Quinidine Gluconate

×

Overview

What is Quinidine Gluconate?

Quinidine is an antimalarial schizonticide and an antiarrhythmic agent with Class Ia 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. The structural formula is represented below:

Quinidine gluconate contains 62.3% of the anhydrous quinidine alkaloid, whereas quinidine sulfate contains 82.86%. In prescribing Quinidine Gluconate Extended-release Tablets, this factor should be considered.

Each tablet, for oral administration, contains 324 mg of quinidine gluconate (202 mg of quinidine base) in a matrix to provide extended-release.

Quinidine Gluconate Extended-release Tablets contain the following inactive ingredients: carnauba wax, ethylcellulose, magnesium stearate and povidone.

This product meets USP Drug Release Test 1.

What does Quinidine Gluconate look like?

What are the available doses of Quinidine Gluconate?

Sorry No records found.

What should I talk to my health care provider before I take Quinidine Gluconate?

Sorry No records found

How should I use Quinidine Gluconate?

In patients with symptomatic atrial fibrillation/flutter whose symptoms are not adequately controlled by measures that reduce the rate of ventricular response, quinidine gluconate is indicated as a means of restoring normal sinus rhythm. If this use of quinidine gluconate does not restore sinus rhythm within a reasonable time (see), then quinidine gluconate should be discontinued.

The dose of quinidine delivered by quinidine gluconate extended-release tablets may be titrated by breaking a tablet in half. If tablets are crushed or chewed, their extended-release properties will be lost.

The dosage of quinidine varies considerably depending upon the general condition and the cardiovascular state of the patient.

What interacts with Quinidine Gluconate?

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.

What are the warnings of Quinidine Gluconate?

Mortality

In many trials of antiarrhythmic therapy for non-life-threatening arrhythmias, active antiarrhythmic therapy has resulted in increased mortality; the risk of active therapy is probably greatest in patients with structural heart disease.

In the case of quinidine used to prevent or defer recurrence of atrial flutter/fibrillation, the best available data come from a meta-analysis described under CLINICAL PHARMACOLOGY/Clinical Effects above. In the patients studied in the trials there analyzed, the mortality associated with the use of quinidine was more than three times as great as the mortality associated with the use of placebo.

Another meta-analysis, also described under CLINICAL PHARMACOLOGY/Clinical Effects, showed that in patients with various non-life-threatening ventricular arrhythmias, the mortality associated with the use of quinidine was consistently greater than that associated with the use of any of a variety of alternative antiarrhythmics.

Proarrhythmic Effects

Like many other drugs (including all other Class Ia antiarrhythmics), quinidine prolongs the QT interval, and this can lead to a life-threatening ventricular arrhythmia (see). The risk of is increased by bradycardia, hypokalemia, hypomagnesemia or 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 QT 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 QT 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.

Paradoxical Increase in Ventricular Rate in Atrial Flutter/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.

Exacerbated Bradycardia in Sick Sinus Syndrome

In patients with the sick sinus syndrome, quinidine has been associated with marked sinus node depression and bradycardia.

Pharmacokinetic Considerations

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.)

Vagolysis

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.

What are the precautions of Quinidine Gluconate?

Heart Block

In patients without implanted pacemakers who are at high risk of complete atrioventricular block (e.g., those with digitalis intoxication, second degree atrioventricular block, or severe intraventricular conduction defects), quinidine should be used only with caution.

Drug and Diet Interactions

Diltiazem significantly decreases the clearance and increases the t of quinidine, but quinidine does not alter the kinetics of diltiazem.

Drugs that alkalinize the urine () reduce renal elimination of quinidine.

By pharmacokinetic mechanisms that are not well understood, quinidine levels are increased by coadministration of or Very rarely, and again by mechanisms not understood, quinidine levels are decreased by coadministration of

Hepatic elimination of quinidine may be accelerated by coadministration of drugs () that induce production of cytochrome P450IIIA4.

Perhaps because of competition for the P450IIIA4 metabolic pathway, quinidine levels rise when is coadministered.

Coadministration of usually does not affect quinidine pharmacokinetics, but in some studies the ß-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 on quinidine pharmacokinetics have not been adequately studied.

Hepatic clearance of quinidine is significantly reduced during coadministration of with corresponding increases in serum levels and half-life.

Grapefruit juice

Grapefruit juice inhibits P450 3A4-mediated metabolism of quinidine to 3-hydroxyquinidine. Although the clinical significance of this interaction is unknown, grapefruit juice should be avoided.

Dietary salt

The rate and extent of quinidine absorption may be affected by changes in dietary salt intake; a decrease in dietary salt intake may lead to an increase in plasma quinidine concentrations.

Quinidine slows the elimination of 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 are also raised when quinidine is coadministered, although the effect appears to be smaller.

By a mechanism that is not understood, quinidine potentiates the anticoagulatory action of and the anticoagulant dosage may need to be reduced.

