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Quinidine (Systemic)


VA CLASSIFICATION
Primary: CV300
Secondary: AP101

Commonly used brand name(s): Apo-Quinidine; Biquin Durules; Cardioquin; Novoquinidin; Quin-Release; Quinaglute Dura-tabs; Quinate; Quinidex Extentabs.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antiarrhythmic—

antimalarial—

Indications

Accepted

Ventricular arrhythmias (treatment)—Quinidine is indicated in the treatment of recurrent, documented, life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia {01}. Quinidine should not be used to treat ventricular arrhythmias of lesser severity, such as asymptomatic ventricular premature contractions {01}.

Note: Quinidine is a class IA antiarrhythmic agent (Vaughan Williams classification) with some similarities in antiarrhythmic action to the class IC antiarrhythmic agents encainide and flecainide, and the class IA agent moricizine. In a multicenter, randomized, placebo-controlled trial called the Cardiac Arrhythmias Suppression Trial (CAST), patients with prior myocardial infarction received either encainide, flecainide, or moricizine during an open-label titration phase, and the same drug or a matching placebo for the remaining long-term phase of the trial. The objective of the trial was to determine whether suppression of asymptomatic or mildly symptomatic ventricular arrhythmias would reduce the rate of death due to arrhythmia {43} {86}.
After a mean follow-up of 10 months, the encainide and flecainide arms of the study were terminated due to an excessive mortality or nonfatal cardiac arrest rate (7.7%), compared with that seen in patients assigned to matching placebo (3%) {43}. The moricizine arm of the trial was continued in a second trial (CAST II), but this trial also was terminated early when an increase in mortality in the moricizine-treated patients occurred during the first 14-day period of the trial {45}.
Scientists have speculated that the adverse results in the CAST trials may be attributed to proarrhythmic effects of the study drugs {43} {46} {47} {86}. Because these and previous studies with class I agents to suppress ventricular arrhythmias in patients after myocardial infarction have not resulted in a decrease in mortality {45}, quinidine is generally not recommended for treating less severe ventricular arrhythmias {01}.


Atrial fibrillation or flutter (treatment)—Quinidine is indicated in the treatment of symptomatic atrial fibrillation or flutter in patients whose symptoms are not controlled by measures to reduce the rate of ventricular response {01}. When used in the treatment of atrial fibrillation or flutter, quinidine should be discontinued if sinus rhythm is not restored within a reasonable time {01}.

Atrial fibrillation or flutter (reduction of frequency of relapse)—Chronic quinidine therapy is indicated for some patients at high risk for symptomatic atrial fibrillation or flutter, such as those who have had previous episodes that are so frequent and poorly tolerated as to outweigh the risks of prophylactic therapy with quinidine {01}. Quinidine should be used only after alternative measures, such as use of other drugs to control the ventricular rate, have been found to be inadequate {01}. In patients with histories of symptomatic episodes of atrial fibrillation or flutter, the goal of therapy should be to increase the average time between episodes {01}.

Note: A meta-analysis of six clinical trials published between 1970 and 1984 found that patients treated with quinidine for the maintenance of sinus rhythm after cardioversion from chronic atrial fibrillation had a higher risk of mortality (2.9%) than patients in the control group (0.8%) {84}.


Malaria (treatment)1—Intravenous quinidine is indicated in the treatment of life-threatening Plasmodium falciparum malaria. {01}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Quinidine bisulfate: 494.56 {30}
    Quinidine gluconate: 520.58 {10}
    Quinidine sulfate: 782.96 {10}
    Quinidine polygalacturonate: 536.58 {03}

Mechanism of action/Effect:

Antiarrhythmic—Quinidine blocks open-state, inward-current sodium channels in cardiac tissues, causing a decrease in the rate and amplitude of phase 0 depolarization of the action potential {07} {08}. Because the sodium channels require a higher transmembrane potential (voltage) and longer time to recover from inactivation, the refractory period is prolonged {07} {08}. Outward-current potassium channels also are blocked, causing a prolongation of phase 3 repolarization {07} {08}. Quinidine also reduces the slope of phase 4 depolarization in Purkinje fibers, which results in decreased automaticity {29}. Although quinidine directly affects the atrioventricular (AV) node, decreasing conduction, it also has a vagolytic effect (through an anticholinergic action), which can increase conduction through the AV node {29}. On the electrocardiogram, quinidine widens the QRS complex and prolongs the QT interval {29}. In the Vaughan Williams classification of antiarrhythmics, quinidine is considered to be a Class IA antiarrhythmic {01}.

Antimalarial—Quinidine primarily kills the schizont parasite at the asexual intra-erythrocytic cycle stage of the Plasmodium falciparum malaria protozoan parasite {01}. Quinidine also kills the gametocyte parasite stages of Plasmodium malariae , Plasmodium vivax , {01} and Plasmodium ovale {87}.


Other actions/effects:

Quinidine acts as a vasodilator by blocking alpha-adrenergic receptors {01}. It also has a negative inotropic effect {01} {08}. Quinidine inhibits the action of cytochrome P450 2D6 hepatic enzyme, which can interfere with the metabolism of certain medications {01}. See Drug interactions and/or related problems section.

Absorption:

Absolute bioavailability of quinidine is about 70% or greater {15} {75}, but interpatient bioavailability can vary due to first-pass hepatic metabolism {01} {15} {75}. Food slows absorption, but does not affect the extent of absorption, of quinidine sulfate immediate-release tablets {01} or quinidine polygalacturonate tablets {88}. Food increases the rate and extent of absorption of quinidine gluconate extended-release tablets {04}.

Distribution:


Volume of distribution (Vol D):

Approximately 3 L/kg, but may be reduced in patients with congestive heart failure and increased in patients with cirrhosis {01}.


Protein binding:

High (approximately 70 to 90%) {76}.

Protein binding is mainly to alpha-1-acid glycoprotein and to albumin {01}. Total serum concentrations of quinidine may be increased when alpha-1-acid glycoprotein concentrations are increased, such as in cases of trauma, surgery, cardiac arrest, and during acute myocardial infarction {14} {76}. Protein binding may be decreased in patients with liver disease, in neonates, and in infants younger than 18 months of age {76}. Although total serum quinidine concentrations may be increased, the free fraction of the drug (the main determinant of the drug effect) may fall within a normal therapeutic range {14} {89}. In this instance, measuring the free fraction of serum quinidine concentrations (instead of total serum quinidine concentrations) may be helpful in guiding therapy {14}.

Biotransformation:

Hepatic—Quinidine undergoes oxidative metabolism in the liver by the P450 3A4 enzyme {01}. Of several metabolites, the 3-hydroxyquinidine (3HQ) has approximately half of the antiarrhythmic activity of quinidine, can exceed quinidine serum concentrations, and has a larger volume of distribution than quinidine {01}.

Half-life:


Elimination:

Range, 4 to 17 hours; average, approximately 6 hours {29}.


Time to peak concentration:


Oral:

Quinidine bisulfate, extended-release: Approximately 4 hours {30}.

Quinidine gluconate, extended-release: 3 to 5 hours {04}.

