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QuiNIDine

Pronunciation

Pronunciation

(KWIN i deen)

Index Terms

  • Quinidex
  • Quinidine Gluconate
  • Quinidine Polygalacturonate
  • Quinidine Sulfate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection, as gluconate:

Generic: 80 mg/mL (10 mL)

Tablet, Oral, as sulfate:

Generic: 200 mg, 300 mg

Tablet Extended Release, Oral, as gluconate:

Generic: 324 mg

Tablet Extended Release, Oral, as sulfate:

Generic: 300 mg [DSC]

Pharmacologic Category

  • Antiarrhythmic Agent, Class Ia
  • Antimalarial Agent

Pharmacology

Class Ia 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

Vd: Adults: 2 to 3 L/kg, decreased with congestive heart failure (0.5 L/kg), malaria; increased with cirrhosis

Metabolism

Extensively hepatic (50% to 90%) to inactive compounds

Excretion

Urine (15% to 25% as unchanged drug)

Time to Peak

Serum: Oral: Sulfate: Immediate release: 2 hours; Extended release: 6 hours; Gluconate: Extended release: 3 to 5 hours

Half-Life Elimination

Plasma: Children: 2.5 to 6.7 hours; Adults: 6 to 8 hours; prolonged with elderly, cirrhosis, and congestive heart failure

Protein Binding

Newborns: 50% to 70%; Adults: 80% to 88%

Binds mainly to alpha 1-acid glycoprotein and to a lesser extent albumin; protein-binding changes may occur in periods of stress due to increased alpha 1-acid glycoprotein concentrations (eg, acute myocardial infarction) or in certain disease states due to decreased alpha 1-acid glycoprotein concentrations (eg, cirrhosis,hyperthyroidism, malnutrition)

Special Populations: Renal Function Impairment

Vd and renal Cl may be reduced.

Special Populations: Elderly

Elimination t½ may be increased.

Special Populations Note

Heart failure: Total Cl and Vd are decreased.

Use: Labeled Indications

Quinidine gluconate and sulfate salts: Conversion and prevention of relapse into atrial fibrillation and/or flutter; suppression of ventricular arrhythmias. Note: Due to proarrhythmic effects, use should be reserved for life-threatening arrhythmias. Moreover, the use of quinidine has largely been replaced by more effective/safer antiarrhythmic agents and/or nonpharmacologic therapies (eg, radiofrequency ablation).

Quinidine gluconate (IV formulation): Conversion of atrial fibrillation/flutter and ventricular tachycardia. Note: The use of IV quinidine gluconate for these indications has been replaced by more effective/safer antiarrhythmic agents (eg, amiodarone and procainamide).

Quinidine gluconate (IV formulation) and quinidine sulfate: Treatment of malaria (Plasmodium falciparum)

Use: Unlabeled

Paroxysmal supraventricular tachycardia, paroxysmal AV junctional rhythm, and symptomatic atrial or ventricular premature contractions; short QT syndrome; Brugada syndrome

Contraindications

Hypersensitivity to quinidine or any component of the formulation; 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

Dosing: Adult

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

Atrial fibrillation/flutter (pharmacological conversion): Oral: Note: Discontinue use if at any time during therapy, the QRS complex widens to 130% of its pretreatment duration, the QTc interval widens to 130% of its pretreatment duration and is >500 msecs, P waves disappear, or the patient develops significant tachycardia, symptomatic bradycardia, or hypotension; consider other means of cardioversion (eg direct current cardioversion). Discontinue if sinus rhythm is not restored in a reasonable amount of time. For patients with structural heart disease or other risk factors for toxicity, initiate or dose-adjust in a setting where continuous monitoring and resuscitation are available. Monitor patients for 2 to 3 days once the appropriate dose has been achieved.

