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.
Note: Dosage expressed in terms of the salt: 267 mg of quinidine gluconate = 200 mg of quinidine sulfate. Use has largely been replaced by more effective/safer antiarrhythmic agents and/or nonpharmacologic therapies (eg, radiofrequency ablation). A clinician who is experienced with using quinidine should be consulted prior to prescribing this medication.
Atrial fibrillation/flutter, pharmacological conversion (alternative agent):
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 therapy if sinus rhythm is not restored. 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 (Ref).
Immediate-release formulation: Quinidine sulfate: Initial: Oral: 200 mg every 6 hours; if after 4 or 5 doses there is no conversion, may increase to 400 mg every 6 hours (Ref).
Extended-release formulation: Quinidine gluconate: Initial: Oral: 324 mg every 8 hours for 2 days; if ineffective, may increase to 648 mg every 12 hours for 2 days; if ineffective, may increase to 648 mg every 8 hours for up to 4 days. If higher doses are not tolerated, a 4-day duration at a lower dose may be considered (Ref).
Paroxysmal atrial fibrillation/flutter, maintenance of sinus rhythm (alternative agent):
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 (Ref).
Immediate-release formulation: Quinidine sulfate: Initial: Oral: 200 mg every 6 hours; may increase dose cautiously to desired effect; usual dosage range: ~1 to 1.5 g/day in 4 divided doses (Ref).
Extended-release formulation: Quinidine gluconate: Initial: Oral: 324 mg every 8 to 12 hours; may increase dose cautiously to desired effect; usual dosage range: ~1 to 1.5 g/day in 2 or 3 divided doses (Ref).
Ventricular arrhythmias:
Note: Use has largely been replaced by more effective/safer antiarrhythmic agents and/or nonpharmacologic therapies (eg, radiofrequency ablation); however, may still be used for patients with refractory ventricular tachycardia or Brugada syndrome. 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 (Ref).
Immediate-release formulation: Quinidine sulfate: Initial: Oral: 200 mg every 6 hours; may increase dose cautiously to desired effect; usual dosage range: ~1 to 1.5 g per day in 4 divided doses (Ref).
Extended-release formulation: Quinidine gluconate: Initial: Oral: 324 mg every 8 to 12 hours; may increase dose cautiously to the desired effect; usual dosage range: ~1 to 1.5 g per day in 2 or 3 divided doses (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution due to reduced clearance. The following guidelines have been used by some clinicians (Ref):
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.
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution due to reduced clearance.
Refer to adult dosing.
(For additional information see "Quinidine: Pediatric drug information")
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 (Ref). 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 (Ref):
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 (Ref).
IV: Not recommended; use with extreme caution: Quinidine gluconate: 2 to 10 mg/kg/dose every 3 to 6 hours as needed (Ref). Note: Dosing has not been evaluated in clinical trials.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no specific recommendations in the manufacturer’s labeling; use with caution; based on experience in adult patients, dosing adjustment suggested
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution; hepatic impairment decreases clearance.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions are for the extended-release (ER) and immediate-release (IR) products unless otherwise indicated.
