quinidine gluconate
Quinaglute Dura-Tabs, Quinalan

quinidine sulfate
Apo-Quinidine ◆, Quinidex Extentabs, Quinora

Available forms
Available by prescription only
Injection: 80 mg/ml (gluconate) containing 50 mg/ml of quinidine
Tablets: 200 mg, 300 mg (sulfate)
Tablets (sustained-release): 300 mg (sulfate), 324 mg (gluconate)

Indications and dosages
 Atrial flutter or fibrillation conversion. Adults: 200 mg (sulfate or equivalent base) P.O. q 2 to 3 hours for five to eight doses with subsequent daily increases until sinus rhythm is restored or toxic effects develop. Give quinidine only after digitalization to avoid increasing AV conduction. Maximum, 3 to 4 g daily.
 Maintenance dosage, 200 to 400 mg P.O. sulfate t.i.d. or q.i.d. Or, 600 mg P.O. q 8 to 12 hours daily sulfate (sustained-release). Or 648 mg P.O. (gluconate sustained-release) q 12 hours; or 324 to 648 P.O. (gluconate sustained-release) q 8 hours.
 Paroxysmal supraventricular tachycardia. Adults: 400 to 600 mg (sulfate) P.O. q 2 to 3 hours until toxic effects develop or arrhythmia subsides.
 Premature atrial contractions, PVCs, paroxysmal AV junctional rhythm or atrial or ventricular tachycardia, maintenance of cardioversion. Adults: Give test dose of 200 mg P.O. of sulfate (or 200 mg gluconate I.M.); then monitor vital signs before beginning therapy with 200 to 300 mg P.O. sulfate or equivalent base q 4 to 6 hours. Or, initially, 600 mg of gluconate I.M.; then up to 400 mg q 2 hours, p.r.n. Or, 800 mg I.V. gluconate diluted in 40 ml of D₅W, infused at 16 mg (1 ml)/minute. Or, 600 mg of sulfate (sustained-release) or 324 to 648 mg of gluconate (sustained-release) q 8 to 12 hours.
Children: Give test dose of 2 mg/kg P.O. sulfate; then give 30 mg/kg daily P.O. or 900 mg/m² daily P.O., I.V., or I.M. in five divided doses.
 Malaria (when quinine dihydrochloride is unavailable) ◇. Adults: Give quinidine gluconate by continuous I.V. infusion. Initial loading dose of 10 mg/kg diluted in 250 ml of normal saline solution and infused over 1 to 2 hours, followed by continuous maintenance infusion of 0.02 mg/kg/minute (20 mcg/kg/minute) for 72 hours or until parasitemia is reduced to less than 1% or oral therapy can be started. Alternatively, 300 to 600 mg or, 10 mg/kg quinidine sulfate P.O. q 8 hours for 5 to 7 days.
Children: I.V. dosage is the same as for adults.

Pharmacodynamics
Antiarrhythmic action: A class IA antiarrhythmic, quinidine depresses phase 0 of the action potential. It’s considered a myocardial depressant because it decreases myocardial excitability and conduction velocity and may depress myocardial contractility. It also exerts anticholinergic activity, which may modify its direct myocardial effects. In therapeutic doses, quinidine reduces conduction velocity in the atria, ventricles, and His-Purkinje system. It helps control atrial tachyarrhythmias by prolonging the effective refractory period (ERP) and increasing the action potential duration in the atria, ventricles, and His-Purkinje system. Because ERP prolongation exceeds action potential duration, tissue remains refractory even after returning to resting membrane potential (membrane-stabilizing effect).
 Quinidine shortens the effective refractory period of the AV node. Because anticholinergic action of quinidine may increase AV node conductivity, a cardiac glycoside should be administered for atrial tachyarrhythmias before quinidine therapy begins, to prevent ventricular tachyarrhythmias. Quinidine also suppresses automaticity in the His-Purkinje system and ectopic pacemakers, making it useful in treating PVCs. At therapeutic doses, quinidine prolongs the QRS complex and QT interval; these ECG effects may be used as an index of drug effectiveness and toxicity.

