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Quinidine

Pronunciation: (KWIN-ih-deen)
Class: Antiarrhythmic agent Quinidine Sulfate

Trade Names:
Quinidine Sulfate
- Tablets 200 mg
- Tablets 300 mg
- Tablets, sustained-release 300 mg

Biquin Durules (Canada)
Quinidine Gluconate

Trade Names:
Quinidine Gluconate
- Tablets, sustained-release 324 mg
- Injection 80 mg/mL

Pharmacology

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Depresses myocardial excitability, conduction velocity, and contractility; prolongs effective refractory period and increases conduction time; indirect anticholinergic effects; may decrease vagal tone at low doses paradoxically increasing conduction through the AV node.

Pharmacokinetics

Absorption

Quinidine gluconate

Rapidly absorbed from GI tract. Bioavailability is 70% to 80% (sustained-release). T _max is 3 to 5 h. With food, absorption is increased in both rate (27%) and extent (17%).

Quinidine sulfate

Bioavailability is about 70%, varies widely (45% to 100%) between patients. T _max is about 2 h. The rate of absorption is somewhat slower when taken with food.

Distribution

Vd is 2 to 3 L/kg (healthy adults), decreased to 0.5 L/kg (CHF), increased to 3 to 5 L/kg (liver cirrhosis). Protein binding occurs in adults 80% to 88%, decreased protein binding in pregnant women, infants, and neonates (about 50% to 70%). Protein binding is increased in chronic renal failure.

Metabolism

Occurs in the liver (60% to 80%) to some active metabolites, mainly to the active 3-hydroxy-quinidine (3HQ).

Elimination

T _½ is 6 to 8 h (adult), 3 to 4 h (children), and 12 h (3HQ). Cl is 3 to 5 mL/min/kg (adult), may be 2 to 3 times as rapid in children. Elimination occurs in the urine (20% unchanged). Urine acidification increases excretion, alkalinization decreases excretion.

Special Populations

Renal Function Impairment

Vd and renal Cl may be reduced.

Elderly

Elimination t _½ may be increased.

CHF

Total Cl and Vd are decreased.

Hepatic cirrhosis

Elimination t _½ may be prolonged and increase Vd.

Indications and Usage

Treatment of premature atrial, atrioventricular junctional, and ventricular contractions; treatment of paroxysmal supraventricular tachycardia, paroxysmal atrioventricular junctional rhythm, atrial flutter, paroxysmal and chronic atrial fibrillation, and paroxysmal ventricular tachycardia not associated with complete heart block; maintenance therapy after electrical conversion of atrial fibrillation or flutter.

Quinidine gluconate (IV administration)

Treatment of life-threatening Plasmodium falciparum malaria.

Contraindications

Myasthenia gravis; history of thrombocytopenic purpura associated with quinidine administration; digitalis intoxication; complete heart block; left bundle branch block; complete atrioventricular (AV) block with AV nodal or idioventricular pacemaker; aberrant ectopic impulses and abnormal rhythms because of escape mechanisms; history of drug-induced torsades de pointes; history of long QT syndrome.

Dosage and Administration

The following oral doses are expressed as quinidine sulfate salt:

Premature Atrial and Ventricular Contractions
Adults

PO 200 to 300 mg 3 to 4 times daily.

Children

PO 30 mg/kg/day or 900 mg/m ² /day in 5 divided doses.

Paroxysmal Supraventricular Tachycardia
Adults

PO 400 to 600 mg every 2 to 3 h until event is abated.

Atrial Flutter

Administer after digitalization and individualize dose.

Conversion of Atrial Fibrillation
Adults

PO 200 mg every 2 to 3 h for 5 to 8 doses, then maintain with 200 to 300 mg 3 to 4 times daily (immediate-release tablets) or 300 to 600 mg 2 to 3 times daily (sustained-release tablets); do not exceed 3 to 4 g/day.

Quinidine Gluconate
Adults

PO 324 to 648 mg (1 to 2 tablets) every 8 to 12 h.

Parenteral Quinidine Gluconate
Acute Tachycardia Adults

IM 600 mg initially, then 400 mg as needed up to every 2 h.

Children

IV 2 to 10 mg/kg/dose every 3 to 6 h as needed.

P. falciparum Malaria Adults

IV 15 mg/kg infused over 4 h initially, then 7.5 mg/kg over 4 h every 8 h for 7 days or until oral therapy can be instituted or 10 mg/kg over 1 to 2 h initially, then 0.02 mg/kg/min for up to 72 h or until oral therapy can be instituted.

General Advice

Use IV route only when rapid response is needed or oral route is not feasible.
Position patient supine during IV administration to minimize hypotension.
For direct IV push, administer slowly at 1 mL/min.
For intermittent IV infusion, dilute 800 mg per 50 mL or more with D5W; give at a rate of 16 mg/min or less. Use infusion device for accuracy/safety.
Administer IM injection in deltoid muscle.
Give oral preparation with full glass of water on empty stomach (1 h before or 2 h after other medication) to enhance absorption; if GI distress develops, administer with or just after meal.
Do not break or crush or allow patient to chew sustained-release preparations. Instruct patient to swallow whole.

