Skip to Content

QuiNIDine

Medically reviewed by Drugs.com. Last updated on Apr 7, 2020.

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 [DSC])

Tablet, Oral, as sulfate:

Generic: 200 mg, 300 mg

Tablet Extended Release, Oral, as gluconate:

Generic: 324 mg

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), increased with cirrhosis (3 to 5 L/kg)

Metabolism

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

Excretion

Urine (5% to 20% as unchanged drug)

Time to Peak

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

Half-Life Elimination

Plasma: Children: 3 to 4 hours; Adults: 6 to 8 hours; prolonged with elderly, cirrhosis, and congestive heart failure

Protein Binding

Neonates and infants: 50% to 70%; Older children and 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

Volume of distribution and renal clearance may be reduced.

Special Populations: Hepatic Function Impairment

Hepatic cirrhosis: Elimination half-life may be prolonged and increased volume of distribution.

Special Populations: Elderly

Elimination half-life may be increased.

Special Populations Note

Heart failure: Total clearance and volume of distribution 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: Quinidine injection has been discontinued in the United States for more than 1 year.

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 formulation: 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 formulation:

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 formulation: Quinidine sulfate: Initial: 200 mg every 6 hours; may increase cautiously to desired effect.

Extended-release formulation: Quinidine gluconate: Initial: 324 mg every 8 to 12 hours; the dose may be increased cautiously to desired effect. Usual dose range: 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: Quinidine is available in gluconate and sulfate salt formulations which are not interchangeable on a mg per mg basis, due to differences in the amount of quinidine base supplied; 267 mg of quinidine gluconate equals 200 mg of quinidine sulfate. Doses are expressed in terms of salt (gluconate or sulfate), not base. Quinidine injection has been discontinued in the US for >1 year.

Malaria, treatment (severe, life-threatening): Infants, Children, and Adolescents: 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 loading dose). Change to oral quinine once parasite density is <1% and patient can receive oral medication to complete treatment course; total duration of treatment (quinidine/quinine): 3 days in Africa or South America; 7 days in Southeast Asia; use in combination with doxycycline, tetracycline, or clindamycin; omit quinidine loading dose if patient received >40 mg/kg of quinine in preceding 48 hours or mefloquine within preceding 12 hours (CDC 2013). Note: Close monitoring, including telemetry, is required; if severe cardiac adverse effects occur, infusion rate may need to be decreased or drug temporarily discontinued.

Tachyarrhythmias, including supraventricular tachycardia, atrial fibrillation, atrial flutter, and ventricular tachycardia: Children and Adolescents: Limited data available; not considered first-line therapy (Bozic 2018; Ramesh Iyer 2008):

Oral: Quinidine sulfate, immediate release: Usual dose: 30 mg/kg/day in divided doses every 6 hours; more frequent dosing may be necessary due to the increased clearance seen in pediatric patients; range: 15 to 60 mg/kg/day; maximum adult daily dose: 2,400 mg/day (Kliegman 2016; Nelson 1996; Park 2014; Szefler 1982).

IV: Not recommended; use with extreme caution: Quinidine gluconate: 2 to 10 mg/kg/dose every 3 to 6 hours as needed (Nelson 1996; Park 2014). Note: Dosing has not been evaluated in clinical trials.

Reconstitution

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

Extemporaneously Prepared

10 mg/mL Oral Liquid

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, 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):1804-1809.9775343

Administration

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

Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. IR tablet formulation is available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, selection of IR formulation should be strongly considered for cardiovascular and other high-risk labeled and off-label indications for quinidine.

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

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

Acetylcholinesterase Inhibitors: Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase Inhibitors may diminish the therapeutic effect of Anticholinergic Agents. 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: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. 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

Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. 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 (Oral): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Amisulpride (Oral). 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 greater risk. Consider therapy modification

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

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

Amphetamines: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities (including serotonin syndrome) if used with a strong CYP2D6 inhibitor. Initiate amphetamine therapy at lower doses, monitor frequently, and adjust doses as needed. Discontinue amphetamines if serotoinin syndrome occurs. 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: Aripiprazole dose reductions are required for indications other than major depressive disorder. Dose reductions vary based on formulation, initial starting dose, and the additional use of CYP3A4 inhibitors. 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: Decrease aripiprazole lauroxil dose to next lower strength if used with strong CYP2D6 inhibitors for over 14 days. No dose adjustment needed if using the lowest dose (441 mg) or if a CYP2D6 PM. Max dose is 441 mg if also taking strong CYP3A4 inhibitors. 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 (patients who weigh up to 70 kg: 0.5 mg/kg/day; adults or patients who weigh 70 kg or more: 40 mg/day) in patients receiving a strong CYP2D6 inhibitor. Increase to usual target dose after 4 weeks if needed. 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 adult betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-gp inhibitor. Avoid concomitant use of betrixaban and P-gp inhibitors in patients with severe renal impairment (CrCL less than 30 mL/min). Consider therapy modification

