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Quinidine Sulfate

Pronunciation

Class: Class Ia Antiarrhythmics
Note: This monograph also contains information on Quinidine Gluconate
VA Class: CV300
CAS Number: 7054-25-3

Warning(s)

  • Mortality
  • In many antiarrhythmic drug trials for non-life-threatening arrhythmias, active antiarrhythmic drug therapy was associated with increased mortality.163 167 168 169 170

  • Risk associated with antiarrhythmic drug therapy probably is greatest in patients with structural heart disease.163 167 168 169 170

  • A meta-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

  • A meta-analysis in patients with various non-life-threatening ventricular arrhythmias showed mortality associated with quinidine was consistently greater than that associated with various other antiarrhythmic agents (i.e., flecainide, mexiletine, propafenone, tocainide).163 167 168 169 170

Introduction

Antiarrhythmic agent (class IA); antimalarial.119 160 163 167 168 169 170

Uses for Quinidine Sulfate

Comparably effective to procainamide for atrial or ventricular arrhythmias; choice based on pharmacokinetics and adverse effect profile.b

Supraventricular Tachyarrhythmias

Used principally for prophylactic therapy to maintain normal sinus rhythm after conversion of atrial fibrillation and/or flutter by other means.b

Abnormal ventricular rate and CHF should first be controlled by administration of digoxin.b Electrical cardioversion usually is considered treatment of choice for conversion of atrial fibrillation or flutter.b

Prevention of recurrence of atrial fibrillation or flutter is controversial because mortality may increase despite recurrence suppression.b

May maintain normal sinus rhythm for long periods in recent onset of atrial fibrillation or flutter without CHF, atrial enlargement, or left ventricular hypertrophy, but long-standing atrial fibrillation is likely to recur even with quinidine maintenance therapy.b

Generally, quinidine should not be used prophylactically for atrial fibrillation if ventricular rate is adequately controlled by digoxin and patient is asymptomatic.b

Treatment of paroxysmal atrial tachycardia or paroxysmal AV junctional rhythm.b

Atrial Premature Complexes

Treatment of atrial premature complexes; however, these arrhythmias usually are treated with digoxin.b

Ventricular Premature Complexes (VPCs)

Treatment of VPCs; however, parenteral lidocaine is considered drug of choice because quinidine can decrease myocardial contractility.b

Like other antiarrhythmic drugs, not shown to decrease mortality rate in VPCs associated with AMI.b

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Avoid in treatment of asymptomatic VPCs.b

Not for treatment of cardiac glycoside-induced ventricular arrhythmias.b

VT

Treatment of paroxysmal VT that is not associated with complete heart block; however, treatment with cardioversion or lidocaine usually is preferred.b

Suppression and prevention of recurrent ventricular arrhythmias (e.g., sustained VT) that in the judgment of the clinician are life-threatening.b

Because of arrhythmogenic potential and lack of evidence for improved survival for class I antiarrhythmic agents,146 147 not recommended for less severe VTs; avoid treatment in asymptomatic VPCs.b

Malaria

Treatment of severe malaria caused by Plasmodium falciparum or other Plasmodium species.102 104 105 119 122 124 126 134 142 143 144 153

Severe malaria usually caused by P. falciparum;143 144 P. knowlesi also can cause severe disease.143 Can be rapidly progressive and fatal (most deaths occur within first 24–48 hours of illness);143 initial aggressive treatment with a parenteral antimalarial regimen indicated as soon as possible after diagnosis (regardless of Plasmodium species involved) and whenever suspected based on possible exposure and symptoms.143 144

For initial treatment of severe malaria in adults or children, CDC recommends a regimen of IV quinidine gluconate in conjunction with doxycycline, tetracycline, or clindamycin (oral or IV as tolerated).143 144 After at least 24 hours and when parasitemia is reduced to <1% and an oral regimen can be tolerated, IV quinidine gluconate can be discontinued and oral quinine sulfate initiated to complete 7 or 3 days of total quinidine and quinine therapy as determined by geographic origin of infecting parasite (7 days if acquired in Southeast Asia or 3 days if acquired elsewhere).143 144 Oral antimalarials not recommended for initial treatment of severe malaria.143

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.142 143 148 153 (See Availability for Use in Treatment of Severe Malaria under Cautions.)

