Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral:
Nuedexta: Dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg
Pharmacology
Mechanism of Action
Dextromethorphan may relieve the symptoms of PBA by binding to sigma-1 receptors in the brain which may be involved in behavior, however the exact mechanism of action is not known. In the treatment of agitation and/or aggression in Alzheimer disease (off-label use), dextromethorphan may potentially relieve symptoms by several proposed mechanisms, including N-methyl-D-aspartase antagonism, sigma-1 receptor agonism, serotonin and norepinephrine reuptake inhibition, and nicotinic alpha-3-beta-4 receptor antagonism (Cummings 2015). However, the exact mechanism of action within this condition is not known.
Quinidine is used to block the rapid metabolism of dextromethorphan, thereby increasing serum concentrations. The dose of quinidine in this combination product provides serum concentrations 1% to 3% of those needed to treat cardiac arrhythmias.
Pharmacokinetics/Pharmacodynamics
Absorption
Bioavailability of dextromethorphan increased ~20-fold when administered with quinidine
Metabolism
Dextromethorphan: Hepatic via CYP2D6 to dextrorphan (active); Quinidine: Hepatic via CYP3A4 to 3-hydroxyquinidine (active) and other metabolites
Excretion
Urine (~20% as unchanged)
Time to Peak
Dextromethorphan: 3 to 4 hours; Quinidine: 1 to 2 hours
Half-Life Elimination
Dextromethorphan: 13 hours in extensive metabolizers; Quinidine: 7 hours in extensive metabolizers
Protein Binding
Dextromethorphan: 60% to 70%; Quinidine: 80% to 89%
Use: Labeled Indications
Pseudobulbar affect: Treatment of pseudobulbar affect (PBA)
Use: Off Label
Agitation and/or aggression in Alzheimer diseasec
Data from a 10-week, phase-2, randomized, double-blind controlled study suggests dextromethorphan and quinidine may be beneficial in the treatment of agitation and/or aggression in those with Alzheimer disease Cummings 2015. Of note, the patients in the trial were predominantly outpatients. Additional data may be necessary to further define the role of dextromethorphan and quinidine in this condition.
Contraindications
Hypersensitivity to dextromethorphan, quinidine, quinine, mefloquine, or any component of the formulation; concomitant use with quinidine or other medications containing quinidine, quinine, or mefloquine; history of quinine-, mefloquine-, or quinidine-induced thrombocytopenia, hepatitis, bone marrow depression, or lupus-like syndrome; concurrent administration with or within 2 weeks of discontinuing an MAO inhibitor; patients with prolonged QT interval, congenital QT syndrome, or history of torsade de pointes; patients with heart failure; concurrent use of drugs that prolong the QT interval and are metabolized by CYP2D6 (eg, pimozide, thioridazine); patients with complete atrioventricular (AV) block without an implanted pacemaker or patients at high risk of complete AV block
Dosage and Administration
Dosing: Adult
Pseudobulbar affect: Oral: Dextromethorphan 20 mg/quinidine 10 mg once daily for 7 days, then increase to dextromethorphan 20 mg/quinidine 10 mg every 12 hours; reassess patient periodically to determine if continued use is necessary. Do not exceed dextromethorphan 40 mg/quinidine 20 mg in a 24-hour period.
Agitation/aggression in Alzheimer disease (off-label use): Oral: Dextromethorphan 20 mg/quinidine 10 mg once daily for 7 days, then increase to dextromethorphan 20 mg/quinidine 10 mg twice daily (Cummings 2015). Additional data may be necessary to further define the role of dextromethorphan and quinidine in this condition. Note: The trial further increased the dosage after 14 days to dextromethorphan 30 mg/quinidine 10 mg twice daily but that dosage form is not commercially available.
Administration
May be administered with or without food. Administer twice-daily doses every 12 hours.
Dietary Considerations
Avoid grapefruit juice.