Quinidine gluconate, immediate-release: 1 to 3 hours {05}.

Quinidine polygalacturonate, immediate-release: Approximately 2 hours {03}.

Quinidine sulfate, extended-release: Approximately 6 hours {32}.

Quinidine sulfate, immediate-release: Approximately 2 hours {01}.



Intramuscular:

Less than 2 hours {02}.



Intravenous:

Immediate.


Therapeutic serum concentration

2 to 6 mcg per mL {01}; however, this range refers to total serum quinidine concentrations (both the protein-bound and free fractions) and may not be an accurate predictor of the therapeutic or toxic effects of quinidine, especially in disease states in which protein binding of quinidine is altered (see Protein binding section) {14} {89}. In such cases, measurement of the free fraction of quinidine might be helpful {14}, although there is no established reference range for the unbound concentration {53}. Therapy should be guided by individual patient response {14}.

Elimination:
    Renal—Approximately 20% of quinidine is excreted unchanged in the urine when urine pH is below 7 {01}. Urinary excretion may decrease to as little as 5% in more alkaline urine {01}. Renal elimination involves both glomerular filtration and active tubular secretion, moderated by pH-dependent tubular reabsorption {01}.


In dialysis—
        Quinidine is not adequately removed by dialysis {01}.



Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to quinine or other cinchona alkaloids may be sensitive to quinidine {05}. Quinidine should not be administered to patients who have experienced thrombocytopenic purpura with quinine {01}.

Carcinogenicity/Mutagenicity

Adequate and well-controlled studies in humans have not been done.

Pregnancy/Reproduction
Fertility—
Adequate and well-controlled studies in humans have not been done {01}.

Pregnancy—
Although adequate and well-controlled studies on the use of quinidine in pregnant women have not been done {01}, quinidine has been used during pregnancy for the treatment of cardiac arrhythmias and is considered to be the class IA drug of choice in this patient population {70}. Adverse effects that have occurred during pregnancy are mild uterine contractions, premature labor, and neonatal thrombocytopenia {70}. At toxic doses, quinidine has been reported to cause spontaneous abortion and possible cranial nerve VIII injury; however, in general, adverse effects are uncommon {70}.

FDA Pregnancy Category C {01}.

Breast-feeding

Quinidine is distributed into breast milk and appears at concentrations slightly lower than maternal serum concentrations {01}. A nursing infant's quinidine serum concentration will most likely be lower than that of the mother, although the lower level of protein binding of quinidine in a neonate may increase its risk for toxicity, even at low total serum concentrations; therefore, it is recommended that quinidine not be administered to nursing mothers {01}.

Pediatrics

The pharmacokinetics and pharmacodynamics of quinidine have not been studied extensively in the pediatric population, and use of quinidine in the treatment of cardiac arrhythmias in children is largely empirical {77} {78}. Children may require a higher dose of quinidine than adults, possibly because children have a higher rate of clearance of quinidine, which may be related to a faster metabolism {77} {78}. Additionally, children may be more tolerant to the side effects of quinidine, experiencing fewer gastrointestinal side effects, such as vomiting, anorexia, and diarrhea {78}.

In clinical trials for malaria, children received the same dose, on a mg per kg of body weight (mg/kg) basis, as adults, and quinidine was considered to be as safe and effective in children as in adults {01}.


Geriatrics


Appropriate studies on the relationship of age to the effects of quinidine have not been performed in the geriatric population; however, it has been reported that quinidine's elimination half-life is increased and total clearance is decreased in healthy elderly volunteers when compared with younger individuals {75}. Protein binding also may be slightly reduced in the elderly {75}.

Surgical

Use of quinidine during surgery can prolong the blockade effects of nondepolarizing neuromuscular blocking agents {71}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Alkalizers, urinary{01}{05} , such as:
Carbonic anhydrase inhibitors{01}
Diuretics, thiazide{01}
Sodium bicarbonate{01}    (concurrent use may reduce renal elimination of quinidine by increasing urinary pH, thereby enhancing renal reabsorption {01})


» Amiodarone{35}{36}{37}{54}{56}    (concurrent use with quinidine may have additive effects on prolongation of the QT interval, increasing the risk of cardiac proarrhythmia {01}, specifically torsades de pointes ventricular tachycardia. Additionally, concurrent use has been reported to increase serum quinidine concentrations, on average, by 32% {54}; concurrent use of the two agents is not recommended except in unusual circumstances {85}, in which case the dose of quinidine should be reduced by 30 to 50% {54})


Antacids{17}    (concurrent use may decrease the bioavailability of quinidine and may decrease renal elimination by raising urine pH; it is recommended that quinidine and antacid administration be separated by at least 2 hours {17} {89})


Anticholinergics{01}{05} (see Appendix II )    (concurrent use with quinidine may produce additive anticholinergic effects {01} {05})


» Antidepressants, tricyclic{01}{62} , such as
Amitriptyline{35}{36} or
Clomipramine{35} or
Desipramine{35} or
Doxepin{35}{36} or
Imipramine{35}{36} or
Nortriptyline{35}    (concurrent use with quinidine may have additive effects on prolongation of the QT interval, increasing the risk of cardiac proarrhythmia, specifically torsades de pointes ventricular tachycardia {01}; additionally, quinidine inhibits the action of cytochrome P450 2D6 enzyme, which possibly can reduce the metabolism of amitriptyline, clomipramine, desipramine, imipramine, and nortriptyline {01} {62})


Bretylium    (both bretylium and quinidine have alpha-adrenergic blocking activity, and concurrent use may have additive vasodilating [hypotensive] effects {01})


Cimetidine{57}{63}    (concurrent use with cimetidine has been reported to increase quinidine's elimination half-life and area under the plasma concentration–time curve [AUC] by 23% and 15%, respectively {57}; the interaction may be a result of cimetidine-induced inhibition of cytochrome P450 3A4 enzyme metabolism of quinidine {57} {63} or competition for renal tubular secretion {42})


» Digitalis glycosides{01}{16}    (concurrent use with quinidine has resulted in increased plasma digoxin concentrations, possibly due to an initial displacement of digoxin from quinidine binding sites {48} {89}, and a reduction in the renal and nonrenal clearance and volume of distribution of digoxin {16} {49} {50}; the extent of the interaction is proportional to plasma quinidine concentrations and, on average, concurrent use results in 100% increases in serum digoxin concentrations, although increases of over 300% have been reported {49} {50} {89}; concurrent use of quinidine with digitoxin has resulted in increases in serum digitoxin concentrations of 30 to 67%, the smaller increases possibly resulting from impairment of extrarenal clearance of digitoxin by quinidine {61}. Quinidine should not be administered during digitalis intoxication because the effects of the two medications, which slow AV conduction [by different mechanisms], are additive and can result in complete AV block {01})


