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Teicoplanin is for gram-positive bacteria only. It does not treat E.coli.
Teicoplanin is not for intraventricular use. The manufacturer strongly discourage injecting Teicoplanin into the brain.

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Quinidine (Cardin) - Uses, Dose, MOA, Brands, Side effects

Quinidine (Cardin) is a Class 1a anti-arrhythmic drug that reduces myocardial toxicity. It is used in the treatment and prevention of arrhythmias. It is also used to treat patients with complicated malaria.

Quinidine Uses:

Quinidine gluconate and sulfate salts:
- Protection against atrial fibrillation and/or flutter relapse; preventing ventricular arrhythmias.

Note: Caution advised as the drug has proarrhythmic effects; only be used if life-threatening solution required. Newer and safer alternatives, as well as nonpharmacologic approaches, are preferred.

Quinidine gluconate (IV formulation):
- Helps in suppressing atrial fibrillation/flutter and in the conversion of ventricular tachycardia.

Note: Newer and safer alternatives, as well as nonpharmacologic approaches, are preferred nowadays.

Guideline recommendation:
- Ventricular arrhythmias: Symptomatic ventricular arrhythmias in patients with Brugada Syndrome irrespective of Implantable Cardioverter defibrillator are recommended to be intensified on quinidine or catheter ablation (Heart Association/American College of Cardiology/Heart Rhythm Society).
- The drug may benefit patients with short QT syndrome and recurrent sustained ventricular arrhythmias.
Quinidine gluconate (IV formulation):
- The drug may be given against life threatening Malaria

Quinidine (Cardin) Dose in Adults

Note: Dosage expressed in terms of the salt: 267 mg of quinidine gluconate = 200 mg of quinidine sulfate.

Quinidine (Cardin) Dose in the pharmacological conversion of Atrial fibrillation/flutter:

Note: If QRS complex widens to 130% of its pretreatment duration, the QTc interval widens to 130% of its pretreatment duration and is >500 msecs, P waves disappear, or the patient develops significant tachycardia, symptomatic bradycardia, or hypotension discontinue the drug; Consider other means of cardioversion (eg direct current cardioversion). If sinus rhythm is not restored in a reasonable amount of time discontinue. For patients with structural heart disease or other risk factors for toxicity, initiate or dose-adjust in a setting where continuous monitoring and resuscitation are available. 48-72 hr monitoring is advised in patients on achieving the adequate effect.

Immediate-release formulations:
- Quinidine sulfate: Initial: 400 mg/dose QID; Review on 4th or 5th dose for conversion, if not achieved dose may be increased with monitoring for adverse effects.
Extended-release formulations:
- Quinidine sulfate: Initial: 300 mg TDS or BD; if not achieved dose may be increased with monitoring for adverse effects
- Quinidine gluconate:
  - Initial: 648 mg TDS; Review on 4th or 5th dose for conversion, if not achieved dose may be increased with monitoring for adverse effects. or
  - Initial: 324 mg TDS for 2 days; then 648 mg BD for 2 days; then 648 mg TDS for up to 4 days. The 4-day stretch may come at one of the lower doses if a lower dose is the highest tolerated dosing regimen.

Quinidine (Cardin) Dose to maintain sinus rhythm in patients with paroxysmal atrial fibrillation or flutter:

Note:

Reduce total daily dose if at any time during therapy, the QRS complex widens to 130% of its pretreatment duration, the QTc interval widens to 130% of its pretreatment duration and is >500 msecs, P waves disappear, or the patient develops significant tachycardia, symptomatic bradycardia, or hypotension.
For patients with structural heart disease or other risk factors for toxicity, initiate or dose-adjust in a setting where continuous monitoring and resuscitation are available. Monitor patients for 2 to 3 days once the appropriate dose has been achieved.
Immediate-release formulations:
- Quinidine sulfate: Initial: 200 mg QID; may increase cautiously to the desired effect.
Extended-release formulations:
- Quinidine sulfate: Initial: 300 mg BD to TDS; if not achieved dose may be increased with monitoring for adverse effects
- Quinidine gluconate: Initial: 324 mg every BD to TDS; if not achieved dose may be increased with monitoring for adverse effects. Usual dose range: 324 to 648 mg TDS.