Immediate release formulations: Quinidine sulfate: Initial: 400 mg/dose every 6 hours; if after 4 or 5 doses there is no conversion, may increase cautiously to desired effect

Extended release formulations:

Quinidine sulfate: Initial: 300 mg every 8 to 12 hours; the dose may be increased cautiously to desired effect

Quinidine gluconate: Initial: 648 mg every 8 hours; if after 3 or 4 doses there is no conversion, may increase cautiously to desired effect.

or

Initial: 324 mg every 8 hours for 2 days; then 648 mg every 12 hours for 2 days; then 648 mg every 8 hours for up to 4 days. The 4 day stretch may come at one of the lower doses if a lower dose is the highest tolerated dosing regimen.

Maintenance of sinus rhythm in patients with paroxysmal atrial fibrillation/flutter or life-threatening ventricular arrhythmias: Oral: Note: Dosing regimens for suppression of life-threatening ventricular arrhythmias have not been adequately studied. Reduce total daily dose if at any time during therapy, the QRS complex widens to 130% of its pretreatment duration, the QTc interval widens to 130% of its pretreatment duration and is >500 msecs, P waves disappear, or the patient develops significant tachycardia, symptomatic bradycardia, or hypotension. For patients with structural heart disease or other risk factors for toxicity, initiate or dose-adjust in a setting where continuous monitoring and resuscitation are available. Monitor patients for 2 to 3 days once the appropriate dose has been achieved.

Immediate release formulations: Quinidine sulfate: Initial: 200 mg every 6 hours; the dose may be increased cautiously to desired effect.

Extended release formulations:

Quinidine sulfate: Initial: 300 mg every 8 to 12 hours; the dose may be increased cautiously to desired effect

Quinidine gluconate: Initial: 324 mg every 8 to 12 hours; the dose may be increased cautiously to desired effect. Usual dose range according to the AHA/ACC/HRS guidelines for management of atrial fibrillation: 324 to 648 mg every 8 hours (AHA/ACC/HRS [January, 2014]).

Severe malaria, treatment: IV (quinidine gluconate): 10 mg/kg infused over 60 to 120 minutes followed by 0.02 mg/kg/minute continuous infusion for ≥24 hours; alternatively, may administer 24 mg/kg loading dose over 4 hours, followed by 12 mg/kg over 4 hours every 8 hours (beginning 8 hours after initiation of the loading dose); complete treatment with oral quinine once parasite density <1% and patient can receive oral medication; total duration of treatment (quinidine/quinine): 3 days (Africa or South America) or 7 days (Southeast Asia); use in combination with doxycycline, tetracycline, or clindamycin (CDC malaria guidelines, 2009). Note: Close monitoring, including telemetry, required.

Dosing: Geriatric

Oral: Refer to adult dosing.

IV: Refer to adult dosing. Initiate therapy at the low end of the dosage range.

Dosing: Pediatric

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

Severe malaria, treatment: Children: IV (quinidine gluconate): 10 mg/kg infused over 60 to 120 minutes followed by 0.02 mg/kg/minute continuous infusion for ≥24 hours; alternatively, may administer 24 mg/kg loading dose over 4 hours, followed by 12 mg/kg over 4 hours every 8 hours (beginning 8 hours after initiation of the loading dose); complete treatment with oral quinine once parasite density <1% and patient can receive oral medication; total duration of treatment (quinidine/quinine): 3 days (Africa or South America) or 7 days (Southeast Asia); use in combination with doxycycline, tetracycline, or clindamycin (CDC malaria guidelines, 2009). Note: Close monitoring, including telemetry, required.

Dosing: Renal Impairment

No dosage adjustment provided in manufacturer’s labeling. Use with caution. The following guidelines have been used by some clinicians (Aronoff, 2007): Oral:

CrCl ≥10 mL/minute: No dosage adjustment necessary.

CrCl <10 mL/minute: Administer 75% of normal dose.

Hemodialysis: Dose following hemodialysis.

Peritoneal dialysis: Supplemental dose is not necessary.

CRRT: No dosage adjustment required; monitor serum concentrations.