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 investigational new drug (IND) protocol for initial treatment of severe malaria.143 144 171 172 WHO recommends IV artesunate as the drug of choice for treatment of severe malaria.161

Although oral quinidine sulfate has been used for treatment of malaria,167 170 including uncomplicated malaria caused by multidrug-resistant P. falciparum,102 104 108 109 110 112 oral quinine sulfate is not included in CDC recommendations for treatment of uncomplicated or severe P. falciparum malaria.143 144

Assistance with diagnosis or treatment of malaria or assistance obtaining IV quinidine gluconate or IV artesunate for treatment of severe malaria is available by contacting CDC Malaria Hotline at 770-488-7788 or 855-856-4713 from 9:00 a.m. to 5:00 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after hours and on weekends and holidays.143 144 171 172

Quinidine Sulfate Dosage and Administration

General

Arrhythmias

  • Initiate quinidine or adjust quinidine dosage in a setting where facilities and personnel for patient monitoring and resuscitation are continuously available, especially if used in patients with known structural heart disease or other risk factors for toxicity.163 167 168 169 170

  • ECG monitoring of cardiac function and determination of plasma concentrations are recommended, especially when given IV or when >2 g is administered orally daily, and in patients with an increased risk of adverse reactions to quinidine (e.g., severe heart disease, hypotension, hepatic or renal disease).b

  • Use for conversion of atrial fibrillation/flutter only after alternative measures (e.g., use of other drugs to control ventricular rate) have been inadequate.163 167 168 169 170 Discontinue quinidine if sinus rhythm is not restored within a reasonable amount of time.119 163 167 168 169 170

  • Discontinue quinidine and consider other means of conversion if QRS complex widens to 130% of its pretreatment duration, QTc interval widens to 130% of its pretreatment duration and is >500 milliseconds, P waves disappear, or patient develops clinically important tachycardia, symptomatic bradycardia, or hypotension.119 163 167 168 169 170

Malaria

  • Initiate IV quinidine gluconate regimen as soon as possible after severe malaria diagnosed (regardless of Plasmodium species involved) and whenever suspected based on possible exposure and symptoms.143 144

  • CDC and others recommend IV quinidine gluconate regimen be administered in an intensive care facility with close monitoring.111 122 123 124 125 126 134 141 143 153

  • Monitor BP, plasma quinidine concentrations, and ECG closely and monitor blood glucose periodically in patients receiving quinidine for treatment of malaria; adjust dosage accordingly.102 104 111 134 141 143 144

  • Because most deaths from severe malaria occur within first 24–48 hours of illness, an initial IV loading dose usually used to rapidly provide therapeutic plasma concentrations.143 144 Do not use a loading dose if patient received >40 mg/kg of quinine in the previous 48 hours or received mefloquine in the previous 12 hours.143

  • Calculate loading dose and infusion rate carefully to prevent acute cardiac events.153 Consider that risk of serious ventricular arrhythmias associated with quinidine is increased by bradycardia, hypokalemia, hypomagnesemia, and concomitant use of drugs that can prolong QT interval (e.g., halofantrine [an antimalarial drug not commercially available in US], mefloquine, quinine).134 143 153

  • CDC recommends consultation with a cardiologist and a clinician with experience in treating malaria.143 144 153 A cardiologist may be helpful if attempting to resume IV infusion of quinidine gluconate in patients who develop prolongation of QT interval or hypotension during treatment.153

Administration

Administer quinidine sulfate orally.163 167 Administer quinidine gluconate orally168 169 or by IV infusion.119

IM administration of quinidine gluconate is not recommended because absorption may vary depending on patient’s peripheral perfusion.119

Oral Administration

Administer quinidine sulfate orally as conventional167 170 or extended-release tablets.163

Administer quinidine gluconate orally as extended-release tablets.168 169

May be administered with food or antacids to decrease adverse GI effects.b Avoid grapefruit juice.156 163 168 169 (See Specific Drugs and Foods under Interactions.)