» Erythromycin{35}{36}{60}{65}    (concurrent use with quinidine may have additive effects on QT interval prolongation, increasing the risk of cardiac proarrhythmia, specifically torsades de pointes ventricular tachycardia {35}. Increases in quinidine serum concentrations as a result of a decrease in quinidine clearance have been reported with concurrent use of erythromycin {60}; the mechanism of this interaction may be attributed either to competition for the same metabolic enzyme or to inhibition of cytochrome P450 3A4 enzyme metabolism of quinidine by metabolites of erythromycin {60} {65})


» Haloperidol{01}    (concurrent use with quinidine may have additive effects on QT interval prolongation, increasing the risk of cardiac proarrhythmia, specifically torsades de pointes ventricular tachycardia {35}; additionally, because haloperidol undergoes partial or full metabolism by cytochrome P450 2D6 and/or cytochrome P450 3A4 enzymes, serum concentrations of haloperidol may be increased as a result of inhibition of and/or competition for these enzymes by quinidine {01} {35} {62} {69})


Medications that induce metabolism by cytochrome P450 3A4 (and possibly other) hepatic enzymes{01} , such as:
Phenobarbitol{01} or
Phenytoin{01} or
Rifampin{01}    (concurrent use may increase the metabolism of quinidine {01})


Medications (or substances) that inhibit metabolism by cytochrome P450 3A4 (and possibly other) hepatic enzymes, such as:
Grapefruit juice{66}{67} or
Itraconazole{64} or
Ketoconazole{19} or
Ritonavir{31}    (concurrent use may increase serum quinidine concentrations by inhibiting its metabolism {19} {89}; concurrent use with itraconazole has resulted in 58% and 59% increases in quinidine elimination half-life and peak plasma concentrations, respectively {64}; grapefruit juice has been reported to have the potential to inhibit the in vitro metabolism of quinidine {66} {67})


» Medications that prolong the QT interval{01} , such as
Antiarrhythmic agents, other, such as
Disopyramide{01}{35} or
Ibutilide{35} or
Sotalol{35}{36}{40}
Astemizole{35}{36} or
Bepridil{35}{36} or
Chloroquine{36} or
Cisapride{35}{39} or
Clarithromycin{41} or
Diphenhydramine{35} or
Fludrocortisone{35} or
Halofantrine{36}{38} or
Indapamide{35} or
Maprotiline{35} or
Pentamidine{35} or
Pimozide{35}{36} or
Risperidone{35} or
Sparfloxacin{36} or
Tamoxifen{35} or
Thiothixene{35} or
Trimethoprim and sulfamethoxazole combination{35}    (concurrent use with quinidine may have additive effects on prolongation of the QT interval, increasing the risk of cardiac proarrhythmia {01}, specifically torsades de pointes ventricular tachycardia)


Medications that undergo full or partial hepatic metabolism by the cytochrome P450 3A4 enzyme, such as{01}
Diltiazem{20} or
Felodipine{01} or
Nicardipine{01} or
Nifedipine{01}{68} or
Nimodipine{01}    (because quinidine also undergoes hepatic metabolism by the cytochrome P450 3A4 enzyme, competition for the same enzyme may, theoretically, affect the clearance of either or both drugs {01} {60}; increases in quinidine serum concentrations have been reported with concurrent use of diltiazem {20}; inhibition of nifedipine metabolism has been reported with concurrent use of quinidine {01} {68})


Medications that undergo full or partial metabolism by the cytochrome P450 2D6 enzyme{01} , such as:
Codeine{01}{62} or
Dextromethorphan{25}{62} or
Encainide{22}{62} or
Flecainide{23}{62} or
Hydrocodone{01} or
Propafenone{24}{62}    (quinidine inhibits the action of cytochrome P450 2D6 enzyme, possibly reducing the metabolism of these drugs {01}. In the case of an active parent drug [e.g., flecainide, encainide, propafenone], plasma concentrations may be increased; in the case of an active metabolite, metabolic conversion may be inhibited [e.g., codeine, dextromethorphan, hydrocodone] {01} {22} {23} {24} {25} {79})


» Mefloquine{83}    (mefloquine has been reported to have myocardial depressant effects [by a mechanism not fully defined], resulting in sinus bradycardia, first-degree atrioventricular [AV] block, and prolongation of the QTc interval {83}; it is recommended that mefloquine not be administered concurrently with quinidine {83})


Neuromuscular blocking agents, such as:
Decamethonium{01} or
d-Tubocurarine{01} or
Pancuronium{01} or
Succinylcholine{01}    (quinidine can potentiate the blockade effects of these medications by blocking acetylcholine receptor channels and by suppressing the release of acetylcholine {01} {58})


Quinine    (concurrent use with quinidine may increase the possibility of cinchonism)


» Phenothiazines, such as
Chlorpromazine{35}{36} or
Perphenazine{62} or
Prochlorperazine{35} or
Thioridazine{35}{36}{62}    (concurrent use with quinidine may have additive effects on prolongation of the QT interval, increasing the risk of cardiac proarrhythmia, specifically torsades de pointes ventricular tachycardia {01}; additionally, quinidine inhibits the action of cytochrome P450 2D6 enzyme, possibly reducing the metabolism of these drugs {01})


» Procainamide{01}{35}{36}{55}    (concurrent use may increase serum concentrations of procainamide, possibly by competing with quinidine for shared renal clearance pathways {01} {55}; in one patient, the addition of quinidine to procainamide therapy increased serum procainamide concentrations by 70% {55}; additionally, concurrent use with quinidine may have additive effects on prolongation of the QT interval, increasing the risk of cardiac proarrhythmia, specifically torsades de pointes ventricular tachycardia {35} {36})


Propranolol{01}    (although some studies have reported increases in peak serum concentrations and decreases in the volume of distribution and total clearance of quinidine {01}, in one study, concurrent use of propranolol and quinidine resulted in no significant change in quinidine half-life, peak serum concentration, or AUC {59})


Verapamil{01}    (concurrent use may reduce hepatic clearance of quinidine and result in increased quinidine serum concentrations and half-life; additive hypotensive effects because of additive peripheral alpha-adrenergic receptor blockade also may occur {01})


Warfarin{01}{05}    (concurrent use may increase the anticoagulant effect of warfarin; a dosage adjustment of warfarin may be necessary {01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Atrioventricular (AV) block, complete{01} or
» Pacemaker-dependent conduction disturbance, idioventricular or junctional, without an artificial pacemaker{01}    (quinidine can cause further slowing of AV conduction and decrease the automaticity of latent or subsidiary pacemakers [i.e., Purkinje fibers] {01})


» Hypersensitivity to quinidine{01}
» Long-QT syndrome, pre-existing{01} or
» QT interval prolongation occurring with quinidine or other QT interval–prolonging drugs, history of{01} or
» Torsades de pointes, history of{01}    (these conditions increase the risk for development of torsades de pointes with quinidine therapy {01}; quinidine should not be administered to patients with pre-existing long-QT syndrome or a history of torsades de pointes)


» Myasthenia gravis{01} or
» Other disease states adversely affected by an anticholinergic agent{01}    (patients with myasthenia gravis may be at risk for increased paralysis with quinidine therapy {29}; other disease states that are adversely affected by anticholinergic agents may be aggravated by the anticholinergic effects of quinidine {01})