Quinidine (Cardin) Dose in the treatment of severe Malaria:

IV (quinidine gluconate): 10 mg/kg infused over 1 to 2 hours followed by 0.02 mg/kg/minute continuous infusion for ≥24 hours;
alternatively, may administer 24 mg/kg loading dose over 4 hours, followed by 12 mg/kg over 4 hours every 8 hours (beginning 8 hours after initiation of the loading dose);
complete treatment with oral quinine once parasite density <1% and the patient can receive oral medication;
The total duration of treatment (quinidine/quinine): 3 days (Africa or South America) or 7 days (Southeast Asia);
use in combination with doxycycline, tetracycline, or clindamycin.

Note: Close monitoring, including telemetry, required.

Quinidine (Cardin) Dose in the treatment of Ventricular arrhythmias (off-label dose): Oral:

Note: Dosing regimens for suppression of ventricular arrhythmias have not been adequately studied. If QRS complex widens to 130% of its pretreatment duration, the QTc interval widens to 130% of its pretreatment duration and is >500 msecs, P waves disappear, or the patient develops significant tachycardia, symptomatic bradycardia, or hypotension discontinue the drug; Consider other means of cardioversion (eg direct current cardioversion). If sinus rhythm is not restored in a reasonable amount of time discontinue. For patients with structural heart disease or other risk factors for toxicity, initiate or dose-adjust in a setting where continuous monitoring and resuscitation are available. 48-72 hr monitoring is advised in patients on achieving the adequate effect.

Immediate-release formulation:
- Quinidine sulfate: Initial: 200 mg QID; may increase dose cautiously up to 600 mg BD to QID.
Extended-release formulation:
- Quinidine gluconate: Initial: 324 mg BD to TDS; may increase dose cautiously up to 648 mg BD to TDS.

Quinidine (Cardin) Dose in Childrens

Note: Quinidine is available in gluconate and sulfate salt formulations which are not interchangeable on an mg per mg basis, due to differences in the amount of quinidine base supplied; 267 mg of quinidine gluconate equals 200 mg of quinidine sulfate. Doses are expressed in terms of salt (gluconate or sulfate), not base.

Dose in the treatment of severe, life-threatening malaria:

Infants, Children, and Adolescents:
- IV: Quinidine gluconate: 10 mg/kg infused over 1 to 2 hours, followed by 0.02 mg/kg/minute continuous infusion for ≥1 day;
- alternatively, may administer 24 mg/kg loading dose over 4 hours, followed by 12 mg/kg over 4 hours TDS (beginning 8 hours after loading dose).
- Change to oral quinine once parasite density is <1% and the patient can receive oral medication to complete treatment course;
- The total duration of treatment (quinidine/quinine): 3 days in Africa or South America; 7 days in Southeast Asia;
- Use in combination with doxycycline, tetracycline, or clindamycin; omit quinidine loading dose if the patient has received >40 mg/kg of quinine in preceding 48 hours or mefloquine within preceding 12 hours.

Note: Caution advised; cardiac monitoring, in case of adverse events reduce dose or discontinue as required

Quinidine (Cardin) Dose in the treatment of Tachyarrhythmias, including supraventricular tachycardia, atrial fibrillation, atrial flutter, and ventricular tachycardia:

Children and Adolescents: Limited data available; not considered first-line therapy:
- Oral: Quinidine sulfate, immediate release: Usual dose: 30 mg/kg/day in divided doses every 6 hours; more frequent dosing may be necessary due to the increased clearance seen in pediatric patients; range: 15 to 60 mg/kg/day;
- The maximum adult daily dose: 2,400 mg/day.
- IV: Not recommended; use with extreme caution: Quinidine gluconate: 2 to 10 mg/kg/dose every 3 to 6 hours as needed.
- Note: Dosing has not been evaluated in clinical trials.

Pregnancy Risk Factor C

Studies on animal reproduction have not been done.
Quinidine crosses the placenta, and can be detected within the amniotic fluid and cord blood as well as in neonatal serum.
Quinidine can be used to treat severe malaria in pregnant women. It has also been used to treat arrhythmias during pregnancy (European Society of Cardiology 2003).

Use during breastfeeding:

Breast milk can contain Quinidine in slightly lower levels than the maternal serum.
Manufacturer recommends that breastfeeding mothers avoid this product.