To determine possible idiosyncrasy to quinidine, administer a test dose of 200 mg of quinidine sulfate orally several hours before initiating full dosage.b For children, the test dose for idiosyncrasy is 2 mg/kg (up to 200 mg) of quinidine sulfate orally.164 b

Extended-release Tablets

Used principally for maintenance therapy in the management of arrhythmias.b

Quinidine gluconate extended-release tablets may be broken in half in order to titrate dosage; however, do not chew or crush.168 169

IV Administration

For solution and drug compatibility, see Compatibility under Stability.

Arrhythmias: Administer by IV infusion.119

Malaria: Administer by continuous or intermittent IV infusion.102 104 111 119 122 123 124 125 134 143 144

Dilution

Arrhythmias: Dilute contents of multiple-dose vial containing 800 mg of quinidine gluconate (10 mL of 80-mg/mL injection) in 40 mL of 5% dextrose injection to provide solution containing 16 mg/mL.119

Malaria (continuous IV infusion regimen): Dilute loading dose of 6.25 mg/kg of quinidine (10 mg/kg of quinidine gluconate)119 134 141 143 153 in approximately 5 mL/kg of 0.9% sodium chloride injection.119

Malaria (intermittent IV infusion regimen): Dilute loading dose of 15 mg/kg of quinidine (24 mg/kg of quinidine gluconate)119 143 153 in 250 mL of 0.9% sodium chloride injection.119

Rate of Administration

Minimize length of IV tubing because of quinidine adsorption to PVC tubing.119 (See Compatibility under Stability.)

Overly rapid IV administration can cause potentially severe cardiovascular effects.119 (See IV Administration under Cautions.)

Arrhythmias: Up to 0.25 mg/kg per minute (i.e., about 1 mL/kg per hour of 16-mg/mL dilution).119

Malaria (continuous IV infusion regimen): Give loading dose of 6.25 mg/kg of quinidine (10 mg/kg of quinidine gluconate) by IV infusion over 1–2 hours, followed by continuous IV infusions given at a rate of 12.5 mcg/kg of quinidine per minute (20 mcg/kg of quinidine gluconate per minute) for at least 24 hours.119 134 143 153 Decrease infusion rate or interrupt flow if corrected QT interval is >0.6 seconds, corrected QT interval exceeds baseline by >25%, QRS widening is >50% of baseline, or clinically important hypotension unresponsive to fluid expansion develops.111 124 128 143

Malaria (intermittent IV infusion regimen): Give loading dose of 15 mg/kg of quinidine (24 mg/kg of quinidine gluconate) by IV infusion over 4 hours, followed 4 hours later (i.e., 8 hours after the beginning of the loading-dose infusion) by maintenance doses of 7.5 mg/kg of quinidine (12 mg/kg of quinidine gluconate) given by IV infusion over 4 hours at 8-hour intervals.119 143 153 Decrease infusion rate or interrupt flow if corrected QT interval is >0.6 seconds, corrected QT interval exceeds baseline by >25%, QRS widening exceeds baseline by >50%, or clinically important hypotension unresponsive to fluid expansion develops.143

Dosage

Available as quinidine sulfate163 167 170 and quinidine gluconate.119 168 169 Dosage for treatment of arrhythmias usually expressed in terms of the salt;119 163 167 168 169 170 dosage for treatment of malaria expressed in terms of the base or salt.119 143 144

On a molar basis, approximately 267 mg of quinidine gluconate is equivalent to 200 mg of quinidine sulfate.b

Each 100 mg of quinidine gluconate contains 62.5 mg of quinidine.119

Pediatric Patients

Quinidine Sulfate
Arrhythmias
Oral

15–60 mg/kg of quinidine sulfate daily given in divided doses every 6 hours has been recommended by some clinicians.164 165 Others recommend 30 mg/kg daily or 900 mg/m2 daily, given in 5 divided doses.b

Quinidine Gluconate
Arrhythmias
Oral

20–60 mg/kg of quinidine gluconate daily given in divided doses every 8 hours has been recommended by some clinicians.165

IV

30 mg/kg daily or 900 mg/m2 daily of quinidine gluconate, given in 5 divided doses, is recommended by some clinicians.b

