Quinidine

QUINIDEX

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What it isClass IA antiarrhythmic; Brugada syndrome and, with dextromethorphan, pseudobulbar affect.

Why this oneIt is one of the few agents for Brugada syndrome, and it is a potent CYP2D6 inhibitor used deliberately to block dextromethorphan metabolism.

What limits itQT prolongation and cinchonism. It raises digoxin levels; excess mortality when used for ordinary arrhythmia.

FDA-approved for

arrhythmias (~1950)

FDA label

Read the full label on DailyMed ↗

FDA dosing	Population	Start	Target	Max
Conversion of symptomatic atrial fibrillation/flutter to sinus rhythm (after ventricular rate control has failed)	Adult	400 mg (2 tablets) q6h	If no conversion after 4-5 doses, cautiously increase; discontinue if not converted in reasonable time	Gated by ECG limits (QRS/QTc widening to 130% of pretreatment, QTc >500 ms)
Reduction of frequency of relapse into atrial fibrillation/flutter (high-risk symptomatic patients)	Adult	200 mg q6h	Cautiously raise if tolerated, level within therapeutic range, and inter-episode time not satisfactorily increased	Reduce total daily dose for QRS/QTc widening to 130% of pretreatment, P-wave disappearance, tachy-/bradycardia, or hypotension
Suppression of recurrent life-threatening ventricular arrhythmias (e.g., sustained VT)	Adult	Regimens not adequately studied; generally similar to 200 mg q6h	Guide by programmed electrical stimulation and/or Holter with exercise where possible	Same ECG-gated limits
Life-threatening P. falciparum malaria	Adult & peds	Part of approved regimen centered on Quinidine Gluconate Injection (see that label)	Per gluconate injection regimen	Per gluconate injection regimen

Titration Conversion of A-fib/flutter: increase only after 4-5 doses without conversion; relapse prevention: raise only if regimen well tolerated and serum level still well within therapeutic range

Renal No specific adjustment given; renal dysfunction slows quinidine elimination — can lead to toxicity unless dosage appropriately reduced

Hepatic No specific adjustment given; hepatic dysfunction slows quinidine elimination — can lead to toxicity unless dosage appropriately reduced

200 mg quinidine sulfate = 166 mg quinidine base; 400 mg = 332 mg base

Instructions

Initiate or adjust dose in a setting with continuous monitoring and resuscitation facilities, especially with structural heart disease or other toxicity risk factors
Use for A-fib/flutter only after ventricular rate control (e.g., digitalis, beta-blockers) has failed to control symptoms
Discontinue/reduce if QRS widens to 130% of pretreatment, QTc widens to 130% and exceeds 500 ms, P waves disappear, or significant tachycardia, symptomatic bradycardia, or hypotension develops
Continue monitoring 2-3 days after initiating the discharge regimen
A single recurrence of tachyarrhythmia is not therapeutic failure — goal is increased time between episodes

Contraindications

Thrombocytopenic purpura during prior therapy with quinidine or quinine
Cardiac rhythm dependent on a junctional or idioventricular pacemaker (incl. complete AV block) without a functioning artificial pacemaker
Patients who might be adversely affected by an anticholinergic agent (e.g., myasthenia gravis)

Cautions

Increased mortality: in trials for non-life-threatening arrhythmias, quinidine mortality was >3x placebo (atrial flutter/fib metaanalysis) and consistently greater than alternative antiarrhythmics for non-life-threatening ventricular arrhythmias
Proarrhythmia: QTc prolongation and torsades de pointes — extreme care in preexisting long-QT, prior torsades, or prior marked QTc lengthening; risk increased by bradycardia, hypokalemia, hypomagnesemia, hypocalcemia, or high quinidine levels
Paradoxical increase in ventricular rate in atrial flutter/fibrillation — consider prior AV-nodal blockade (digitalis, verapamil, diltiazem, beta-blocker)
Marked sinus node depression and bradycardia in sick sinus syndrome
Use with caution in patients at high risk of complete AV block without pacemaker (digitalis intoxication, second-degree AV block, severe intraventricular conduction defects)
Vagal maneuvers to terminate paroxysmal SVT may be ineffective (vagolytic effect)

Adverse reactions

Diarrhea (35%), upper GI distress (22%), nausea, vomiting, heartburn/esophagitis
Lightheadedness (15%), headache (7%), fatigue (7%), palpitations (7%), angina-like pain (6%)
Cinchonism: tinnitus, reversible high-frequency hearing loss, vertigo, blurred vision, diplopia, confusion, delirium
Hepatotoxicity incl. granulomatous hepatitis (first weeks of therapy)
Autoimmune/inflammatory: thrombocytopenic purpura, hemolytic anemia, vasculitis, lupus-like syndrome, fever, urticaria, agranulocytosis
Syncope; rare acute psychotic reactions

Pregnancy Pregnancy Category C — no animal reproduction studies; no adequate human studies; give only if clearly needed; crosses to fetus (neonatal serum level equaled mother's in one case, no apparent ill effect)

Lactation Present in human milk slightly below maternal serum levels; avoid administration in lactating women who continue to nurse, if possible

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