» Thrombocytopenic purpura, quinidine or quinine-induced, history of{01}    (increased risk of recurrence with quinidine therapy {01})


Risk-benefit should be considered when the following medical problems exist
» AV block, second-degree, without an artificial pacemaker{01} or
» Intraventricular conduction defects, severe, without an artificial pacemaker{01} or
» Sick sinus syndrome{01}    (quinidine can cause further slowing of AV conduction, which can result in complete AV block in patients with pre-existing second degree AV block and/or severe intraventricular conduction defects, unless an artificial pacemaker is in place {01}; quinidine can cause severe bradycardia and sinus node depression in patients with sick sinus syndrome {01})


» Bradycardia{01} or
» Electrolyte disorders (resulting from dialysis, diarrhea, diuretic therapy or use of other medications, prolonged vomiting, etc.), such as
Hypocalcemia{01} or
» Hypokalemia{01} or
Hypomagnesemia{01}    (these conditions increase the risk for development of torsades de pointes with quinidine therapy {01}; electrolyte disturbances should be corrected prior to administration of quinidine {01})


Congestive heart failure{01}    (the volume of distribution of quinidine may be reduced in patients with congestive heart failure, which can lead to an increased risk of quinidine toxicity {01}; although quinidine has negative inotropic activity, this effect does not appear to predominate in patients with severe congestive heart failure {52}; however, these patients may be especially sensitive to the hypotensive vasodilatory effects of quinidine {52})


Hepatic function impairment{01}    (plasma protein binding of quinidine is decreased and volume of distribution of quinidine is increased in patients with hepatic function impairment {01} {29} {51}; although clearance of quinidine is not affected, elimination half-life is prolonged [presumably due to the increased volume of distribution] in these patients, increasing the risk of toxicity {01})


Renal function impairment{01}    (elimination of quinidine may be decreased in patients with renal function impairment {01})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Blood pressure determinations    (blood pressure should be monitored continuously for 2 to 3 days while oral therapy is initiated and should be monitored continuously during intravenous therapy {26}; quinidine therapy should be discontinued if significant hypotension occurs {01})


» Electrocardiogram (ECG) monitoring{01}    (ECG should be monitored continuously [with frequent determinations of the QT interval] for 2 to 3 days during initiation of oral therapy and throughout intravenous administration of quinidine {26} {90})


» Potassium concentrations, serum{26}    (recommended for those patients at risk for developing hypokalemia, such as those concurrently taking diuretics {26})


Quinidine concentrations, serum{01}    (monitoring of serum quinidine concentrations should begin 24 to 48 hours after initiation of quinidine {72}, and sampling should be done 1 hour before the next dose {53}; antiarrhythmic effects usually are seen with quinidine serum concentrations between 2 and 5 mcg per mL {72}. However, this range refers to total serum quinidine concentrations [both the protein-bound and free fractions] and may not be an accurate predictor of the therapeutic or toxic effect of quinidine, especially in disease states in which protein binding of quinidine is altered [i.e., acute myocardial infarction, chronic renal failure, infection, and inflammatory arthritis] {14} {89}. In such cases, monitoring the free [or unbound] fraction of quinidine might be helpful [although there is no established reference range for the unbound concentration] {53}, but therapy should be guided by individual patient response {14}; additionally, the QTc is a better predictor of quinidine-induced ventricular arrhythmias than serum quinidine concentrations {01} {89} {90})


Malaria patients:
Blood glucose determinations and
Hydration    (malaria can be complicated by dehydration, hypoglycemia, and hyperinsulinemia and quinidine has been reported to stimulate the release of insulin, aggravating malaria-induced hypoglycemia {28}; therefore, it is recommended that hydration and blood glucose be monitored in malaria patients {28} {33}.)




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Quinidine prolongs the electrocardiographic QT interval, which can be proarrhythmic {01}. QT interval prolongation may induce torsades de pointes , a life-threatening ventricular tachycardia {01} {11}. Other electrocardiographic changes that may occur with quinidine (generally with overdosage {90}) include P wave disappearance {01} and QRS complex widening {01} {11}. Other ventricular arrhythmias that have occurred with quinidine therapy include frequent extrasystoles and ventricular tachycardia, fibrillation, and flutter {01}.

When quinidine is used to treat atrial fibrillation or flutter, the change in the atrial rate may be preceded by a reduction in the degree of atrioventricular (AV) block, causing an increase in the rate of beats conducted to the ventricles {01}. This may result in a paradoxical increase in the ventricular rate {01}. This response may be minimized if partial AV block is achieved through prior digitalization or prior administration of verapamil, diltiazem, or a beta-adrenergic blocking agent {01}.

Those indicating need for medical attention
Incidence less frequent
    
Cinchonism{42} (confusion; blurred and/or double vision; delirium; disturbed color perception; dizziness or lightheadedness; headache; noises or ringing in the ear; visual intolerance of light)
    
fever{42}
    
hepatitis{18}{42} (primarily fever, but may include abdominal pain and/or yellow eyes or skin)—an incidence of 2.2% has been reported{18}
    
hypotension{11} (dizziness; lightheadedness)
    
syncope{21} (fainting)—episodes of syncope may be attributed to ventricular arrhythmias and may occur in 1 to 8% of quinidine-treated patients{21}

Note: Symptoms of cinchonism {01} usually are signs of quinidine intoxication, but symptoms have occurred after a single dose {01}.
Quinidine-induced hepatitis usually occurs early during treatment (onset 3 to 44 days) and resolves once quinidine is discontinued {18} {42}. Although fever appears to be the distinguishing symptom of hepatitis, other symptoms may include a bleeding tendency, gastrointestinal symptoms, rash, and thrombocytopenia, suggesting a possible hypersensitivity reaction {18} {42}.
Hypotension is the result of quinidine-induced vasodilation and occurs more commonly after intravenous administration, especially with rapid infusion rates {42}.


Incidence rare
    
Blood dyscrasias, such as hemolytic anemia{01} (unusual tiredness; pale skin color), and thrombocytopenia{01} (may be seen as nosebleeds or bleeding gums)
    
skin rash{42}
    
systemic lupus erythematosus–like condition{01} (chest pain; fever; general discomfort; joint pain; joint swelling; muscle pain; skin rash)

Note: Quinidine therapy of a month or longer has been associated with a rare incidence of a condition resembling systemic lupus erythematosus {12}. Clinical symptoms may include adenopathy, arthralgias, arthritis, fever, malaise, myalgias, pericarditis with or without effusions, pleuritis with or without effusions, and skin rash {34} {12}. Clinical symptoms usually resolve within days or weeks after discontinuation of quinidine, although the resolution of laboratory value changes, such as a positive ANA titer, may take weeks or months {12} {13}. Development of a positive ANA titer does not always lead to development of clinical symptoms; therefore, screening asymptomatic patients with serial ANA titers is not recommended {13}.




Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Fatigue{01} (unusual tiredness)
    
gastrointestinal symptoms, including anorexia{42} (loss of appetite), diarrhea{01}
nausea{01}
and vomiting{01}
    
muscle weakness{42}

Note: As many as one third of patients experience diarrhea, nausea, and/or vomiting, which has resulted in discontinuation of quinidine therapy, although many patients may become tolerant to these effects {29} {42}. The occurrence of gastrointestinal adverse effects may be less frequent with administration of a sustained-release dosage form {42} or if quinidine is administered with food {30}.






Overdose
For specific information on the agents used in the management of quinidine overdose, see the following monographs:    • Charcoal, Activated (Oral-Local); and/or
   • Isoproterenol, Metaraminol , and/or Norepinephrine in Sympathomimetic Agents—Cardiovascular Use (Parenteral-Systemic) ; and/or
   • Magnesium Sulfate (Systemic)

For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute and chronic
    
Abdominal pain{42}
    
cardiac arrhythmias and conduction disturbances{42} (dizziness, faint feeling or fainting, and/or palpitations)
    
cinchonism{01}{42} (confusion; blurred and/or double vision; delirium; disturbed color perception; dizziness or lightheadedness; headache; noises or ringing in the ear; visual intolerance of light)
    
coma{42} (loss of consciousness)
    
confusion{01}
    
diarrhea{01}
    
hypotension{01} (dizziness, lightheadedness, or fainting)
    
respiratory arrest{42} (cessation of breathing)
    
seizures{42}
    
vomiting{01}

Note: Cardiac arrhythmias and conduction disturbances that have occurred with quinidine overdose include atrioventricular (AV) block, atrioventricular junctional or ventricular bradycardia, bundle branch block, depressed myocardial contractility, QRS complex widening, QT interval prolongation, sinus bradycardia, sinoatrial (SA) block, sinus tachycardia, torsades de pointes , ventricular fibrillation, ventricular tachycardia, and asystole {42}.



Treatment of overdose
Treatment should be symptomatic and supportive and may include the following:

• To decrease absorption—Although the use of gastric lavage decreased the elimination half-life of quinidine in one case report, the clinical benefit of gastric lavage has not been confirmed, and it should be used only if ingestion has occurred within 1 hour {73}. Similarly, the use of activated charcoal should be considered only if ingestion has occurred within 1 hour {74}.


• To enhance elimination—Medications that delay the elimination of quinidine, such as urinary alkalizers (i.e., carbonic-anhydrase inhibitors, sodium bicarbonate, thiazide diuretics), should be withdrawn, if possible, to avoid prolonging the half-life of quinidine {01}. However, attempting to facilitate quinidine elimination by acidifying the urine is not recommended and is considered hazardous {01}.


Specific treatment:

• For torsades de pointes ventricular tachycardia, quinidine should be withdrawn and cardioversion or overdrive pacing should be performed immediately {01}. Further quinidine therapy should be guided by the length of the QT interval corrected for heart rate (QTc) {01}. To prevent the recurrence of torsades de pointes , sustained overdrive pacing or administration of isoproterenol may be used {01}. If the postcardioversion QTc interval is prolonged, other factors that might contribute to QTc prolongation, such as hypokalemia, hypomagnesemia, and hypocalcemia, should be corrected {01}. Intravenous magnesium sulfate also has been shown to be effective in the treatment of torsades de pointes in the absence of hypomagnesemia {80} {81}.


• For hypotension due to quinidine-induced alpha-adrenergic receptor blockade {01} (vasodilation) and not to an arrhythmia, treatment may involve Trendelenburg positioning and volume repletion (saline infusion) {01}. Other procedures may involve increasing peripheral vascular resistance by using vasopressors, such as norepinephrine or metaraminol {01} {42}.


Monitoring: The QTc interval is the best predictor of quinidine-induced ventricular arrhythmias, although serum quinidine concentrations can be monitored as well {01}.

Supportive care: Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Quinidine (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to quinidine

Pregnancy—Quinidine has caused mild uterine contractions, premature labor, and neonatal thrombocytopenia





Breast-feeding—Quinidine is distributed into breast milk; it is not recommended in nursing mothers because of risk of toxicity in the neonate
Other medications, especially amiodarone, digitalis glycosides, and medications that cause QT interval prolongation, such as amitriptyline, astemizole, bepridil, chloroquine, chlorpromazine, cisapride, clarithromycin, clomipramine, desipramine, diphenhydramine, disopyramide, doxepin, erythromycin, fludrocortisone, halofantrine, haloperidol, ibutilide, imipramine, indapamide, maprotiline, mefloquine, nortriptyline, pentamidine, perphenazine, pimozide, procainamide, prochlorperazine, resperidone, sotalol, sparfloxacin, tamoxifen, thioridazine, thiothixene, and trimethoprim and sulfamethoxazole combination
Other medical problems, especially bradycardia; complete atrioventricular (AV) block; electrolyte disorders, such as hypocalcemia, hypokalemia, and hypomagnesemia; history of QTc interval lengthening occurring with quinidine or other drugs; history of quinidine- or quinine-induced thrombocytopenic purpura; history of torsades de pointes ; idioventricular or junctional pacemaker-dependent conduction disturbance without an artificial pacemaker; myasthenia gravis or other disease state adversely affected by an anticholinergic agent; pre-existing long-QT syndrome; sick sinus syndrome; second degree AV block without an artificial pacemaker; or severe intraventricular conduction defects without an artificial pacemaker

Proper use of this medication
» Compliance with therapy; taking exactly as directed; not taking more or less medication than is prescribed

Taking medication with food may lessen gastrointestinal irritation {30}

Proper administration of extended-release tablets:Quinidine gluconate: Tablets may be broken in half, but should not be crushed or chewed {04}

Quinidine bisulfate and quinidine sulfate: Tablets should not be broken, crushed, or chewed {30}. Patients taking quinidine bisulfate ( Biquin Durules) may notice a leftover empty tablet shell in the stool

» Proper dosing
Missed dose: Taking as soon as possible if remembered within 2 hours; if remembered later, not taking at all; not doubling doses

» Proper storage

Precautions while using this medication
Seeing the physician regularly to check progress of therapy

Checking with physician before discontinuing medication

Caution if any kind of surgery (including dental surgery) or emergency treatment is required

Possible dizziness or lightheadedness: Caution when getting up suddenly from a lying or sitting position

» Possible fainting: Caution when driving or doing things that may be dangerous if fainting occurs

» Checking with physician if fainting or other side/adverse effects occur

Carrying medical identification card


Side/adverse effects
Signs of potential side effects, especially signs of cinchonism, such as confusion, blurred and/or double vision, delirium, disturbed color perception, dizziness or lightheadedness, headache, noises or ringing in the ear, and visual intolerance of light; fever; hepatitis; hypotension; syncope; blood dyscrasias; skin rash; and systemic lupus erythematosus–like condition


General Dosing Information
The dosage of quinidine should be adjusted to meet the individual requirements of each patient on the basis of clinical response and may vary considerably depending upon the general condition and cardiovascular state of the patient {01}.

Patients with symptomatic atrial fibrillation or flutter should be treated with quinidine only after control of the ventricular rate with agents such as digitalis or beta-adrenergic blocking agents has failed to provide satisfactory control of symptoms {01}.