>10%:
Gastrointestinal: Diarrhea (ER: 24%; IR: 35%), gastrointestinal distress (IR: upper: 22%; including esophagitis, heartburn)
Nervous system: Dizziness (ER: 3%; IR: 15%)
1% to 10%:
Cardiovascular: Angina pectoris (IR: 6%), cardiac arrhythmia (ER: 3%; new or exacerbation of cardiac arrhythmia), ECG abnormality (ER: 3%; including prolonged QT interval on ECG), palpitations (IR: 7%)
Dermatologic: Skin rash (5% to 6%)
Gastrointestinal: Nausea and vomiting (ER: 3%)
Nervous system: Asthenia (2% to 5%), ataxia (IR: 1%), cerebral ischemia (ER: 2%), fatigue (IR: 7%), headache (3% to 7%), nervousness (IR: 2%), sleep disturbance (IR: 3%), tremor (IR: 2%)
Ophthalmic: Visual disturbance (IR: 3%)
Miscellaneous: Fever (ER: 6%)
Frequency not defined:
Cardiovascular: Bradycardia (exacerbated, in sick sinus syndrome), flushing, hypotension, vasculitis
Dermatologic: Exfoliative dermatitis, pruritus, psoriasiform eruption, urticaria
Hematologic & oncologic: Agranulocytosis
Hypersensitivity: Angioedema
Immunologic: Sjögren disease
Neuromuscular & skeletal: Arthralgia, increased creatine phosphokinase in blood specimen, myalgia
Ophthalmic: Uveitis
Respiratory: Bronchospasm, pneumonitis
Miscellaneous: Cinchonism
Postmarketing:
Cardiovascular: Syncope (Davies 1965, Selzer 1964), torsades de pointes (Faber 1994), ventricular arrhythmia (including extrasystoles, ventricular fibrillation, ventricular flutter, ventricular tachycardia) (Selzer 1964)
Dermatologic: Dyschromia, skin photosensitivity
Hematologic & oncologic: Hemolytic anemia (including autoimmune hemolytic anemia) (Zeigler 1979), immune thrombocytopenia (Arnold 2013), leukopenia (Nair 1981), lymphadenopathy (Lau 1990), thrombocytopenia (may be severe)
Hepatic: Hepatotoxicity (including granulomatous hepatitis) (El-Khatib 2020, Hogan 1984)
Nervous system: Acute psychosis (including auditory hallucination, delusion, paranoid ideation, psychomotor agitation, visual hallucination) (Deleu 1987), apprehension, depression, seizure (Selzer 1964)
Neuromuscular & skeletal: Lupus-like syndrome (Lavie 1985)
Ophthalmic: Mydriasis, night blindness, optic neuritis, scotoma, vision color changes, visual field loss
Renal: Nephrotic syndrome (Chisholm 1985)
Hypersensitivity to quinidine or any component of the formulation; thrombocytopenia; thrombocytopenic purpura; heart block greater than first degree; idioventricular conduction delays (except in patients with a functioning artificial pacemaker); those adversely affected by anticholinergic activity (eg, myasthenia gravis); concurrent use of quinolone antibiotics which prolong QT interval, cisapride, or ritonavir.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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 with quinidine use in patients with G6PD (glucose-6-phosphate dehydrogenase) deficiency (Luzzatto 2020).
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Vagolysis: Quinidine opposes atrial and atrioventricular node effects of vagal stimulation. Vagal maneuvers to terminate paroxysmal supraventricular tachycardia may be ineffective.
Dosage form specific issues:
• Different salts: Do not interchange the different salt products.
Quinidine injection has been discontinued in the United States for more than 1 year.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as sulfate:
Generic: 200 mg, 300 mg
Tablet Extended Release, Oral, as gluconate:
Generic: 324 mg
Yes
Tablet, controlled release (quiNIDine Gluconate ER Oral)
324 mg (per each): $8.65 - $9.06
Tablets (quiNIDine Sulfate Oral)
200 mg (per each): $15.09
300 mg (per each): $15.90
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral: Do not crush, chew, or break ER 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 indications for quinidine.
Oral: Administer with water on an empty stomach, but may administer with food or milk to decrease GI upset; best to administer in a consistent manner with regards to meals and around-the-clock to promote less variation in peak and trough serum concentrations; swallow extended-release tablets whole, do not chew or crush; some preparations of quinidine gluconate extended-release tablets may be split in half to facilitate dosage titration; tablets are not scored.
Parenteral: Quinidine gluconate: Note: Minimize use of PVC tubing to enhance bioavailability (quinidine may be significantly adsorbed to polyvinyl chloride tubing); shorter tubing lengths are recommended by the manufacturer.
Malaria: IV: Infusion duration of load and subsequent doses are determined by regimen used, refer to dosing for specific details.
Arrhythmia: Intermittent IV infusion: After dilution, infuse slowly via an infusion pump; maximum rate: 0.25 mg/kg/minute; monitor ECG along with closely monitoring patient for possible hypersensitivity or idiosyncratic reactions. Note: The use of IV quinidine gluconate for these indications has been replaced by more effective/safer antiarrhythmic agents.
