|Labeler Name||Eli Lilly and Company|
|Dosage & Substance||solution quinidine gluconate|
|Date First Marketed||July 12, 1950|
Quinidine gluconate injection is indicated for the treatment of life–threatening malaria.
Quinidine gluconate injection is also indicated (when rapid therapeutic effect is required, or when oral therapy is not feasible) as a means of restoring normal sinus rhythm in patients with symptomatic atrial fibrillation/flutter whose symptoms are not adequately controlled by measures that reduce the rate of ventricular response. If this use of quinidine gluconate does not restore sinus rhythm within a reasonable time, then its use should be discontinued.
Quinidine gluconate injection is also indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that in the judgement of the physician are life–threatening. Because of the proarrhythmic effects of quinidine, its use with ventricular arrhythmias of lesser severity is generally not recommended, and treatment of patients with asymptomatic ventricular premature contractions should be avoided. Where possible, therapy should be guided by the results of programmed electrical stimulation and/or Holter monitoring with exercise.
Antiarrhythmic drugs (including quinidine) have not been shown to enhance survival in patients with ventricular arrhythmias.
Quinidine is contraindicated in patients who are known to be allergic to it, or who have developed thrombocytopenic purpura during prior therapy with quinidine or quinine.
In the absence of a functioning artificial pacemaker, quinidine is also contraindicated in any patient whose cardiac rhythm is dependent upon a junctional or idioventricular pacemaker, including patients in complete atrioventricular block.
Quinidine is also contraindicated in patients who, like those with myasthenia gravis, might be adversely affected by an anticholinergic agent.
Quinidine preparations have been used for many years, but there are only sparse data from which to estimate the incidence of various adverse reactions. The adverse reactions most frequently reported have consistently been gastrointestinal, including diarrhea, nausea, vomiting, and heart–burn/esophagitis. In one study of 245 adult outpatients who received quinidine to suppress premature ventricular contractions, the incidences of reported adverse experiences were as shown in the table below. The most serious quinidine–associated adverse reactions are described above under Warnings.
"upper gastrointestinal distress"
change in sleep habits
Intramuscular injections of quinidine gluconate are typically followed by moderate to severe local pain. Some patients will develop tender nodules at the site of injection that persist for several weeks.
Vomiting and diarrhea can occur as isolated reactions to therapeutic levels of quinidine, but they may also be the first signs of cinchonism, a syndrome that may also include tinnitus, reversible high–frequency hearing loss, deafness, vertigo, blurred vision, diplopia, photophobia, headache, confusion, and delirium. Cinchonism is most often a sign of chronic quinidine toxicity, but it may appear in sensitive patients after a single moderate dose.
A few cases of hepatotoxicity, including granulomatous hepatitis, have been reported in patients receiving quinidine. All of these have appeared during the first few weeks of therapy, and most (not all) have remitted once quinidine was withdrawn.
Autoimmune and inflammatory syndromes associated with quinidine therapy have included fever, urticaria, flushing, exfoliative rash, bronchospasm, pneumonitis, psoriasiform rash, pruritus and lymphadenopathy, hemolytic anemia, vasculitis, thrombocytopenic purpura, uveitis, angioedema, agranulocytosis, the sicca syndrome, arthralgia, myalgia, elevation in serum levels of skeletal–muscle enzymes, and a disorder resembling systemic lupus erythematosus.
Convulsions, apprehension, and ataxia have been reported, but it was not clear that these were not simply the results of hypotension and consequent cerebral hypoperfusion. There are many reports of syncope. Acute psychotic reactions have been reported to follow the first dose of quinidine, but these reactions appear to be extremely rare.
Other adverse reactions occasionally reported include depression, mydriasis, disturbed color perception, night blindness, scotomata, optic neuritis, visual field loss, photo–sensitivity, and abnormalities of pigmentation.
Overly rapid infusion of quinidine (see Dosage and Administration) may cause peripheral vascular collapse and severe hypotension.
Like many other drugs (including all other class 1a antiarrhythmics), quinidine prolongs the QTc interval, and this can lead to, a life–threatening ventricular arrhythmia (see Overdosage). The risk of is increased by any of bradycardia, hypokalemia, hypomagnesemia, and high serum levels of quinidine, but it may appear in the absence of any of these risk factors. The best predictor of this arrhythmia appears to be the length of the QTc interval, and quinidine should be used with extreme care in patients who have preexisting long–QT syndromes, who have histories of of any cause, or who have previously responded to quinidine (or other drugs that prolong ventricular repolarization) with marked lengthening of the QTc interval. Estimation of the incidence of in patients with therapeutic levels of quinidine is not possible from the available data.
Other ventricular arrhythmias that have been reported with quinidine include frequent extrasystoles, ventricular tachycardia, ventricular flutter, and ventricular fibrillation.
When quinidine is administered to patients with atrial flutter/fibrillation, the desired pharmacologic reversion to sinus rhythm may (rarely) be preceded by a slowing of the atrial rate with a consequent increase in the rate of beats conducted to the ventricles. The resulting ventricular rate may be very high (greater than 200 beats per minute) and poorly tolerated. This hazard may be decreased if partial atrioventricular block is achieved prior to initiation of quinidine therapy, using conduction–reducing drugs such as digitalis, verapamil, diltiazem, or a ß–receptor blocking agent.