When used to convert atrial fibrillation or flutter to normal sinus rhythm, quinidine should be discontinued if sinus rhythm is not restored within a reasonable time {01}.

For treatment of patients with life-threatening ventricular arrhythmias, quinidine therapy should be guided by the results of programmed electrical stimulation and/or Holter monitoring with exercise {01}.

Quinidine therapy should be initiated in a hospital, and the patient should be monitored for 2 or 3 days {26}. Dosage adjustments of quinidine in patients at risk for toxicity, such as those with structural heart disease, also should be performed in a hospital {01}.


Oral Dosage Forms

QUINIDINE BISULFATE EXTENDED-RELEASE TABLETS

Note: 250 mg of quinidine bisulfate is equivalent to 200 mg of quinidine sulfate {30} or 166 mg quinidine base {32}.


Usual adult dose
Ventricular arrhythmias
Oral, initially, a test dose of 200 mg of quinidine sulfate, administered in the morning to rule out hypersensitivity, followed by 500 mg quinidine bisulfate administered in the evening {30}. Beginning the following day, 500 to 750 mg of quinidine bisulfate every twelve hours {30}. The usual maintenance dose is 500 mg to 1.25 grams of quinidine bisulfate every morning and evening {30}.

Atrial fibrillation or flutter, prior to scheduled conversion
The above described regimen should be given, beginning two days before the scheduled cardioversion {30}. The starting dose for maintenance after cardioversion is 750 mg of quinidine bisulfate every morning and evening {30}.


Usual adult prescribing limits
2.5 grams of quinidine bisulfate daily {30}.

Usual pediatric dose
Safety and efficacy have not been established.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


0.25 gram (equivalent to 0.2 gram of quinidine sulfate) (Rx) [Biquin Durules]

Packaging and storage:
Store between 15 and 30 ºC (59 and 86 ºF), in a well-closed container, and protect from light {30}.

Auxiliary labeling:
   • Do not take other medicines without advice from your doctor.
   • Swallow tablets whole {30}. Do not break or chew {30}.


QUINIDINE GLUCONATE TABLETS

Note: 325 mg of quinidine gluconate is approximately equivalent to 202 mg of quinidine base {05}.


Usual adult dose
Atrial fibrillation or flutter (treatment)
Optimal dosing regimens for the conversion of atrial fibrillation or flutter to normal sinus rhythm have not been established. The following regimen has been used to treat atrial fibrillation: Oral, 325 mg of quinidine gluconate every two or three hours for five to eight doses, gradually increasing the dose daily until sinus rhythm is restored or toxic effects occur {05}. Maintenance doses range from 325 mg to 488 mg of quinidine gluconate three or four times a day {05}.

If at any point during administration of quinidine the QRS complex widens to 130% of its pretreatment duration; the QT interval corrected for heart rate (QTc) widens to 130% of its pretreatment duration and is then longer than 500 milliseconds (ms); P waves disappear; or the patient develops significant tachycardia, symptomatic bradycardia, or hypotension, then quinidine should be discontinued, and other means of conversion, such as direct-current cardioversion, should be considered {04}.

Ventricular arrhythmias
Dosing regimens for the treatment of ventricular arrhythmias have not been established.


Usual adult prescribing limits
6500 mg of quinidine gluconate daily {05}.

Usual pediatric dose
[Atrial fibrillation or flutter or ventricular arrhythmias]1
Initial doses should be approximately 30 to 40 mg of quinidine gluconate per kg of body weight per day or 550 to 800 mg of quinidine gluconate per square meter of body surface area per day {77}. Doses of up to 75 mg of quinidine gluconate per kg of body weight per day or 1500 mg of quinidine gluconate per square meter of body surface area per day may be necessary in some children {77}.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


325 mg (Rx) [Quinate]

Packaging and storage:
Store below 40 ºC (104 ºF), preferably between 15 and 30 ºC (59 and 86 ºF), in a well-closed container, unless otherwise specified by manufacturer. Protect from light.

Auxiliary labeling:
   • Do not take other medicines without advice from your doctor.


QUINIDINE GLUCONATE EXTENDED-RELEASE TABLETS

Note: 324 mg of quinidine gluconate is approximately equivalent to 202 mg of quinidine base {05}.


Usual adult dose
Atrial fibrillation or flutter (treatment)
An optimal quinidine dosing regimen for the conversion of atrial fibrillation or flutter to normal sinus rhythm has not been established. The following regimens have been used:

Oral, 648 mg of quinidine gluconate every eight hours {04}. If conversion to normal sinus rhythm does not occur after three or four doses, the dose may be carefully increased {04}.

Alternative regimen: Oral, 324 mg of quinidine gluconate every eight hours for two days; 648 mg of quinidine gluconate every twelve hours for two days, then 648 mg of quinidine gluconate every eight hours for up to four days {04}. If a lower dose is the highest tolerated, it may be used during the last four-day dosing period {04}.

If at any point during administration of quinidine the QRS complex widens to 130% of its pretreatment duration; the QT interval corrected for heart rate (QTc) widens to 130% of its pretreatment duration and is then longer than 500 milliseconds (ms); P waves disappear; or the patient develops significant tachycardia, symptomatic bradycardia, or hypotension, then quinidine should be discontinued, and other means of conversion, such as direct-current cardioversion, should be considered {04}.

Atrial fibrillation or flutter (reduction of frequency of relapse)
Oral, 324 mg of quinidine gluconate every eight or twelve hours {04}. If the dose is well tolerated, quinidine serum concentrations are well within the therapeutic range, and the average time between arrhythmic episodes has not been satisfactorily prolonged, the dose may be carefully increased {04}. If the QRS complex widens to 130% of its pretreatment duration; the QTc interval widens to 130% of its pretreatment duration and is then longer than 500 milliseconds (ms); P waves disappear; or the patient develops significant tachycardia, symptomatic bradycardia, or hypotension, the total daily dose should be reduced {04}.

Ventricular arrhythmias
Quinidine dosing regimens for the suppression of life-threatening ventricular arrhythmias have not been adequately studied {04}. Regimens that have been used are similar to the regimen for the reduction of frequency of relapse of atrial fibrillation or flutter stated above {04}.


Usual adult prescribing limits
1944 mg of quinidine gluconate daily {04}.

Usual pediatric dose
[Atrial fibrillation or flutter or ventricular arrhythmias]1
Initial doses should be approximately 30 to 40 mg of quinidine gluconate per kg of body weight per day or 550 to 800 mg of quinidine gluconate per square meter of body surface area per day {77}. Doses of up to 75 mg of quinidine gluconate per kg of body weight per day or 1500 mg of quinidine gluconate per square meter of body surface area per day may be necessary in some children {77}.


Strength(s) usually available
U.S.—


324 mg (Rx) [Quinaglute Dura-tabs] [Quin-Release][Generic]

Canada—


324 mg (Rx) [Quinaglute Dura-tabs][Generic]

Note: Quinaglute tablets may be broken in half for dosage titration but should not be crushed or chewed {04}.


Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer. Protect from light.