Atrial fibrillation/flutter, pharmacological conversion: Pharmacologic conversion of atrial fibrillation/flutter to normal sinus rhythm.
Paroxysmal atrial fibrillation/flutter, maintenance of sinus rhythm: Maintenance of normal sinus rhythm in patients with atrial fibrillation/flutter.
Ventricular arrhythmias: Suppression of recurrent ventricular arrhythmias.
QuiNIDine may be confused with cloNIDine, quiNINE
Substrate of CYP2C9 (Minor), CYP2E1 (Minor), CYP3A4 (Major), P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (Strong), CYP3A4 (Weak), P-glycoprotein;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase 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. Risk D: Consider Therapy Modification
Agents with Clinically Relevant Anticholinergic Effects: QuiNIDine may increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Ajmaline: May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase serum concentration of Ajmaline. Risk X: Avoid
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Aliskiren. Risk C: Monitor
Alkalinizing Agents: May increase serum concentration of QuiNIDine. Risk C: Monitor
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of ALPRAZolam. Risk C: Monitor
Amantadine: May increase anticholinergic effects of QuiNIDine. QuiNIDine may increase serum concentration of Amantadine. Risk C: Monitor
AMILoride: May increase adverse/toxic effects of QuiNIDine. AMILoride may decrease therapeutic effects of QuiNIDine. Risk C: Monitor
Aminolevulinic Acid (Systemic): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Systemic). Risk X: Avoid
Aminolevulinic Acid (Topical): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Topical). Risk C: Monitor
Amiodarone: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects of Amiodarone. Management: Consider alternatives to this drug combination. If combined, consider dose reductions of the class IA antiarrhythmic (30% to 50%) and monitor for QTc interval prolongation and ventricular arrhythmias. Risk D: Consider Therapy Modification
Amisulpride (Oral): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Amitriptyline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Amitriptyline. CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Amitriptyline. Risk C: Monitor
Amoxapine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Amoxapine. Risk C: Monitor
Amphetamines: CYP2D6 Inhibitors (Strong) may increase 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. Risk C: Monitor
ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure 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. Risk D: Consider Therapy Modification
ARIPiprazole: CYP2D6 Inhibitors (Strong) may increase serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions or avoidance are required for indications other than major depressive disorder. Dose adjustments vary based on formulation, initial starting dose, and the additional use of CYP3A4 inhibitors. See interact monograph for details Risk D: Consider Therapy Modification
Atazanavir: May increase serum concentration of QuiNIDine. Risk X: Avoid
Atomoxetine: CYP2D6 Inhibitors (Strong) may increase 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. Risk D: Consider Therapy Modification
Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Benzhydrocodone: CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Benzhydrocodone. Risk C: Monitor
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Bilastine. Risk X: Avoid
Bornaprine: May increase adverse/toxic effects of QuiNIDine. Risk C: Monitor
Brexpiprazole: CYP2D6 Inhibitors (Strong) may increase 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 Risk D: Consider Therapy Modification
Broom: CYP2D6 Inhibitors (Strong) may increase serum concentration of Broom. Specifically, the concentrations of sparteine, a constituent of broom, may be increased. Risk C: Monitor
CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase serum concentration of CarBAMazepine. Risk C: Monitor
Carbetocin: May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
Cardiac Glycosides: QuiNIDine may increase 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. Risk D: Consider Therapy Modification
Carvedilol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Carvedilol. Risk C: Monitor
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Celiprolol. Risk C: Monitor
Ceritinib: May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Certoparin: May increase serum concentration of QuiNIDine. Risk C: Monitor
Chloroquine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Chlorpheniramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Chlorpheniramine. Risk C: Monitor
Chlorprothixene: May increase QTc-prolonging effects of QuiNIDine. Risk X: Avoid
Cimetidine: May increase serum concentration of QuiNIDine. Risk C: Monitor
Citalopram: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Citalopram. Risk X: Avoid
Clarithromycin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Clarithromycin. Risk X: Avoid
Clofazimine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