In patients with the sick sinus syndrome, quinidine has been associated with marked sinus node depression and bradycardia.
Renal or hepatic dysfunction causes the elimination of quinidine to be slowed, while congestive heart failure causes a reduction in quinidine’s apparent volume of distribution. Any of these conditions can lead to quinidine toxicity if dosage is not appropriately reduced. In addition, interactions with coadministered drugs can alter the serum concentration and activity of quinidine, leading either to toxicity or to lack of efficacy if the dose of quinidine is not appropriately modified (see Precautions/Drug Interactions).
Because quinidine opposes the atrial and A–V nodal effects of vagal stimulation, physical or pharmacological vagal maneuvers undertaken to terminate paroxysmal supraventricular tachycardia may be ineffective in patients receiving quinidine.
There are only scattered reports of overdosage with intravenous quinidine, but overdoses with oral quinidine have been well described. Death has been described after a 5–gram ingestion by a toddler, while an adolescent was reported to survive after ingesting 8 grams of quinidine.
The most important ill effects of acute quinidine overdoses are ventricular arrhythmias and hypotension. Other signs and symptoms of overdose may include vomiting, diarrhea, tinnitus, high–frequency hearing loss, vertigo, blurred vision, diplopia, photophobia, headache, confusion, and delirium.
— Serum quinidine levels can be conveniently assayed and monitored, but the electrocardiographic QTc interval is a better predictor of quinidine–induced ventricular arrhythmias.
The necessary treatment of hemodynamically unstable polymorphic ventricular tachycardia (including) is withdrawal of treatment with quinidine and either immediate cardioversion or, if a cardiac pacemaker is in place or immediately available, immediate overdrive pacing. After pacing or cardioversion, further management must be guided by the length of the QTc interval.
Quinidine–associated ventricular tachyarrhythmias with normal underlying QTc intervals have not been adequately studied. Because of the theoretical possibility of QT–prolonging effects that might be additive to those of quinidine, other antiarrhythmics with Class I (disopyramide, procainamide) or Class III activities should (if possible) be avoided. Similarly, although the use of bretylium in quinidine overdose has not been reported, it is reasonable to expect that the α–blocking properties of bretylium might be additive to those of quinidine, resulting in problematic hypotension.
If the post–cardioversion QTc interval is prolonged, then the pre–cardioversion polymorphic ventricular tachyarrhythmia was (by definition). In this case, lidocaine and bretylium are unlikely to be of value, and other Class I antiarrhythmics (disopyramide, procainamide) are likely to exacerbate the situation. Factors contributing to QTc prolongation (especially hypokalemia and hypomagnesemia) should be sought out and (if possible) aggressively corrected. Prevention of recurrent may require sustained overdrive pacing or the cautious administration of isoproterenol (30–150 ng/kg/min).
— Quinidine–induced hypotension that is not due to an arrhythmia is likely to be a consequence of quinidine–related α–blockade and vasorelaxation. Simple repletion of central volume (Trendelenburg positioning, saline infusion) may be sufficient therapy; other interventions reported to have been beneficial in this setting are those that increase peripheral vascular resistance, including α–agonist catecholamines (norepinephrine, metaraminol) and the Military Anti–Shock Trousers.
— To obtain up–to–date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the (PDR). In managing overdose, consider the possibilities of multiple–drug overdoses, drug–drug interactions, and unusual drug kinetics in your patient.
— Adequate studies of orally–administered activated charcoal in human overdoses of quinidine have not been reported, but there are animal data showing significant enhancement of systemic elimination following this intervention, and there is at least one human case report in which the elimination half–life of quinidine in the serum was apparently shortened by repeated gastric lavage. Activated charcoal should be avoided if an ileus is present; the conventional dose is 1 gram/kg, administered every 2–6 hours as a slurry with 8 mL/kg of tap water.
Although renal elimination of quinidine might theoretically be accelerated by maneuvers to acidify the urine, such maneuvers are potentially hazardous and of no demonstrated benefit.
Quinidine is not usefully removed from the circulation by dialysis.
Following quinidine overdose, drugs that delay elimination of quinidine (cimetidine, carbonic–anhydrase inhibitors, diltiazem, thiazide diuretics) should be withdrawn unless absolutely required.
Quinidine is an antimalarial schizonticide and an antiarrhythmic agent with class 1a activity; it is the d–isomer of quinine and its molecular weight is 324.43. Quinidine gluconate is the gluconate salt of quinidine; its chemical name is cinchonan–9–ol, 6’–methoxy–, (9S)–, mono–D–gluconate; its structural formula is
its empirical formula is C20H24N2O2•C6H12O7, and its molecular weight is 520.58, of which 62.3% is quinidine base.
Each vial of Quinidine Gluconate Injection contains 800 mg (1.5 mmol) of quinidine gluconate (500 mg of quinidine) in 10 mL of Sterile Water for Injection, 0.005% of edetate disodium, 0.25% phenol, and (as needed) D–gluconic acid δ–lactone to adjust the pH.