Quinidine (Cardin) Dose in Kidney Disease:

No dosage adjustment provided in the 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.

Dose in Liver disease:

No dosage adjustment provided in the manufacturer’s labeling. Use with caution due to reduced clearance.

Side effects of Quinidine (Cardin):

Cardiovascular:
- Palpitations
- Angina Pectoris
- Cardiac Arrhythmia
- ECG Abnormality
- Cerebral Ischemia
- Prolonged Q-T Interval On ECG
- Syncope
Central Nervous System:
- Dizziness
- Fatigue
- Headache
- Disturbed Sleep
- Nervousness
- Ataxia
Dermatologic:
- Skin Rash
Gastrointestinal:
- Diarrhea
- Gastrointestinal Distress
- Nausea And Vomiting
- Esophagitis
Neuromuscular & Skeletal:
- Weakness
- Tremor
Ophthalmic:
- Visual Disturbance
Miscellaneous:
- Fever

Contraindications to Quinidine (Cardin):

Allergy to drugs or their constituents
thrombocytopenia;
Thrombocytopenic purpura
myasthenia gravis;
Heart block of the 2nd and 3rd degrees;
idioventricular conduction delay (except for patients with an artificial pacemaker that is in use);
Those adversely affected or unable to tolerate anticholinergic activity
concurrent use of antimicrobials that increase QTc as fluoroquinolones, cisapride, amprenavir, or ritonavir

Warnings and precautions

Hepatotoxicity:
- It has been linked to severe hepatotoxic reactions including granulomatous liver disease.
Hypersensitivity reactions
- Hypersensitivity reactions can occur during use.
Proarrhythmic effects
- Be aware of proarrhythmic effects. This could cause QT prolongation or a subsequent torsade-de-pointes. To prevent QT prolongation, monitor and adjust the dose. Patients with congenital long QT syndrome (diagnosed or suspected) should not be given this medication.
Arrhythmias:
- Use when appropriate: [US Boxed Warn]: The survival rate in non-life-threatening arrhythmias has not been proven and antiarrhythmic drugs may increase mortality. This is most common with structural heart disease. Quinidine may increase mortality in the treatment of atrial fibrillation/flutter.
Atrial fibrillation/flutter:
- Patients with atrial fibrillation and flutter may experience an increase in the ventricular response rate. Before initiating, it is important to control AV conduction.
Conduction disturbances:
- Patients at high risk of heart block should be cautious.
Electrolyte imbalance:
- Before and during therapy, correct electrolyte imbalances, particularly hypokalemia and hypomagnesemia.
G6PD deficiency:
- Patients with G6PD (glucose-6phosphate dehydrogenase deficiency) may experience hemolysis.
Left ventricular dysfunction/heart failure (HF):
- Patients with reduced left-ventricular ejection fraction should be cautious; it may worsen or worsen the condition.
Hepatic impairment
- Patients with hepatic impairment should be cautious.

