Quinidine

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include vomiting, diarrhea, ringing in your ears or hearing problems, dizziness or spinning sensation, blurred vision, irregular heartbeat, confusion, or feeling like you might pass out.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

• vomiting and diarrhea;

• ringing in the ears, hearing loss, severe dizziness;

• feeling like you might pass out;

• changes in vision, pain behind your eyes, increased sensitivity of your eyes to light;

• white patches on your eyes;

• cloudiness in the pupils or iris of your eyes;

• a new or a worsening irregular heartbeat pattern;

• pale or yellowed skin, dark colored urine, fever, confusion or weakness;

• nausea, stomach pain, low fever, loss of appetite, clay-colored stools;

• seizure (convulsions);

• easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin; or

• bronchospasm (wheezing, chest tightness, trouble breathing).

Less serious side effects may include:

• mild nausea, vomiting, or diarrhea;

• heartburn;

• depressed mood;

• muscle or joint pain;

• headache, dizziness;

• mild skin rash;

• skin dryness, peeling, or flaking; or

• flushing (warmth, redness, or tingly feeling).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Heart block In patients without implanted pacemakers who are at high risk of complete atrioventricular block (eg, those with digitalis intoxication, second–degree atrioventricular block, or severe intraventricular conduction defects), Quinidine should be used only with caution.

Drug interactions Altered pharmacokinetics of Quinidine: Drugs that alkalinize the urine (carbonic–anhydrase inhibitors, sodium bicarbonate, thiazide diuretics) reduce renal elimination of Quinidine.

By pharmacokinetic mechanisms that are not well understood, Quinidine levels are increased by coadministration of amiodarone or cimetidine. Very rarely, and again by mechanisms not understood, Quinidine levels are decreased by coadministration of nifedipine.

Hepatic elimination of Quinidine may be accelerated by coadministration of drugs (phenobarbital, phenytoin, rifampin) that induce production of cytochrome P450IIIA4.

Perhaps because of competition of the P450IIIA4 metabolic pathway, Quinidine levels rise when ketaconazole is coadministered.

Coadministration of propranolol usually does not affect Quinidine pharmacokinetics, but in some studies, the ß–blocker appeared to cause increases in the peak serum levels of Quinidine, decreases in Quinidine's volume of distribution and decreases in total Quinidine clearance. The effects (if any) of coadministration of other ß–blockers on Quinidine pharmacokinetics have not been adequately studied.

Hepatic clearance of Quinidine is significantly reduced during coadministration of verapamil, with corresponding increases in serum levels and half–life.

Altered pharmacokinetics of other drugs: Quinidine slows the elimination of digoxin and simultaneously reduces digoxin's apparent volume of distribution. As a result, serum digoxin levels may be as much as doubled. When Quinidine and digoxin are coadministered, digoxin doses usually need to be reduced. Serum levels of digitoxin are also raised when Quinidine is coadministered, although the effect appears to be smaller.

By a mechanism that is not understood, Quinidine potentiates the anticoagulatory action of warfarin, and the anticoagulant dosage may need to be reduced.

Cytochrome P450IID6 is an enzyme critical to the metabolism of many drugs, notably including mexiletine, some phenothiazines, and most polycyclic antidepressants. Constitutional deficiency of cytochrome P450IID6 is found in less than 1% of Orientals, in about 2% of American blacks, and in about 8% of American whites. Testing with debrisoquine is sometimes used to distinguish the P450IID6–deficient "poor metabolizers" from the majority–phenotype "extensive metabolizers."

When drugs whose metabolism is P450IID6–dependent are given to poor metabolizers, the serum levels achieved are higher, sometimes much higher, than the serum levels achieved when identical doses are given to extensive metabolizers. To obtain similar clinical benefit without toxicity, doses given to poor metabolizers may need to be greatly reduced. In the cases of prodrugs whose actions are actually mediated by P450IID6–produced metabolites (for example, codeine and hydrocodone, whose analgesic and antitussive effects appear to be mediated by morphine and hydromorphone, respectively), it may not be possible to achieve the desired clinical benefits in poor metabolizers.

Quinidine is not metabolized by cytochrome P450IID6, but therapeutic serum levels of Quinidine inhibit the action of cytochrome P450IID6, effectively converting extensive metabolizers into poor metabolizers. Caution must be exercised whenever Quinidine is prescribed together with drugs metabolized by cytochrome P450IID6.

Perhaps by competing for pathways of renal clearance, coadministration of Quinidine causes an increase in serum levels of procainamide.

Serum levels of haloperidol are increased when Quinidine is coadministered.

