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QuiNIDine

Medically reviewed on Nov 15, 2018

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 0 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: Hepatic Function Impairment

Hepatic cirrhosis: Elimination t½ may be prolonged and increase Vd.

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).

Guideline recommendation: Ventricular arrhythmias: Based on the American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) patients with Brugada syndrome with or without an implantable cardioverter-defibrillator (ICD) experiencing symptomatic ventricular arrhythmias are recommended to receive intensification of therapy with quinidine or catheter ablation (AHA/ACC/HRS [Al-Khatib 2017]; Belhassen 2015). Patients with short QT syndrome and recurrent sustained ventricular arrhythmias may benefit from treatment with quinidine (AHA/ACC/HRS [Al-Khatib 2017]).

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

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.

Paroxysmal atrial fibrillation/flutter, maintenance of sinus rhythm: Oral: Note: 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; may increase cautiously to desired effect.

Extended-release formulations:

Quinidine sulfate: Initial: 300 mg every 8 to 12 hours; may increase 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]).

Malaria (severe), 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.

Ventricular arrhythmias (off-label dose): Oral: Note: Dosing regimens for suppression of 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 formulation: Quinidine sulfate: Initial: 200 mg every 6 hours; may increase dose cautiously up to 600 mg every 6 to 12 hours (AHA/ACC/HRS [Al-Khatib 2017]).

Extended-release formulation: Quinidine gluconate: Initial: 324 mg every 8 to 12 hours; may increase dose cautiously up to 648 mg every 8 to 12 hours (AHA/ACC/HRS [Al-Khatib 2017]).

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.

Reconstitution

Parenteral: Quinidine gluconate: IV: Dilute with D5W to a maximum concentration of 16 mg/mL

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

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.

IV: Quinidine gluconate: Administer by IV infusion with continuous ECG and blood pressure monitoring. IM administration is not recommended. 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.

Storage

Solution for injection: Store at room temperature of 25°C (77°F). Solutions diluted to 16 mg/mL in D5W are stable for up to 24 hours at room temperature or 48 hours at 4°C (40°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: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase the serum concentration of Ajmaline. Avoid combination

Amifampridine: May diminish the anticholinergic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Amifampridine. Monitor therapy

Amiodarone: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

Amisulpride: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Amisulpride. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification

Amphetamines: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Amphetamines. 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

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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

Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification

Benzhydrocodone: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Benzhydrocodone. Monitor therapy

Betrixaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease the betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-glycoprotein inhibitor. Consider therapy modification

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in patients with moderate to severe renal insufficiency who are receiving p-glycoprotein inhibitors. Consider therapy modification

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

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

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

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

Ceritinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification

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

Chloroquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. 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

Citalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Citalopram. Avoid combination

Clarithromycin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clarithromycin. Avoid combination

Clofazimine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

CloZAPine: May enhance the anticholinergic effect of QuiNIDine. CloZAPine may enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may increase the serum concentration of CloZAPine. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

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. See full monograph for details. Consider therapy modification

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Crizotinib: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Crizotinib. Crizotinib may enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Crizotinib may increase the serum concentration of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

CYP2D6 Substrates (High risk with Inhibitors): CYP2D6 Inhibitors (Strong) may decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Exceptions: Ajmaline; Dapoxetine; Indoramin; Tamoxifen; Timolol (Ophthalmic); Tropisetron. Consider therapy modification

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

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). 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 (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). 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 (High risk with Inducers). 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

Dasatinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Dasatinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Deutetrabenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Deutetrabenazine. Management: The total daily dose of deutetrabenazine should not exceed 36 mg, and the maximum single dose of deutetrabenazine should not exceed 18 mg with concurrent use of a strong CYP2D6 inhibitor. Consider therapy modification

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

Domperidone: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Domperidone. Avoid combination

Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Doxepin-Containing Products. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification

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

Droperidol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Droperidol. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification

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

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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 P-gp inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification

Eliglustat: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Management: Reduce the eliglustat dose to 84 mg daily. Avoid use of eliglustat in combination with a strong CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor. Consider therapy modification

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

Encorafenib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification

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

EPHEDrine (Nasal): May diminish the therapeutic effect of QuiNIDine. Monitor therapy

EPHEDrine (Systemic): May diminish the therapeutic effect of QuiNIDine. QuiNIDine may diminish the therapeutic effect of EPHEDrine (Systemic). Monitor therapy

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

Escitalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Escitalopram. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification

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

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

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

Fingolimod: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Avoid combination

Flecainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flecainide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification

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

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

Flupentixol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flupentixol. Avoid combination