Pharmacokinetics
Absorption: Although all quinidine salts are well absorbed from the GI tract, individual serum drug levels vary greatly. For extended-release forms, onset of action may be slightly slower but duration of effect is longer because drug delivery system allows longer-than-usual dosing intervals.
Distribution: Drug is well distributed in all tissues except the brain and concentrates in the heart, liver, kidneys, and skeletal muscle. Distribution volume decreases in patients with heart failure, possibly requiring reduction in maintenance dosage. About 80% of drug is bound to plasma proteins; the unbound (active) fraction may increase in patients with hypoalbuminemia from various causes, including hepatic insufficiency. Usual therapeutic serum levels depend on assay method. In specific assay (enzyme multiplied immunoassay technique, high-performance liquid chromatography, fluorescence polarization) levels range from 2 to 5 mcg/ml. In nonspecific assay (fluorometric), they range from 4 to 8 mcg/ml.
Metabolism: About 60% to 80% of drug is metabolized in the liver to two metabolites that may have some pharmacologic activity.
Excretion: About 10% to 30% is excreted in urine within 24 hours as unchanged drug. Urine acidification increases quinidine excretion; alkalinization decreases excretion. Most of drug is eliminated in the urine as metabolites; elimination half-life ranges from 5 to 12 hours (usual half-life is about 61/2 hours). Duration of effect ranges from 6 to 8 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to quinidine or related cinchona derivatives, patients with idiosyncratic reactions to them, and patients with intraventricular conduction defects, cardiac glycoside toxicity when AV conduction is grossly impaired, abnormal rhythms caused by escape mechanisms, and a history of drug-induced torsades de pointes or QT syndrome.
  Use cautiously in patients with impaired renal or hepatic function, asthma, muscle weakness, or infection accompanied by a fever because hypersensitivity reactions may be masked.

Interactions
Drug-drug. Amiodarone, cimetidine: Increases quinidine levels and possibility of fatal cardiac dysrhythmias. Use together cautiously.
Antacids, sodium bicarbonate, thiazide diuretics: Decreases quinidine elimination when urine pH increases. Monitor patient closely.
Anticholinergics: May cause additive anticholinergic effects. Use together cautiously.
Anticonvulsants, such as phenobarbital and phenytoin: Increases rate of quinidine metabolism, decreasing quinidine levels. Monitor drug levels closely.
Antihypertensives: May cause additive hypotensive effects, mainly when given I.V. Monitor blood pressure closely.
Cholinergic drugs: May fail to terminate paroxysmal supraventricular tachycardia. Anticholinergic effects of quinidine may negate the effects of these drugs when treating myasthenia gravis. Use together cautiously.
Coumarin: May potentiate anticoagulant effect of coumarin, possibly leading to hypoprothrombinemic hemorrhage. Monitor patient closely.
Digitoxin, digoxin: May cause increased (possibly toxic) digoxin levels. Some experts recommend a 50% reduction in digoxin dosage when quinidine therapy starts, with subsequent monitoring of serum levels.
Neuromuscular blockers: May potentiate anticholinergic effects. Avoid giving quinidine immediately after these drugs; if quinidine must be used, respiratory support may be needed.
Nifedipine: May decrease quinidine levels. Monitor patient closely.
Phenothiazines, reserpine: May cause additive cardiac depressant effects. Avoid use together.
Procainamide: Increases procainamide and NAPA levels, causing toxicity. Monitor patient closely.
Propranolol: Decreases quinidine clearance. Monitor patient.
Rifampin: May increase quinidine metabolism and decrease serum quinidine levels. Adjust quinidine dosage as needed when rifampin therapy starts or stops.
Verapamil: May cause significant hypotension in patients with hypertrophic cardiomyopathy. Monitor patient closely.
Drug-herb. Jimsonweed: May adversely affect CV function. Discourage use together.
Licorice: May prolong QT interval and cause additive effects. Tell patient to use cautiously together.
Drug-food. Grapefruit juice: Delays onset of quinidine effect. Tell patient to take with liquid other than grapefruit juice.

Adverse reactions
CNS: vertigo, headache, light-headedness, fatigue, confusion, ataxia, depression, dementia, fever.
CV: PVCs, ventricular tachycardia, atypical ventricular tachycardia (torsades de pointes), hypotension, complete AV block, tachycardia, ECG changes (particularly widening of QRS complex and QT and PR intervals).
EENT: tinnitus, blurred vision, diplopia, photophobia.
GI: petechial hemorrhage of buccal mucosa, diarrhea, nausea, vomiting, anorexia, abdominal pain, excessive salivation.
Hematologic: hemolytic anemia, thrombocytopenia, agranulocytosis.
Hepatic: hepatotoxicity.
Respiratory: acute asthmatic attack, respiratory arrest.
Skin: rash, pruritus, urticaria, photosensitivity.
Other: angioedema, cinchonism, lupus erythematosus.

