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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.
Medication Safety Issues
Sound-alike/look-alike issues:
QuiNIDine may be confused with cloNIDine, quiNINE, Quinora®
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication (I.V. formulation) among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Pronunciation
(KWIN i deen)
Index Terms
Generic Available
Yes
Canadian Brand Names
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 Moreover, the use of quinidine has largely been replaced by more effective/safer antiarrhythmic agents and/or nonpharmacologic therapies (eg, radiofrequency ablation).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 Note: The use of I.V. quinidine gluconate for these indications has been replaced by more effective/safer antiarrhythmic agents (eg, amiodarone and procainamide).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/Investigational
Paroxysmal supraventricular tachycardia, paroxysmal AV junctional rhythm, and symptomatic atrial or ventricular premature contractions
Pregnancy Risk Factor
C
Lactation
Enters breast milk/compatible
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; monitor and adjust dose to prevent QTc prolongation.
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), 2E1 (minor), 3A4 (major); Inhibits CYP2C9 (weak), 2D6 (strong), 3A4 (strong)
Drug Interactions
Alfuzosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. Risk X: Avoid combination
Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Almotriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan. Management: Limit initial almotriptan dose to 6.25mg and maximum dose to 12.5mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider therapy modification
Alosetron: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron. Risk C: Monitor therapy
Amiodarone: Antiarrhythmic Agents (Class Ia) may enhance the QTc-prolonging effect of Amiodarone. Amiodarone may increase the metabolism of Antiarrhythmic Agents (Class Ia). 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
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 (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 increase the metabolism of QuiNIDine. Risk D: Consider therapy modification
Beta-Blockers: QuiNIDine may decrease the metabolism of Beta-Blockers. Exceptions: Atenolol; Carteolol; Nadolol. Risk C: Monitor therapy
Calcium Channel Blockers (Dihydropyridine): May decrease the serum concentration of QuiNIDine. Exceptions: Felodipine; Nisoldipine. Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May increase the serum concentration of QuiNIDine. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciclesonide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ciclesonide. Specifically, concentrations of the active des-ciclesonide metabolite may be increased. Risk C: Monitor therapy
Cimetidine: May decrease the metabolism of QuiNIDine. Risk D: Consider therapy modification
Ciprofloxacin: 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: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a strong CYP3A4 inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Risk D: Consider therapy modification
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
CYP3A4 Substrates: CYP3A4 Inhibitors (Strong) may decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dabigatran Etexilate: QuiNIDine may increase the serum concentration of Dabigatran Etexilate. Risk X: Avoid combination
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Dextromethorphan: QuiNIDine may decrease the metabolism of Dextromethorphan. Risk D: Consider therapy modification
Dihydrocodeine: QuiNIDine may diminish the analgesic effect of Dihydrocodeine. Risk D: Consider therapy modification
Dronedarone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Risk X: Avoid combination
Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
Dutasteride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. Risk C: Monitor therapy
Eplerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone. Risk X: Avoid combination
Everolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. Risk X: Avoid combination
FentaNYL: CYP3A4 Inhibitors (Strong) may increase the serum concentration of FentaNYL. Risk D: Consider therapy modification
Fesoterodine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Management: Avoid fesoterodine doses greater than 4mg daily in patients who are also receiving strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Fluconazole: May decrease the metabolism of QuiNIDine. Risk C: Monitor therapy
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Halofantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine. Risk X: Avoid combination
Haloperidol: QuiNIDine may increase the serum concentration of Haloperidol. Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Hydrocodone: QuiNIDine may diminish the analgesic effect of Hydrocodone. Risk D: Consider therapy modification
Ixabepilone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. Risk D: Consider therapy modification
Kaolin: May decrease the absorption of QuiNIDine. Risk D: Consider therapy modification
Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Macrolide Antibiotics: May decrease the metabolism of QuiNIDine. Exceptions: Azithromycin; Dirithromycin [Off Market]; Spiramycin. Risk D: Consider therapy modification