Severe Malaria
IV

Continuous IV infusion regimen: Initial loading dose of 6.25 mg/kg of quinidine (10 mg/kg of quinidine gluconate) given by IV infusion over 1–2 hours,119 134 143 144 followed by a maintenance infusion of 12.5 mcg/kg of quinidine per minute (20 mcg/kg of quinidine gluconate per minute) continued for ≥24 hours and until parasitemia is reduced to <1% and oral quinine sulfate can be substituted.111 119 122 123 124 125 134 141 143 144 Some clinicians state initial loading dose should not exceed 375 mg of quinidine (600 mg of quinidine gluconate).134

Intermittent IV infusion regimen: Initial loading dose of 15 mg/kg of quinidine (24 mg/kg of quinidine gluconate) given by IV infusion over 4 hours, followed 4 hours later (i.e., 8 hours after the beginning of the loading-dose infusion) by maintenance doses of 7.5 mg/kg of quinidine (12 mg/kg of quinidine gluconate) given by IV infusion over 4 hours at 8-hour intervals until 3 maintenance doses have been administered and parasitemia is reduced to <1% and oral quinine sulfate can be substituted.119 143 144 153

After ≥24 hours of quinidine gluconate and when clinically indicated, switch to oral quinine sulfate therapy to complete a total of 7 or 3 days of total quinidine and quinine therapy as determined by geographic origin of infecting parasite (7 days if acquired in Southeast Asia or 3 days if acquired elsewhere).122 123 141 143 144

IV quinidine gluconate regimen followed by oral quinine sulfate is used in conjunction with a 7-day regimen of doxycycline, tetracycline, or clindamycin (given IV or orally as tolerated).143

Adults

Quinidine Sulfate
Arrhythmias
Oral

Conversion of atrial fibrillation/flutter (conventional tablets): Manufacturers recommend 400 mg of quinidine sulfate (332 mg of quinidine) every 6 hours initially; dose may be cautiously increased if conversion is not attained after 4 or 5 doses.167 170

Conversion of atrial fibrillation/flutter (extended-release tablets): Manufacturer recommends 300 mg of quinidine sulfate (249 mg of quinidine) every 8–12 hours initially; dose may be cautiously increased if conversion not attained, quinidine serum concentrations are within the therapeutic range, and the drug is well tolerated.163

If successful conversion of atrial fibrillation does not occur when quinidine serum concentrations are in the therapeutic range, further dosage increases generally are unsuccessful and increase the possibility of toxicity.b

Reduction in frequency of relapse into atrial fibrillation/flutter (conventional tablets): Manufacturers recommend 200 mg of quinidine sulfate (166 mg of quinidine) every 6 hours initially.167 170 Dose may be cautiously increased if well tolerated, serum quinidine concentrations are within therapeutic range, and average time between arrhythmic episodes has not been satisfactorily increased.167 170 Use such prophylaxis only if alternative measures have been inadequate and if potential benefits outweigh risks;167 170 consider mortality risk.167 170

Reduction in frequency of relapse into atrial fibrillation/flutter (extended-release tablets): Manufacturer recommends 300 mg of quinidine sulfate (249 mg of quinidine) every 8–12 hours initially.163 Dose may be cautiously increased if well tolerated, serum quinidine concentrations are within therapeutic range, and average time between arrhythmic episodes has not been satisfactorily increased.163 Use such prophylaxis only if alternative measures have been inadequate and if potential benefits outweigh risks;163 consider mortality risk.163

Manufacturers state that dosage regimens for suppression of life-threatening ventricular arrhythmias have not been adequately studied, but regimens similar to those used in the management of atrial fibrillation/flutter have been described.163 167 170 Whenever possible, such therapy should be guided by results of programmed electrical stimulation and/or Holter monitoring with exercise.163 167 170

Malaria
Oral

300–600 mg or 10 mg/kg of quinidine sulfate every 8 hours for 5–7 days has been used for treatment of uncomplicated P. falciparum malaria.102 103 108 109 110

Not included in CDC recommendations for treatment of uncomplicated or severe malaria.143 144 (See Malaria under Uses.)

