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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(KWIN i deen)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Quinidine gluconate and sulfate salts: Conversion and prevention of relapse into atrial fibrillation and/or flutter; suppression of ventricular arrhythmias. Note: Due to proarrhythmic effects, use should be reserved for life-threatening arrhythmias. Moreover, the use of quinidine has largely been replaced by more effective/safer antiarrhythmic agents and/or nonpharmacologic therapies (eg, radiofrequency ablation).
Quinidine gluconate (I.V. formulation): Conversion of atrial fibrillation/flutter and ventricular tachycardia. Note: The use of I.V. quinidine gluconate for these indications has been replaced by more effective/safer antiarrhythmic agents (eg, amiodarone and procainamide).
Quinidine gluconate (I.V. formulation) and quinidine sulfate: Treatment of malaria (Plasmodium falciparum)
Use: Unlabeled
Paroxysmal supraventricular tachycardia, paroxysmal AV junctional rhythm, and symptomatic atrial or ventricular premature contractions; short QT syndrome; Brugada syndrome
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal reproduction studies have not been conducted. Quinidine crosses the placenta and can be detected in the amniotic fluid, cord blood, and neonatal serum. Quinidine is indicated for use in the treatment of severe malaria infection in pregnant women (CDC, 2011; Smereck, 2011) and has also been used to treat arrhythmias in pregnancy when other agents are ineffective (European Society of Cardiology, 2003).
Lactation
Enters breast milk/not recommended (AAP rates "compatible"; AAP 2001 update pending)
Contraindications
Hypersensitivity to quinidine or any component of the formulation; thrombocytopenia; thrombocytopenic purpura; myasthenia gravis; heart block greater than first degree; idioventricular conduction delays (except in patients with a functioning artificial pacemaker); those adversely affected by anticholinergic activity; concurrent use of quinolone antibiotics which prolong QT interval, cisapride, amprenavir, or ritonavir
Warnings/Precautions
Boxed warnings:
• Arrhythmias: Appropriate use: See “Disease-related concerns” below.
Concerns related to adverse effects:
• Hepatotoxicity: Has been associated with severe hepatotoxic reactions, including granulomatous hepatitis.
• Hypersensitivity reactions: With use, hypersensitivity reactions may occur.
• Proarrhythmic effects: Watch for proarrhythmic effects; may cause QT prolongation and subsequent torsade de pointes. Monitor and adjust dose to prevent QTc prolongation. Avoid use in patients with diagnosed or suspected congenital long QT syndrome.
Disease-related concerns:
• Arrhythmias: Appropriate use: [U.S. Boxed Warning]: Antiarrhythmic drugs have not been shown to enhance survival in non-life-threatening ventricular arrhythmias and may increase mortality; the risk is greatest with structural heart disease. Quinidine may increase mortality in treatment of atrial fibrillation/flutter.
• Atrial fibrillation/flutter: May increase ventricular response rate in patients with atrial fibrillation or flutter; control AV conduction before initiating.
• Conduction disturbances: Use with caution in patients at risk for heart block; can unmask sick sinus syndrome (causes bradycardia).
• Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy.
• G6PD deficiency: Hemolysis may occur in patients with G6PD (glucose-6-phosphate dehydrogenase) deficiency.
• Heart failure (HF): Use with caution in patients with HF; may precipitate or exacerbate condition.
• Hepatic impairment: Use with caution in patients with hepatic impairment; reduced dosage recommended.
Concurrent drug therapy issues:
• Antiarrhythmics: Use with caution with concurrent use of other antiarrhythmics.
• Digoxin: Use may cause digoxin-induced toxicity; adjust digoxin's dose.
Dosage form specific issues:
• Different salts: Do not interchange the different salt products.
Other warnings/precautions:
• CAST trial: In the Cardiac Arrhythmia Suppression Trial (CAST), recent (>6 days but <2 years ago) myocardial infarction patients with asymptomatic, non-life-threatening ventricular arrhythmias did not benefit and may have been harmed by attempts to suppress the arrhythmia with flecainide or encainide. An increased mortality or nonfatal cardiac arrest rate (7.7%) was seen in the active treatment group compared with patients in the placebo group (3%). The applicability of the CAST results to other populations is unknown. Antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias.