Effects on lab test results
• May increase liver enzyme levels.
• May decrease hemoglobin, hematocrit, and platelet and granulocyte counts.

Overdose and treatment
The most serious effects of overdose include severe hypotension, ventricular arrhythmias (including torsades de pointes), and seizures. QRS complexes and QT and PR intervals may be prolonged, and ataxia, anuria, respiratory distress, irritability, and hallucinations may develop.
 If ingestion was recent, gastric lavage, emesis, and activated charcoal may be used to decrease absorption. Urine acidification may be used to help increase quinidine elimination.
 Treatment involves general supportive measures (including CV and respiratory support) with hemodynamic and ECG monitoring. Norepinephrine may be used to reverse hypotension (after adequate hydration has been ensured). Avoid CNS depressants because CNS depression may occur, possibly with seizures. Cardiac pacing may be needed. Isoproterenol or ventricular pacing possibly may be used to treat torsades de pointes tachycardia.
 I.V. infusion of 1/6 M sodium lactate solution reduces cardiotoxic effect of quinidine. Hemodialysis, although rarely warranted, also may be effective.

Special considerations
• Check apical pulse rate, blood pressure, and ECG before starting therapy.
 ALERT When changing route of administration or oral salt form, alter dosage to compensate for variations in quinidine base content.
 ALERT Don’t confuse quinidine with Quinamm, quinine, or clonidine.
• When drug is used to treat atrial tachyarrhythmias, ventricular rate may be accelerated from anticholinergic effects of drug on AV node. This can be prevented by previous treatment with a cardiac glycoside.
• Because conversion of chronic atrial fibrillation may increase the risk of embolism, give an anticoagulant for several weeks before quinidine therapy begins.
• Use I.V. route only for acute arrhythmias; it’s typically avoided because of the risk of severe hypotension.
• Don’t use discolored (brownish) quinidine solution.
• For maintenance, give only by oral or I.M. route. Dosage requirements vary. Some patients may need drug q 4 hours, others q 6 hours. Adjust dose by both clinical response and blood levels.
• Decrease dosage in patients with heart failure and hepatic disease.
• Drug may increase toxicity of cardiac glycoside derivatives. Use cautiously in patients receiving cardiac glycosides. Monitor digoxin levels and expect to reduce dosage of cardiac glycoside derivatives. Many clinicians recommend that digoxin dosage be reduced by half when quinidine therapy starts.
• Monitor ECG, especially when giving large doses. Quinidine-induced cardiotoxicity causes conduction defects (50% widening of the QRS complex), ventricular tachycardia or flutter, frequent PVCs, and complete AV block. When these signs appear, stop drug and monitor patient closely.
• Lidocaine may be effective in treating quinidine-induced arrhythmias because it increases AV conduction.
• Quinidine may cause hemolysis in patients with G6PD deficiency.
• Monitor liver function test results during first 4 to 8 weeks of therapy.
• Adverse GI effects, especially diarrhea, indicate toxicity. Check quinidine blood levels, and suspect toxicity when they exceed 8 mcg/ml. GI symptoms may be minimized by giving drug with meals.
• Small amounts of quinidine are removed by hemodialysis; drug isn’t removed by peritoneal dialysis.
• Amount of quinidine in the various salt forms varies as follows: gluconate: 62% quinidine (324 mg of gluconate, 202 mg sulfate); sulfate: 83% quinidine. The sulfate form is considered the standard dosage preparation.
• Quinidine gluconate is as or more active in vitro as quinine dihydrochloride against Plasmodium falciparum. Because the latter drug is only available through the CDC, quinidine gluconate may be useful in treating severe malaria when delay of therapy may be life-threatening.
Pregnant patients
• Drug has some oxytocic effects. Safety for use during pregnancy and labor and delivery hasn’t been established.
Breast-feeding patients
• Because drug appears in breast milk, an alternative to breast-feeding is recommended during therapy.
Pediatric patients
• Safety and efficacy in children haven’t been established.
Geriatric patients
• Dosage reduction may be needed. Because of highly variable metabolism, monitor serum levels.

Patient education
• Instruct patient to report rash, fever, unusual bleeding, bruising, ringing in ears, or visual disturbance.
• Stress importance of taking drug exactly as prescribed.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use