ClomiPRAMINE: May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
CloZAPine: May increase QTc-prolonging effects of QuiNIDine. CloZAPine may increase anticholinergic effects of QuiNIDine. QuiNIDine may increase 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. Risk D: Consider Therapy Modification
Codeine: CYP2D6 Inhibitors (Strong) may decrease therapeutic effects of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider Therapy Modification
Crizotinib: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects of Crizotinib. Crizotinib may increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Crizotinib may increase 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. Risk D: Consider Therapy Modification
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of QuiNIDine. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of QuiNIDine. Risk C: Monitor
CYP3A4 Inhibitors (Moderate): May increase serum concentration of QuiNIDine. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of QuiNIDine. Risk C: Monitor
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase active metabolite exposure of Dabigatran Etexilate. Risk C: Monitor
Dabrafenib: May increase QTc-prolonging effects of QuiNIDine. Dabrafenib may decrease serum concentration of QuiNIDine. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, and reduced quinidine efficacy. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification
Dapoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Dapoxetine. Risk C: Monitor
Dasatinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Desipramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Desipramine. Risk C: Monitor
Deutetrabenazine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Deutetrabenazine. Management: The total daily dose of deutetrabenazine should not exceed 36 mg with concurrent use of a strong CYP2D6 inhibitor. Risk D: Consider Therapy Modification
Dextromethorphan: CYP2D6 Inhibitors (Strong) may increase serum concentration of Dextromethorphan. Risk C: Monitor
Diamorphine: QuiNIDine may increase active metabolite exposure of Diamorphine. Management: Use caution and reduce the diamorphine dose during coadministration with quinidine. Risk D: Consider Therapy Modification
Dihydrocodeine: QuiNIDine may decrease analgesic effects of Dihydrocodeine. Specifically, quinidine may prevent the metabolic conversion of dihydrocodeine to its active metabolite Risk C: Monitor
Domperidone: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Domperidone. Risk X: Avoid
Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
DOXOrubicin (Conventional): CYP2D6 Inhibitors (Strong) may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor
DroPERidol: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
DULoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of DULoxetine. Risk C: Monitor
Edoxaban: QuiNIDine may increase 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. Risk D: Consider Therapy Modification
Eliglustat: CYP2D6 Inhibitors (Strong) may increase 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. Risk D: Consider Therapy Modification
Encorafenib: May increase QTc-prolonging effects of QuiNIDine. Encorafenib may decrease serum concentration of QuiNIDine. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, and decreased quinidine concentrations. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification
Ensartinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ensartinib. Risk X: Avoid
Entrectinib: May increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk X: Avoid
EPHEDrine (Nasal): May decrease therapeutic effects of QuiNIDine. Risk C: Monitor
EPHEDrine (Systemic): QuiNIDine may decrease therapeutic effects of EPHEDrine (Systemic). EPHEDrine (Systemic) may decrease therapeutic effects of QuiNIDine. Risk C: Monitor
Erythromycin (Systemic): May increase QTc-prolonging effects of QuiNIDine. Erythromycin (Systemic) may increase serum concentration of QuiNIDine. Risk X: Avoid
Escitalopram: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Etelcalcetide: May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide Phosphate. Risk C: Monitor
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide. Risk C: Monitor
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Everolimus. Risk C: Monitor
Fenfluramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Fenfluramine. Management: Limit fenfluramine dose to 20 mg/day without concurrent stiripentol or to 17 mg/day with concomitant stiripentol and clobazam when used with a strong CYP2D6 inhibitor. Risk D: Consider Therapy Modification
Fesoterodine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Fesoterodine. Risk C: Monitor
Fexinidazole: May increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk X: Avoid
Finerenone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Finerenone. Risk C: Monitor
Fingolimod: May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid
Flecainide: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Flibanserin: CYP3A4 Inhibitors (Weak) may increase serum concentration of Flibanserin. Risk C: Monitor