Adverse Reactions
Frequency not defined: Hypotension, syncope
>10%:
Cardiovascular: QTc prolongation (modest prolongation is common, however, excessive prolongation is rare and indicates toxicity)
Central nervous system: Lightheadedness (15%)
Gastrointestinal: Diarrhea (35%), upper GI distress, bitter taste, anorexia, nausea, vomiting, stomach cramping (22%)
1% to 10%:
Cardiovascular: Angina (6%), palpitation (7%), new or worsened arrhythmia (proarrhythmic effect)
Central nervous system: Syncope (1% to 8%), headache (7%), fatigue (7%), sleep disturbance (3%), tremor (2%), nervousness (2%), incoordination (1%)
Dermatologic: Rash (5%)
Neuromuscular & skeletal: Weakness (5%)
Ocular: Blurred vision
Otic: Tinnitus
Respiratory: Wheezing
<1% (Limited to important or life-threatening): Tachycardia, QTc prolongation (excessive), torsade de pointes, heart block, ventricular fibrillation, ventricular tachycardia, paradoxical increase in ventricular rate during atrial fibrillation/flutter, exacerbated bradycardia (in sick sinus syndrome), vascular collapse, confusion, delirium, vertigo, hearing impaired, respiratory depression, pneumonitis, bronchospasm, fever, urticaria, flushing, exfoliative rash, psoriaform rash, pruritus, lymphadenopathy, hemolytic anemia, vasculitis, thrombocytopenic purpura, thrombocytopenia, pancytopenia, uveitis, angioedema, agranulocytosis, sicca syndrome, arthralgia, myalgia, CPK increased, drug-induced lupus-like syndrome, cerebral hypoperfusion (possibly resulting in ataxia, apprehension, and seizure), acute psychotic reactions, depression, hallucinations, mydriasis, disturbed color perception, night blindness, scotoma, optic neuritis, visual field loss, photosensitivity, abnormal pigmentation, granulomatous hepatitis, hepatotoxic reaction (rare), eczematous dermatitis, livedo reticularis
Postmarketing and/or case reports: Melanin pigmentation of the hard palate, esophagitis, nephropathy, cholestasis, pneumonitis, lichen planus
Note: Cinchonism, a syndrome which may include tinnitus, high-frequency hearing loss, deafness, vertigo, blurred vision, diplopia, photophobia, headache, confusion, and delirium has been associated with quinidine use. Usually associated with chronic toxicity, this syndrome has also been described after brief exposure to a moderate dose in sensitive patients. Vomiting and diarrhea may also occur as isolated reactions to therapeutic quinidine levels.
Metabolism/Transport Effects
Substrate of CYP2C9 (minor), CYP2E1 (minor), CYP3A4 (major), P-glycoprotein; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C9 (weak), CYP2D6 (strong), CYP3A4 (weak), P-glycoprotein
Drug Interactions
Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Amiodarone: May enhance the QTc-prolonging effect of Antiarrhythmic Agents (Class Ia). Amiodarone may increase the serum concentration of Antiarrhythmic Agents (Class Ia). Management: Risk of QTc prolongation and Torsades de Pointes may be increased; consider alternative therapy when possible. Risk D: Consider therapy modification
Antacids: May decrease the excretion of QuiNIDine. Exceptions: Aluminum Hydroxide. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of QuiNIDine. Management: Itraconazole, voriconazole, and posaconazole are specifically contraindicated with quinidine. Use of quinidine with any azole antifungal may require quinidine dose adjustment and should be done with caution and close monitoring. Risk X: Avoid combination
ARIPiprazole: CYP2D6 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions are required with concomitant use of a strong CYP2D6 inhibitor except in the treatment of major depressive disorder. Consult labeling for specific recommendations. Risk D: Consider therapy modification
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole systemic exposure/affects with concomitant use of a weak CYP3A4 inhibitor. Decrease aripiprazole dose to 25% of the usual dose in patients receiving both a CYP3A4 and a CYP2D6 inhibitor (regardless of potencies). Risk C: Monitor therapy
Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Atomoxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Atomoxetine. Management: Initiate atomoxetine at a reduced dose (adult doses -- patients up to 70kg: 0.5mg/kg/day; patients 70kg or more: 40mg/day) in patients receiving a strong CYP2D6 inhibitor. Risk D: Consider therapy modification
Barbiturates: May enhance the hepatotoxic effect of QuiNIDine. Barbiturates may decrease the serum concentration of QuiNIDine. Risk C: Monitor therapy
Beta-Blockers: QuiNIDine may decrease the metabolism of Beta-Blockers. Exceptions: Atenolol; Carteolol; Carteolol (Ophthalmic); Nadolol. Risk C: Monitor therapy