Quinidine Gluconate
Arrhythmias
Oral

Conversion of atrial fibrillation/flutter (extended-release tablets): Manufacturers recommend 648 mg of quinidine gluconate (403 mg of quinidine) every 8 hours initially; dose may be cautiously increased if conversion is not attained after 3 or 4 doses.168 169 Alternatively, manufacturers state that a regimen of 324 mg of quinidine gluconate (202 mg of quinidine) may be given every 8 hours for 2 days, then 648 mg of quinidine gluconate (403 mg of quinidine) every 12 hours for 2 days, and then 648 mg of quinidine gluconate (403 mg of quinidine) every 8 hours for up to 4 days.168 169 If the 648-mg dose is not tolerated, the lower dosage can be continued for the last 4 days.168 169

Reduction in frequency of relapse into atrial fibrillation/flutter (extended-release tablets): Manufacturers recommend 324 mg of quinidine gluconate (202 mg of quinidine) every 8 or 12 hours initially.168 169 Dose may be cautiously increased if well tolerated, serum quinidine concentrations are within therapeutic range, and average time between arrhythmic episodes has not been satisfactorily increased.168 169 Use such prophylaxis only if alternative measures have been inadequate and if potential benefits outweigh risks;168 169 consider mortality risk.168 169

Manufacturers state that dosage regimens for suppression of life-threatening ventricular arrhythmias have not been adequately studied, but regimens similar to those used in the management of atrial fibrillation/flutter have been described.168 169 Whenever possible, such therapy should be guided by results of programmed electrical stimulation and/or Holter monitoring with exercise.168 169

IV

Treatment of symptomatic atrial fibrillation/flutter: Initially, up to 0.25 mg/kg of quinidine gluconate per minute (i.e., up to 1 mL/kg per hour) of 16-mg/mL dilution.119 Discontinue IV infusion as soon as sinus rhythm is restored.119

Most arrhythmias responsive to IV quinidine respond to a total IV dosage <5 mg/kg, although 10 mg/kg may be required in some patients.119 If conversion to sinus rhythm has not occurred after infusion of quinidine gluconate 10 mg/kg, discontinue the infusion and consider other means of cardioversion.119

Although dosing regimens for the management of life-threatening ventricular arrhythmias have not been systematically evaluated, regimens similar to that used in the management of atrial fibrillation/flutter have been described.119

Severe Malaria
IV

Continuous IV infusion regimen: Initial loading dose of 6.25 mg/kg of quinidine (10 mg/kg of quinidine gluconate) given by IV infusion over 1–2 hours,119 134 141 143 144 followed by a maintenance infusion of 12.5 mcg/kg of quinidine per minute (20 mcg/kg of quinidine gluconate per minute) continued for ≥24 hours and until parasitemia is reduced to <1% and oral quinine sulfate can be substituted.111 119 122 123 124 125 134 141 143 144 Some clinicians state initial loading dose should not exceed 375 mg of quinidine (600 mg of quinidine gluconate).134

Intermittent IV infusion regimen: Initial loading dose of 15 mg/kg of quinidine (24 mg/kg of quinidine gluconate) given by IV infusion over 4 hours, followed 4 hours later (i.e., 8 hours after the beginning of the loading-dose infusion) by maintenance doses of 7.5 mg/kg of quinidine (12 mg/kg of quinidine gluconate) given by IV infusion over 4 hours at 8-hour intervals until 3 maintenance doses have been administered and parasitemia is reduced to <1% and oral quinine sulfate can be substituted.119 143 144 153

After ≥24 hours of quinidine gluconate and when clinically indicated, switch to oral quinine sulfate therapy to complete a total of 7 or 3 days of total quinidine and quinine therapy as determined by geographic origin of infecting parasite (7 days if acquired in Southeast Asia or 3 days if acquired elsewhere).122 123 141 143 144

IV quinidine gluconate regimen followed by oral quinine sulfate is used in conjunction with a 7-day regimen of doxycycline, tetracycline, or clindamycin (given IV or orally as tolerated).143 144