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling. Use with caution due to reduced clearance.

Extemporaneously Prepared

A 10 mg/mL oral liquid preparation may be made with tablets and one of three different vehicles (cherry syrup, a 1:1 mixture of Ora-Sweet® and Ora-Plus®, or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®). Crush six 200 mg tablets in a mortar and reduce to a fine powder. Add 15 mL of the chosen vehicle and mix to a uniform paste; mix while adding vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label "shake well" and "protect from light". Stable for 60 days when stored in amber plastic prescription bottles in the dark at room temperature or refrigerated.

Allen LV and Erickson MA, "Stability of Bethanechol Chloride, Pyrazinamide, Quinidine Sulfate, Rifampin, and Tetracycline in Extemporaneously Compounded Oral Liquids," Am J Health Syst Pharm, 1998, 55(17):1804-9.9775343

Administration

Administer around-the-clock to promote less variation in peak and trough serum levels

Oral: Do not crush, chew, or break sustained release dosage forms. Some preparations of quinidine gluconate extended release tablets may be split in half to facilitate dosage titration; tablets are not scored.

Parenteral: Minimize use of PVC tubing to enhance bioavailability; shorter tubing lengths are recommended by the manufacturer

Dietary Considerations

Administer with food or milk to decrease gastrointestinal irritation. Avoid changes in dietary salt intake.

Compatibility

Stable in D5W, NS.

Y-site administration: Incompatible with furosemide.

Storage

Solution for injection: Store at room temperature of 25°C (77°F).

Tablets: Store at controlled room temperature of 20°C to 25°C (68°F to 77°F). Protect from light.

Drug Interactions

AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification

Ajmaline: QuiNIDine may enhance the arrhythmogenic effect of Ajmaline. QuiNIDine may increase the serum concentration of Ajmaline. Avoid combination

Amiodarone: May enhance the QTc-prolonging effect of Antiarrhythmic Agents (Class Ia). Amiodarone may increase the serum concentration of Antiarrhythmic Agents (Class Ia). Management: Avoid whenever possible. While considered contraindicated in some places, amiodarone U.S. prescribing information suggests that use could be considered under some circumstances, with careful monitoring. Reduce quinidine or procainamide dose by one third. Avoid combination

Analgesics (Opioid): Anticholinergic Agents may enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

Antacids: May decrease the excretion of QuiNIDine. Exceptions: Aluminum Hydroxide. Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of QuiNIDine. Applicable Isavuconazonium considerations are addressed in separate monographs. Exceptions: Isavuconazonium Sulfate. Avoid combination

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: See full interaction monograph for details. Consider therapy modification

ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Please refer to the full interaction monograph for details concerning the recommended dose adjustments. Consider therapy modification

Atazanavir: May increase the serum concentration of QuiNIDine. Monitor therapy

AtoMOXetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of AtoMOXetine. Management: Initiate atomoxetine at a reduced dose (adult doses -- patients up to 70kg: 0.5mg/kg/day; patients 70kg or more: 40mg/day) in patients receiving a strong CYP2D6 inhibitor. Consider therapy modification

Boceprevir: May increase the serum concentration of QuiNIDine. Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Bosutinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib. Avoid combination

Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy

Brexpiprazole: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual with a strong CYP2D6 inhibitor; this recommendation does not apply if treating major depressive disorder. Reduce to 25% of usual if used with both a strong CYP2D6 inhibitor and a CYP3A4 inhibitor. Consider therapy modification

Calcium Channel Blockers (Dihydropyridine): May decrease the serum concentration of QuiNIDine. Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of QuiNIDine. QuiNIDine may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Exceptions: Felodipine; Nisoldipine. Monitor therapy

Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Exceptions: Cannabidiol. Monitor therapy

Carbonic Anhydrase Inhibitors: May decrease the excretion of QuiNIDine. Exceptions: Brinzolamide; Dorzolamide. Monitor therapy