Boceprevir: May increase the serum concentration of QuiNIDine. Risk C: Monitor therapy
Calcium Channel Blockers (Dihydropyridine): QuiNIDine may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Calcium Channel Blockers (Dihydropyridine) may decrease the serum concentration of QuiNIDine. Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of QuiNIDine. Exceptions: Felodipine; Nisoldipine. Risk C: Monitor therapy
Carbonic Anhydrase Inhibitors: May decrease the excretion of QuiNIDine. Exceptions: Brinzolamide; Dorzolamide. Risk C: Monitor therapy
Cardiac Glycosides: QuiNIDine may increase the serum concentration of Cardiac Glycosides. Management: Upon quinidine initiation, consider reducing cardiac glycoside dose by 25% to 50%, with continued monitoring of glycoside serum concentrations and clinical response until the quinidine reaches steady state (5-10 days). Risk D: Consider therapy modification
Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of QuiNIDine. Management: Consider alternatives to cimetidine. If the combination cannot be avoided, monitor for increased quinidine concentrations/toxicity with cimetidine initiation/dose increase, or decreased concentrations/effects with cimetidine discontinuation/dose decrease. Risk D: Consider therapy modification
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciprofloxacin (Systemic): May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Codeine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk D: Consider therapy modification
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Risk D: Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination
Crizotinib: May increase the serum concentration of QuiNIDine. Risk X: Avoid combination
CYP2D6 Substrates: CYP2D6 Inhibitors (Strong) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Cyproterone: May decrease the serum concentration of CYP2E1 Substrates. Risk C: Monitor therapy
Dabigatran Etexilate: QuiNIDine may increase the serum concentration of Dabigatran Etexilate. Management: Canadian (but not U.S.) prescribing information recommends dosing dabigatran 2 hours prior to quinidine, and limiting dabigatran VTE prevention dose post hip/knee replacement to 150 mg/day in patients receiving quinidine. Risk D: Consider therapy modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Risk D: Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Dextromethorphan: QuiNIDine may increase the serum concentration of Dextromethorphan. Management: Avoid concurrent use of these agents when possible, unless the increased psychoactive effects of dextromethorphan are desired. Since codeine activation is also inhibited by quinidine, codeine is unlikely to be suitable as an alternative antitussive. Risk D: Consider therapy modification
Dihydrocodeine: QuiNIDine may diminish the analgesic effect of Dihydrocodeine. Risk D: Consider therapy modification
Diltiazem: May increase the serum concentration of QuiNIDine. Risk C: Monitor therapy
Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
Eribulin: May enhance the QTc-prolonging effect of Antiarrhythmic Agents (Class Ia). Risk C: Monitor therapy
Etravirine: May decrease the serum concentration of QuiNIDine. Risk C: Monitor therapy
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Risk D: Consider therapy modification
Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy
Fingolimod: May enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class Ia). Management: Obtain baseline ECG (if not recently available) if initiating fingolimod during treatment with class Ia antiarrhythmic agents. Monitor for bradycardia and AV block. The Canadian labeling recommends avoiding concomitant use of these agents. Risk C: Monitor therapy
Fluconazole: May decrease the metabolism of QuiNIDine. Risk C: Monitor therapy
Fosphenytoin: May decrease the serum concentration of QuiNIDine. Risk C: Monitor therapy
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Haloperidol: May enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may increase the serum concentration of Haloperidol. Risk D: Consider therapy modification
Hydrocodone: QuiNIDine may decrease serum concentrations of the active metabolite(s) of Hydrocodone. Risk C: Monitor therapy
Indacaterol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Kaolin: May decrease the serum concentration of QuiNIDine. Management: Consider separating doses of kaolin and quinidine by at least 2 hours in order to reduce the risk of interaction. Monitor for decreased therapeutic effects of quinidine if kaolin is simultaneously coadministered. Risk D: Consider therapy modification
Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Lurasidone: May enhance the QTc-prolonging effect of QuiNIDine. Management: Consider alternatives to quinidine in patients with acute lurasidone overdose. If quinidine treatment cannot be avoided, monitor for excessive QTc interval prolongation. Risk D: Consider therapy modification
Macrolide Antibiotics: May decrease the metabolism of QuiNIDine. Exceptions: Azithromycin; Azithromycin (Systemic); Fidaxomicin; Spiramycin. Risk D: Consider therapy modification
Mefloquine: QuiNIDine may enhance the adverse/toxic effect of Mefloquine. Specifically, the risk for QTc-prolongation and the risk for convulsions may be increased. Management: Avoid concurrent use, and delay administration of mefloquine until at least 12 hours after the last dose of quinidine when possible. Risk X: Avoid combination
Neuromuscular-Blocking Agents: QuiNIDine may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
Phenytoin: May decrease the serum concentration of QuiNIDine. Risk C: Monitor therapy
Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. Risk X: Avoid combination
Potassium-Sparing Diuretics: May diminish the therapeutic effect of QuiNIDine. Risk C: Monitor therapy
Primidone: May decrease the serum concentration of QuiNIDine. Risk C: Monitor therapy
Propafenone: QuiNIDine may enhance the QTc-prolonging effect of Propafenone. QuiNIDine may increase the serum concentration of Propafenone. Risk X: Avoid combination
Protease Inhibitors: May decrease the metabolism of QuiNIDine. Risk X: Avoid combination
Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Risk C: Monitor therapy
QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification
QUEtiapine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Reserpine: May enhance the adverse/toxic effect of QuiNIDine. Risk C: Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of QuiNIDine. Management: Consider alternatives to combination treatment with quinidine and rifampin due to large potential decreases in quinidine concentrations. Monitor for decreased quinidine concentrations/effects with initiation/dose increase of any rifamycin derivative. Risk D: Consider therapy modification
Rivaroxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rivaroxaban. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of QuiNIDine. Fluvoxamine appears to be the only SSRI of concern. Exceptions: Citalopram; Escitalopram; PARoxetine; Sertraline; Vilazodone. Risk D: Consider therapy modification
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk X: Avoid combination
Sucralfate: May decrease the serum concentration of QuiNIDine. Specifically, sucralfate may decrease the absorption of quinidine. Management: Administer quinidine at least 2 hours before or at least 6 hours after sucralfate. Risk D: Consider therapy modification
Telaprevir: May enhance the adverse/toxic effect of QuiNIDine. Telaprevir may increase the serum concentration of QuiNIDine. Risk C: Monitor therapy
Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Toremifene: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Toremifene. The risk for potentially dangerous arrhythmias may be increased. Risk X: Avoid combination
TraMADol: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Risk C: Monitor therapy
Tricyclic Antidepressants: May enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may increase the serum concentration of Tricyclic Antidepressants. Risk D: Consider therapy modification
Vandetanib: QTc-Prolonging Agents may enhance the arrhythmogenic effect of Vandetanib. Risk X: Avoid combination
Vemurafenib: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Vemurafenib. Risk X: Avoid combination
Verapamil: QuiNIDine may enhance the hypotensive effect of Verapamil. Verapamil may increase the serum concentration of QuiNIDine. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): QuiNIDine may enhance the anticoagulant effect of Vitamin K Antagonists. Note that the INR/PT might be unchanged in the face of increased bleeding. Risk C: Monitor therapy
Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Food: Changes in dietary salt intake may alter the rate and extent of quinidine absorption. Quinidine serum levels may be increased if taken with food. Food has a variable effect on absorption of sustained release formulation. The rate of absorption of quinidine may be decreased following the ingestion of grapefruit juice. Excessive intake of fruit juice or vitamin C may decrease urine pH and result in increased clearance of quinidine with decreased serum concentration. Alkaline foods may result in increased quinidine serum concentrations. Management: Avoid changes in dietary salt intake. Grapefruit juice should be avoided. Take around-the-clock to avoid variation in serum levels and with food or milk to avoid GI irritation.
