Quinidine Sulfate

/ Rekah

Adult dosage: For Atrial fibrillation and flutter, Chronic therapy to reduce recurrence: immediate-release tablet, 200 mg ORALLY every 6 h; if needed and patient tolerates, may raise dose cautiously. For Ventricular arrhythmia, Life-threatening: immediate-release tablet, 200 mg ORALLY every 6 h; if needed and patient tolerates, may raise dose cautiously. The dosage should be adapted in renal or hepatic insufficiency.
Children dosage: Quinidine is not recommended in children.

Cardiac arrhythmia.

Do not take with food or drinks which change alkalinity of urine such as citrus fruits or juices.

Ringing in the ears, headache, nausea and disturbed vision, may occur during prolonged use. In the treatment of atrial flutter, reversion to sinus rhythm may be preceded by a progressive reduction in the degree of AV block to a 1:1 ratio. May produce clinically important depression of cardiac function manifested by hypotension, bradycardia, or heart-block. Therapy should be carefully monitored. Evidence of quinidine cardiotoxicity (excessive prolongations of QT interval, widening of QRS complex, and ventricular tachyarrhythmias) requires immediate discontinuation of the drug, together with subsequent close clinical and ECG monitoring of the patient. Use with exteme caution when there is incomplete AV block. The cardiotoxic effect is increased by hyperkalemia, and decreased by hypokalemia. Syncopal episodes, which usually result from ventricular tachycardia or fibrillation, can sometimes prove fatal. Patients exhibiting renal, cardiac or hepatic insufficiency. Patients with prolonged AV conduction, sustained decompensation, cardiogenic shock, hypotension, bradycardia or disturbed potassium balance. Presence of obstructive changes in the digestive tract.
For full details see prescribing information.

Ventricular extrasystoles occurring at a rate of one or more every 6 normal beats, widening of the QRS complex and prolonged QT interval, complete AV block, ventricular tachycardia and fibrillation, ventricular flutter, torsade de pointes, arterial embolism, hypotension, syncope, nausea, vomiting, abdominal pain, diarrhea, hypersensitivity, acute hemolytic anemia, hypoprothrombinemia, thrombocytopenic purpura, agranulocytosis, headache, fever, vertigo, excitement, confusion, visual disturbances, cutaneous flushing with pruritus.

The following drug interactions should be considered when prescribing quinidine sulfate.
Pharmacokinetic reason:
– Drugs that alkalinize the urine (carbonic-anhydrase inhibitors (acetazolamide), sodium bicarbonate, thiazide diuretics) reduce renal elimination of quinidine.
– Amiodarone or cimetidine: increase levels of quinidine levels by pharmacokinetic mechanisms that are not well understood.
– Nifedipine: decrease quinidine levels by mechanism not understood.
– Phenobarbital, phenytoin, Rifampicin: Hepatic elimination of quinidine may be accelerated by coadministration of drugs that induce production of cytochrome P450 3A4.
– Ketaconazole, Itraconazole, Voriconazole: quinidine levels rise when coadministered with Ketaconazole, Itraconazole and Voriconazole, Perhaps because of competition for the P450 3A4 metabolic pathway,
– Propranolol: Coadministration of propranolol usually does not affect quinidine pharmacokinetics, but in some studies the β-blocker appeared to cause increases in the peak serum levels of quinidine, decreases in quinidine’s volume of distribution, and decreases in total quinidine clearance. The effects (if any) of coadministration of other β-blockers on quinidine pharmacokinetics have not been adequately studied.
– Diltiazem: significantly decreases the clearance and increases the t1/2 of quinidine, but quinidine does not alter the kinetics of diltiazem.
– Verapamil: Hepatic clearance of quinidine is significantly reduced during coadministration of verapamil, with corresponding increases in serum levels and half-life.
– Digoxin: Quinidine slows the elimination of digoxin and simultaneously reduces digoxin’s apparent volume of distribution. As a result, serum digoxin levels may be as much as doubled. When quinidine and digoxin are coadministered, digoxin doses usually need to be reduced. Serum levels of digoxin are also raised when quinidine is coadministered, although the effect appears to be smaller.
– Warfarin: quinidine potentiates the anticoagulatory action of warfarin,by a mechanism that is not understood. The anticoagulant dosage may need to be reduced. Cytochrome P450 2D6 is an enzyme critical to the metabolism of many drugs, notably including mexiletine, some phenothiazines, and most polycyclic antidepressants. Constitutional deficiency of cytochrome P450 2D6 is found in less than 1% of Orientals, in about 2% of American blacks, and in about 8% of American whites. Testing with debrisoquine is sometimes used to distinguish the P450 2D6-deficient “poor metabolizers” from the majority-pheno-type “extensive metabolizers”. When drugs whose metabolism is P450 2D6-dependent are given to poor metabolizers, the serum levels achieved are higher, sometimes much higher, than the serum levels achieved when identical doses are given to extensive metabolizers. To obtain similar clinical benefit without toxicity, doses given to poor metabolizers may need to be greatly reduced. In the cases of prodrugs whose actions are actually mediated by P450 2D6-produced metabolites (for example, codeine and hydrocodone, whose analgesic and antitussive effects appear to be mediated by morphine and hydromorphone, respectively), it may not be possible to achieve the desired clinical benefits in poor metabolizers. Quinidine is not metabolized by cytochrome P450IID6, but therapeutic serum levels of quinidine inhibit the action of cytochrome P450IID6, effectively converting extensive metabolizers into poor metabolizers. Caution must be exercised whenever quinidine is prescribed together with drugs metabolized by cytochrome P450 2D6.
– Procainamide: Perhaps by competing for pathways of renal clearance, coadministration of quinidine causes an increase in serum levels of procainamide. – Haloperidol, Droperidol: Serum levels are increased when quinidine is coadministered.
– Aripiprazole: Concurrent use of Aripiprazole and this product may result in increased aripiprazole levels.
– Nortriptyline: Concurrent use of Nortriptyline and this product may result in increased nortriptyline plasma concentrations; and increased risk of cardiotoxicity.
– Dihydropyridine calcium-channel blockers: Presumably because both drugs are metabolized by cytochrome P450 2D6, coadministration of quinidine causes variable slowing of the metabolism of nifedipine. Interactions with other dihydropyridine calcium-channel blockers have not been reported, but these agents (including felodipine, nicardipine, and nimodipine) are all dependent upon 3A4 for metabolism, so similar interactions with quinidine should be anticipated. b) pharmacodynamics reason Quinidine’s anitcholinergic, vasodilating, and negative inotropic actions may be additive to those of other drugs with these effects, and antagonistic to those of drugs with cholinergic, vasoconstricting, and positive inotropic effects. For example, when quinidine and verapamil are coadministered in doses that are each well tolerated as monotherapy, hypotension attributable to additive peripheral α-blockade is sometimes reported. Quinidine potentiates the actions of depolarizing (succinylcholine, decamethonium) and nondepolarizing (d-tubocurarine, pancuronium) neuromuscular blockingagents. These phenomena are not well understood, but they are observed in animal models as well as in humans. In addition, in vitro addition of quinidine to the serum of pregnant women reduces the activity of pseudocholinesterase, an enzyme that is essential to the metabolism of succinylcholine. – HIV protease inhibitors eg indinavir, ritonavir, nelfinavir: Concurrent use of this product and HIV protease inhibitors may result in an increased risk of quinidine toxicity (ventricular arrhythmias, hypotension, exacerbation of heart failure).
– Dofetilide, astemizole, cisapride, Pimozide, antibiotic of macrolide group (such erythromycin), ketolide antibiotics (eg, telithromycin), risperidone, norepinephrine reuptake inhibitors: Concurrent use of their medicines and this product may result in an increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest).
– Mefloquine: Concurrent use of Mefloquine and this product may result in increased risk of QT prolongation.
– Amiloride: Concurrent use of Amiloride and this product may result in an increased risk of arrhythmias in patients with ventricular tachycardia.
– Procainamide: Concurrent use of this product and Procainamide: may result in hypotension and an increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest). Non-interactions of quinidine with other drugs Quinidine has no clinically significant effect on the pharmacokinetics of diltiazem, flecainide, mephenytoin, metoprolol, propafenone, propranolol, quinine, timolol, or tocainide. Conversely, the pharmacokinetics of quinidine are not significantly affected by caffeine, ciprofloxacin, digoxin, digitoxin, diltiazem, felodipine, terfenadine omeprazole, or quinine. Quinidine’s pharmacokinetics are also unaffected by cigarette smoking.