Prescribing Limits

Pediatric Patients

Arrhythmias
Quinidine Gluconate or Quinidine Sulfate
Oral

2.4 g of quinidine sulfate or quinidine gluconate daily.165

Severe Malaria
Quinidine Gluconate
IV

Continuous IV infusion regimen: Maximum initial loading dose of 375 mg of quinidine (600 mg of quinidine gluconate).134

Adults

Severe Malaria
Quinidine Gluconate
IV

Continuous IV infusion regimen: Maximum initial loading dose of 375 mg of quinidine (600 mg of quinidine gluconate).134

Special Populations

Hepatic Impairment

Dosage reduction may be necessary to avoid toxicity.119 163 167 168 169 170

Renal Impairment

Dosage reduction may be necessary to avoid toxicity.119 163 167 168 169 170

In patients with severe malaria receiving IV quinidine gluconate, CDC states that initial (including loading) doses do not need to be reduced in those with renal failure.143 If renal failure persists or clinical improvement does not occur in such patients, CDC recommends reducing maintenance IV infusion rate by one-third to one-half on the third day of treatment.143

CHF

Dosage reduction may be necessary to avoid toxicity.119 163 167 168 169 170

Geriatric Patients

Select dosage with caution, usually starting at the low end of the dosage range, and consider age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.119

Cautions for Quinidine Sulfate

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

Mortality

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 more than 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

Proarrhythmic Effects

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

Paradoxical Increase in Ventricular Rate in Atrial Flutter/Fibrillation

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

Exacerbated Bradycardia in Sick Sinus Syndrome

Possible marked sinus node depression and bradycardia.b

IV Administration

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

Sensitivity Reactions

Hypersensitivity 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

Cardiovascular Effects

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

Availability for Use in Treatment of Severe Malaria

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

Pregnancy

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

Lactation

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

Pediatric Use

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

Geriatric Use

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

Hepatic Impairment

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

Renal Impairment

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

Interactions for Quinidine Sulfate

Appears to be metabolized principally by CYP3A4.119 163 167 168 169 170 Not metabolized by CYP2D6.119 163 167 168 169 170

Inhibits CYP2D6; therapeutic serum quinidine concentrations may effectively convert CYP2D6 extensive metabolizers into CYP2D6 poor metabolizers.119 163 167 168 169 170 174

Drugs or Foods Affecting or Metabolized by Hepatic Microsomal Enzymes

Possible pharmacokinetic interactions with drugs that are inhibitors, inducers, or substrates of CYP3A4.119 163 167 168 169 170

Use caution if drugs metabolized by CYP2D6 (e.g., mexiletine, some phenothiazines, polycyclic antidepressants) are used concomitantly with quinidine;119 163 167 168 169 170 reduced dosage of such drugs may be necessary to obtain clinical benefit without toxicity.119 163 167 168 169 170 If some prodrugs that require CYP2D6 for conversion to an active metabolite (e.g., codeine, hydrocodone) are used concomitantly with quinidine, it may not be possible to achieve desired clinical benefits of those drugs.119 163 167 168 169 170

Specific Drugs and Foods

Drug or Food

Interaction

Comments

Alkalinizing agents (e.g., carbonic anhydrase inhibitors [e.g., acetazolamide], thiazide diuretics, some antacids, sodium bicarbonate)

Drugs that increase urine pH may reduce renal excretion of quinidine;119 163 168 169 b toxicity may occurb

Monitor patients closely during initiation of therapy with alkalinizing agentsb

Amiodarone

Increased serum quinidine concentrations119 163 167 168 169 170 b

Reduce quinidine dosage by 33–50% when amiodarone therapy is initiated in patients currently receiving quinidine or discontinue quinidine therapyb

Monitor serum quinidine concentrations carefully and reduce quinidine dosage as necessary in patients receiving amiodaroneb

Observe patients closely for signs of toxicity, including QT prolongationb

Antacids

Concomitant administration may delay oral absorption of quinidineb

Concomitant use of aluminum hydroxide antacid and oral quinidine gluconate does not have a clinically important effect on quinidine absorption169

Antiarrhythmic agents (e.g., diltiazem, flecainide, lidocaine, metoprolol, mexiletine, procainamide, propafenone, propranolol, timolol)