Herb/Nutraceutical: St John's wort may decrease quinidine levels. Ephedra may worsen arrhythmia. Management: Avoid St John's wort and ephedra.
Storage
Solution for injection: Store at room temperature of 25°C (77°F).
Tablets: Store at controlled room temperature of 20°C to 25°C (68°F to 77°F). Protect from light.
Compatibility
Stable in D5W, NS.
Y-site administration: Compatible: Diazepam, milrinone, nesiritide. Incompatible: Furosemide. Variable (consult detailed reference): Heparin.
Mechanism of Action
Class Ia antiarrhythmic agent; depresses phase O of the action potential; decreases myocardial excitability and conduction velocity, and myocardial contractility by decreasing sodium influx during depolarization and potassium efflux in repolarization; also reduces calcium transport across cell membrane
Pharmacodynamics/Kinetics
Distribution: Vd: Adults: 2-3 L/kg, decreased with congestive heart failure (0.5 L/kg), malaria; increased with cirrhosis
Protein binding: Newborns: 50% to 70%; Adults: 80% to 88%
Binds mainly to alpha1-acid glycoprotein and to a lesser extent albumin; protein-binding changes may occur in periods of stress due to increased alpha1-acid glycoprotein concentrations (eg, acute myocardial infarction) or in certain disease states due to decreased alpha1-acid glycoprotein concentrations (eg, cirrhosis,hyperthyroidism, malnutrition)
Metabolism: Extensively hepatic (50% to 90%) to inactive compounds
Bioavailability: Sulfate: ~70% with wide variability between patients (45% to 100%); Gluconate: 70% to 80%
Half-life elimination, plasma: Children: 3-4 hours; Adults: 6-8 hours; prolonged with elderly, cirrhosis, and congestive heart failure
Time to peak, serum: Sulfate: 2 hours; Gluconate: 3-6 hours
Excretion: Urine (15% to 25% as unchanged drug)
Dosage
Note: Dosage expressed in terms of the salt: 267 mg of quinidine gluconate = 200 mg of quinidine sulfate.
Antiarrhythmic: Adults: Oral:
Immediate release formulations: Quinidine sulfate: Initial: 200-400 mg/dose every 6 hours the dose may be increased cautiously to desired effect
Extended release formulations:
Quinidine sulfate: Initial: 300 mg every 8-12 hours; the dose may be increased cautiously to desired effect
Quinidine gluconate: Initial: 324 mg every 8-12 hours; the dose may be increased cautiously to desired effect
Severe malaria, treatment: Children and Adults: I.V. (quinidine gluconate): 10 mg/kg infused over 60-120 minutes followed by 0.02 mg/kg/minute continuous infusion for ≥24 hours; alternatively, may administer 24 mg/kg loading dose over 4 hours, followed by 12 mg/kg over 4 hours every 8 hours (beginning 8 hours after initiation of the loading dose); complete treatment with oral quinine once parasite density <1% and patient can receive oral medication; total duration of treatment (quinidine/quinine): 3 days (Africa or South America) or 7 days (Southeast Asia); use in combination with doxycycline, tetracycline or clindamycin (CDC malaria guidelines, 2009). Note: Close monitoring, including telemetry, required.
Dosing adjustment in renal impairment: The FDA-approved labeling recommends that caution should be used in patients with renal impairment; however, no specific dosage adjustment guidelines are available. The following guidelines have been used by some clinicians (Aronoff, 2007): Oral:
Clcr ≥10 mL/minute: No adjustment required.
Clcr <10 mL/minute: Administer 75% of normal dose.
