Yes

Antiarrhythmic Agent, Class I-A

Prophylaxis after cardioversion of atrial fibrillation and/or flutter to maintain normal sinus rhythm; prevent recurrence of paroxysmal supraventricular tachycardia, paroxysmal A-V junctional rhythm, paroxysmal ventricular tachycardia, paroxysmal atrial fibrillation, and atrial or ventricular premature contractions; has activity against Plasmodium falciparum malaria

C

Hypersensitivity to quinidine or any component; 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

Monitor and adjust dose to prevent QTc prolongation. Watch for proarrhythmic effects. May precipitate or exacerbate CHF. Reduce dosage in hepatic impairment. In patients with atrial fibrillation or flutter, block the AV node before initiating. Correct hypokalemia before initiating therapy. Hypokalemia may worsen toxicity. Use may cause digoxin-induced toxicity (adjust digoxin's dose). Use caution with concurrent use of other antiarrhythmics. Avoid use in myasthenia gravis (may worsen condition). Hypersensitivity reactions can occur. Can unmask sick sinus syndrome (causes bradycardia). Has been associated with severe hepatotoxic reactions, including granulomatous hepatitis. Hemolysis may occur in patients with G-6-PD (glucose-6-phosphate dehydrogenase) deficiency.

Incidence not determined: 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, diarrhea, anorexia, nausea, vomiting, stomach cramping (22%)

1% to 10%:

Cardiovascular: Angina (6%), palpitation (7%), new or worsened arrhythmias (proarrhythmic effect)

Central nervous system: Syncope(1% to 8%), headache (7%), fatigue (7%), weakness (5%), sleep disturbance (3%), tremor (2%), nervousness (2%), incoordination (1%)

Dermatologic: Rash (5%)

Ocular: Blurred vision

Otic: Tinnitus

Respiratory: Wheezing

<1% (Limited to important or life-threatening symptoms): 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, impaired hearing, 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, increased CPK, drug-induced lupus-like syndrome, cerebral hypoperfusion (possibly resulting in ataxia, apprehension and seizures), 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

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 in sensitive patients after brief exposure to a moderate dose. Vomiting and diarrhea may also occur as isolated reactions to therapeutic quinidine levels.

Has a low toxic:therapeutic ratio and may easily produce fatal intoxication (acute toxic dose: 1 g in adults); symptoms of overdose include sinus bradycardia, sinus node arrest or asystole, P-R, QRS or Q-T interval prolongation, torsade de pointes (polymorphous ventricular tachycardia) and depressed myocardial contractility, which along with alpha-adrenergic or ganglionic blockade, may result in hypotension and pulmonary edema; other effects are anticholinergic (dry mouth, dilated pupils, and delirium) as well as seizures, coma and respiratory arrest.

Treatment is primarily symptomatic and effects usually respond to conventional therapies (fluids, positioning, vasopressors, anticonvulsants, antiarrhythmics). Note: Do not use other type 1a or 1c antiarrhythmic agents to treat ventricular tachycardia; sodium bicarbonate may treat wide QRS intervals or hypotension; markedly impaired conduction or high degree A-V block, unresponsive to bicarbonate, indicates consideration of a pacemaker is needed.

CYP3A3/4 substrate/inhibitor, CYP2D6 inhibitor

Amiloride may cause prolonged ventricular conduction leading to arrhythmias.

Amiodarone may increase quinidine blood levels; monitor quinidine levels.

Cimetidine: Increase quinidine blood levels; closely monitor levels or use an alternative H₂ antagonist.

Cisapride and quinidine may increase risk of malignant arrhythmias; concurrent use is contraindicated.

Codeine: Analgesic efficacy may be reduced.

Digoxin blood levels may be increased. Monitor digoxin blood levels.

Enzyme inducers (aminoglutethimide, carbamazepine, phenobarbital, phenytoin, primidone, rifabutin, rifampin) may decrease quinidine blood levels.

Metoprolol: Increased metoprolol blood levels.

Mexiletine blood levels may be increased.

Nifedipine blood levels may be increased by quinidine; nifedipine may decrease quinidine blood levels.

Drugs which prolong the QT interval include amiodarone, amitriptyline, astemizole, bepridil, disopyramide, erythromycin, haloperidol, imipramine, pimozide, procainamide, sotalol, and thioridazine. Effects may be additive; use with caution.

Propafenone blood levels may be increased.

Propranolol blood levels may be increased.

Ritonavir, nelfinavir and amprenavir may increase quinidine levels and toxicity; concurrent use is contraindicated.