Fluconazole: May increase QTc-prolonging effects of QuiNIDine. Fluconazole may increase serum concentration of QuiNIDine. Risk X: Avoid
Fluorouracil Products: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Fluorouracil Products. 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. Risk D: Consider Therapy Modification
FLUoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of FLUoxetine. Risk C: Monitor
Flupentixol: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Flupentixol. Risk X: Avoid
FluPHENAZine: CYP2D6 Inhibitors (Strong) may increase serum concentration of FluPHENAZine. Risk C: Monitor
FluvoxaMINE: May increase serum concentration of QuiNIDine. QuiNIDine may increase serum concentration of FluvoxaMINE. Risk C: Monitor
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Gadobenate Dimeglumine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Gefitinib: CYP2D6 Inhibitors (Strong) may increase serum concentration of Gefitinib. Risk C: Monitor
Gemifloxacin: May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid
Gilteritinib: May increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. If use is necessary, monitor for QTc interval prolongation and arrhythmias. Risk D: Consider Therapy Modification
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor
Grapefruit Juice: May increase serum concentration of QuiNIDine. Risk X: Avoid
Halofantrine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Haloperidol: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
HYDROcodone: CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of HYDROcodone. Specifically, concentrations of hydromorphone may be decreased. Risk C: Monitor
HydrOXYzine: May increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk C: Monitor
Iboga: May increase QTc-prolonging effects of QuiNIDine. QuiNIDine may increase serum concentration of Iboga. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, and iboga toxicities. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification
Iloperidone: CYP2D6 Inhibitors (Strong) may increase serum concentration of Iloperidone. CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. 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. Risk D: Consider Therapy Modification
Imipramine: May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
Indoramin: CYP2D6 Inhibitors (Strong) may increase serum concentration of Indoramin. Risk C: Monitor
Inotuzumab Ozogamicin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Itraconazole: May increase serum concentration of QuiNIDine. Risk X: Avoid
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ixabepilone. Risk C: Monitor
Ketoconazole (Systemic): May increase QTc-prolonging effects of QuiNIDine. Ketoconazole (Systemic) may increase serum concentration of QuiNIDine. Risk X: Avoid
Lacosamide: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase adverse/toxic effects of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor
Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Lapatinib. Risk C: Monitor
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Larotrectinib. Risk C: Monitor
Lefamulin: May increase QTc-prolonging effects of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. Risk X: Avoid
Lemborexant: CYP3A4 Inhibitors (Weak) may increase 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. Risk D: Consider Therapy Modification
Levofloxacin-Containing Products (Systemic): May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid
Levoketoconazole: QT-prolonging CYP3A4 Substrates may increase QTc-prolonging effects of Levoketoconazole. Levoketoconazole may increase serum concentration of QT-prolonging CYP3A4 Substrates. Risk X: Avoid
Lofepramine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Lofepramine. The active metabolite of lofepramine is desipramine. Risk C: Monitor
Lofexidine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Lomitapide: CYP3A4 Inhibitors (Weak) may increase 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. Risk D: Consider Therapy Modification
Lonafarnib: May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
Loperamide: QuiNIDine may increase CNS depressant effects of Loperamide. Loperamide may increase QTc-prolonging effects of QuiNIDine. QuiNIDine may increase serum concentration of Loperamide. Risk C: Monitor
Maprotiline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Maprotiline. Risk C: Monitor
Mavorixafor: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Mavorixafor. Risk C: Monitor
Mefloquine: QuiNIDine may increase adverse/toxic effects 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. Risk X: Avoid
Meglumine Antimoniate: May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
Mequitazine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Mequitazine. Risk X: Avoid
Methadone: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Methoxsalen (Systemic): Photosensitizing Agents may increase photosensitizing effects of Methoxsalen (Systemic). Risk C: Monitor
Metoclopramide: CYP2D6 Inhibitors (Strong) may increase 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 toxicity when combined. Risk D: Consider Therapy Modification