Maraviroc: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. Management: When used with a strong CYP3A4 inhibitor, the adult dose of maraviroc should be decreased to 150 mg twice daily. 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
Nilotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib. Risk X: Avoid combination
Nisoldipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. Risk X: Avoid combination
Paricalcitol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol. Risk C: Monitor therapy
P-Glycoprotein Inducers: May decrease the serum concentration of P-Glycoprotein 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 Inhibitors: May increase the serum concentration of P-Glycoprotein 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 Substrates: P-Glycoprotein Inhibitors may increase the serum concentration of P-Glycoprotein 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 increase the metabolism of QuiNIDine. Risk D: Consider therapy modification
Pimecrolimus: CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus. 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
Prasugrel: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Prasugrel. Risk C: Monitor therapy
Primidone: May increase the metabolism of QuiNIDine. Risk D: Consider therapy modification
Protease Inhibitors: May decrease the metabolism of QuiNIDine. Risk X: Avoid combination
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
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
Ranolazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. Risk X: Avoid combination
Rifamycin Derivatives: May increase the metabolism of QuiNIDine. Risk D: Consider therapy modification
Rivaroxaban: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rivaroxaban. Risk X: Avoid combination
Salmeterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. Risk X: Avoid combination
Saxagliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Saxagliptin. Management: Limit saxagliptin dosage to 2.5 mg/day and monitor for increased saxagliptin levels/effects (e.g., hypoglycemia) with concomitant use of a strong CYP3A4 inhibitor. Monitor for decreased saxagliptin levels/effects if discontinuing CYP3A4 inhibitor. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of QuiNIDine. Fluvoxamine appears to be the only SSRI of concern. Exceptions: Citalopram; Escitalopram; PARoxetine; Sertraline. Risk D: Consider therapy modification
Silodosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin. Risk X: Avoid combination
Sorafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sorafenib. Risk C: Monitor therapy
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
Tadalafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tadalafil. Management: Erectile dysfunction: tadalafil max = 2.5 mg/day (daily use) or 10 mg/72 hrs (as needed use). Avoid use of tadalafil for treatment of pulmonary arterial hypertension in patients also receiving a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease the metabolism of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the formation of highly potent active metabolites. Risk X: Avoid combination
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
Tolvaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination
Topotecan: P-Glycoprotein Inhibitors may increase the serum concentration of Topotecan. 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 decrease the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): QuiNIDine may enhance the anticoagulant effect of Vitamin K Antagonists. Note that the prothrombin time 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: Dietary salt intake may alter the rate and extent of quinidine absorption. A decrease in dietary salt may lead to an increase in quinidine serum concentrations. Avoid changes in dietary salt intake. 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. In addition, CYP3A4 metabolism of quinidine may be reduced by grapefruit juice. Grapefruit juice should be avoided. Excessive intake of fruit juices 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.
Herb/Nutraceutical: St John's wort may decrease quinidine levels. Avoid ephedra (may worsen arrhythmia).
Storage
Do not use discolored parenteral solution.
Compatibility
Stable in D5W, NS.
Y-site administration: Compatible: Diazepam, milrinone. Incompatible: Furosemide. Variable (consult detailed reference): Heparin.
Compatibility when admixed: Compatible: Bretylium, cimetidine, milrinone, ranitidine, verapamil. Incompatible: Atracurium. Variable (consult detailed reference): Amiodarone.
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, malaria; increased with cirrhosis; crosses placenta; enters breast milk
Protein binding:
Newborns: 50% to 70%; decreased protein binding with cyanotic congenital heart disease, cirrhosis, or acute myocardial infarction
Adults: 80% to 90%
Metabolism: Extensively hepatic (50% to 90%) to inactive compounds
Bioavailability: Sulfate: 80%; Gluconate: 70%
Half-life elimination, plasma: Children: 2.5-6.7 hours; Adults: 6-8 hours; prolonged with elderly, cirrhosis, and congestive heart failure
Time to peak, serum: Sulfate: 2 hours; Gluconate: 3-5 hours
Excretion: Urine (15% to 25% as unchanged drug)
Dosage
Dosage expressed in terms of the salt: 267 mg of quinidine gluconate = 200 mg of quinidine sulfate.