Possible additive or antagonistic cardiac effects; toxic effects may be additiveb

Mexiletine: Possible increased mexiletine concentrations119 163 167 168 169 170

Procainamide: Increased serum procainamide concentrations119 163 167 168 169 170

Propranolol: Usually does not affect quinidine pharmacokinetics, but increased peak quinidine concentrations and decreased volume of distribution and decreased clearance has been reported;119 no clinically important effect on propranolol pharmacokinetics119 163 167 168 169 170

Flecainide, metoprolol, propafenone: Quinidine has no clinically important effect on pharmacokinetics of these antiarrhythmics119 163 167 168 169 170

Mexiletine: Use caution119

Anticholinergic agents

Possible additive effects119 163 167 168 169 170 b

Anticoagulants (oral)

Quinidine potentiates anticoagulant effect of warfarin119 163 167 168 169 170

Closely observe patients; b anticoagulant dosage may need to be reduced119

Anticonvulsants (e.g., mephenytoin, phenytoin, phenobarbital)

Phenytoin, phenobarbital: Possible accelerated clearance of quinidine119 163 167 168 169 170 b

Mephenytoin: Quinidine has no clinically important effect on mephenytoin pharmacokinetics119 163 167 168 169 170

Use caution when anticonvulsant is initiated or discontinued in patients receiving quinidineb

Caffeine

No clinically important effect on quinidine pharmacokinetics119 163 167 168 169 170

Calcium-channel blocking agents (e.g., diltiazem, felodipine, nifedipine, verapamil)

Diltiazem: Decreased clearance and increased half-life of quinidine;119 163 167 168 169 170 no clinically important effect on diltiazem pharmacokinetics119 163 167 168 169 170

Felodipine: No clinically important effect on quinidine pharmacokinetics;119 163 167 168 169 170 possible decreased metabolism of felodipine119 163 167 168 169 170

Nifedipine: Decreased serum quinidine concentrations;119 129 132 136 137 139 163 167 168 169 170 decreased rate of nifedipine metabolism119 163 167 168 169 170

Verapamil: Decreased hepatic clearance of quinidine;119 163 167 168 169 170 possible additive effects119 163 167 168 169 170 and hypotension in patients with arrhythmia or hypertrophic cardiomyopathy116 117

Nifedipine: Monitor serum quinidine concentrations whenever nifedipine is initiated or discontinued in patients maintained on the antiarrhythmic; adjust quinidine dosage accordingly129 132 136 137 139

Verapamil: Concomitant use in such patients should probably be avoided116

Cholinergic agents

Quinidine antagonizes the effects of cholinergic agents119 163 167 168 169 170

Use with caution, if at all, in patients with myasthenia gravis; dose of anticholinesterase drugs (e.g., neostigmine, pyridostigmine) may have to be increasedb

Cigarette smoking

No clinically important effect on quinidine pharmacokinetics119 163 167 168 169 170

Cimetidine

Increased serum quinidine concentrations119 163 167 168 169 170 b

Clinical importance uncertainb

Ciprofloxacin

No clinically important effect on quinidine pharmacokinetics119 163 167 168 169 170

Clarithromycin

Torsades de pointes reported rarely in patients receiving concomitant quinidine and clarithromycin159

If quinidine and clarithromycin are used concomitantly, monitor ECGs and serum quinidine concentrations159

Dextromethorphan

Substantial increase in bioavailability of dextromethorphan due to CYP2D6 inhibition; used for therapeutic benefit in fixed combination containing dextromethorphan and quinidine (Nuedexta)174

Digoxin

Increased plasma concentrations of digoxin119 163 167 168 169 170 b (in ≥90% of patients) which may result in GI and cardiac toxicity;b no clinically important effect on quinidine pharmacokinetics119 163 167 168 169 170

Monitor serum digoxin concentrations carefully when quinidine therapy is initiated in a patient receiving digoxin;b reduce digoxin dosage as needed119 b

Observe patient closely for signs of toxicityb

Grapefruit juice

May delay GI absorption of quinidine157 163 168 169 and inhibit metabolism of quinidine to 3-hydroxyquinidine;157 may delay effects on QTc interval156 157