Auxiliary labeling:
   • Swallow tablet whole. Do not crush or chew {04}.
   • Do not take other medicines without advice from your doctor.


QUINIDINE POLYGALACTURONATE TABLETS

Note: 275 mg of quinidine polygalacturonate is equivalent to 200 mg of quinidine sulfate or 166 mg of quinidine base {03}.


Usual adult dose
Atrial fibrillation or flutter (treatment)
An optimal quinidine dosing regimen for the conversion of atrial fibrillation or flutter to normal sinus rhythm has not been established. The following regimen has been used: Oral, 550 mg of quinidine polygalacturonate every six hours {03}. If conversion to normal sinus rhythm has not occurred after four or five doses, the dose may be carefully increased {03}. If at any time during administration of quinidine the QRS complex widens to 130% of its pretreatment duration; the QTc interval widens to 130% of its pretreatment duration and is then longer than 500 milliseconds (ms); P waves disappear; or the patient develops significant tachycardia, symptomatic bradycardia, or hypotension, then quinidine should be discontinued and other means of conversion, such as direct-current cardioversion, should be considered {03}.

Atrial fibrillation or flutter (reduction of frequency of relapse)
Oral, 275 mg of quinidine polygalacturonate every six to eight hours {03}. If the dose is well tolerated, quinidine serum concentrations are well within the therapeutic range, and the time between episodes has not been satisfactorily prolonged, the dose may be carefully increased {03}. If the QRS complex widens to 130% of its pretreatment duration; the QTc interval widens to 130% of its pretreatment duration and is then longer than 500 milliseconds (ms); P waves disappear; or the patient develops significant tachycardia, symptomatic bradycardia, or hypotension, the total daily dose should be reduced {03}.

Ventricular arrhythmias
Quinidine dosing regimens for the suppression of life-threatening ventricular arrhythmias have not been adequately studied {04}. Regimens that have been used are similar to the regimen for the reduction of frequency of relapse of atrial fibrillation or flutter stated above {04}. Where possible, therapy should be guided by the results of programmed electrical stimulation and/or Holter monitoring with exercise {88}.


Usual pediatric dose
Atrial fibrillation or flutter or ventricular arrhythmias
Safety and efficacy have not been established.


Strength(s) usually available
U.S.—


275 mg (equivalent to 200 mg of quinidine sulfate) (Rx) [Cardioquin]

Canada—


275 mg (equivalent to 200 mg of quinidine sulfate) (Rx) [Cardioquin]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • Do not take other medicines without advice from your doctor.


QUINIDINE SULFATE TABLETS USP

Note: 200 mg of quinidine sulfate is equivalent to 166 mg of quinidine base {32}.


Usual adult dose
Atrial fibrillation or flutter (treatment)
An optimal quinidine dosing regimen for the treatment of atrial fibrillation or flutter has not been established {01}. The following regimen has been used: Oral, 400 mg of quinidine sulfate every six hours {01}. If conversion to normal sinus rhythm does not occur after four or five doses, the dose may be carefully increased {01}. If at any point during administration the QRS complex widens to 130% of its pretreatment duration; the QTc interval widens to 130% of its pretreatment duration and is then longer than 500 milliseconds (ms); P waves disappear; or the patient develops significant tachycardia, symptomatic bradycardia, or hypotension, then quinidine should be discontinued, and other means of conversion, such as direct-current cardioversion, should be considered {01}.

Atrial fibrillation or flutter (reduction of frequency of relapse)
Oral, 200 mg of quinidine sulfate every six hours {01}. If the dose is well tolerated, quinidine serum concentrations are well within the therapeutic range, and the time between episodes has not been satisfactorily prolonged, the dose may be carefully increased {01}. If the QRS complex widens to 130% of its pretreatment duration; the QTc interval widens to 130% of its pretreatment duration and is then longer than 500 milliseconds (ms); P waves disappear; or the patient develops significant tachycardia, symptomatic bradycardia, or hypotension, the total daily dose should be reduced {01}.

Ventricular arrhythmias
Quinidine dosing regimens for the suppression of life-threatening ventricular arrhythmias have not been adequately studied {01}. Regimens that have been used are similar to the regimen for the reduction of frequency of relapse of atrial fibrillation or flutter stated above {01}.


Usual pediatric dose
[Atrial fibrillation or flutter or ventricular arrhythmias]1
Initial doses should be approximately 20 to 30 mg of quinidine sulfate per kg of body weight per day or 400 to 600 mg of quinidine sulfate per square meter of body surface area per day {77}. Doses of up to 60 mg of quinidine sulfate per kg of body weight per day or 1100 mg of quinidine sulfate per square meter of body surface area per day may be necessary in some children {77}.


Strength(s) usually available
U.S.—


200 mg (Rx)[Generic]


300 mg (Rx)[Generic]

Canada—


200 mg (Rx) [Apo-Quinidine] [Novoquinidin][Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed, light-resistant container.

Auxiliary labeling:
   • Do not take other medicines without advice from your doctor.


QUINIDINE SULFATE EXTENDED-RELEASE TABLETS USP

Note: 300 mg of quinidine sulfate is equivalent to 249 mg of quinidine base {32}.


Usual adult dose
Atrial fibrillation or flutter (treatment)
An optimal quinidine dosing regimen for the treatment of atrial fibrillation or flutter has not been established {32}. The following regimen has been used: Oral, 300 mg of quinidine sulfate every eight to twelve hours {32}. If this regimen is well tolerated, if quinidine serum concentrations are still well within the therapeutic range, and if this regimen has not resulted in conversion, the dose may be cautiously increased {32}. If at any point during administration the QRS complex widens to 130% of its pretreatment duration; the QTc interval widens to 130% of its pretreatment duration and is then longer than 500 milliseconds (ms); P waves disappear; or the patient develops significant tachycardia, symptomatic bradycardia, or hypotension, then quinidine should be discontinued, and other means of conversion, such as direct-current cardioversion, should be considered {32}.

Atrial fibrillation or flutter (reduction of frequency of relapse)
Oral, 300 mg of quinidine sulfate every eight to twelve hours {32}. If the dose is well tolerated, quinidine serum concentrations are well within the therapeutic range, and the time between episodes has not been satisfactorily prolonged, the dose may be carefully increased {32}. If the QRS complex widens to 130% of its pretreatment duration; the QTc interval widens to 130% of its pretreatment duration and is then longer than 500 milliseconds (ms); P waves disappear; or the patient develops significant tachycardia, symptomatic bradycardia, or hypotension, the total daily dose should be reduced {32}.

Ventricular arrhythmias
Quinidine dosing regimens for the suppression of life-threatening ventricular arrhythmias have not been adequately studied {32}. Regimens that have been used are similar to the regimen for the reduction of frequency of relapse of atrial fibrillation or flutter stated above {32}.


Usual pediatric dose
[Atrial fibrillation or flutter or ventricular arrhythmias]1
Initial doses should be approximately 20 to 30 mg of quinidine sulfate per kg of body weight per day or 400 to 600 mg of quinidine sulfate per square meter of body surface area per day {77}. Doses of up to 60 mg of quinidine sulfate per kg of body weight per day or 1100 mg of quinidine sulfate per square meter of body surface area per day may be necessary in some children {77}.


