Drug class: Class Ia Antiarrhythmics
- Antimalarial Agents
VA class: CV300
CAS number: 7054-25-3

Medically reviewed by Drugs.com on Nov 6, 2023. Written by ASHP.

Introduction

Antiarrhythmic agent (class Ia); antimalarial.^{119 163 167 168 169 170}

Uses for quiNIDine

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

Supraventricular Tachyarrhythmias

Used for conversion of atrial fibrillation or flutter in patients whose symptoms are not adequately controlled by measures to reduce ventricular rate; also may be used to maintain normal sinus rhythm after conversion.^{119 163 167 169 170 301} However, used infrequently because of adverse effects (e.g., QT-interval prolongation, torsades de pointes, increased mortality) and considered an alternative to other antiarrhythmic agents.³⁰¹

Has been used for treatment of other supraventricular tachycardias (e.g., paroxysmal atrial tachycardia, paroxysmal AV junctional rhythm); however, other therapies preferred.^{300 b}

Ventricular Arrhythmias

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 arrhythmias; avoid treatment in asymptomatic VPCs.^b (See Boxed Warning.)

Parenteral lidocaine is considered drug of choice for treatment of VPCs because quinidine can decrease myocardial contractility.^b

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

Malaria

Treatment of severe malaria caused by Plasmodium falciparum or other Plasmodium species^{† [off-label]}.^{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^{† [off-label]} 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 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, QT_c 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 orally^{168 169} 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 conventional^{167 170} 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 sulfate^{163 167 170} 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† [off-label]

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† [off-label]

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† [off-label]

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

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 >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 QT_c 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}

Drug Interactions

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

quiNIDine 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 absorption^{156 157 163 168 169} 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 adults^{119 163 167 168 169 170} 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

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

Drug Compatibility

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.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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

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

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