Storage/Stability

Store vial at room temperature. Parenteral solution must be clear and colorless. Solution is stable for 24 h. Store tablets in tight, light-resistant container.

Drug Interactions

Amiodarone, antacids, cimetidine, verapamil

May increase quinidine levels.

Anticoagulants

May increase effect of anticoagulant; may cause hemorrhage.

Barbiturates, nifedipine, primidone, sucralfate

May decrease quinidine levels.

Beta-blockers

May increase effect of beta-blocker.

Dextromethorphan

May increase plasma dextromethorphan concentrations.

Digitoxin, digoxin

May increase digoxin plasma levels.

Hydantoins

May reduce therapeutic effect of quinidine.

Nondepolarizing neuromuscular blocking agents, succinylcholine

May increase neuromuscular blockade effect.

Propafenone

Increased propafenone levels.

Rifampin

May increase quinidine metabolism.

Laboratory Test Interactions

Triamterene will interfere with the fluorescent measurement of quinidine levels.

Adverse Reactions

Cardiovascular

Widening of QRS complex; cardiac asystole; ventricular ectopy; hypotension; paradoxical tachycardia.

CNS

Headache; fever; vertigo; excitement; confusion; delirium; syncope.

Dermatologic

Rash; urticaria; pruritus; flushing; photosensitivity.

EENT

Mydriasis; blurred vision; photophobia, diplopia, night blindness; tinnitus.

GI

Nausea; vomiting; anorexia; abdominal pain; diarrhea.

Genitourinary

Lupus nephritis.

Hepatic

Hepatitis.

Hematologic

Acute hemolytic anemia; agranulocytosis; thrombocytopenic purpura.

Miscellaneous

Lupus erythematosus-like syndrome; cinchonism (headache, tinnitus, nausea, disturbed vision, deafness, dizziness, vertigo, lightheadedness); hypersensitivity reactions; arthralgia; myalgia.

Precautions

Warnings

Mortality rates increased when used to treat non-life-threatening arrhythmias.

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Hypersensitivity

May occur; administer single 200 mg tablet of quinidine sulfate or 200 mg IM injection of quinidine gluconate before starting therapy to determine if patient has idiosyncrasy to quinidine.

Renal Function

Use drug with caution because of potential for toxicity.

Hepatic Function

Use drug with caution because of potential for toxicity.

Atrial flutter or fibrillation

Pretreat these patients with digitalis preparation.

Bioequivalence

Different salts have different amounts of quinidine base. Do not interchange without taking this into consideration.

Cardiotoxicity

May occur; immediately discontinue drug.

Hepatotoxicity (including granulomatous hepatitis)

Has occurred. Consider possibility if unexplained fever or elevated hepatic enzymes develop.

Malaria

Dose schedules may result in hypotension, ECG changes, and cinchonism.

Parenteral therapy

Use only when oral therapy is not possible or when rapid therapeutic effect is required.

Potassium balance

Effect of quinidine is enhanced by potassium and reduced if hypokalemia is present.

Cardiac impairment

Use drug with caution because of potential for toxicity.

Syncope

Occasionally occurs in patients on long-term therapy; may be fatal. Often caused by torsades de pointes.

Vagolytic effects

May antagonize vagal maneuvers or administration of cholinergic drugs used to terminate paroxysmal supraventricular tachycardia.

Overdosage

Symptoms

Cardiorespiratory depression, lethargy, confusion, coma, seizures, headache, paresthesia, vertigo, vomiting, abdominal pain, diarrhea, nausea, tachyarrhythmias, depressed automaticity and conduction, hypotension, syncope, heart failure, cinchonism, hypokalemia, visual/auditory disturbances, tinnitus, acidosis.

Patient Information

Instruct patient/family to administer medication around clock as directed and to continue taking medication even if symptoms improve.
Advise patient to take with food if GI upset occurs.
Tell patient that sustained-release tablet should not be crushed or chewed.
Instruct patient/family how to take pulse. Advise them to check pulse prior to each dose and to contact health care provider if rate or rhythm changes.
Advise patient to carry medical identification (eg, card, bracelet) indicating disease and drug therapy at all times.
Advise patient to notify other health care providers/dentist prior to other therapy/surgery.
Emphasize importance of regular medical follow-up, even in absence of adverse reactions or problems related to this drug therapy.
Caution patient to wear dark glasses as needed to decrease light sensitivity and inform patient that dark glasses may be needed both indoors and outside.
Instruct patient to report the following symptoms to health care provider immediately: visual disturbances (eg, blurring), tinnitus, bleeding, bruising, fever, headache, dizziness, severe diarrhea, or skin rash/eruption.
Advise patient that drug causes dizziness and blurred vision and to use caution while driving or performing other tasks requiring mental alertness.
Caution patient to avoid exposure to sunlight and to use sunscreen or wear protective clothing to avoid photosensitivity reaction.