Quinidine: Drug Interaction

Risk Factor C (Monitor therapy)
Acetylcholinesterase Inhibitors	May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors.
Amphetamines	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Amphetamines.
Antacids	May decrease the excretion of QuiNIDine. Exceptions: Aluminum Hydroxide.
Anticholinergic Agents	May enhance the adverse/toxic effect of other Anticholinergic Agents.
Aprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Atazanavir	May increase the serum concentration of QuiNIDine.
Benzhydrocodone	CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Benzhydrocodone.
Bosentan	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Botulinum Toxin-Containing Products	May enhance the anticholinergic effect of Anticholinergic Agents.
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.
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.
Cannabinoid-Containing Products	Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Exceptions: Cannabidiol.
Carbonic Anhydrase Inhibitors	May decrease the excretion of QuiNIDine. Exceptions: Brinzolamide; Dorzolamide.
Celiprolol	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol.
Chloral Betaine	May enhance the adverse/toxic effect of Anticholinergic Agents.
Cobicistat	May increase the serum concentration of QuiNIDine.
CYP3A4 Inducers (Moderate)	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
CYP3A4 Inhibitors (Moderate)	May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors).
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.
Dapoxetine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Dapoxetine.
Darunavir	May increase the serum concentration of QuiNIDine.
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Dihydrocodeine	QuiNIDine may diminish the analgesic effect of Dihydrocodeine. Specifically, quinidine may prevent the metabolic conversion of dihydrocodeine to its active metabolite
DilTIAZem	May increase the serum concentration of QuiNIDine.
DULoxetine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of DULoxetine.
Duvelisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
EPHEDrine (Nasal)	May diminish the therapeutic effect of QuiNIDine.
EPHEDrine (Systemic)	May diminish the therapeutic effect of QuiNIDine. QuiNIDine may diminish the therapeutic effect of EPHEDrine (Systemic).
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Erdafitinib	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Etravirine	May decrease the serum concentration of QuiNIDine.
Everolimus	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus.
Fesoterodine	CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine.
Flibanserin	CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin.
FluvoxaMINE	May increase the serum concentration of QuiNIDine. QuiNIDine may increase the serum concentration of FluvoxaMINE.
Fosamprenavir	May increase the serum concentration of QuiNIDine.
Fosaprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fosnetupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Galantamine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Galantamine.
Gastrointestinal Agents (Prokinetic)	Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).
Glucagon	Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased.
HYDROcodone	CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of HYDROcodone. Specifically, concentrations of hydromorphone may be decreased.
Indinavir	May increase the serum concentration of QuiNIDine.
Indoramin	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Indoramin.
Itopride	Anticholinergic Agents may diminish the therapeutic effect of Itopride.
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.
Larotrectinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Larotrectinib	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib.
Loperamide-Loperamide Oxide	QuiNIDine may enhance the CNS depressant effect of Loperamide-Loperamide Oxide. Loperamide-Loperamide Oxide may enhance the QTcprolonging effect of QuiNIDine. QuiNIDine may increase the serum concentration of LoperamideLoperamide Oxide.
Metoprolol	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Metoprolol.
Mianserin	May enhance the anticholinergic effect of Anticholinergic Agents.
Mirabegron	Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron.
Naldemedine	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine.
Naloxegol:	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol.
Nebivolol	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Nebivolol.
Netupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Neuromuscular-Blocking Agents	QuiNIDine may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents.
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.
NiMODipine	CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine.
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.
Ombitasvir, Paritaprevir, and Ritonavir	May increase the serum concentration of QuiNIDine. Management: Canadian labeling recommends avoiding this combination.
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir	May increase the serum concentration of QuiNIDine. Management: Canadian labeling recommends avoiding this combination.
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.
Palbociclib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
P-glycoprotein/ABCB1 Inhibitors	May increase the serum concentration of Pglycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of pglycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.).
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.
PHENobarbital	May enhance the hepatotoxic effect of QuiNIDine. PHENobarbital may decrease the serum concentration of QuiNIDine.
Phenytoin	May decrease the serum concentration of QuiNIDine.
Potassium-Sparing Diuretics	May diminish the therapeutic effect of QuiNIDine.
Primidone	May decrease the serum concentration of QuiNIDine.
Propranolol	QuiNIDine may increase the serum concentration of Propranolol.
Prucalopride	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride.
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.
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.
Ramosetron	Anticholinergic Agents may enhance the constipating effect of Ramosetron.
Ranolazine	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine.
Ranolazine	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Reserpine	May enhance the adverse/toxic effect of QuiNIDine.
RifAXIMin	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin.
Sarilumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Silodosin	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin.
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Simeprevir	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Talazoparib	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Management: These listed exceptions are discussed in detail in separate interaction monographs.
Tamsulosin	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tamsulosin.
Tegaserod	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod.
Thiazide and Thiazide-Like Diuretics	Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics.
Timolol (Ophthalmic)	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Timolol (Ophthalmic).
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Topiramate	Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate.
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.
Tropisetron	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tropisetron.
Valbenazine	CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Valbenazine.
Verapamil	QuiNIDine may enhance the hypotensive effect of Verapamil. Verapamil may increase the serum concentration of QuiNIDine.
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.
Risk Factor D (Consider therapy modification)
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. Iif used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib.
Amiodarone	QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTcprolonging 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.
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.
ARIPiprazole	CYP2D6 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: See full interaction monograph for details.
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.
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.
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.
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.
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.
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.
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).