Cardiac Glycosides: QuiNIDine may increase the serum concentration of Cardiac Glycosides. Management: Upon quinidine initiation, consider reducing cardiac glycoside dose by 25% to 50%, with continued monitoring of glycoside serum concentrations and clinical response until the quinidine reaches steady state (5-10 days). Consider therapy modification

Cimetidine: May increase the serum concentration of QuiNIDine. Management: Consider alternatives to cimetidine. If the combination cannot be avoided, monitor for increased quinidine concentrations/toxicity with cimetidine initiation/dose increase, or decreased concentrations/effects with cimetidine discontinuation/dose decrease. Consider therapy modification

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination

Cobicistat: May increase the serum concentration of QuiNIDine. Monitor therapy

Codeine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Consider therapy modification

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Consider therapy modification

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Crizotinib: May enhance the QTc-prolonging effect of QuiNIDine. Crizotinib may increase the serum concentration of QuiNIDine. Avoid combination

CYP2D6 Substrates: CYP2D6 Inhibitors (Strong) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Ajmaline; Dapoxetine; Tamoxifen; Tropisetron. Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification

Dabigatran Etexilate: QuiNIDine may increase the serum concentration of Dabigatran Etexilate. Management: Consider giving dabigatran 2 hrs before oral quinidine; other dose reductions may be needed. Specific recommendations vary by U.S. vs Canadian labeling, renal function, and indication for dabigatran. Refer to full monograph or dabigatran labeling. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dalfampridine: QuiNIDine may increase the serum concentration of Dalfampridine. Management: Recommendations differ significantly between international labelings in regards to the concomitant use of dalfampridine (referred to as fampridine in Canada) and quinidine. Consult appropriate product labeling. Monitor therapy

Dapoxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Dapoxetine. Monitor therapy

Darunavir: May increase the serum concentration of QuiNIDine. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Dextromethorphan: QuiNIDine may increase the serum concentration of Dextromethorphan. Management: Avoid concurrent use of these agents when possible, unless the increased psychoactive effects of dextromethorphan are desired. Since codeine activation is also inhibited by quinidine, codeine is unlikely to be suitable as an alternative antitussive. Consider therapy modification

Dihydrocodeine: QuiNIDine may diminish the analgesic effect of Dihydrocodeine. Specifically, quinidine may prevent the metabolic conversion of dihydrocodeine to its active metabolite Monitor therapy

DiltiaZEM: May increase the serum concentration of QuiNIDine. Monitor therapy

DOXOrubicin (Conventional): CYP2D6 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP2D6 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

DULoxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of DULoxetine. Monitor therapy

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination

Enzalutamide: May decrease the serum concentration of QuiNIDine. Avoid combination

Erythromycin (Systemic): May enhance the QTc-prolonging effect of QuiNIDine. Erythromycin (Systemic) may increase the serum concentration of QuiNIDine. Avoid combination

Etravirine: May decrease the serum concentration of QuiNIDine. Monitor therapy

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification

Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Monitor therapy

Fingolimod: May enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class Ia). Avoid combination

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy

FluvoxaMINE: May increase the serum concentration of QuiNIDine. QuiNIDine may increase the serum concentration of FluvoxaMINE. Monitor therapy

Fosamprenavir: May increase the serum concentration of QuiNIDine. Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fosphenytoin: May enhance the QTc-prolonging effect of QuiNIDine. Fosphenytoin may decrease the serum concentration of QuiNIDine. Management: Consider alternatives when possible. Monitor patients receiving this combination closely forsigns and symptoms of excessive QTc interval prolongation and arrhythmia, as well as for decreased serum concentrations/therapeutic effects of quinidine. Consider therapy modification

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination

Grapefruit Juice: May increase the serum concentration of QuiNIDine. Avoid combination

Haloperidol: May enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may increase the serum concentration of Haloperidol. Avoid combination

Highest Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of other Highest Risk QTc-Prolonging Agents. Avoid combination