Hemodialysis: Dose following hemodialysis
Peritoneal dialysis: Supplemental dose is not necessary
CRRT: No dosage adjustment required; monitor serum concentrations
Dosing adjustment/comments in hepatic impairment: Use caution; hepatic impairment decreases clearance; dosage adjustments are not provided in the manufacturers' labeling although toxicity may occur if the dose is not appropriately adjusted.
Administration: Oral
Do not crush, chew, or break sustained release dosage forms. Give around-the-clock to promote less variation in peak and trough serum levels. Some preparations of quinidine gluconate extended release tablets may be split in half to facilitate dosage titration; tablets are not scored.
Administration: I.V.
Minimize use of PVC tubing to enhance bioavailability; shorter tubing lengths are recommended by the manufacturer
Administration: I.V. Detail
pH: 5.5-7.0 (injection)
Monitoring Parameters
Cardiac monitor required during I.V. administration; CBC, liver and renal function tests, should be routinely performed during long-term administration
Reference Range
Therapeutic: 2-5 mcg/mL (SI: 6.2-15.4 micromole/L). Patient-dependent therapeutic response occurs at levels of 3-6 mcg/mL (SI: 9.2-18.5 micromole/L). Optimal therapeutic level is method dependent; >6 mcg/mL (SI: >18 micromole/L).
Dietary Considerations
Administer with food or milk to decrease gastrointestinal irritation. Avoid changes in dietary salt intake.
Patient Education
Take around-the-clock. Do not crush, chew, or break sustained release dosage forms. Do not take with grapefruit juice. You will need regular cardiac checkups and blood tests while taking this medication. You may experience dizziness, drowsiness, visual changes, abnormal taste, nausea, vomiting, loss of appetite, headaches, or diarrhea (if persistent consult prescriber). Report chest pain, palpitation, or erratic heartbeat; respiratory difficulty or wheezing; CNS changes (confusion, delirium, fever, consistent dizziness); skin rash; sense of fullness or ringing in ears; or vision changes.
Geriatric Considerations
Clearance may be decreased with a resultant increased half-life. Must individualize dose. Bioavailability and half-life are increased in the elderly due to decreases in both renal and hepatic function with age.
Cardiovascular Considerations
As with other Class Ia agents, it is prudent to avoid quinidine use in patients with cardiovascular disease, particularly recent myocardial infarction and heart failure, due to a possible increase in proarrhythmia and mortality. Quinidine may be used to pharmacologically convert atrial fibrillation to normal sinus rhythm. Patients should be monitored (ECG) in a controlled setting when initiating therapy. Therapy should be discontinued or the dose reduced if the QT interval increases ≥25% from baseline. Proarrhythmia (torsade de pointes) may occur early or after months of therapy. It is important to note (see Drug Interactions) that quinidine may increase digoxin levels by twofold, often necessitating a reduction of the digoxin dosage by 50% when quinidine therapy is initiated.
Dental Health: Effects on Dental Treatment
When taken over a long period of time, the anticholinergic side effects from quinidine can cause a reduction of saliva production or secretion contributing to discomfort and dental disease (ie, caries, oral candidiasis, and periodontal disease).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Quinidine is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, mepivacaine and levonordefrin [Carbocaine® 2% with Neo-Cobefrin®]) be used with caution.
Dental Comment
Quinidine is known to prolong the QT interval. The QT interval is measured as the time and distance between the Q point of the QRS complex and the end of the T wave in the ECG tracing. After adjustment for heart rate, the QT interval is defined as prolonged if it is more than 450 msec in men and 460 msec in women. A long QT syndrome was first described in the 1950s and 60s as a congenital syndrome involving QT interval prolongation and syncope and sudden death. Some of the congenital long QT syndromes were characterized by a peculiar electrocardiographic appearance of the QRS complex involving a premature atria beat followed by a pause, then a subsequent sinus beat showing marked QT prolongation and deformity. This type of cardiac arrhythmia was originally termed “torsade de pointes” (translated from the French as “twisting of the points”). Quinidine is considered as having a risk of causing torsade de pointes. Since it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval, a medical consult is suggested.
Mental Health: Effects on Mental Status
May cause dizziness; may rarely cause confusion or delirium
Mental Health: Effects on Psychiatric Treatment
Contraindicated with ziprasidone. May cause anemia; use caution with clozapine and carbamazepine. Concurrent use with TCAs may raise serum levels or produce AV block; avoid combination. Concurrent use with beta-blockers may increase bradycardia.
