteins in adults and older children;119 163 167 168 169 170 lower protein binding in pregnant women, infants, and neonates (may be as low as 50–70% in neonates and infants).119 163 167 168 169 170

Elimination

Metabolism

Metabolized in the liver by CYP3A4;2 119 163 167 168 169 170 some metabolites have antiarrhythmic activity.119 163 167 168 169 170

Major metabolite is 3-hydroxyquinidine (3HQ);119 163 167 168 169 170 animal studies indicate 3HQ has at least half of the antiarrhythmic activity of quinidine.119 163 167 168 169 170

Elimination Route

Eliminated mainly in urine, with less than 5% of a dose excreted in feces.b

Rate of quinidine excretion increases when the pH of urine ≤6; the rate of excretion decreases and plasma concentrations increase when the urine is alkaline.b

Half-life

6–8 hours (range: 3–16 hours or longer) in healthy adults119 163 167 168 169 170 and 3–4 hours in children.119 163 167 168 169 170

12.8 hours in malaria.102

Storage

Oral

20–25°C in tight container.163 167 170 Protect from light and moisture.163 167 170

20–25°C in tight container.168 169 Protect from light.168 169

Parenteral

25°C (may be exposed to 15–30°C).119

Diluted solutions (16 mg/mL in 5% dextrose injection) are stable for 24 hours at room temperature and up to 48 hours at 4°C.119

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Minimize length of IV tubing because of quinidine adsorption to PVC tubing.119 3% adsorption with 12 inches vs 30% with 112 inches.119

• A class I (membrane-stabilizing) antiarrhythmic agent with actions similar to those of procainamide.b

• Decreases myocardial excitability and conduction velocity, and may depress myocardial contractility.b

• Possesses anticholinergic properties that may modify the direct myocardial effects of the drug.b

• The exact mechanism has not been determined conclusively, but is believed to combine with fast sodium channels in their inactive state and thereby inhibit recovery after repolarization in a time- and voltage-dependent manner, which is associated with subsequent dissociation of the drug from the sodium channels.b

• Suppresses automaticity in the His-Purkinje system.b Decreases conduction velocity in the atria, ventricles, and His-Purkinje system, and may decrease or cause no change in conduction velocity through the AV node.

• May suppress atrial fibrillation or flutter by prolonging the effective refractory period (ERP) and increasing the action potential duration in atrial and ventricular muscle and in the His-Purkinje system.b

• May produce sinus tachycardia via its anticholinergic effects.b

• Has a direct negative inotropic effect, but therapeutic plasma concentrations of the drug do not usually depress contractility in the normal heart.b

• May reduce peripheral resistance and blood pressure by blockade of α-adrenergic receptors and by its effects on myocardial contractility; decreased blood pressure is most likely to occur with high plasma concentrations of the drug.b At high plasma concentrations, quinidine may produce sinus tachycardia because of reflex sympathetic response to the drug’s hypotensive effect.b

• When used as an antimalarial agent, acts principally as an intraerythrocytic schizonticide; the drug has little effect on sporozoites or preerythrocytic parasites.119

• Gametocidal against Plasmodium vivax and P. malariae, but not P. falciparum.119

• Appears to be more active (in vitro on a weight basis) than quinine against P. falciparum.102 103 104 112

Maintenance of sinus rhythm after conversion from atrial fibrillation: In six clinical trials (published between 1970 and 1984) with a total of 808 patients, quinidine (418 patients) was compared to nontreatment (258 patients) or placebo (132 patients) for the maintenance of sinus rhythm after cardioversion from chronic atrial fibrillation. Quinidine was consistently more efficacious in maintaining sinus rhythm, but a meta-analysis found that mortality in the quinidine-exposed patients (2.9%) was significantly greater than mortality in the patients who had not been treated with active drug (0.8%). Suppression of atrial fibrillation with quinidine has theoretical patient benefits (e.g., improved exercise tolerance; reduction in hospitalization for cardioversion; lack of arrhythmia-related palpitations, dyspnea and chest pain; reduced incidence of systemic embolism and/or stroke), but these benefits have never been demonstrated in clinical trials. Some of these benefits (e.g., reduction in stroke incidence) may be achievable by other means (anticoagulation).

By slowing the atrial rate in atrial flutter/fibrillation, quinidine can decrease the degree of atrioventricular block and cause an increase, sometimes marked, in the rate at which supraventricular impulses are successfully conducted by the atrioventricular node, with a resultant paradoxical increase in ventricular rate (see WARNINGS).