HYDROcodone: QuiNIDine may decrease serum concentrations of the active metabolite(s) of HYDROcodone. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Indinavir: May increase the serum concentration of QuiNIDine. Monitor therapy

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy

Ivabradine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Kaolin: May decrease the serum concentration of QuiNIDine. Management: Consider separating doses of kaolin and quinidine by at least 2 hours in order to reduce the risk of interaction. Monitor for decreased therapeutic effects of quinidine if kaolin is simultaneously coadministered. Consider therapy modification

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification

Loperamide: QuiNIDine may enhance the adverse/toxic effect of Loperamide. Specifically, the combination may result in enhanced CNS effects of loperamide (eg, miosis, respiratory depression) and/or possible proarrhythmic effects. QuiNIDine may increase the serum concentration of Loperamide. Monitor therapy

Lopinavir: May enhance the QTc-prolonging effect of QuiNIDine. Lopinavir may increase the serum concentration of QuiNIDine. Specifically, lopinavir/ritonavir may increase the serum concentration of quinidine. Avoid combination

Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Lurasidone: May enhance the QTc-prolonging effect of QuiNIDine. Management: Consider alternatives to quinidine in patients with acute lurasidone overdose. If quinidine treatment cannot be avoided, monitor for excessive QTc interval prolongation. Consider therapy modification

Mefloquine: QuiNIDine may enhance the adverse/toxic effect of Mefloquine. Specifically, the risk for QTc-prolongation and the risk for convulsions may be increased. Management: Avoid concurrent use, and delay administration of mefloquine until at least 12 hours after the last dose of quinidine when possible. Avoid combination

Mequitazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Mequitazine. Avoid combination

Metoprolol: CYP2D6 Inhibitors may increase the serum concentration of Metoprolol. Management: Consider an alternative for one of the interacting drugs in order to avoid metoprolol toxicity. If the combination must be used, monitor response to metoprolol closely. Metoprolol dose reductions may be necessary. Consider therapy modification

MiFEPRIStone: May enhance the QTc-prolonging effect of QuiNIDine. MiFEPRIStone may increase the serum concentration of QuiNIDine. Management: Avoid quinidine during and 2 weeks following mifepristone for treatment of hyperglycemia in Cushing's syndrome. The interaction magnitude could be lower with single doses used to terminate pregnancy, but neither effect has been studied clinically. Avoid combination

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Moderate Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy

Nebivolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Nebivolol. Monitor therapy

Nelfinavir: May increase the serum concentration of QuiNIDine. Avoid combination

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Neuromuscular-Blocking Agents: QuiNIDine may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Nicergoline: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MMDL metabolite may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MDL metabolite may be decreased. Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy

Ombitasvir, Paritaprevir, and Ritonavir: May increase the serum concentration of QuiNIDine. Management: Canadian labeling recommends avoiding this combination. Monitor therapy

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May increase the serum concentration of QuiNIDine. Management: Canadian labeling recommends avoiding this combination. Monitor therapy

OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

Perhexiline: CYP2D6 Inhibitors may increase the serum concentration of Perhexiline. Management: Consider alternatives to this combination if possible. If combined, monitor for increased perhexiline serum concentrations and toxicities (eg, hypoglycemia, neuropathy, liver dysfunction). Perhexiline dose reductions will likely be required. Consider therapy modification

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

PHENobarbital: May enhance the hepatotoxic effect of QuiNIDine. PHENobarbital may decrease the serum concentration of QuiNIDine. Monitor therapy

Phenytoin: May decrease the serum concentration of QuiNIDine. Monitor therapy

Pimozide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pimozide. Avoid combination

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination

Potassium-Sparing Diuretics: May diminish the therapeutic effect of QuiNIDine. Monitor therapy

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification

Primidone: May decrease the serum concentration of QuiNIDine. Monitor therapy

Propafenone: QuiNIDine may enhance the QTc-prolonging effect of Propafenone. QuiNIDine may increase the serum concentration of Propafenone. Avoid combination