Sparfloxacin, gatifloxacin, and moxifloxacin may result in additional prolongation of the QT interval; concurrent use is contraindicated.

Timolol blood levels may be increased.

Urinary alkalinizers (antacids, sodium bicarbonate, acetazolamide) increase quinidine blood levels.

Verapamil and diltiazem increase quinidine blood levels.

Warfarin effects may be increased by quinidine; monitor INR closely during addition or withdrawal of quinidine.

Do not use discolored parenteral solution

Class 1A 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

Distribution: V_d: Adults: 2-3.5 L/kg, decreased with congestive heart failure, malaria; increased with cirrhosis; crosses the placenta; appears in breast milk

Protein binding:

Newborns: 60% to 70%; decreased protein binding with cyanotic congenital heart disease, cirrhosis, or acute myocardial infarction

Adults: 80% to 90%

Metabolism: Extensively in the liver (50% to 90%) to inactive compounds

Bioavailability: Sulfate: 80%; Gluconate: 70%

Plasma half-life: Children: 2.5-6.7 hours; Adults: 6-8 hours; increased half-life with elderly, cirrhosis, and congestive heart failure

Elimination: In urine (15% to 25% as unchanged drug)

Dosage expressed in terms of the salt: 267 mg of quinidine gluconate = 200 mg of quinidine sulfate.

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 less than or equal to 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 less than or equal to 10 mg/minute; may require as much as 500-750 mg

Dosing adjustment in renal impairment: Cl_cr <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.

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; food has a variable effect on absorption of sustained release formulation

Cardiac monitor required during I.V. administration; CBC, liver and renal function tests, should be routinely performed during long-term administration

Therapeutic: 2-5 mg/mL (SI: 6.2-15.4 mmol/L). Patient dependent therapeutic response occurs at levels of 3-6 mg/mL (SI: 9.2-18.5 mmol/L). Optimal therapeutic level is method dependent; >6 mg/mL (SI: >18 mmol/L).

As with other Class Ic 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 (EKG) in a controlled setting when initiating therapy. Therapy should be discontinued or the dose reduced if the Q-T interval increases greater than or equal to 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.

May cause dizziness; may rarely cause confusion or delirium

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

No information available to require special precautions

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)

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 capsules. 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 (exercise, yogurt, or boiled milk may help - if persistent consult prescriber). Report chest pain, palpitation, or erratic heartbeat; difficulty breathing or wheezing; CNS changes (confusion, delirium, fever, consistent dizziness); skin rash; sense of fullness or ringing in ears; or changes in vision. Pregnancy precautions: Inform prescriber if you are or intend to be pregnant.

Do not crush sustained release drug product

Injection, as gluconate: 80 mg/mL (10 mL)

Tablet, as polygalacturonate: 275 mg

Tablet, as sulfate: 200 mg, 300 mg

Tablet:

Sustained action, as sulfate: 300 mg

Sustained release, as gluconate: 324 mg

A 10 mg/mL quinidine sulfate solution made with six 200 mg capsules, 15 mL alcohol USP, and citric acid syrup USP qs ad to a total amount of 120 mL is stable for 30 days under refrigeration

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Bauman JL, Bauerfeind RA, Hoff JV, et al, "Torsade de Pointes Due to Quinidine: Observation in 31 Patients," Am Heart J, 1984, 107(3):425-30.

Haapanen EJ and Pellinen TJ, "Hemoperfusion in Quinidine Intoxication," Acta Med Scand, 1981, 210(6):515-6.

Lesne M, Devos M, and Reynaert M, "Enterogastric Cycle and Intoxication With Hydroquinidine: A Case Report," Clin Toxicol, 1981, 18(6):659-62.

Panisko DM and Keystone JS, "Treatment of Malaria - 1990," Drugs, 1990, 39(2):160-89.

Spinler SA, Cheng JW, Kindwall KE, et al, "Possible Inhibition of Hepatic Metabolism of Quinidine by Erythromycin," Clin Pharmacol Ther, 1995, 57(1):89-94.

Swiryn S and Kim SS, "Quinidine-Induced Syncope," Arch Intern Med, 1983, 143(2):314-6.

Szefler SJ, Pieroni DR, Gingell RL, et al, "Rapid Elimination of Quinidine in Pediatric Patients," Pediatrics, 1982, 70(3):370-5.

Wang L, Sheldon RS, Mitchell LB, et al, "Amiloride-Quinidine Interaction: Adverse Outcomes," Clin Pharmacol Ther, 1994, 56(6 Pt 1):659-67.

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