Non-life-threatening ventricular arrhythmias: In studies of patients with a variety of ventricular arrhythmias (mainly frequent ventricular premature beats and non-sustained ventricular tachycardia, quinidine (total n=502) has been compared with flecainide (n=141), mexiletine (n=246), propafenone (n=53), and tocainide (n=67). In each of these studies, the mortality in the quinidine group was numerically greater than the mortality in the comparator group. When the studies were combined in a meta-analysis, quinidine was associated with a statistically significant threefold relative risk of death.

At therapeutic doses, quinidine's only consistent effect upon the surface electrocardiogram is an increase in the QT interval. This prolongation can be monitored as a guide to safety, and it may provide better guidance than serum drug levels (see 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 QTc 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 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 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 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 Interactions).

Vagolysis

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.

Thrombocytopenia

Quinidine-induced thrombocytopenia is an immune-mediated disorder characterized by a drug-dependent antibody that is itself nonreactive, but when soluble drug is present at pharmacologic concentrations, binds tightly to specific platelet membrane glycoproteins, causing platelet destruction.1 Serologic testing for quinidine-specific antibody is commercially available and may be useful for identifying the specific cause of thrombocytopenia in individual cases. Testing is important because a patient with quinidine-dependent antibodies should not be re-exposed to quinidine.

A case control study found a 125-fold increased risk of severe thrombocytopenia (platelets <30,000 µL, requiring hospitalization) with quinidine.2 The incidence of quinidine-induced thrombocytopenia was 1.8 cases per 1,000 patient years of exposure. The incidence of less severe thrombocytopenia may be higher.

Typically, a patient with immune thrombocytopenia will have taken drug for about 1 week or intermittently over a longer period of time (possibly years) before presenting with petechiae or bruising. Systemic symptoms, such as lightheadedness, chills, fever, nausea, and vomiting, often may precede bleeding events. Thrombocytopenia may be severe. Patients should have risk/benefit re-evaluated in order to continue treatment with quinidine. If the drug is stopped, symptoms usually resolve within 1 or 2 days and platelet count returns to normal in less than 1 week. If quinidine is not stopped, there is a risk of fatal hemorrhage. The onset of thrombocytopenia may be more rapid upon re-exposure.

Heart block

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.

Thrombocytopenia

Quinidine should be discontinued in case of any signs or symptoms of thrombocytopenia (see WARNINGS).

Drug and Diet Interactions

Altered pharmacokinetics of quinidine: Diltiazem significantly decreases the clearance and increases the t1/2 of quinidine, but quinidine does not alter the kinetics of diltiazem.

Drugs that alkalinize the urine (carbonic-anhydrase inhibitors, sodium bicarbonate, thiazide diuretics) reduce renal elimination of quinidine.

By pharmacokinetic mechanisms that are not well understood, quinidine levels are increased by coadministration of amiodarone or cimetidine. Very rarely, and again by mechanisms not understood, quinidine levels are decreased by coadministration of nifedipine.

Hepatic elimination of quinidine may be accelerated by coadministration of drugs (phenobarbital, phenytoin, rifampin) that induce production of cytochrome P450IIIA4.

Perhaps because of competition for the P450IIIA4 metabolic pathway, quinidine levels rise when ketoconazole is coadministered.

Coadministration of propranolol usually does not affect quinidine pharmacokinetics, but in some studies the β-blocker appeared to cause increases in the peak serum levels of quinidine, decreases in quinidine's volume of distribution, and decreases in total quinidine clearance. The effects (if any) of coadministration of other β-blockers on quinidine pharmacokinetics have not been adequately studied.

Hepatic clearance of quinidine is significantly reduced during coadministration of verapamil, with corresponding increases in serum levels and half-life.

Grapefruit juice: Grapefruit juice inhibits P450 3A4-mediated metabolism of quinidine to 3-hydroxyquinidine. Although the clinical significance of this interaction is unknown, grapefruit juice should be avoided.

Dietary salt: The rate and extent of quinidine absorption may be affected by changes in dietary salt intake; a decrease in dietary salt intake may lead to an increase in plasma quinidine concentrations.

Altered pharmacokinetics of other drugs: Quinidine slows the elimination of digoxin and simultaneously reduces digoxin's apparent volume of distribution. As a result, serum digoxin levels may be as much as doubled. When quinidine and digoxin are coadministered, digoxin doses usually need to be reduced. Serum levels of digitoxin are also raised when quinidine is coadministered, although the effect appears to be smaller.

By a mechanism that is not understood, quinidine potentiates the anticoagulatory action of warfarin, and the anticoagulant dosage may need to be reduced.

Cytochrome P450IID6 is an enzyme critical to the metabolism of many drugs, notably including mexiletine, some phenothiazines, and most polycyclic antidepressants. Constitutional deficiency of cytochrome P450IID6 is found in less than 1% of Orientals, in about 2% of American blacks, and in about 8% of American whites. Testing with debrisoquine is sometimes used to distinguish the P450IID6-deficient "poor metabolizers" from the majority-phenotype "extensive metabolizers".

When drugs whose metabolism is P450IID6-dependent are given to poor metabolizers, the serum levels achieved are higher, sometimes much higher, than the serum levels achieved when identical doses are given to extensive metabolizers. To obtain similar clinical benefit without toxicity, doses given to poor metabolizers may need to be greatly reduced. In the case of prodrugs whose actions are actually mediated by P450IID6-produced metabolites (for example, codeine and hydrocodone, whose analgesic and antitussive effects appear to be mediated by morphine and hydromorphone, respectively), it may not be possible to achieve the desired clinical benefits in poor metabolizers.

Quinidine is not metabolized by cytochrome P450IID6, but therapeutic serum levels of quinidine inhibit the action of cytochrome P450IID6, effectively converting extensive metabolizers into poor metabolizers. Caution must be exercised whenever quinidine is prescribed together with drugs metabolized by cytochrome P450IID6.

Perhaps by competing for pathways of renal clearance, coadministration of quinidine causes an increase in serum levels of procainamide.

Serum levels of haloperidol are increased when quinidine is coadministered.

Presumably because both drugs are metabolized by cytochrome P450IIIA4, coadministration of quinidine causes variable slowing of the metabolism of nifedipine. Interactions with other dihydropyridine calcium channel blockers have not been reported, but these agents (including felodipine, nicardipine, and nimodipine) are all dependent upon P450IIIA4 for metabolism, so similar interactions with quinidine should be anticipated.

Altered pharmacodynamics of other drugs: Quinidine's anticholinergic, vasodilating, and negative inotropic actions may be additive to those of other drugs with these effects, and antagonistic to those of drugs with cholinergic, vasoconstricting, and positive inotropic effects. For example, when quinidine and verapamil are coadministered in doses that are each well tolerated as monotherapy, hypotension attributable to additive peripheral α-blockade is sometimes reported.

Quinidine potentiates the actions of depolarizing (succinylcholine, decamethonium) and non-depolarizing (d-tubocurarine, pancuronium) neuromuscular blocking agents. These phenomena are not well understood, but they are observed in animal models as well as in humans. In addition, in vitro addition of quinidine to the serum of pregnant women reduces the activity of pseudo-cholinesterase, an enzyme that is essential to the metabolism of succinylcholine.

Non-interactions of quinidine with other drugs: Quinidine has no clinically significant effect on the pharmacokinetics of diltiazem, flecainide, mephenytoin, metoprolol, propafenone, propranolol, quinine, timolol, or tocainide.

Conversely, the pharmacokinetics of quinidine are not significantly affected by caffeine, ciprofloxacin, digoxin, felodipine, omeprazole, or quinine. Quinidine's pharmacokinetics are also unaffected by cigarette smoking.

INFORMATION FOR PATIENTS

Before prescribing Quinidine Gluconate as prophylaxis against recurrence of atrial fibrillation, the physician should inform the patient of the risks and benefits to be expected (see CLINICAL PHARMACOLOGY). Discussion should include the facts:

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

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.

Nursing mothers

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.

Geriatric use

Safety and efficacy of quinidine in elderly patients have not been systematically studied.

Pediatric use

In antimalarial trials, quinidine was as safe and effective in pediatric patients as in adults. Notwithstanding the known pharmacokinetic differences between children and adults (see Pharmacokinetics and Metabolism), children in these trials received the same doses (on a mg/kg basis) as adults.

Safety and effectiveness of antiarrhythmic use in children have not been established.

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.

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.

NDC 53489-141-01

Quinidine Gluconate
Extended-Release
Tablets USP

324 mg

Rx Only
100 Tablets

SUN
PHARMA