Nursing: Physical Assessment/Monitoring
I.V. requires use of infusion pump and continuous cardiac and hemodynamic monitoring. Monitor cardiac functioning closely at beginning of therapy, when titrating dosage, and on a regular basis. Quinidine has a low TI and overdose may easily produce severe and life-threatening reactions.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as gluconate: 80 mg/mL (10 mL) [equivalent to quinidine base 50 mg/mL]
Tablet, oral, as sulfate: 200 mg, 300 mg
Tablet, extended release, oral, as gluconate: 324 mg [equivalent to quinidine base 202 mg]
Tablet, extended release, oral, as sulfate: 300 mg [equivalent to quinidine base 249 mg]
Pricing: U.S. (www.drugstore.com)
Tablet, controlled release (QuiNIDine Gluconate CR)
324 mg (90): $72.99
Tablet, controlled release (QuiNIDine Sulfate CR)
300 mg (90): $83.99
Tablets (Quinidine Sulfate)
200 mg (90): $19.99
300 mg (90): $35.99
Extemporaneously Prepared
A 10 mg/mL oral liquid preparation may be made with tablets and one of three different vehicles (cherry syrup, a 1:1 mixture of Ora-Sweet® and Ora-Plus®, or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®). Crush six 200 mg tablets in a mortar and reduce to a fine powder. Add 15 mL of the chosen vehicle and mix to a uniform paste; mix while adding vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label "shake well" and "protect from light". Stable for 60 days when stored in amber plastic prescription bottles in the dark at room temperature or refrigerated.
Allen LV and Erickson MA, "Stability of Bethanechol Chloride, Pyrazinamide, Quinidine Sulfate, Rifampin, and Tetracycline in Extemporaneously Compounded Oral Liquids," Am J Health Syst Pharm, 1998, 55(17):1804-9.
References
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Centers for Disease Control and Prevention, “Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Children: Recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics,” MMWR Recomm Rep, 2009, 58(RR-11):1-166. Available at http://aidsinfo.nih.gov/contentfiles/Pediatric_OI.pdf
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Echt DS, Liebson PR, Mitchell LB, et al, “Mortality and Morbidity in Patients Receiving Encainide, Flecainide, or Placebo: The Cardiac Arrhythmia Suppression Trial,” N Engl J Med, 1991, 324(12):781-8.
European Society for Cardiology, Task Force on the Management of Cardiovascular Diseases During Pregnancy of the European Society of Cardiology, "Expert Consensus Document on Management of Cardiovascular Diseases During Pregnancy," Eur Heart J, 2003, 24(8):761-81.
Flaker GC, Blackshear JL, McBride R, et al, “Antiarrhythmic Drug Therapy and Cardiac Mortality in Atrial Fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators,” J Am Coll Cardiol, 1992, 20:527-32.
Fuster V, Ryden LE, Cannom DS, et al, “ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation-Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society,” J Am Coll Cardiol, 2006, 48(4):854-906.
Morganroth J and Goin JE, “Quinidine-Related Mortality in the Short-to-Medium Term Treatment of Ventricular Arrhythmias. A Meta-analysis,” Circulation, 1991, 84(5):1977-83.
Oberg KC, O'Toole MF, Gallastegui JL, et al, “'Late' Proarrhythmia Due to Quinidine,” Am J Cardiol, 1994, 74(2):192-4.
Smereck J, "Malaria in Pregnancy: Update on Emergency Management," J Emerg Med, 2011, 40(4):393-6.
Wann SL, Curtis AB, January CT, et al, “2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline): A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines,” Circulation, 2011, 123 (1):104-23.
Wolpert C, Schimpf R, Veltmann C, et al, “Clinical Characteristics and Treatment of Short QT Syndrome,” Exp Rev Cardiovasc Ther, 2005, 3(4):611-7.
Zipes DP, Camm AJ, Borggrefe M, et al, “ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death),” J Am Coll Cardiol, 2006, 48(5):247-346.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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