Pregnancy: Animal reproductive studies have not been conducted with quinidine. There are no adequate and well-controlled studies in pregnant women. Quinidine should be given to a pregnant woman only if clearly needed. Human placental transport of quinidine has not been systematically studied. In one neonate whose mother had received quinidine throughout her pregnancy, the serum level of quinidine was equal to that of the mother, with no apparent ill effect. The level of quinidine in amniotic fluid was about three times higher than that found in serum. In another case, the levels of quinidine and 3-hydroxyquinidine in cord blood were about 30% of simultaneous maternal levels.
Labor and Delivery: Quinine is said to be oxytocic in humans, but there are no adequate data as to quinidine’s effects (if any) on human labor and delivery.
Lactation: Quinidine is present in human milk at levels slightly lower than those in maternal serum; a human infant ingesting such milk should (scaling directly by weight) be expected to develop serum quinidine levels at least an order of magnitude lower than those of the mother. On the other hand, the pharmacokinetics and pharmacodynamics of quinidine in human infants have not been adequately studied, and neonates’ reduced protein binding of quinidine may increase their risk of toxicity at low total serum levels. Administration of quinidine should (if possible) be avoided in lactating women who continue to nurse.
Fertility: There are no animal data as to quinidine’s potential to impair fertility.

Overdoses with various oral formulations of 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.
Arrhythmias: 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 torsades de pointes) 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 antiarrhythmic 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) torsades depointes. In this case, lidocaine and bretylium are unlikely to be of value, and other Class I antiarrhythmic (disopyramide, procainamide) are likely to exacerbate the situation. Factors contributing to QTC prolongation (especially hypokalemia, hypomagnesemia, and hypocalcemia) should be sought out and (if possible) aggressively corrected. Prevention of recurrent torsades may require sustained overdrive pacing or the cautious administration of isoproterenol (30 to 150 ng/kg/min).
Hypotension: 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.
Treatment: 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 Physicians’ Desk Reference(PDR). In managing overdose, consider the possibilities of multiple-drug overdoses, drug-drug interactions, and unusual drug kinetics in your patient.
Accelerated removal: 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 to 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 usually removed from the circulation by dialysis. Following quinidine overdose, drugs that delay elimination of quinidine (cimetidine, carbonicanhydrase inhibitors, thiazide diuretics) should be withdrawn unless absolutely required.