Propranolol: QuiNIDine may increase the serum concentration of Propranolol. Monitor therapy

Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy

QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy

Reserpine: May enhance the adverse/toxic effect of QuiNIDine. Monitor therapy

Rifamycin Derivatives: May decrease the serum concentration of QuiNIDine. Management: Consider alternatives to combination treatment with quinidine and rifampin due to large potential decreases in quinidine concentrations. Monitor for decreased quinidine concentrations/effects with initiation/dose increase of any rifamycin derivative. Consider therapy modification

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy

RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy

Ritonavir: May increase the serum concentration of QuiNIDine. Avoid combination

Saquinavir: May enhance the QTc-prolonging effect of QuiNIDine. Saquinavir may increase the serum concentration of QuiNIDine. Avoid combination

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid using drugs with substantial anticholinergic effects in patients receiving secretin whenever possible. If such agents must be used in combination, monitor closely for a diminished response to secretin. Consider therapy modification

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Avoid combination

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Sucralfate: May decrease the serum concentration of QuiNIDine. Specifically, sucralfate may decrease the absorption of quinidine. Management: Administer quinidine at least 2 hours before or at least 6 hours after sucralfate. Consider therapy modification

Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Avoid combination

Tamsulosin: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. Monitor therapy

Telaprevir: May enhance the adverse/toxic effect of QuiNIDine. Telaprevir may increase the serum concentration of QuiNIDine. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Thioridazine: CYP2D6 Inhibitors may increase the serum concentration of Thioridazine. Avoid combination

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination

Tipranavir: May increase the serum concentration of QuiNIDine. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination

TraMADol: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of TraMADol. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of TraMADol. CYP2D6 Inhibitors (Strong) may increase the serum concentration of TraMADol. Monitor therapy

Tricyclic Antidepressants: May enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may increase the serum concentration of Tricyclic Antidepressants. Consider therapy modification

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification

Verapamil: QuiNIDine may enhance the hypotensive effect of Verapamil. Verapamil may increase the serum concentration of QuiNIDine. Monitor therapy

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination

Vitamin K Antagonists (eg, warfarin): QuiNIDine may enhance the anticoagulant effect of Vitamin K Antagonists. Note that the INR/PT might be unchanged in the face of increased bleeding. Monitor therapy

Vortioxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Vortioxetine. Management: The vortioxetine dose should be reduced by 50% when used together with a strong CYP2D6 inhibitor. Following cessation of the strong CYP2D6 inhibitor, the vortioxetine dose should be returned to the normal level. Consider therapy modification

Adverse Reactions

Frequency not always defined.

Cardiovascular: Palpitations (7%), angina pectoris (6%), cardiac arrhythmia (3%; new or worsened; proarrhythmic effect), ECG abnormality (3%), cerebral ischemia (2%), prolonged Q-T interval on ECG (modest prolongation is common; however, excessive prolongation is rare and indicates toxicity), syncope

Central nervous system: Dizziness (3% to 15%), fatigue (7%), headache (3% to 7%), disturbed sleep (3%), nervousness (2%), ataxia (1%)

Dermatologic: Skin rash (5% to 6%)

Gastrointestinal: Diarrhea (24% to 35%), gastrointestinal distress (upper; 22%), nausea and vomiting (3%), esophagitis

Neuromuscular & skeletal: Weakness (2% to 5%), tremor (2%)

Ophthalmic: Visual disturbance (3%)

Miscellaneous: Fever (6%)