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Drug Interactions
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Reduce afatinib by 10 mg if not tolerated. Some non-US labeling recommends avoiding combination if possible. If used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification
Ajmaline: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase the serum concentration of Ajmaline. Avoid combination
Amiodarone: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification
Amisulpride: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Amisulpride. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification
Amphetamines: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Amphetamines. Monitor therapy
Antacids: May decrease the excretion of QuiNIDine. Exceptions: Aluminum Hydroxide. Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy
Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: See full interaction monograph for details. Consider therapy modification
ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Please refer to the full interaction monograph for details concerning the recommended dose adjustments. Consider therapy modification
Asunaprevir: May increase the serum concentration of CYP2D6 Substrates (High risk with 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 (adult doses -- patients up to 70kg: 0.5mg/kg/day; patients 70kg or more: 40mg/day) in patients receiving a strong CYP2D6 inhibitor. Consider therapy modification
Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification
Benzhydrocodone: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Benzhydrocodone. Monitor therapy
Betrixaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease the adult betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-glycoprotein inhibitor. Consider therapy modification
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in patients with moderate to severe renal insufficiency who are receiving p-glycoprotein inhibitors. Consider therapy modification
Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy
Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy
Brexpiprazole: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual with a strong CYP2D6 inhibitor, reduce to 25% of usual if used with both a strong CYP2D6 inhibitor and a 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: Upon quinidine initiation, consider reducing cardiac glycoside dose by 25% to 50%, with continued monitoring of glycoside serum concentrations and clinical response until the quinidine reaches steady state (5-10 days). Consider therapy modification
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Monitor therapy
Ceritinib: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Ceritinib. Ceritinib 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
Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Monitor therapy
Chloroquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification
Cimetidine: May increase the serum concentration of QuiNIDine. Management: Consider alternatives to cimetidine. If the combination cannot be avoided, monitor for increased quinidine concentrations/toxicity with cimetidine initiation/dose increase, or decreased concentrations/effects with cimetidine discontinuation/dose decrease. Consider therapy modification
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination
Citalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Citalopram. Avoid combination
Clarithromycin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clarithromycin. Avoid combination
CloBAZam: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Clofazimine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification
CloZAPine: May enhance the anticholinergic effect of QuiNIDine. CloZAPine may enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may increase the serum concentration of CloZAPine. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification
Cobicistat: May increase the serum concentration of QuiNIDine. Monitor therapy
Codeine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Consider therapy modification
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See full monograph for details. Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Crizotinib: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Crizotinib. Crizotinib may enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Crizotinib may increase the serum concentration of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Consider therapy modification
CYP2D6 Substrates (High risk with Inhibitors): CYP2D6 Inhibitors (Strong) may decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Exceptions: Ajmaline; Dapoxetine; Indoramin; Metoprolol; Tamoxifen; Timolol (Ophthalmic); Tropisetron. Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Consider therapy modification
Dabigatran Etexilate: 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
Dacomitinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index. Consider therapy modification
Dalfampridine: QuiNIDine may increase the serum concentration of Dalfampridine. Management: Recommendations differ significantly between international labelings in regards to the concomitant use of dalfampridine (referred to as fampridine in Canada) and quinidine. Consult appropriate product labeling. Monitor therapy
Dapoxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Dapoxetine. Monitor therapy
Darunavir: May increase the serum concentration of QuiNIDine. Monitor therapy
Dasatinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Dasatinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Deutetrabenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Deutetrabenazine. Management: The total daily dose of deutetrabenazine should not exceed 36 mg, and the maximum single dose of deutetrabenazine should not exceed 18 mg with concurrent use of a strong CYP2D6 inhibitor. Consider therapy modification
Dextromethorphan: QuiNIDine may increase the serum concentration of Dextromethorphan. Management: Avoid concurrent use of these agents when possible, unless the increased psychoactive effects of dextromethorphan are desired. Since codeine activation is also inhibited by quinidine, codeine is unlikely to be suitable as an alternative antitussive. Consider therapy modification
Dihydrocodeine: QuiNIDine may diminish the analgesic effect of Dihydrocodeine. Specifically, quinidine may prevent the metabolic conversion of dihydrocodeine to its active metabolite Monitor therapy
DilTIAZem: May increase the serum concentration of QuiNIDine. Monitor therapy
Domperidone: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Domperidone. Avoid combination
Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Doxepin-Containing Products. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification
DOXOrubicin (Conventional): CYP2D6 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP2D6 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Droperidol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Droperidol. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification
DULoxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of DULoxetine. Monitor therapy
Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain P-gp inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification
Eliglustat: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Management: Reduce the eliglustat dose to 84 mg daily. Avoid use of eliglustat in combination with a strong CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor. Consider therapy modification
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination
Encorafenib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification
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): May diminish the therapeutic effect of QuiNIDine. QuiNIDine may diminish the therapeutic effect of EPHEDrine (Systemic). 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
Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
Erythromycin (Systemic): May enhance the QTc-prolonging effect of QuiNIDine. Erythromycin (Systemic) may increase the serum concentration of QuiNIDine. Avoid combination
Escitalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Escitalopram. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification
Etravirine: May decrease the serum concentration of QuiNIDine. Monitor therapy
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Monitor therapy
Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Monitor therapy
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
Flupentixol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flupentixol. Avoid combination
FluvoxaMINE: May increase the serum concentration of QuiNIDine. QuiNIDine may increase the serum concentration of FluvoxaMINE. Monitor therapy
Fosamprenavir: May increase the serum concentration of QuiNIDine. Monitor therapy
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Fosphenytoin: May enhance the QTc-prolonging effect of QuiNIDine. Fosphenytoin may decrease the serum concentration of QuiNIDine. Management: Consider alternatives when possible. Monitor patients receiving this combination closely forsigns and symptoms of excessive QTc interval prolongation and arrhythmia, as well as for decreased serum concentrations/therapeutic effects of quinidine. Consider therapy modification
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Gadobenate Dimeglumine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification
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
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
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Monitor therapy
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Grapefruit Juice: May increase the serum concentration of QuiNIDine. Avoid combination
Halofantrine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Halofantrine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification
Haloperidol: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification
HYDROcodone: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of HYDROcodone. Specifically, concentrations of hydromorphone may be decreased. Monitor therapy
Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Iloperidone: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP2D6 inhibitor. Consider therapy modification
Imatinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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
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
Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Avoid combination
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
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
Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification
Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Lurasidone: May enhance the QTc-prolonging effect of QuiNIDine. Management: Consider alternatives to quinidine in patients with acute lurasidone overdose. If quinidine treatment cannot be avoided, monitor for excessive QTc interval prolongation. Consider therapy modification
Mefloquine: QuiNIDine may enhance the adverse/toxic effect of Mefloquine. Specifically, the risk for QTc-prolongation and the risk for convulsions may be increased. Management: Avoid concurrent use, and delay administration of mefloquine until at least 12 hours after the last dose of quinidine when possible. Avoid combination
Memantine: NMDA Receptor Antagonists may enhance the adverse/toxic effect of Memantine. Monitor therapy
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: Reduce metoclopramide dose to 5 mg 4 times daily (30 minutes before each meal and at bedtime) and limit the maximum daily dose to 20 mg if combined with strong CYP2D6 inhibitors. Consider therapy modification
Metoprolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Metoprolol. 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
Monoamine Oxidase Inhibitors: May enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Avoid combination
Moxifloxacin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Moxifloxacin (Systemic). Avoid combination
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Monitor therapy
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy
Nebivolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Nebivolol. Monitor therapy
Nelfinavir: May increase the serum concentration of QuiNIDine. Avoid combination
Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Neuromuscular-Blocking Agents: QuiNIDine may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy
Nicergoline: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MMDL metabolite may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MDL metabolite may be decreased. Monitor therapy
Nilotinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Nilotinib. Avoid combination
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy
Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Monitor therapy
OLANZapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification
Ombitasvir, Paritaprevir, and Ritonavir: May increase the serum concentration of QuiNIDine. Management: Canadian labeling recommends avoiding this combination. Monitor therapy
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May increase the serum concentration of QuiNIDine. Management: Canadian labeling recommends avoiding this combination. Monitor therapy
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
Panobinostat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Parecoxib: May increase the serum concentration of Dextromethorphan. Monitor therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification
Perhexiline: CYP2D6 Inhibitors may increase the serum concentration of Perhexiline. Management: Consider alternatives to this combination if possible. If combined, monitor for increased perhexiline serum concentrations and toxicities (eg, hypoglycemia, neuropathy, liver dysfunction). Perhexiline dose reductions will likely be required. Consider therapy modification
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Exceptions: Loperamide. Monitor therapy
PHENobarbital: May enhance the hepatotoxic effect of QuiNIDine. PHENobarbital may decrease the serum concentration of QuiNIDine. Monitor therapy
Phenytoin: May decrease the serum concentration of QuiNIDine. Monitor therapy
Pilsicainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pilsicainide. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification
Pimozide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pimozide. Avoid combination
Pimozide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pimozide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Avoid combination
Piperaquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Piperaquine. Avoid combination
Pitolisant: 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. Consider therapy modification
Primaquine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Primaquine. Management: Monitor for signs and symptoms of possible treatment failure with primaquine in patients who are taking strong CYP2D6 inhibitors. If efficacy of primaquine is compromised, may consider adjusting therapies. Consider therapy modification
Primidone: May decrease the serum concentration of QuiNIDine. Monitor therapy
Probucol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Probucol. Avoid combination
Propafenone: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification
Propranolol: QuiNIDine may increase the serum concentration of Propranolol. Monitor therapy
Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy
QT-prolonging Agents (Indeterminate Risk - Avoid): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
QT-prolonging Agents (Indeterminate Risk - Caution): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
QT-prolonging Class IA Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of other QT-prolonging Class IA Antiarrhythmics (Highest Risk). Exceptions: Ajmaline. Avoid combination
QT-prolonging Class III Antiarrhythmics (Highest Risk): QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Avoid combination
QT-prolonging Kinase Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification
QT-prolonging Miscellaneous Agents (Highest Risk): QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification
QUEtiapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QUEtiapine. Avoid combination
QuiNIDine: May increase the serum concentration of Dextromethorphan. Management: Avoid concurrent use of these agents when possible, unless the increased psychoactive effects of dextromethorphan are desired. Since codeine activation is also inhibited by quinidine, codeine is unlikely to be suitable as an alternative antitussive. Consider therapy modification
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy
Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
Reserpine: May enhance the adverse/toxic effect of QuiNIDine. Monitor therapy
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
RisperiDONE: QuiNIDine may enhance the QTc-prolonging effect of RisperiDONE. QuiNIDine may increase the serum concentration of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification
Ritonavir: May increase the serum concentration of QuiNIDine. Avoid combination
Saquinavir: May enhance the QTc-prolonging effect of QuiNIDine. Avoid combination
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Consider therapy modification
Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors): Dextromethorphan may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase the serum concentration of Dextromethorphan. Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes). Consider therapy modification
Serotonergic Agents (High Risk): Dextromethorphan may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Exceptions: FLUoxetine; Isocarboxazid; Linezolid; Methylene Blue; Moclobemide; PARoxetine; Phenelzine; Tranylcypromine. Monitor therapy
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
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
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Management: These listed exceptions are discussed in detail in separate interaction monographs. Monitor therapy
Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Avoid combination
Tamsulosin: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. Monitor therapy
Tegaserod: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod. Monitor therapy
Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Tetrabenazine adult dose should be reduced by 50% when starting a strong CYP2D6 inhibitor. Maximum tetrabenazine adult dose is 50 mg/day when used with a strong CYP2D6 inhibitor. Consider therapy modification
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy
Thioridazine: May enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may increase the serum concentration of Thioridazine. Avoid combination
Timolol (Ophthalmic): CYP2D6 Inhibitors (Strong) may increase the serum concentration of Timolol (Ophthalmic). Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination
Tipranavir: May increase the serum concentration of QuiNIDine. Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination
TraMADol: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of TraMADol. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of TraMADol. CYP2D6 Inhibitors (Strong) may increase the serum concentration of TraMADol. Monitor therapy
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
Tricyclic Antidepressants: May enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may increase the serum concentration of Tricyclic Antidepressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Exceptions: Doxepin (Systemic); Doxepin (Topical). Consider therapy modification
Tropisetron: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tropisetron. Monitor therapy
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (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. Monitor therapy
Vemurafenib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Vemurafenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Consider a venetoclax dose reduction by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. 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
Test Interactions
See individual agents.
Adverse Reactions
Also see individual agents.
>10%: Gastrointestinal: Diarrhea (13%)
1% to 10%:
Cardiovascular: Peripheral edema (5%)
Central nervous system: Dizziness (10%)
Endocrine & metabolic: Increased gamma-glutamyl transferase (3%)
Gastrointestinal: Vomiting (5%), flatulence (3%)
Genitourinary: Urinary tract infection (4%)
Infection: Influenza (4%)
Neuromuscular & skeletal: Weakness (5%)
Respiratory: Cough (5%)
Warnings/Precautions
Concerns related to adverse effects:
- Anticholinergic effects: May cause anticholinergic effects; use caution in patients with myasthenia gravis or other conditions which may be affected.
- Dizziness: May cause dizziness; use caution in patients with motor impairment or history of falls.
- Hepatotoxicity: Quinidine has been associated with hepatitis, including granulomatous hepatitis, occurring generally during the first few weeks of therapy. Most cases resolve when quinidine is discontinued.
- Hypersensitivity reactions: Agranulocytosis, angioedema, bronchospasm, hemolytic anemia, increased skeletal muscle enzymes, lymphadenopathy, myalgia, pneumonitis, rash, sicca syndrome, uveitis, vasculitis may be associated with use.