Metoprolol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Metoprolol. Risk C: Monitor
Mexiletine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Mexiletine. Risk C: Monitor
Midazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Midazolam. Risk C: Monitor
Midostaurin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
MiFEPRIStone: May increase QTc-prolonging effects of QuiNIDine. MiFEPRIStone may increase serum concentration of QuiNIDine. Risk X: Avoid
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Morphine (Systemic). Risk C: Monitor
Moxifloxacin (Systemic): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Moxifloxacin (Systemic). Risk X: Avoid
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Nadolol. Risk C: Monitor
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Naldemedine. Risk C: Monitor
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Naloxegol. Risk C: Monitor
Nebivolol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Nebivolol. Risk C: Monitor
Nelfinavir: May increase serum concentration of QuiNIDine. Risk X: Avoid
Neuromuscular-Blocking Agents: QuiNIDine may increase neuromuscular-blocking effects of Neuromuscular-Blocking Agents. Risk C: Monitor
Nicergoline: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Nicergoline. Specifically, concentrations of the MMDL metabolite may be increased. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Nicergoline. Specifically, concentrations of the MDL metabolite may be decreased. Risk C: Monitor
NIFEdipine (Topical): QuiNIDine may increase therapeutic effects of NIFEdipine (Topical). NIFEdipine (Topical) may decrease serum concentration of QuiNIDine. Risk C: Monitor
NIFEdipine: May decrease serum concentration of QuiNIDine. NIFEdipine may increase serum concentration of QuiNIDine. QuiNIDine may increase serum concentration of NIFEdipine. Risk C: Monitor
Nilotinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Nilotinib. Risk X: Avoid
NiMODipine: CYP3A4 Inhibitors (Weak) may increase serum concentration of NiMODipine. Risk C: Monitor
Nirmatrelvir and Ritonavir: May increase serum concentration of QuiNIDine. Risk X: Avoid
Nortriptyline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Nortriptyline. Risk C: Monitor
OLANZapine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Oliceridine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Oliceridine. Risk C: Monitor
Olmutinib: CYP2D6 Inhibitors (Strong) may increase serum concentration of Olmutinib. Risk C: Monitor
Ondansetron: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Opipramol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Opipramol. Risk C: Monitor
Osimertinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
OxyCODONE: CYP2D6 Inhibitors (Strong) may increase serum concentration of OxyCODONE. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of OxyCODONE. Specifically, oxymorphone concentrations may be reduced. Risk C: Monitor
Oxytocin: May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
Pacritinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Pacritinib. 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. Risk C: Monitor
PARoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of PARoxetine. Risk C: Monitor
Patiromer: May decrease serum concentration of QuiNIDine. Management: Administer quinidine at least 3 hours before or 3 hours after patiromer. Risk D: Consider Therapy Modification
PAZOPanib: QuiNIDine may increase QTc-prolonging effects of PAZOPanib. QuiNIDine may increase serum concentration of PAZOPanib. Risk X: Avoid
Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Perhexiline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Perhexiline. Risk C: Monitor
Perphenazine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Perphenazine. Risk C: Monitor
Pilsicainide: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Pimozide: CYP2D6 Inhibitors (Strong) may increase serum concentration of Pimozide. Risk X: Avoid
Piperaquine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Piperaquine. Risk X: Avoid
Pitolisant: CYP2D6 Inhibitors (Strong) may increase serum concentration of Pitolisant. Management: Reduce the pitolisant dose by 50% if a strong CYP2D6 inhibitor is initiated. For patients already receiving strong CYP2D6 inhibitors, initial doses of pitolisant should be reduced and depends on age and patient weight. See full monograph for details. Risk D: Consider Therapy Modification
Porfimer: Photosensitizing Agents may increase photosensitizing effects of Porfimer. Risk X: Avoid
Posaconazole: May increase serum concentration of QuiNIDine. Risk X: Avoid
Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider Therapy Modification
Primaquine: CYP2D6 Inhibitors (Strong) may decrease therapeutic effects of Primaquine. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Primaquine. Management: Consider alternatives to the combination of primaquine and strong CYP2D6 inhibitors. If concomitant use is necessary, monitor for signs and symptoms of possible primaquine treatment failure. Risk D: Consider Therapy Modification