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 (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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 (High risk with Inhibitors). Avoid combination

Gadobenate Dimeglumine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

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

Gemifloxacin: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Avoid combination

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

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

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

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

Halofantrine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Halofantrine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

Haloperidol: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

HYDROcodone: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of HYDROcodone. Specifically, concentrations of hydromorphone may be decreased. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Iloperidone: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP2D6 inhibitor. Consider therapy modification

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

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

Inotuzumab Ozogamicin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Inotuzumab Ozogamicin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

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

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

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

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

Levofloxacin-Containing Products (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Avoid combination

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

Lofexidine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Lofexidine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

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-Loperamide Oxide: QuiNIDine may enhance the adverse/toxic effect of Loperamide-Loperamide Oxide. 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-Loperamide Oxide. 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

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

Methadone: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Methadone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

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

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Midostaurin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Midostaurin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. 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

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

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

Moxifloxacin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Moxifloxacin (Systemic). Avoid combination

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

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 (High risk with Inhibitors). 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

Nilotinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Nilotinib. Avoid combination

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

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Monitor therapy

OLANZapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification

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

Ondansetron: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

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

Osimertinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Osimertinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification

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

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

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

Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

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 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.). Exceptions: Loperamide. 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

Pilsicainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pilsicainide. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

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

Pimozide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pimozide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Avoid combination

Piperaquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Piperaquine. Avoid combination

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification

Posaconazole: May increase the serum concentration of QuiNIDine. 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 Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. 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

Primaquine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Primaquine. Management: Monitor for signs and symptoms of possible treatment failure with primaquine in patients who are taking strong CYP2D6 inhibitors. If efficacy of primaquine is compromised, may consider adjusting therapies. Consider therapy modification

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

Probucol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Probucol. Avoid combination

Propafenone: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

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

QT-prolonging Agents (Indeterminate Risk - Avoid): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Agents (Indeterminate Risk - Caution): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Class IA Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of other QT-prolonging Class IA Antiarrhythmics (Highest Risk). Exceptions: Ajmaline. Avoid combination

QT-prolonging Class III Antiarrhythmics (Highest Risk): QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Avoid combination

QT-prolonging Kinase Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

QT-prolonging Miscellaneous Agents (Highest Risk): QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

QUEtiapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QUEtiapine. Avoid combination

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

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

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

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

Ribociclib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ribociclib. Avoid combination

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

RisperiDONE: QuiNIDine may enhance the QTc-prolonging effect of RisperiDONE. QuiNIDine may increase the serum concentration of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

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

Saquinavir: May enhance the QTc-prolonging effect of QuiNIDine. Avoid combination

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of 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 (High risk with Inducers). Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Sodium Stibogluconate: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sodium Stibogluconate. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

Sparfloxacin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sparfloxacin. Avoid combination

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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 (High risk with Inhibitors). 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

Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Management: These listed exceptions are discussed in detail in separate interaction monographs. Monitor therapy

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

Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Tetrabenazine adult dose should be reduced by 50% when starting a strong CYP2D6 inhibitor. Maximum tetrabenazine adult dose is 50 mg/day when used with a strong CYP2D6 inhibitor. Consider therapy modification

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

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

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

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 (High risk with Inducers). 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. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Exceptions: Doxepin (Systemic); Doxepin (Topical). Consider therapy modification

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

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

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

Vemurafenib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Vemurafenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification

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

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

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%, postmarketing, and/or case reports: 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, flushing, granulomatous hepatitis, hemolytic anemia, hepatotoxicity (rare), hypotension, immune thrombocytopenia, increased creatine phosphokinase, lupus-like syndrome, lymphadenopathy, myalgia, mydriasis, nocturnal amblyopia, optic neuritis, pneumonitis, pruritus, psoriasiform eruption, scotoma, skin photosensitivity, Sjogren’s syndrome, thrombocytopenia, torsades de pointes, urticaria, uveitis, vasculitis, ventricular fibrillation, ventricular tachycardia (including paradoxical, during atrial fibrillation/flutter), visual field loss, vision color changes

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: [US 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, 2013; 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 dizziness, headache, tinnitus, change in hearing, or flushing. Have patient report immediately to prescriber signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating), abnormal heartbeat, tachycardia, angina, deafness, passing out, vision changes, color blindness, blindness, pinpoint red spots on skin, abdominal pain, severe nausea, vomiting, severe diarrhea, , anxiety, chills, muscle weakness, sweating a lot, signs of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (bruising or bleeding; severe loss of strength and energy; dark urine or jaundice; pale skin; change in amount of urine passed; vision changes; change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance; or fever), or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (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 health care 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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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