Children: Test dose for idiosyncratic reaction (sulfate, oral or gluconate, I.M.): 2 mg/kg or 60 mg/m2
Oral (quinidine sulfate): 15-60 mg/kg/day in 4-5 divided doses or 6 mg/kg every 4-6 hours; usual 30 mg/kg/day or 900 mg/m2/day given in 5 daily doses
I.V. not recommended (quinidine gluconate): 2-10 mg/kg/dose given at a rate ?10 mg/minute every 3-6 hours as needed
Adults: Test dose: Oral, I.M.: 200 mg administered several hours before full dosage (to determine possibility of idiosyncratic reaction)
Oral (for malaria):
Sulfate: 100-600 mg/dose every 4-6 hours; begin at 200 mg/dose and titrate to desired effect (maximum daily dose: 3-4 g)
Gluconate: 324-972 mg every 8-12 hours
I.M.: 400 mg/dose every 2-6 hours; initial dose: 600 mg (gluconate)
I.V.: 200-400 mg/dose diluted and given at a rate ?10 mg/minute; may require as much as 500-750 mg
Dosing adjustment in renal impairment: Clcr <10 mL/minute: Administer 75% of normal dose.
Hemodialysis: Slightly hemodialyzable (5% to 20%); 200 mg supplemental dose posthemodialysis is recommended.
Peritoneal dialysis: Not dialyzable (0% to 5%)
Dosing adjustment/comments in hepatic impairment: Larger loading dose may be indicated; reduce maintenance doses by 50% and monitor serum levels closely.
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.
Administration: I.V.
Give around-the-clock to promote less variation in peak and trough serum levels. Maximum I.V. infusion rate: 10 mg/minute. Minimize use of PVC tubing to enhance bioavailability.
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 ?mol/L). Patient-dependent therapeutic response occurs at levels of 3-6 mcg/mL (SI: 9.2-18.5 ?mol/L). Optimal therapeutic level is method dependent; >6 mcg/mL (SI: >18 ?mol/L).
Dietary Considerations
Administer with food or milk to decrease gastrointestinal irritation. Avoid changes in dietary salt intake.
Patient Education
Take exactly as directed, around-the-clock; do not take additional doses or discontinue without consulting prescriber. 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, or visual changes (use caution when driving or engaging in tasks requiring alertness until response to drug is known); abnormal taste, nausea or vomiting, or loss of appetite (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); headaches (prescriber may recommend mild analgesic); 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. Pregnancy precaution: Inform prescriber if you are or intend to become pregnant.
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
Assess other medications patient may be taking for effectiveness and interactions. I.V. requires use of infusion pump and continuous cardiac and hemodynamic monitoring. Assess results of laboratory tests, therapeutic effectiveness (monitor cardiac functioning closely), and adverse reactions at beginning of therapy, when titrating dosage, and on a regular basis with long-term therapy. Note: Quinidine has a low TI and overdose may easily produce severe and life-threatening reactions. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report.
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, as sulfate: 200 mg, 300 mg
Tablet, extended release, as gluconate: 324 mg [equivalent to quinidine base 202 mg]
Tablet, extended release, 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): $60.08
Tablet, controlled release (Quinidine Sulfate CR)
300 mg (90): $46.99
Tablets (Quinidine Sulfate)
200 mg (90): $19.99
300 mg (90): $36.99
Extemporaneously Prepared
A 10 mg/mL oral liquid preparation made from tablets and 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®) was stable for 60 days when stored in amber plastic prescription bottles in the dark at room temperature (25°C) or under refrigeration (5°C). Grind six 200 mg tablets in a mortar into a fine powder; add 15 mL of the vehicle and mix well to form a uniform paste; mix while adding the vehicle in geometric proportions to almost 120 mL; transfer to a calibrated bottle and qsad to 120 mL; label “shake well” and “protect from light” (Allen, 1998).
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
Buxton AE, Lee KL, Fisher JD, et al, “A Randomized Study of the Prevention of Sudden Death in Patients With Coronary Artery Disease. Multicenter Unsustained Tachycardia Trial Investigators,” N Engl J Med, 1999, 341:1882-90.
Coplen SE, Antman EM, Berlin JA, et al, “Efficacy and Safety of Quinidine Therapy for Maintenance of Sinus Rhythm After Cardioversion. A Meta-analysis of Randomized Control Trials,” Circulation, 1990, 82:1106-16.
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.
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.
International Brand Names
Lexi-Comp.com
Last full review/revision September 2009
Content last modified September 2009
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