Quinidex Extentabs - Drug Monograph

Introduction

Quinidex Extentabs (quinidine sulfate extended-release tablets) is an antiarrhythmic medication belonging to Class IA of the Vaughan Williams classification. Originally approved by the FDA in the mid-20th century, this extended-release formulation provides sustained plasma concentrations of quinidine, a naturally occurring alkaloid derived from cinchona bark. Quinidex Extentabs are specifically designed for maintenance therapy in cardiac arrhythmias, offering the advantage of less frequent dosing compared to immediate-release formulations.

Mechanism of Action

Quinidine exerts its antiarrhythmic effects through multiple mechanisms:

• Sodium channel blockade: Decreases the maximum rate of depolarization (phase 0) of the cardiac action potential
• Potassium channel blockade: Prolongs action potential duration and effective refractory period
• Vagolytic effects: Antagonizes muscarinic receptors, which can paradoxically increase AV nodal conduction
• Alpha-adrenergic blockade: Causes peripheral vasodilation
• Negative inotropic effect: Reduces myocardial contractility

These combined actions suppress abnormal automaticity and slow conduction velocity, particularly in atrial and ventricular tissue.

Indications

FDA-approved indications:

• Maintenance of normal sinus rhythm after conversion of atrial fibrillation and/or flutter
• Prevention of recurrent paroxysmal atrial fibrillation
• Suppression of ventricular arrhythmias (including ventricular tachycardia)

Off-label uses may include treatment of malaria (particularly chloroquine-resistant Plasmodium falciparum) and certain myotonic disorders.

Dosage and Administration

• Initial dose: 300-600 mg every 8-12 hours
• Maintenance: 200-400 mg every 6-8 hours
• Maximum recommended dose: 3-4 grams daily

• Renal impairment: Reduce dose by 30-50% for CrCl <50 mL/min
• Hepatic impairment: Use with caution and consider dose reduction
• Elderly: Initiate at lower end of dosing range due to decreased clearance
• Pediatric: Safety and effectiveness not established

• Swallow tablets whole; do not crush or chew
• Administer with food to minimize gastrointestinal upset
• Consistent timing of doses is critical for maintaining therapeutic levels

Pharmacokinetics

• Extended-release formulation provides gradual absorption
• Bioavailability: approximately 70-80%
• Peak concentrations: 3-5 hours post-dose

• Volume of distribution: 2-3 L/kg
• Protein binding: 80-90% primarily to albumin and alpha-1 acid glycoprotein
• Crosses placenta and enters breast milk

• Extensive hepatic metabolism via cytochrome P450 3A4 (CYP3A4)
• Primary metabolites: 3-hydroxyquinidine (active), O-desmethylquinidine

• Half-life: 6-8 hours (prolonged in extended-release formulation)
• Renal excretion: 10-20% as unchanged drug
• Clearance: Decreased in heart failure, hepatic disease, and renal impairment

Contraindications

• Known hypersensitivity to quinidine or other cinchona alkaloids
• History of thrombocytopenia during quinidine therapy
• Myasthenia gravis
• Complete AV block without functioning pacemaker
• History of torsades de pointes
• Digoxin toxicity (unless life-threatening arrhythmia present)
• Concurrent use with medications that significantly prolong QT interval

Warnings and Precautions

• Mortality increase observed in patients with non-life-threatening ventricular arrhythmias
• Proarrhythmic effects, including torsades de pointes, can occur

• Cinchonism: Monitor for tinnitus, hearing loss, visual disturbances
• Hematologic effects: Regular CBC monitoring for thrombocytopenia, hemolytic anemia
• Hypotension: May occur due to alpha-adrenergic blockade
• Exacerbation of myasthenia gravis and other neuromuscular disorders
• Hepatitis and other hepatic reactions reported
• Lupus-like syndrome possible with long-term use

Drug Interactions

• Enzyme inducers (rifampin, phenobarbital): Decreased quinidine levels
• Enzyme inhibitors (cimetidine, verapamil, ketoconazole): Increased quinidine levels
• Digoxin: Quinidine doubles digoxin concentrations
• Warfarin: Enhanced anticoagulant effect
• Other QT-prolonging agents: Additive risk of torsades de pointes
• Beta-blockers: Additive myocardial depression
• Calcium channel blockers: Enhanced hypotension and AV conduction effects

• Monitor drug levels and clinical effects
• Adjust doses based on therapeutic drug monitoring
• Avoid combinations with significant interaction potential when possible

Adverse Effects

• Gastrointestinal: Diarrhea, nausea, vomiting, abdominal pain
• Neurologic: Dizziness, headache, tinnitus
• Cardiovascular: Hypotension, palpitations

• Torsades de pointes and other ventricular arrhythmias
• Thrombocytopenia (immune-mediated)
• Hemolytic anemia
• Hepatitis and liver function abnormalities
• Cinchonism (tinnitus, hearing loss, blurred vision)
• Lupus erythematosus-like syndrome
• Hypersensitivity reactions including anaphylaxis

Monitoring Parameters

• ECG: Baseline, after dose changes, and regularly during therapy

- QRS duration (should not increase >25%) - QT interval (should not exceed 500-520 ms)

• Serum quinidine levels: Therapeutic range 2-5 mcg/mL
• Complete blood count with platelets: Baseline and periodically
• Liver function tests: Baseline and periodically
• Renal function: Baseline and periodically
• Digoxin levels if co-administered
• Blood pressure and heart rate at each visit

• Draw trough levels just before next dose
• Target concentration: 2-5 mcg/mL for antiarrhythmic effects
• Levels >6 mcg/mL associated with increased toxicity risk

Patient Education

• Take exactly as prescribed; do not stop abruptly
• Swallow tablets whole; do not crush or chew
• Report immediately:

- Irregular heartbeat, dizziness, or fainting - Unexplained bleeding or bruising - Fever, rash, or dark urine - Hearing changes or ringing in ears - Vision changes

• Avoid grapefruit juice during therapy
• Inform all healthcare providers about quinidine use
• Carry medical identification indicating quinidine therapy
• Regular follow-up and monitoring are essential
• Potential for drug interactions with many medications

References

1. FDA prescribing information for quinidine extended-release tablets 2. Zipes DP, et al. ACC/AHA/ESC guidelines for management of patients with ventricular arrhythmias. Circulation. 2006;114(10):e385-e484 3. Roden DM. Antiarrhythmic drugs. In: Brunton LL, Hilal-Dandan R, Knollmann BC, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 13th ed. McGraw-Hill; 2018 4. Grace AA, Camm AJ. Quinidine. N Engl J Med. 1998;338(1):35-45 5. Woosley RL, et al. Effect of quinidine on the QT interval. Circulation. 1985;71(1):15-21 6. Holford NHG. Clinical pharmacokinetics of quinidine. Clin Pharmacokinet. 1987;12(5):332-343 7. American College of Cardiology/American Heart Association/Heart Rhythm Society atrial fibrillation guidelines. 2019 8. Micromedex® DrugDex® evaluations. Quinidine. Truven Health Analytics