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

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Brexpiprazole: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual with strong CYP2D6 inhibitors, reduce to 25% of usual if used with both a strong CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor; these recommendations do not apply if treating major depressive disorder 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: Measure cardiac glycoside serum concentrations before initiating treatment with quinidine. Reduce cardiac glycoside concentrations by either reducing the dose by 30% to 50% or by modifying the dosing frequency. Consider therapy modification

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

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

Ceritinib: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Ceritinib. 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

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

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

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

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

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. Monitor therapy

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-gp inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See interaction monograph for details. Consider therapy modification

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

Crizotinib: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Crizotinib. 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

CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). Monitor therapy

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). Management: Consider avoiding this combination. Some combinations are specifically contraindicated by manufacturers; others may have recommended dose adjustments. If combined, monitor for increased substrate effects. Consider therapy modification

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Monitor therapy

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

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

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

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). Avoid combination

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

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: QuiNIDine may increase the serum concentration of Edoxaban. Management: In patients treated for DVT/PE, reduce the edoxaban dose to 30 mg daily when combined with quinidine. No dose adjustment is recommended for patients treated for atrial fibrillation. Monitor for increased edoxaban toxicities (ie, bleeding) when combined. Consider therapy modification

Eliglustat: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Management: Eliglustat dose is 84 mg daily with CYP2D6 inhibitors. Use is contraindicated (COI) when also combined with strong CYP3A4 inhibitors. When also combined with a moderate CYP3A4 inhibitor, use is COI in CYP2D6 EMs or IMs and should be avoided in CYP2D6 PMs. 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

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

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

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

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

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

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

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

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

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 (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Monitor therapy

Fexinidazole [INT]: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Avoid combination

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

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

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

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

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

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

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

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

Gilteritinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. If use is necessary, monitor for QTc interval prolongation and arrhythmias. Consider therapy modification

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

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 and monitor for increased iloperidone toxicities, including QTc interval prolongation and arrhythmias. Consider therapy modification

Imipramine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Imipramine. The concentrations of desipramine may be increased. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Imipramine. Monitor therapy

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

Lacosamide: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Monitor therapy

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

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

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

Lefamulin: May enhance the QTc-prolonging effect of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. Avoid combination

Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Consider therapy modification

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

Lofepramine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Lofepramine. The active metabolite of lofepramine is desipramine. Monitor therapy

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 CNS depressant effect of Loperamide-Loperamide Oxide. Loperamide-Loperamide Oxide may enhance the QTc-prolonging effect of QuiNIDine. 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

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

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

Metoclopramide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Metoclopramide. Management: For gastroparesis: reduce metoclopramide dose to 5mg 4 times/day and limit to 20mg/day; nasal spray not recommended. For GERD: reduce metoclopramide dose to 5mg 4 times/day or to 10mg 3 times/day and limit to 30mg/day. Monitor for EPS when combined. Consider therapy modification

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

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

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

Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Monitor therapy

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

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

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

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

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

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

Ondansetron: QT-prolonging Class IA Antiarrhythmics (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 Agonists: Anticholinergic Agents may enhance the adverse/toxic effect of Opioid Agonists. 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

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

Perphenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Perphenazine. 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: 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: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pitolisant. Management: Reduce the pitolisant dose by 50% if a strong CYP2D6 inhibitor is initiated. For patients receiving strong CYP2D6 inhibitors, initiate pitolisant at 8.9 mg once daily and increase after 7 days to a maximum of 17.8 mg once daily. 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. Avoid combination

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

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

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

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

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

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

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

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

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

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. Monitor therapy

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

Sirolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus. Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Consider therapy modification

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

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 sucralfate. Consider therapy modification

Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy

Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. 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. Management: Avoid concurrent use of strong CYP2D6 inhibitors with tamoxifen when possible, as the combination may be associated with a reduced clinical effectiveness of tamoxifen. Consider therapy modification

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

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

Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. 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: Limit the tetrabenazine dose to 50 mg per day (25 mg per single dose) in patients taking strong CYP2D6 inhibitors. 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

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

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

Tolvaptan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tolvaptan. 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 decrease serum concentrations of the active metabolite(s) of TraMADol. CYP2D6 Inhibitors (Strong) may increase the serum concentration of TraMADol. Monitor therapy

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant weak CYP3A4 inhibitors. Consider therapy modification

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

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

Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Consider therapy modification

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. Management: Reduce valbenazine dose to 40 mg once daily when combined with a strong CYP2D6 inhibitor. Monitor for increased valbenazine effects/toxicities. Consider therapy modification

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 concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. 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

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

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 QT 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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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

Quinidine crosses the placenta and can be detected in the amniotic fluid and neonatal serum.

Patient Education

What is this drug used for?

• It is used to treat certain types of abnormal heartbeats.

• It is used to treat malaria.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness

• Headache

• Noise or ringing in the ears

• Change in hearing

• Flushing

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; 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.

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.

• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating.

• Abnormal heartbeat

• Fast heartbeat

• Chest pain

• 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

• Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome like bruising or bleeding; severe loss of strength and energy; dark urine or yellow skin; pale skin; change in amount of urine passed; vision changes; change in strength on one side is greater than the other, trouble speaking or thinking, change in balance; or fever.

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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