Probucol: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Probucol. Risk X: Avoid
Propafenone: May increase QTc-prolonging effects of QuiNIDine. QuiNIDine may increase serum concentration of Propafenone. Risk X: Avoid
Propofol: May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
Propranolol: QuiNIDine may increase serum concentration of Propranolol. Risk C: Monitor
Protriptyline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Protriptyline. Risk C: Monitor
QT-prolonging Agents (Indeterminate Risk - Avoid): May increase QTc-prolonging effects 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. Risk C: Monitor
QT-prolonging Agents (Indeterminate Risk - Caution): May increase QTc-prolonging effects 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. Risk C: Monitor
QT-prolonging Class IA Antiarrhythmics (Highest Risk): May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid
QT-prolonging Class III Antiarrhythmics (Highest Risk): QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects of QT-prolonging Class III Antiarrhythmics (Highest Risk). Risk X: Avoid
QT-Prolonging Inhalational Anesthetics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
QT-prolonging Kinase Inhibitors (Highest Risk): May increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
QT-prolonging Miscellaneous Agents (Highest Risk): QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase serum concentration of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for increased class IA toxicities, including QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification
QUEtiapine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of QUEtiapine. Risk X: Avoid
Quinidine (Non-Therapeutic): Quinidine (Non-Therapeutic) may increase adverse/toxic effects of QuiNIDine. Risk X: Avoid
Quizartinib: May increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ranolazine. Risk C: Monitor
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider Therapy Modification
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider Therapy Modification
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Repotrectinib. Risk X: Avoid
Reserpine: May increase arrhythmogenic effects of QuiNIDine. Risk C: Monitor
Ribociclib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Ribociclib. Risk X: Avoid
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RifAXIMin. Risk C: Monitor
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider Therapy Modification
RisperiDONE: QuiNIDine may increase QTc-prolonging effects of RisperiDONE. QuiNIDine may increase serum concentration of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for risperidone toxicities, including QTc interval prolongation and TdP. Risperidone dose adjustment may also be needed. See full monograph for details. Risk D: Consider Therapy Modification
Ritonavir: May increase serum concentration of QuiNIDine. Risk X: Avoid
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RomiDEPsin. Risk C: Monitor
Saquinavir: May increase QTc-prolonging effects of QuiNIDine. Risk X: Avoid
Sertindole: QuiNIDine may increase QTc-prolonging effects of Sertindole. QuiNIDine may increase serum concentration of Sertindole. Risk X: Avoid
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Silodosin. Risk C: Monitor
Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentration of Simvastatin. CYP3A4 Inhibitors (Weak) may increase active metabolite exposure of Simvastatin. Risk C: Monitor
Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Conventional). 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. Risk D: Consider Therapy Modification
Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
Sofpironium: CYP2D6 Inhibitors (Strong) may increase serum concentration of Sofpironium. Risk X: Avoid
Sparfloxacin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Sparfloxacin. Risk X: Avoid
Sucralfate: May decrease serum concentration of QuiNIDine. Specifically, sucralfate may decrease the absorption of quinidine. Management: Administer quinidine at least 2 hours before sucralfate. Risk D: Consider Therapy Modification
SUNItinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of SUNItinib. 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. Risk D: Consider Therapy Modification
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor
Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure 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. Risk D: Consider Therapy Modification
Tamsulosin: CYP2D6 Inhibitors (Strong) may increase serum concentration of Tamsulosin. Risk C: Monitor
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Teniposide. Risk C: Monitor
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor
Terbutaline: May increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Tetrabenazine: May increase QTc-prolonging effects of QuiNIDine. QuiNIDine may increase active metabolite exposure 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 quinidine. Additionally, monitor for QTc interval prolongation and ventricular arrhythmias (including torsades de pointes) when these drugs are combined. Risk D: Consider Therapy Modification