Presumably because both drugs are metabolized by cyctochrome P450IIIA4, coadministration of Quinidine causes variable slowing of the metabolism of nifedipine. Interactions with other dihydropyridine calcium–channel blockers have not been reported, but these agents (including felodipine, nicardipine, and nimodipine) are all dependent upon P450IIIA4 for metabolism, so similar interactions with Quinidine should be anticipated.

Altered pharmacodynamics of other drugs: Quinidine's anticholinergic, vasodilating, and negative inotropic actions may be additive to those of other drugs with these effects, and antagonistic to those of drugs with cholinergic, vasoconstricting, and positive inotropic effects. For example, when Quinidine and verapamil are coadministered in doses that are each well tolerated as monotherapy, hypotension attributable to additive peripheral α–blockade is sometimes reported.

Quinidine potentiates the actions of depolarizing (succinylcholine, decamethonium) and nondepolarizing (d–tubocurarine, pancuronium) neuromuscular blocking agents. These phenomena are not well understood, but they are observed in animal models as well as in humans. In addition, in vitro addition of Quinidine to the serum of pregnant women reduces the activity of pseudocholinesterase, an enzyme that is essential to the metabolism of succinylcholine.

Diltiazem significantly decreases the clearance and increases the t½ of Quinidine, but Quinidine does not alter the kinetics of diltiazem. Non–interactions of Quinidine with other drugs: Quinidine has no clinically significant effect on the pharmacokinetics of diltiazem, flecainide, mephenytoin, metoprolol, propafenone, propranolol, quinine, timolol, or tocainide.

Conversely, the pharmacokinetics of Quinidine are not significantly affected by caffeine, ciprofloxacin, digoxin, felodipine, omeprazole, or quinine. Quinidine's pharmacokinetics are also unaffected by cigarette smoking.

Carcinogenesis, mutagenesis, impairment of fertility Animal studies to evaluate Quinidine's carcinogenic or mutagenic potential have not been performed. Similarly, there are no animal data as to Quinidine's potential to impair fertility.

Pregnancy Pregnancy Category C  Animal reproductive studies have not been conducted with Quinidine. There are no adequate and well–controlled studies in pregnant women. Quinidine should be given to a pregnant woman only if clearly needed.

In one neonate whose mother had received Quinidine throughout her pregnancy, the serum level of Quinidine was equal to that of the mother, with no apparent ill effect. The level of Quinidine in amniotic fluid was about three times higher than that found in serum.

Labor and Delivery  Quinine is said to be oxytocic in humans, but there are no adequate data as to Quinidine's effect (if any) on human labor and delivery.

Nursing mothers  Quinidine is present in human milk at levels slightly lower than those in maternal serum; a human infant ingesting such milk should (scaling directly by weight) be expected to develop serum Quinidine levels at least an order of magnitude lower than those of the mother. On the other hand, the pharmacokinetics and pharmacodynamics of Quinidine in human infants have not been adequately studied, and neonates' reduced protein binding of Quinidine may increase their risk of toxicity at low total serum levels. Administration of Quinidine should (if possible) be avoided in lactating women who continue to nurse.

Pediatric use  In antimalarial trials, Quinidine was as safe and effective in pediatric patients as in adults. Notwithstanding the known pharmacokinetic differences between pediatric patients and adults (see Pharmacokinetics and Metabolism), pediatric patients in these trials received the same doses (on a mg/kg basis) as adults.

Safety and effectiveness of antiarrhythmic use in pediatric patients have not been established.

Geriatric use  Safety and efficacy of Quinidine in elderly patients has not been systematically studied. Clinical studies of Quinidine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. The reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy.

NDC 0002-1407-01

10 mL

VIAL No. 530

Lilly

Quinidine GLUCONATE INJECTION USP

80 mg per mL

Multiple Dose

Rx only

NON-RETURNABLE

Elimination t½ may be increased.

Brugada syndrome; Paroxysmal AV junctional rhythm; Paroxysmal supraventricular tachycardia; Short QT syndrome; Symptomatic atrial or ventricular premature contractions

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

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

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

Hemodialysis: Dose following hemodialysis.

Peritoneal dialysis: Supplemental dose is not necessary.

CRRT: No dosage adjustment required; monitor serum concentrations.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Buprenorphine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Monitor therapy

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Indapamide: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Moderate Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. 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. Monitor therapy

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Potassium 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Consider therapy modification

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

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

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

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

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

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

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

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

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

Teneligliptin: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Monitor therapy

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

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

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. Monitor therapy

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

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

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

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

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

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

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

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

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

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

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

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

Xipamide: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Monitor therapy

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