- Lupus-like syndrome: Lupus-like syndrome, with polyarthritis and sometimes a positive antinuclear antibody test, may occur with quinidine. Use is contraindicated in patients with quinidine-, quinine-, or mefloquine-induced lupus-like syndrome.
- Thrombocytopenia: Immune-mediated thrombocytopenia (severe or fatal) may be associated with quinidine use. Unless clearly not drug related, discontinue immediately; continued use may be associated with an increase in fatal hemorrhage. Thrombocytopenia generally resolves within a few days of discontinuation. Therapy should not be restarted in sensitized patients. Use is contraindicated in patients with prior history of immune-mediated thrombocytopenia associated with structurally related drugs (eg, quinine, mefloquine).
Concurrent drug therapy issues:
- High potential for interactions: Concomitant use of moderate or strong CYP3A4 inhibitors may increase quinidine levels and prolong the QTc interval. Quinidine inhibits CYP2D6; concomitant use with CYP2D6 substrates may cause an accumulation of concomitantly administered drug and/or reduce active metabolite formation, decreasing their safety and/or efficacy.
- QT prolonging agents: Use caution with medications which may further prolong the QT interval or cause cardiac arrhythmias. Dose-dependent QTc prolongation may occur. Monitor patients at risk following the first dose. Discontinue if arrhythmia occurs.
- Serotonin syndrome: Symptoms associated with serotonin syndrome such as agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans); especially with higher dextromethorphan doses. Discontinue if such reaction occurs.
Disease-related concerns:
- Cardiovascular disease: Use caution in patients with left ventricular hypertrophy or left ventricular dysfunction which are more common in patients with chronic hypertension, coronary artery disease or history of stroke; risk of QTc prolongation may be increased. Use is contraindicated in patients with prolonged QT interval, congenital QT syndrome, or history of torsade de pointes, patients with heart failure, complete AV block without an implanted pacemaker or patients at high risk of complete AV block. Correct hypokalemia or hypomagnesemia prior to therapy.
- Hepatic impairment: Safety and efficacy have not been established with severe hepatic impairment; increased serum concentrations may occur.
- Renal impairment: Safety and efficacy have not been established with severe renal impairment; increased serum concentrations may occur.
Special populations:
- CYP2D6 poor metabolizers: Dextromethorphan is metabolized by hepatic CYP2D6. Poor metabolizers of CYP2D6 may have exaggerated or prolonged effects of dextromethorphan. Increased risk may be seen with concomitant use of potent CYP2D6 inhibitors; use with caution (Abduljalil 2010; Jurica 2012; Sager 2014; Zhou 2009).
- Dementia: Has not shown to be safe or effective in other types of commonly occurring emotional labilities (eg, neurological disease or injury).
Other warnings/precautions:
- Appropriate use: Periodically reassess the need for treatment; spontaneous improvement of PBA may occur.
- Abuse/misuse: Patients with a history of drug abuse should be monitored closely for signs of abuse/misuse (eg, development of tolerance, increase in dose, drug-seeking behavior). Abuse of dextromethorphan may cause brain damage, cardiac arrhythmia, loss of consciousness, or death.
Monitoring Parameters
QT interval at baseline and 3 to 4 hours after the first dose in patients at risk for QTc prolongation; potassium and magnesium prior to and during therapy; CBC, liver and renal function tests; periodically assess risk factors for arrhythmias during treatment; periodically reassess the need for treatment (spontaneous improvement of PBA may occur); worsening myasthenia gravis or other sensitive conditions due to anticholinergic effects.
Pregnancy
Pregnancy Considerations
Adverse events were observed in animal reproduction studies using this combination. See individual agents.
Patient Education
What is this drug used for?
- It is used to treat sudden laughing and/or crying that happens without your control.
Frequently reported side effects of this drug
- Diarrhea
- Cough
- Dizziness
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- 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
- Lupus like rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, chest pain or shortness of breath, or swelling in the arms or legs
- Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
- Abnormal heartbeat
- Fast heartbeat
- Passing out
- Severe loss of strength and energy
- Severe nausea
- Severe vomiting
- Chills
- Swollen glands
- Swelling of arms or legs
- Depression
- Vision changes
- Serotonin syndrome like dizziness, severe headache, agitation, sensing things that seem real but are not, fast heartbeat, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. 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 brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