Ceritinib	QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTcprolonging 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.
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.
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.
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.
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.
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.
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.
Crizotinib	QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTcprolonging effect of Crizotinib. Crizotinib may enhance the QTc-prolonging effect of QTprolonging 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.
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.
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.
CYP3A4 Inhibitors (Strong)	May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors).
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.
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).
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.
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.
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.
Doxepin-Containing Products	QT-prolonging Agents (Highest Risk) may enhance the QTcprolonging 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Gadobenate Dimeglumine	QT-prolonging Agents (Highest Risk) may enhance the QTcprolonging 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.
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.
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.
Haloperidol	QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTcprolonging 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.
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.
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.
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.
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.
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.
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.
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.
Methadone	QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTcprolonging 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.
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.
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.
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.
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.
Ondansetron	QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTcprolonging 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.
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.
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.
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.
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.
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.
Pramlintide	May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract.
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.
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.
QT-prolonging Kinase Inhibitors (Highest Risk)	May enhance the QTc-prolonging effect of QTprolonging 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.
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.
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.
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.
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.
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.
St John's Wort	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
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.
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.
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.
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).
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.
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.
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.
Risk Factor X (Avoid combination)
Aclidinium	May enhance the anticholinergic effect of Anticholinergic Agents.
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.
Cimetropium	Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium.
Citalopram	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Citalopram.
Clarithromycin	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clarithromycin.
Conivaptan	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Domperidone	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Domperidone.
Eluxadoline	Anticholinergic Agents may enhance the constipating effect of Eluxadoline.
Entrectinib	May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk).
Enzalutamide	May decrease the serum concentration of QuiNIDine.
Erythromycin (Systemic)	May enhance the QTc-prolonging effect of QuiNIDine. Erythromycin (Systemic) may increase the serum concentration of QuiNIDine.
Fingolimod	May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk).
Fluconazole	May enhance the QTc-prolonging effect of QuiNIDine. Fluconazole may increase the serum concentration of QuiNIDine.
Flupentixol	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flupentixol.
Fusidic Acid (Systemic)	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Gemifloxacin	May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk).
Glycopyrrolate (Oral Inhalation)	Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation).
Glycopyrronium (Topical)	May enhance the anticholinergic effect of Anticholinergic Agents.
Grapefruit Juice	May increase the serum concentration of QuiNIDine.
Idelalisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Ipratropium (Oral Inhalation)	May enhance the anticholinergic effect of Anticholinergic Agents.
Itraconazole	May increase the serum concentration of QuiNIDine.
Ketoconazole (Systemic)	May enhance the QTc-prolonging effect of QuiNIDine. Ketoconazole (Systemic) may increase the serum concentration of QuiNIDine.
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.
Levofloxacin-Containing Products (Systemic)	May enhance the QTc-prolonging effect of QTprolonging Class IA Antiarrhythmics (Highest Risk).
Levosulpiride	Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride.
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.
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.
Mequitazine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Mequitazine.
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.
Moxifloxacin (Systemic)	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Moxifloxacin (Systemic).
Nelfinavir	May increase the serum concentration of QuiNIDine.
Nilotinib	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Nilotinib.
Oxatomide	May enhance the anticholinergic effect of Anticholinergic Agents.
PAZOPanib	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib.
Pimozide	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pimozide.
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.
Piperaquine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Piperaquine.
Posaconazole	May increase the serum concentration of QuiNIDine.
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.
Potassium Citrate	Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate.
Probucol	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Probucol.
QT-prolonging Class IA Antiarrhythmics (Highest Risk)	May enhance the QTc-prolonging effect of other QT-prolonging Class IA Antiarrhythmics (Highest Risk). Exceptions: Ajmaline.
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).
QUEtiapine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QUEtiapine.
Revefenacin	Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin.
Ribociclib	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ribociclib.
Ritonavir	May increase the serum concentration of QuiNIDine.
Saquinavir	May enhance the QTc-prolonging effect of QuiNIDine.
Sparfloxacin	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sparfloxacin.
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.
Thioridazine	May enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may increase the serum concentration of Thioridazine.
Tiotropium	Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium.
Tipranavir	May increase the serum concentration of QuiNIDine.
Topotecan	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan.
Umeclidinium	May enhance the anticholinergic effect of Anticholinergic Agents.
VinCRIStine (Liposomal)	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal).
Voriconazole	QuiNIDine may enhance the QTc-prolonging effect of Voriconazole. Voriconazole may increase the serum concentration of QuiNIDine.