Clinical importance unknown,156 157 remain alert for possible interaction156

Manufacturers of extended-release formulations of quinidine state avoid grapefruit juice163 168 169

Haloperidol

Increased serum haloperidol concentrations119 163 167 168 169 170

Hypotensive agents

Possible additive hypotensive effectsb

Observe patients for hypotensive effectsb

Ketoconazole

Increased plasma quinidine concentrations119 163 167 168 169 170

Neuromuscular blocking agents (e.g., pancuronium bromide, succinylcholine chloride, tubocurarine chloride)

Quinidine potentiates the effects of depolarizing and nondepolarizing neuromuscular blocking agents119 163 167 168 169 170

Neostigmine methylsulfate does not appear to reverse these effectsb

Avoid use of quinidine immediately after surgery when the effects of neuromuscular blocking agents may be present; respiratory support may be needed if quinidine must be usedb

Omeprazole

No clinically important effect on quinidine pharmacokinetics119 163 167 168 169 170

Phenothiazines

Possible additive cardiac depressant effectsb

Quinine

Additive pharmacological effectsb

No clinically important effect on quinine or quinidine pharmacokinetics119 163 167 168 169 170

Reserpine

Possible additive cardiac depressant effectsb

Rifampin

Possible accelerated quinidine elimination119 163 167 168 169 170

Quinidine Sulfate Pharmacokinetics

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

Stability

Storage

Oral

Quinidine Sulfate Conventional or Extended-release Tablets

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

Quinidine Gluconate Extended-release Tablets

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

Parenteral

Quinidine Gluconate Injection

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

Solution Compatibility

Compatible

Dextrose 5% in waterHID 119

Sodium chloride 0.9%119

Drug Compatibility
Admixture CompatibilityHID

Compatible

Milrinone lactate

Ranitidine HCl

Verapamil HCl

Incompatible

Atracurium besylate

Variable

Amiodarone HCl

Y-Site CompatibilityHID

Compatible

Diazepam

Milrinone lactate

Nesiritide

Incompatible

Furosemide

Variable

Heparin sodium

Actions

  • 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

Advice to Patients

  • If used for prophylaxis against recurrence of atrial fibrillation, advise patient of the risks and benefits.163 167 168 169 170 Advise patients that the goal is reduction in frequency of episodes of atrial fibrillation (probably not elimination); symptomatic benefits may occur if reduced frequency of fibrillatory episodes is achieved; no data indicate that reduced frequency of fibrillatory episodes reduces risks of irreversible harm through stroke or death; and data are available suggesting that quinidine treatment is likely to increase the risk of death.163 167 168 169 170

  • Importance of informing clinician if rash, fever, unusual bleeding or bruising, ringing in the ears, or visual disturbance occurs.b

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.119 163 167 168 169 170

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.119 163 167 168 169 170

  • Importance of informing patients of other important precautionary information.119 163 167 168 169 170 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Quinidine Gluconate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release

324 mg (equivalent to quinidine 202 mg)*

Quinidine Gluconate Extended-release Tablets

Parenteral

Injection

80 mg (equivalent to quinidine 50 mg) per mL*

Quinidine Gluconate Injection

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Quinidine Sulfate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

200 mg (equivalent to quinidine 166 mg)*

Quinidine Sulfate Tablets

300 mg (equivalent to quinidine 249 mg)*

Quinidine Sulfate Tablets

Tablets, extended-release

300 mg (equivalent to quinidine 249 mg)*

Quinidine Sulfate Extended-release Tablets

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 08/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

QuiNIDine Gluconate CR 324MG Controlled-release Tablets (MUTUAL PHARMACEUTICAL): 90/$72.99 or 270/$200.97

Quinidine Sulfate 200MG Tablets (WATSON LABS): 90/$19.99 or 270/$54.97

Quinidine Sulfate 300MG Tablets (SANDOZ): 90/$35.99 or 270/$100.99

QuiNIDine Sulfate CR 300MG Controlled-release Tablets (TEVA PHARMACEUTICALS USA): 90/$83.99 or 270/$217.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 4, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

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