Strength(s) usually available
U.S.—


300 mg (Rx) [Quinidex Extentabs]

Canada—


300 mg (Rx) [Quinidex Extentabs]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed, light-resistant container.

Auxiliary labeling:
   • Swallow tablets whole. Do not break or chew.
   • Do not take other medicines without advice from your doctor.



Parenteral Dosage Forms

QUINIDINE GLUCONATE INJECTION USP

Note: An overly rapid infusion rate of quinidine has been associated with nausea, vomiting, peripheral vascular collapse, and severe hypotension {02} {11} {82}. If quinidine is to be administered intravenously, patients should be closely monitored with continuous electrocardiographic and blood pressure measurements {11} {82}. Use of quinidine injection by the intramuscular route is not recommended because absorption of quinidine from muscle is erratic and quinidine may cause local irritation and/or muscle necrosis {11} {29}.
800 mg of quinidine gluconate is equivalent to 500 mg of quinidine base {02}.


Usual adult dose
Atrial fibrillation or flutter (treatment)
Intravenous infusion, 800 mg of quinidine gluconate diluted with 5% Dextrose Injection USP to a total volume of 50 mL, administered slowly, under the control of a volumetric pump, at a rate no faster than 0.25 mg per kg of body weight per minute (no faster than 1 mL per kg per hour) with continuous electrocardiogram (ECG) and blood pressure monitoring {02}. Most arrhythmias that will respond to intravenous quinidine will respond to a total dose of less than 5 mg per kg of body weight, but some patients may require as much as 10 mg per kg of body weight {02}. If conversion to sinus rhythm has not been achieved after infusion of 10 mg per kg of body weight, the infusion should be discontinued and other means of conversion should be considered {02}.

During the first few minutes of administration, the patient should be monitored closely for hypersensitivity or idiosyncratic reactions {02}. The infusion should be discontinued as soon as sinus rhythm is restored {02}. If at any point during administration the QRS complex widens to 130% of its pretreatment duration; the QTc interval widens to 130% of its pretreatment duration and is then longer than 500 milliseconds (ms); P waves disappear; or the patient develops significant tachycardia, symptomatic bradycardia, or hypotension, then quinidine should be discontinued {02}.

Ventricular arrhythmias
Quinidine dosing regimens for the suppression of life-threatening ventricular arrhythmias have not been adequately studied but are similar to the regimen for the treatment of symptomatic atrial fibrillation or flutter {02}.

Malaria

Note: Both the intermittent and the continuous regimens have been shown to be effective, with or without concurrent exchange transfusion {02}; however, the continuous intravenous infusion may be associated with fewer side effects, possibly because high peak serum concentrations causing hypotension and cardiotoxicity can be avoided {09}.
Malaria can be complicated by dehydration, hypoglycemia, and hyperinsulinemia {28} {33}. Quinidine has been reported to stimulate the release of insulin, aggravating malaria-induced hypoglycemia {28}. It is recommended that hydration and blood glucose be monitored in malaria patients {28}.



Intravenous infusion, intermittent:
Initially, 24 mg per kg of body weight of quinidine gluconate (15 mg per kg of body weight of quinidine base) in a volume of 250 mL of 0.9% sodium chloride or 5% dextrose infused over four hours {02} {87}. Starting eight hours after the beginning of the initial dose, 12 mg per kg of body weight of quinidine gluconate (7.5 mg per kg of body weight of quinidine base) infused over four hours every eight hours {02}. This regimen should be continued for three to seven days (depending on the location in which the malaria was acquired, e.g., seven days in southeast Asia), except in patients able to swallow {02} {87}. For these patients, quinidine maintenance infusions may be discontinued and oral therapy used at approximately the same daily dose of quinidine, using 300-mg tablets of quinidine sulfate {02}.



Intravenous infusion, continuous:
Initially, 10 mg per kg of body weight of quinidine gluconate (6.25 mg per kg of body weight of quinidine base) in approximately 5 mL per kg of 0.9% sodium chloride or 5% dextrose, infused over one to two hours {02} {87}. This dose is followed by a maintenance infusion of 20 mcg (0.02 mg) per kg of body weight of quinidine gluconate per minute (12.5 mcg per kg of body weight of quinidine base per minute) {02}. In patients able to swallow, the maintenance infusion may be discontinued and a daily amount of oral quinine sulfate, to provide approximately as much daily quinine base as the patient had been receiving of quinidine base, administered every eight hours {02}. The intravenous quinidine or oral quinine therapy should be continued for three to seven days (depending on the location in which the infection was acquired, e.g., seven days in southeast Asia) {02} {87}.

During or {87} after completion of intravenous quinidine or oral quinine therapy, adult patients able to swallow should be administered tetracycline 250 mg four times a day for seven days, or sulfadoxine and pyrimethamine combination ( Fansidar) as a single 1500 mg/75 mg dose {02} {87}. Patients unable to swallow should be administered intravenous doxycycline hyclate, 100 mg, two times a day for seven days {02}. In clinical studies, most patients under this regimen also underwent exchange transfusion {02}.


Note: The patient should undergo continuous ECG and blood pressure monitoring during intravenous quinidine administration {28}. Quinidine infusion should be slowed if quinidine serum concentrations are greater than 6 mcg per mL, if the QT interval is greater than 0.6 second, or if the QRS complex widens to more than 25% beyond baseline {28}.



Usual adult prescribing limits
0.25 mg per kg per minute {02}.

Usual pediatric dose
Malaria
In clinical studies for malaria, small children have been administered the adult dose of the continuous intravenous infusion without a dosage adjustment {02}. See Intravenous infusion, continuous , above.


Strength(s) usually available
U.S.—


80 mg per mL (Rx)[Generic]

Canada—


80 mg per mL (Rx)[Generic]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F) {02}

A solution diluted with 5% dextrose may be stored for up to 24 hours at room temperature or for up to 48 hours at 4 °C (39 °F) {02}.

Preparation of dosage form:
It is recommended that the length of PVC tubing used to administer quinidine be minimized to avoid loss of the medicine {02}. In one study, a length of 112 inches of tubing resulted in a 30% loss, whereas a length of 12 inches resulted in a loss of only 3% {02}.


QUINIDINE SULFATE INJECTION

Usual adult dose
Atrial fibrillation or flutter (treatment)
An initial test dose of 95 mg of quinidine sulfate given intramuscularly is recommended, followed by 190 to 380 mg of quinidine sulfate administered every two to four hours, up to a total dose of 3 grams of quinidine sulfate daily {06}.


Usual adult prescribing limits
3 grams of quinidine sulfate daily {06}.

Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


190 mg per mL (Rx)[Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing. Protect from light.



Revised: 5/26/1999



References
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  1. Panel comment, 1/99.
  1. Panel comment, 1/99.
  1. Manufacturer comment, 1/99.
  1. Panel comment, 1/99.
  1. Panel comment, 1/99.
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