Monitoring parameters:

Cardiac monitor required during IV administration; CBC, liver, and renal function tests, should be routinely performed during long-term administration Consult individual institutional policies and procedures.

How to administer Quinidine (Cardin)?

Oral:

sustained release dosage forms are not to be ground or crushed.
Some preparations of quinidine gluconate extended-release tablets may be divided into two for dose adjustments; tablets are not scored.

IV: Quinidine gluconate:

Administer by IV infusion. Close cardiac monitoring recommended.
IM administration is not recommended. Minimize use of PVC tubing to enhance bioavailability; shorter tubing lengths are recommended by the manufacturer

Mechanism of action of Quinidine (Cardin):

Antiarrhythmic agents belong to Class IIa; affects action phase (depress phase 1); decreases myocardial exitability and conduction velocity by decreasing sodium influx during repolarization and potassium efflux during depolarization; also reduces calcium transportation across the cell membrane

Protein binding:

Infants and neonates: 50 to 70%
Adults and older children: 80%-88%
It binds to alpha 1acid glycoprotein and, to a lesser extent, albumin. Protein-binding changes can occur during times of stress (eg acute myocardial injury) or in certain diseases (eg, cirrhosis (hyperthyroidism), malnutrition).

Metabolism:

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

Bioavailability:

Sulfate: ~70% with wide variability between patients (45% to 100%);
Gluconate: 70% to 80%

Half-life elimination, plasma:

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

Time to peak, serum:

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

Excretion:

Urine (5% to 20% as unchanged drug)

International Brand Names of Quinidine:

Cardin
Cardioquina
Cardioquinol
Chinidin
Chinidin Retard
Chinidinum prolongatum
Chinidinum sulfuricum
Kinidin
Kinidin Durules
Kinidin durules
Kinilentin
Kinitard
Naticardina
Quinaglute Dura-tabs
Quinicardine
Quiniduran
Ritmocor
Sulfas-Chinidin
Wanidine

Quinidine Brand Names in Pakistan:

No Brands Available in Pakistan.

Comments

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Quinidine (Cardin) - Uses, Dose, MOA, Brands, Side effects

Quinidine Uses:

Quinidine gluconate and sulfate salts:

Quinidine gluconate (IV formulation):

Quinidine gluconate (IV formulation):

Quinidine (Cardin) Dose in Adults

Quinidine (Cardin) Dose in the pharmacological conversion of Atrial fibrillation/flutter:

Immediate-release formulations:

Extended-release formulations:

Quinidine (Cardin) Dose to maintain sinus rhythm in patients with paroxysmal atrial fibrillation or flutter:

Immediate-release formulations:

Extended-release formulations:

Quinidine (Cardin) Dose in the treatment of severe Malaria:

Quinidine (Cardin) Dose in the treatment of Ventricular arrhythmias (off-label dose): Oral:

Immediate-release formulation:

Extended-release formulation:

Quinidine (Cardin) Dose in Childrens

Dose in the treatment of severe, life-threatening malaria:

Infants, Children, and Adolescents:

Quinidine (Cardin) Dose in the treatment of Tachyarrhythmias, including supraventricular tachycardia, atrial fibrillation, atrial flutter, and ventricular tachycardia:

Children and Adolescents: Limited data available; not considered first-line therapy:

Pregnancy Risk Factor C

Use during breastfeeding:

Quinidine (Cardin) Dose in Kidney Disease:

The following guidelines have been used by some clinicians (Aronoff 2007): Oral:

Dose in Liver disease:

Side effects of Quinidine (Cardin):

Cardiovascular:

Central Nervous System:

Dermatologic:

Gastrointestinal:

Neuromuscular & Skeletal:

Ophthalmic:

Miscellaneous:

Contraindications to Quinidine (Cardin):

Warnings and precautions

Hepatotoxicity:

Hypersensitivity reactions

Proarrhythmic effects

Arrhythmias:

Atrial fibrillation/flutter:

Conduction disturbances:

Electrolyte imbalance:

G6PD deficiency:

Left ventricular dysfunction/heart failure (HF):

Hepatic impairment