Cytochrome P450IID6 is an enzyme critical to the metabolism of many drugs, notably including some and most Constitutional deficiency of cytochrome P450IID6 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 P450IID6- deficient “poor metabolizers” from the majority-phenotype “extensive metabolizers”.

When drugs whose metabolism is P450IID6-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 case of prodrugs whose actions are actually mediated by P450IID6- produced metabolites (for example, and 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 P450IID6.

Perhaps by competing for pathways of renal clearance, coadministration of quinidine causes an increase in serum levels of

Serum levels of are increased when quinidine is coadministered.

Presumably because both drugs are metabolized by cytochrome P450IIIA4, coadministration of quinidine causes variable slowing of the metabolism of Interactions with other dihydropyridine calcium channel blockers have not been reported, but these agents (including and ) are all dependent upon P450IIIA4 for metabolism, so similar interactions with quinidine should be anticipated.

Quinidine’s anticholinergic, 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 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 ( -tubocurarine, pancuronium) These phenomena are not well understood, but they are observed in animal models as well as in humans. In addition, addition of quinidine to the serum of pregnant women reduces the activity of pseudocholinesterase, an enzyme that is essential to the metabolism of succinylcholine.

Quinidine has no clinically significant effect on the pharmacokinetics of or

Conversely, the pharmacokinetics of quinidine are not significantly affected by or Quinidine’s pharmacokinetics are also unaffected by cigarette smoking.

Information for Patients

Before prescribing quinidine gluconate as prophylaxis against recurrence of atrial fibrillation, the physician should inform the patient of the risks and benefits to be expected (see). Discussion should include the facts:

Carcinogenesis, Mutagenesis, Impairment of Fertility

Animal studies to evaluate quinidine’s carcinogenic or mutagenic potential have not been performed. Similarly, there are no animal data as to quinidine’s potential to impair fertility.

Pregnancy

Pregnancy Category C. 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.

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.

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.

Nursing Mothers

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.

Geriatric Use

Safety and efficacy of quinidine in elderly patients have not been systematically studied.

Pediatric Use

In antimalarial trials, quinidine was as safe and effective in pediatric patients as in adults. Notwithstanding the known pharmacokinetic differences between children and adults (see), children in these trials received the same doses (on a mg/kg basis) as adults.

Safety and effectiveness of antiarrhythmic use in pediatric patients have not been established.

What are the side effects of Quinidine Gluconate?

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 heartburn/esophagitis.

In the reported study that was closest in character to the predominant approved use of quinidine gluconate, 86 adult outpatients with atrial fibrillation were followed for six months while they received slow-release quinidine bisulfate tablets, 600 mg (approximately 400 mg of quinidine base) twice daily. The incidences of adverse experiences reported more than once were as shown in the table below. The most serious quinidine-associated adverse reactions are described above under.

Vomiting and diarrhea can occur as isolated reactions to therapeutic levels of quinidine, but they may also be the first signs of 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 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

Convulsions, apprehension, and ataxia have been reported, but it is 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, photosensitivity, and abnormalities of pigmentation.

	ADVERSE EXPERIENCES REPORTED MORE THAN ONCE		IN 86 PATIENTS WITH ATRIAL FIBRILLATION
	Incidence	(%)
diarrhea	21	(24%)
fever	5	(6%)
rash	5	(6%)
arrhythmia	3	(3%)
abnormal electrocardiogram	3	(3%)
nausea/vomiting	3	(3%)
dizziness	3	(3%)
headache	3	(3%)
asthenia	2	(2%)
cerebral ischemia	2	(2%)

What should I look out for while using Quinidine Gluconate?

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.

What might happen if I take too much Quinidine Gluconate?

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.

How should I store and handle Quinidine Gluconate?

Store below 30°C (86°F).Manufactured by:DANBURY PHARMACAL, INC.Danbury, CT 06810Store below 30°C (86°F).Manufactured by:DANBURY PHARMACAL, INC.Danbury, CT 06810Quinidine Gluconate Extended-release Tablets USP 324 mg are 13/32”, unscored, round, off-white tablets imprinted and supplied in bottles of 100, 250, and 500.Dispense in a well-closed, light-resistant container with child-resistant closure.Store at 20°-25°C (68°-77°F). [See USP controlled room temperature.]Watson Laboratories, Inc.Quinidine Gluconate Extended-release Tablets USP 324 mg are 13/32”, unscored, round, off-white tablets imprinted and supplied in bottles of 100, 250, and 500.Dispense in a well-closed, light-resistant container with child-resistant closure.Store at 20°-25°C (68°-77°F). [See USP controlled room temperature.]Watson Laboratories, Inc.Quinidine Gluconate Extended-release Tablets USP 324 mg are 13/32”, unscored, round, off-white tablets imprinted and supplied in bottles of 100, 250, and 500.Dispense in a well-closed, light-resistant container with child-resistant closure.Store at 20°-25°C (68°-77°F). [See USP controlled room temperature.]Watson Laboratories, Inc.Quinidine Gluconate Extended-release Tablets USP 324 mg are 13/32”, unscored, round, off-white tablets imprinted and supplied in bottles of 100, 250, and 500.Dispense in a well-closed, light-resistant container with child-resistant closure.Store at 20°-25°C (68°-77°F). [See USP controlled room temperature.]Watson Laboratories, Inc.