<1% (Limited to important or life-threatening): Acute psychosis, agranulocytosis, angioedema, arthralgia, bradycardia (exacerbated, in sick sinus syndrome), bronchospasm, cerebrovascular insufficiency (possibly resulting in ataxia, apprehension, and seizure), cinchonism (may include tinnitus, high-frequency hearing loss, deafness, vertigo, blurred vision, diplopia, photophobia, headache, confusion, and delirium; usually associated with chronic toxicity but may occur after brief exposure to a moderate dose), depression, dyschromia, exfoliative dermatitis, granulomatous hepatitis, hemolytic anemia, hepatotoxicity, immune thrombocytopenia, increased creatine phosphokinase, lupus-like syndrome, lymphadenopathy, optic neuritis, pneumonitis, psoriaform eruption, Sjogren’s syndrome, skin photosensitivity, thrombocytopenia, torsades de pointes, uveitis, vasculitis, ventricular fibrillation, ventricular tachycardia (including paradoxical, during atrial fibrillation/flutter), visual field loss

ALERT: U.S. Boxed Warning

Mortality (tablet):

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. In the patients studied in the analyzed trials, the mortality associated with the use of quinidine was more than 3 times as great as the mortality associated with the use of placebo.

Another meta-analysis 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.

Warnings/Precautions

Concerns related to adverse effects:

• Hepatotoxicity: Has been associated with severe hepatotoxic reactions, including granulomatous hepatitis.

• Hypersensitivity reactions: With use, hypersensitivity reactions may occur.

• Proarrhythmic effects: Monitor for proarrhythmic effects; may cause QT prolongation and subsequent torsade de pointes. Monitor and adjust dose to prevent QTc prolongation. Avoid use in patients with diagnosed or suspected congenital long QT syndrome.

Disease-related concerns:

• Arrhythmias: Appropriate use: [U.S. Boxed Warning]: Antiarrhythmic drugs have not been shown to enhance survival in non-life-threatening ventricular arrhythmias and may increase mortality; the risk is greatest with structural heart disease. Quinidine may increase mortality in treatment of atrial fibrillation/flutter.

• Atrial fibrillation/flutter: May increase ventricular response rate in patients with atrial fibrillation or flutter; control AV conduction before initiating.

• Conduction disturbances: Use with caution in patients at risk for heart block; can unmask sick sinus syndrome (causes bradycardia).

• Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy.

• G6PD deficiency: Hemolysis may occur in patients with G6PD (glucose-6-phosphate dehydrogenase) deficiency.

• Left ventricular dysfunction/heart failure (HF): Use with caution in patients with reduced left ventricular ejection fraction; may precipitate or exacerbate condition.

• Hepatic impairment: Use with caution in patients with hepatic impairment; reduced dosage recommended.

Concurrent drug therapy issues:

• Antiarrhythmics: Use with caution with concurrent use of other antiarrhythmics.

• Digoxin: Use may cause digoxin-induced toxicity; adjust digoxin's dose.

Dosage form specific issues:

• Different salts: Do not interchange the different salt products.

Other warnings/precautions:

• CAST trial: In the Cardiac Arrhythmia Suppression Trial (CAST), recent (>6 days but <2 years ago) myocardial infarction patients with asymptomatic, non-life-threatening ventricular arrhythmias did not benefit and may have been harmed by attempts to suppress the arrhythmia with flecainide or encainide. An increased mortality or nonfatal cardiac arrest rate (7.7%) was seen in the active treatment group compared with patients in the placebo group (3%). The applicability of the CAST results to other populations is unknown. Antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias.

Monitoring Parameters

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

Consult individual institutional policies and procedures.

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. Quinidine crosses the placenta and can be detected in the amniotic fluid, cord blood, and neonatal serum. Quinidine is indicated for use in the treatment of severe malaria infection in pregnant women (CDC, 2011; Smereck, 2011) and has also been used to treat arrhythmias in pregnancy when other agents are ineffective (European Society of Cardiology, 2003).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea, abdominal pain, or pyrosis. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), severe dizziness, passing out, bradycardia, tachycardia, arrhythmia, angina, loss of strength and energy, bruising, bleeding, tinnitus, hearing loss, severe nausea, vomiting, mood changes, change in balance, vision changes, sensitivity to light, illogical thinking, or severe headache (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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