Thioridazine: May increase QTc-prolonging effects of QuiNIDine. QuiNIDine may increase serum concentration of Thioridazine. Risk X: Avoid
Timolol (Ophthalmic): CYP2D6 Inhibitors (Strong) may increase serum concentration of Timolol (Ophthalmic). Risk C: Monitor
Timolol (Systemic): CYP2D6 Inhibitors (Strong) may increase serum concentration of Timolol (Systemic). Risk C: Monitor
Tipranavir: May increase serum concentration of QuiNIDine. Risk X: Avoid
Tolterodine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Tolterodine. Risk C: Monitor
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid
Toremifene: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Toremifene. 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. Risk D: Consider Therapy Modification
TraMADol: CYP2D6 Inhibitors (Strong) may increase serum concentration of TraMADol. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of TraMADol. Risk C: Monitor
Triazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Triazolam. Risk C: Monitor
Trimipramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Trimipramine. Risk C: Monitor
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase 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. Risk D: Consider Therapy Modification
Valbenazine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Valbenazine. Management: Reduce valbenazine dose to 40 mg once daily when combined with a strong CYP2D6 inhibitor. Monitor for increased valbenazine effects/toxicities. Risk D: Consider Therapy Modification
Vemurafenib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase 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. Risk D: Consider Therapy Modification
Verteporfin: Photosensitizing Agents may increase photosensitizing effects of Verteporfin. Risk C: Monitor
VinCRIStine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of VinCRIStine. Risk X: Avoid
Vitamin K Antagonists: QuiNIDine may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Voriconazole: QuiNIDine may increase QTc-prolonging effects of Voriconazole. Voriconazole may increase serum concentration of QuiNIDine. Risk X: Avoid
Vortioxetine: CYP2D6 Inhibitors (Strong) may increase 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. Risk D: Consider Therapy Modification
Xanomeline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Xanomeline. Risk C: Monitor
Changes in dietary salt intake may alter the rate and extent of quinidine absorption. Quinidine serum levels may be increased if taken with food. Food has a variable effect on absorption of sustained release formulation. The rate of absorption of quinidine may be decreased following the ingestion of grapefruit juice. Excessive intake of fruit juice or vitamin C may decrease urine pH and result in increased clearance of quinidine with decreased serum concentration. Alkaline foods may result in increased quinidine serum concentrations. Management: Avoid changes in dietary salt intake. Grapefruit juice should be avoided. Take around-the-clock to avoid variation in serum levels and with food or milk to avoid GI irritation.
Quinidine crosses the placenta and can be detected in the amniotic fluid and neonatal serum.
Quinidine is present in breast milk.
Breast milk concentrations may be slightly lower than those in the maternal serum. The manufacturer recommends avoiding use in breastfeeding patients.
Administer with food or milk to decrease gastrointestinal irritation. Avoid changes in dietary salt intake.
ECG; CBC, liver and renal function tests, should be routinely performed during administration.
Consult individual institutional policies and procedures.
Therapeutic trough level: 2 to 6 mcg/mL (SI: 6.2 to 18.5 micromole/L). Modern assays may not be consistent with older medical literature. Values reported in the manufacturer's labeling are derived from assays that used benzene extraction or reverse-phase high-pressure liquid chromatography. Older assays might have given results that were 2 to 3 times higher (Crevasse 1988; manufacturer's labeling).
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)
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)
Metabolism: Extensively hepatic (50% to 90%) to inactive compounds
Bioavailability: Sulfate: ~70% with wide variability between patients (45% to 100%); Gluconate: 70% to 80%
Half-life elimination, plasma: Children: 3 to 4 hours; Adults: 6 to 8 hours; prolonged with elderly, cirrhosis, and congestive heart failure
Time to peak, serum: Oral: Sulfate: Immediate release: 2 hours; Gluconate: Extended release: 3 to 5 hours
Excretion: Urine (5% to 20% as unchanged drug)
Altered kidney function: Volume of distribution and renal clearance may be reduced.
Hepatic function impairment: Hepatic cirrhosis: Elimination half-life may be prolonged and increased volume of distribution.
Older adult: Elimination half-life may be increased.
Heart failure: Total clearance and volume of distribution are decreased.