×

Clinical Information

Chemical Structure

No Image found

Clinical Pharmacology

The absolute of quinidine from quinidine gluconate is 70 to 80%. Relative to a solution of quinidine sulfate, the bioavailability of quinidine from quinidine gluconate is reported to be 1.03. The less-than-complete bioavailability is thought to be due to first-pass elimination by the liver. Peak serum levels generally appear 3 to 5 hours after dosing; when the drug is taken with food, absorption is increased in both rate (27%) and extent (17%). The rate and extent of absorption of quinidine from quinidine gluconate are not significantly affected by the coadministration of an aluminum-hydroxide antacid. The rate of absorption of quinidine following the ingestion of grapefruit juice may be decreased.

The of quinidine is 2 to 3 L/kg in healthy young adults, but this may be reduced to as little as 0.5 L/kg in patients with congestive heart failure, or increased to 3 to 5 L/kg in patients with cirrhosis of the liver. At concentrations of 2 to 5 mg/L (6.5 to 16.2 µmol/L), the fraction of quinidine bound to plasma proteins (mainly to α-acid glycoprotein and to albumin) is 80 to 88% in adults and older children, but it is lower in pregnant women, and in infants and neonates it may be as low as 50 to 70%. Because α-acid glycoprotein levels are increased in response to stress, serum levels of total quinidine may be greatly increased in settings such as acute myocardial infarction, even though the serum content of unbound (active) drug may remain normal. Protein binding is also increased in chronic renal failure, but binding abruptly descends toward or below normal when heparin is administered for hemodialysis.

Quinidine typically proceeds at 3 to 5 mL/min/kg in adults, but clearance in children may be twice or three times as rapid. The elimination half-life is 6 to 8 hours in adults and 3 to 4 hours in children. Quinidine clearance is unaffected by hepatic cirrhosis, so the increased volume of distribution seen in cirrhosis leads to a proportionate increase in the elimination half-life.

Most quinidine is eliminated hepatically via the action of cytochrome P450IIIA4; there are several different hydroxylated metabolites, and some of these have antiarrhythmic activity.

The most important of quinidine’s metabolites is 3-hydroxy-quinidine (3HQ), serum levels of which can approach those of quinidine in patients receiving conventional doses of quinidine gluconate. The volume of distribution of 3HQ appears to be larger than that of quinidine, and the elimination half-life of 3HQ is about 12 hours.

As measured by antiarrhythmic effects on animals, by QT prolongation in human volunteers, or by various techniques, 3HQ has at least half the antiarrhythmic activity of the parent compound, so it may be responsible for a substantial fraction of the effect of quinidine gluconate in chronic use.

When the urine pH is less than 7, about 20% of administered quinidine appears unchanged in the urine, but this fraction drops to as little as 5% when the urine is more alkaline. Renal clearance involves both glomerular filtration and active tubular secretion, moderated by (pH-dependent) tubular reabsorption. The net renal clearance is about 1 mL/min/kg in healthy adults.

When renal function is taken into account, quinidine clearance is apparently independent of patient age.

Assays

Non-Clinical Toxicology

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.

Sulfacetamide preparations are incompatible with silver preparations.

In patients without implanted pacemakers who are at high risk of complete atrioventricular block (e.g., those with digitalis intoxication, second degree atrioventricular block, or severe intraventricular conduction defects), quinidine should be used only with caution.

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 heartburn/esophagitis.

In the reported study that was closest in character to the predominant approved use of quinidine gluconate, 86 adult outpatients with atrial fibrillation were followed for six months while they received slow-release quinidine bisulfate tablets, 600 mg (approximately 400 mg of quinidine base) twice daily. The incidences of adverse experiences reported more than once were as shown in the table below. The most serious quinidine-associated adverse reactions are described above under.

Vomiting and diarrhea can occur as isolated reactions to therapeutic levels of quinidine, but they may also be the first signs of 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 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

Convulsions, apprehension, and ataxia have been reported, but it is 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, photosensitivity, and abnormalities of pigmentation.

×

Reference

This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"

While we update our database periodically, we cannot guarantee it is always updated to the latest version.

×

Review

×

Professional

Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72

×

Tips

×

Interactions

A total of 440 drugs (1549 brand and generic names) are known to interact with Imbruvica (ibrutinib). 228 major drug interactions (854 brand and generic names) 210 moderate drug interactions (691 brand and generic names) 2 minor drug interactions (4 brand and generic names) Show all medications in the database that may interact with Imbruvica (ibrutinib).

Disclaimer: