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    Anti-arrhythmics, Class I-A

    BOXED WARNING

    Alcoholism, bradycardia, cardiac arrhythmias, cardiac disease, coronary artery disease, diabetes mellitus, females, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, long QT syndrome, malnutrition, myocardial infarction, QT prolongation, thyroid disease

    Quinidine has proarrhythmic properties and may induce or worsen cardiac arrhythmias. Quinidine is a Class IA antiarrhythmic agent, and is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Quinidine should be discontinued if significant QT prolongation or TdP occur during therapy. Quinidine has been associated with increased mortality when used to treat various arrhythmias. According to the manufacturer, quinidine should be used with extreme caution in patients with QT prolongation or a history of TdP. Due to the associated risks, quinidine should be avoided whenever possible in patients with pre-existing QT prolongation, acquired or congenital long QT syndrome, or a history of TdP. Further, use quinidine with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, elderly patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic dysfunction may also be at increased risk for QT prolongation.

    DEA CLASS

    Rx

    DESCRIPTION

    Parenteral and oral class IA antiarrhythmic; used for atrial arrhythmias and ventricular tachycardia; also used for severe malaria.

    COMMON BRAND NAMES

    Quinaglute, Quinora

    HOW SUPPLIED

    Quinaglute/Quinidine/Quinidine Gluconate Oral Tab ER: 324mg
    Quinidine/Quinidine Gluconate Intramuscular Inj Sol: 1mL, 80mg
    Quinidine/Quinidine Gluconate Intravenous Inj Sol: 1mL, 80mg
    Quinidine/Quinidine Sulfate/Quinora Oral Tab: 200mg, 300mg

    DOSAGE & INDICATIONS

    For conversion to and/or maintenance of sinus rhythm in patients with atrial fibrillation, atrial flutter, or ventricular tachycardia; or for the treatment of paroxysmal supraventricular tachycardia (PSVT); or for paroxysmal supraventricular tachycardia (PSVT) prophylaxis in patients with reentrant tachycardias, including patients with Wolff-Parkinson-White (WPW) syndrome.
    NOTE: Most adult patients require 10 to 20 mg/kg/day, expressed as quinidine base. Dosages should be adjusted to produce a serum quinidine concentration of 2 to 6 mcg/mL. Quinidine sulfate, quinidine gluconate, and quinidine polygalacturonate (no longer commercially available) contain 83%, 62%, and 80% quinidine base, respectively.
    Oral dosage (quinidine sulfate immediate-release tablets)
    Adults

    Initially, 200 to 300 mg PO every 6 to 8 hours. May be increased to 600 mg PO every 6 hours if needed, based on serum quinidine concentrations. Alternatively, a rapid loading dose can be given, usually 200 mg PO every 2 to 3 hours for 5 to 6 doses or until clinical response or toxicity occurs; this method of administration may be associated with a high incidence of adverse GI effects.

    Adolescents† and Children†

    20 to 60 mg/kg/day PO or 900 mg/m2/day PO, given in divided doses every 6 hours.

    Oral dosage (quinidine sulfate extended-release tablets)
    Adults

    300 to 600 mg PO every 8 to 12 hours.

    Oral dosage (quinidine gluconate extended-release tablets)
    Adults

    Initially, 324 mg to 648 mg PO every 8 to 12 hours. If needed, the dose may be cautiously increased. The total daily dose should be decreased if QRS complex widens to 130% of pre-treatment duration; the QTc interval widens to 130% of pre-treatment duration and is longer than 500 msec; P waves disappear; or if the patient develops significant tachycardia, symptomatic bradycardia, or hypotension. Clinical practice guidelines recommend quinidine 324 to 648 mg PO every 8 hours as an option for the maintenance of sinus rhythm in patients with atrial fibrillation only when other antiarrhythmic drugs cannot be used.

    Intramuscular dosage (quinidine gluconate)
    Adults

    Initially, 600 mg (salt) IM, followed by 400 mg (salt) IM. Repeat as often as every 2 hours if necessary. Dosage adjustment is made according to response.

    Intravenous dosage (quinidine gluconate)
    Adults

    800 mg (salt) IV in 50 mL of 5% Dextrose Injection, administered at a rate of 1 mL/minute with close ECG and blood pressure monitoring.

    For the treatment of severe malaria.
    Intravenous dosage (quinidine gluconate)
    Adults, Adolescents, Children, and Infants (Regimen 1)

    10 mg/kg/dose (6.25 mg/kg/dose base) IV loading dose over 1 to 2 hours, then a continuous maintenance infusion of 0.02 mg/kg/minute (0.0125 mg/kg/minute base) IV for at least 24 hours. Oral quinidine suggested as stepdown in FDA-labeling; however, guidelines suggest quinine. Give in combination with doxycycline, tetracycline, or clindamycin. Continue treatment for 7 days in Southeast Asia or 3 days in Africa or South America. In patients able to swallow and have a parasite density of less than 1%, stepdown to oral quinine sulfate. Severe malaria is most often due to P. falciparum.

    Adults, Adolescents, Children, and Infants (Regimen 2)

    24 mg/kg/dose (15 mg/kg/dose base) IV loading dose over 4 hours, then a maintenance regimen of 12 mg/kg/dose (7.5 mg/kg/dose base) IV infused over 4 hours every 8 hours, starting 8 hours after the beginning of the loading dose. Give in combination with doxycycline, tetracycline, or clindamycin. Continue treatment for 7 days in Southeast Asia or 3 days in Africa or South America. In patients able to swallow and have a parasite density of less than 1%, stepdown to oral quinine sulfate. Severe malaria is most often due to P. falciparum.

    For the treatment of persistent singultus (hiccups)†.
    Oral dosage (quinidine sulfate)
    Adults

    200 mg PO 4 times daily. Quinidine clearance may be reduced in geriatric patients; dosage reduction may be required in individual patients.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Quinidine has a narrow therapeutic index (serum concentration range: 2—6 mcg/ml). Dosage is individualized based on patient weight, age, renal and hepatic function, clinical goals, patient response, and serum quinidine concentrations.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Quinidine is approximately 60—80% metabolized by hepatic enzymes. Dosage should be adjusted based on the degree of hepatic impairment and clinical response; no quantitative recommendations are available.

    Renal Impairment

    CrCl > 10 ml/min: no dosage adjustment needed.
    CrCl <= 10 ml/min: dosage adjustment may be needed.

    ADMINISTRATION

    NOTE: Serum quinidine concentrations should be monitored for patients receiving quinidine (see Therapeutic Drug Monitoring in Dosage section).
     
    For storage information, see specific product information within the How Supplied section.

    Oral Administration

    Administer quinidine with a full glass of water 1 hour before or 2 hours after meals for faster absorption. Do not administer with grapefruit juice which could significantly inhibit the metabolism of quinidine (see Drug Interactions). If gastric irritation occurs, may be administered with or immediately after meals.

    Oral Solid Formulations

    Extended-release tablets: Swallow quinidine whole; do not crush, chew, or break.

    Injectable Administration

    Quinidine gluconate is administered intramuscularly or intravenously.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Intermittent IV infusion:
    Dilute 800 mg in 50 ml of D5W to make an infusion solution containing 16 mg/ml of quinidine gluconate. Solution is stable for 24 hours at room temperature.
    Using an infusion pump, administer IV at a rate not to exceed 1 ml/min. More rapid administration may cause hypotension.
    Because quinidine may be adsorbed to PVC tubing, tubing length should be minimized. For example, the use of 112 inches of tubing results in 30% loss of quinidine, but drug loss is less than 3% when only 12 inches of tubing is used.

    Intramuscular Administration

    Intramuscular injection:
    No dilution necessary.
    Inject quinidine deeply into a large muscle (i.e., upper outer quadrant of the gluteus maximus or lateral part of the thigh). Aspirate prior to injection to avoid injection into a blood vessel.

    STORAGE

    Generic:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Quinaglute:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Quinora:
    - Store at room temperature (between 59 to 86 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    AV block, bundle-branch block, digitalis toxicity

    Quinidine should be used cautiously, if at all, in patients with incomplete AV nodal block because complete block could develop. Quinidine is contraindicated in patients with complete AV block, severe intraventricular conduction defects, left bundle-branch block, or ventricular ectopy. Quinidine is contraindicated in patients with digitalis-induced AV conduction disorders. In addition, the drug should be used with caution in patients with digitalis intoxication even in the absence of conduction disorders, because the drug can cause additive depression of conduction, aggravating digitalis toxicity.

    Heart failure

    Quinidine should be used cautiously in patients with congestive heart failure because the direct negative inotropic effects of the drug can exacerbate this condition.

    Alcoholism, bradycardia, cardiac arrhythmias, cardiac disease, coronary artery disease, diabetes mellitus, females, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, long QT syndrome, malnutrition, myocardial infarction, QT prolongation, thyroid disease

    Quinidine has proarrhythmic properties and may induce or worsen cardiac arrhythmias. Quinidine is a Class IA antiarrhythmic agent, and is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Quinidine should be discontinued if significant QT prolongation or TdP occur during therapy. Quinidine has been associated with increased mortality when used to treat various arrhythmias. According to the manufacturer, quinidine should be used with extreme caution in patients with QT prolongation or a history of TdP. Due to the associated risks, quinidine should be avoided whenever possible in patients with pre-existing QT prolongation, acquired or congenital long QT syndrome, or a history of TdP. Further, use quinidine with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, elderly patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic dysfunction may also be at increased risk for QT prolongation.

    Hypotension

    Quinidine, especially intravenous (IV) quinidine, should not be used in patients with hypotension because the alpha-receptor-blocking properties of the drug can exacerbate existing hypotension.

    Asthma, fever, mefloquine hypersensitivity, quinidine hypersensitivity, quinine hypersensitivity

    Quinidine should not be used in patients with a known mefloquine hypersensitivity, quinine hypersensitivity, or quinidine hypersensitivity. Quinidine should be used cautiously in patients with preexisting asthma or fever because these conditions can mask quinidine hypersensitivity. Repeat use of quinidine is contraindicated in patients who previously developed drug-induced thrombocytopenic purpura as a result of quinidine treatment.

    Myasthenia gravis

    Quinidine use is contraindicated in patients with myasthenia gravis because the drug's anticholinergic properties can increase muscle weakness. In addition, quinidine can interact with drugs used in the treatment of myasthenia (see Drug Interactions).

    Hepatic disease, renal failure, renal impairment

    Renal impairment or hepatic disease results in delayed elimination of quinidine, and these conditions can lead to quinidine toxicity if dosage is not appropriately reduced. Quinidine should be used with particular caution in patients with severe renal impairment or renal failure with a creatinine clearance less than 10 mL/minute.

    Labor, pregnancy

    Quinidine is classified as FDA pregnancy risk category C. Safe use of quinidine during pregnancy has not been established. There have been no adequate or well-controlled pregnancy studies performed in humans. Use of quinidine during pregnancy should be avoided unless the potential maternal benefit justifies the possible risk to the fetus. In one neonate whose mother received quinidine throughout her pregnancy, the serum level of quinidine was equal to that of the mother. The concentration of quinidine in the amniotic fluid was approximately 3 times higher than that of the serum. No adverse effects were noted in the neonate. The effect of quinidine on labor and delivery is unknown; however, quinidine is known to be oxytocic in humans.

    Breast-feeding

    Quinidine is excreted in human milk at concentrations slightly lower than those found in maternal serum. According to the manufacturer, breast-feeding infants would be expected to develop serum quinidine concentrations at least an order of magnitude lower than those of the mother. However, the pharmacokinetics and pharmacodynamics of quinidine in human infants have not been adequately studied. The reduced protein binding of quinidine in neonates may increase their risk of toxicity at low total serum concentrations. The manufacturer recommends that quinidine be avoided if possible in lactating women. However, if pharmacotherapy is necessary in a nursing woman, the American Academy of Pediatrics considers quinidine, as well as procainamide and disopyramide, to be usually compatible with breast-feeding. If quinidine is administered to a breast-feeding mother, monitor the infant carefully for signs and symptoms of quinidine exposure. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Geriatric

    Quinidine renal and/or hepatic clearance may be reduced in some geriatric patients; the quinidine dosage should be individualized to attain clinical goals. Monitor for adverse effects of quinidine more closely in geriatric patients, who have not been systematically evaluated. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. The OBRA guidelines caution that antiarrhythmics can have serious adverse effects (e.g., impairment of mental function, appetite, behavior, heart function, or falls) in older individuals.

    ADVERSE REACTIONS

    Severe

    arrhythmia exacerbation / Early / 3.0-3.0
    esophageal stricture / Delayed / Incidence not known
    esophageal ulceration / Delayed / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    bradycardia / Rapid / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    night blindness / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    optic neuritis / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    vasculitis / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known
    uveitis / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known

    Moderate

    esophagitis / Delayed / 22.0-22.0
    palpitations / Early / 7.0-7.0
    hepatitis / Delayed / Incidence not known
    QT prolongation / Rapid / Incidence not known
    hypotension / Rapid / Incidence not known
    PR prolongation / Rapid / Incidence not known
    scotomata / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    photophobia / Early / Incidence not known
    pneumonitis / Delayed / Incidence not known
    lymphadenopathy / Delayed / Incidence not known
    ataxia / Delayed / Incidence not known
    depression / Delayed / Incidence not known
    confusion / Early / Incidence not known
    delirium / Early / Incidence not known

    Mild

    diarrhea / Early / 24.0-35.0
    pyrosis (heartburn) / Early / 22.0-22.0
    headache / Early / 3.0-7.0
    fatigue / Early / 7.0-7.0
    rash (unspecified) / Early / 5.0-6.0
    fever / Early / 6.0-6.0
    weakness / Early / 5.0-5.0
    vomiting / Early / 3.0-3.0
    nausea / Early / 3.0-3.0
    dizziness / Early / 3.0-3.0
    tremor / Early / 2.0-2.0
    asthenia / Delayed / 2.0-2.0
    syncope / Early / Incidence not known
    mydriasis / Early / Incidence not known
    diplopia / Early / Incidence not known
    maculopapular rash / Early / Incidence not known
    photosensitivity / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    pruritus / Rapid / Incidence not known
    arthralgia / Delayed / Incidence not known
    myalgia / Early / Incidence not known
    injection site reaction / Rapid / Incidence not known
    vertigo / Early / Incidence not known
    tinnitus / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abarelix: (Severe) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation, such as Class IA antiarrhythmics.
    Acebutolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like acebutololl. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure. Reduce the beta-blocker dosage if necessary.
    Acetaminophen; Butalbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Acetaminophen; Butalbital; Caffeine: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy. (Moderate) Quinidine is known to inhibit cytochrome P450 2D6. Codeine is metabolized via this pathway. By interfering with the hepatic conversion of codeine to morphine, quinidine reduces the amount of circulating morphine. The analgesic response to codeine is thus diminished.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of a potent CYP2D6 inhibitor like quinidine with dihydrocodeine-containing products may decrease the metabolism of dihydrocodeine to dihydromorphine. Although theoretical, patients may experience varying degrees of analgesia if they take dihydrocodeine with a CYP2D6 inhibitor.
    Acetaminophen; Codeine: (Moderate) Quinidine is known to inhibit cytochrome P450 2D6. Codeine is metabolized via this pathway. By interfering with the hepatic conversion of codeine to morphine, quinidine reduces the amount of circulating morphine. The analgesic response to codeine is thus diminished.
    Acetaminophen; Diphenhydramine: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
    Acetaminophen; Hydrocodone: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Acetaminophen; Oxycodone: (Moderate) Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone, which represents < 15% of the total administered dose. Potent inhibitors of CYP2D6, such as quinidine, may potentially increase the effects of oxycodone; however, such blockade has not been shown to be of clinical significance during oxycodone treatment. Clinicians should be aware of this possible interaction.
    Acetaminophen; Propoxyphene: (Moderate) Propoxyphene is a substrate and an inhibitor of CYP2D6. Increased serum concentrations of propoxyphene would be expected from concurrent use of a CYP2D6 inhibitor like quinidine.
    Acetaminophen; Tramadol: (Moderate) As quinidine is a potent inhibitor of CYP2D6 and tramadol is partially metabolized by CYP2D6, concurrent therapy may decrease tramadol metabolism. This interaction may result in decreased tramadol efficacy and/or increased tramadol-induced risks of serotonin syndrome or seizures. The analgesic activity of tramadol is due to the activity of both the parent drug and the O-desmethyltramadol metabolite (M1), and M1 formation is dependent on CYP2D6. Therefore, use of tramadol with a CYP2D6-inhibitor may alter tramadol efficacy. In addition, inhibition of CYP2D6 metabolism is expected to result in reduced metabolic clearance of tramadol. This in turn may increase the risk of tramadol-related adverse events including serotonin syndrome and seizures. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Acetazolamide: (Major) Acetazolamide can decrease excretion of quinidine because carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized drug available for renal tubular reabsorption. The effects of quinidine can be prolonged or enhanced.
    Adefovir: (Moderate) Adefovir is eliminated renally by a combination of glomerular filtration and active tubular secretion; coadministration of adefovir dipivoxil with drugs that reduce renal function or compete for active tubular secretion, such as quinidine, may decrease adefovir elimination by competing for common renal tubular transport systems, therefore increasing serum concentrations of either adefovir and/or these coadministered drugs.
    Afatinib: (Major) If the concomitant use of quinidine and afatinib is necessary, consider reducing the afatinib dose by 10 mg per day if the original dose is not tolerated; resume the previous dose of afatinib as tolerated after discontinuation of quinidine. Afatinib is a P-glycoprotein (P-gp) substrate and inhibitor in vitro, and quinidine is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. Administration of another P-gp inhibitor, ritonavir (200 mg twice daily for 3 days), 1 hour before afatinib (single dose) increased the afatinib AUC and Cmax by 48% and 39%, respectively; there was no change in the afatinib AUC when ritonavir was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with ritonavir, and 111% and 105% when ritonavir was administered 6 hours after afatinib. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise.
    Albuterol: (Minor) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Albuterol; Ipratropium: (Minor) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Aldesleukin, IL-2: (Moderate) Quinidine causes a dose-dependent QT prolongation and is metabolized via CYP3A4. Concurrent use of quinidine with CYP3A4 inhibitors such as aldesleukin, IL-2 may result in elevated quinidine plasma concentrations with the potential for enhanced QT-prolonging effects.
    Alfuzosin: (Major) Alfuzosin should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. The manufacturer warns that the QT effect of alfuzosin should be considered prior to administering the drug to patients taking other medications known to prolong the QT interval.
    Aliskiren; Amlodipine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Alkalinizing Agents: (Major) Urinary alkalinization increases the renal tubular reabsorption of quinidine, resulting in higher quinidine serum concentrations which may lead to toxicity. Avoid citric acid; potassium citrate; sodium citrate administration to any patient receiving treatment with quinidine.
    Alvimopan: (Moderate) Alvimopan is a substrate of P-glycoprotein (P-gp). Although the concomitant use of mild to moderate inhibitors of P-gp did not influence the pharmacokinetics of alvimopan, the concomitant use of strong P-gp inhibitors, such as quinidine, has not been studied. Coadministration of quinidine and alvimopan may result in elevated concentrations of alvimopan. If these drugs are coadministered, patients should be monitored for increased toxicity as well as increased therapeutic effect of alvimopan.
    Amantadine: (Minor) Concomitant administration of quinidine with amantadine has been shown to decrease the renal clearance of amantadine. The proposed mechanism is inhibition of the renal tubular secretion of amantadine. The potential for increased pharmacologic effects of amantadine, including adverse events such as dizziness, altered mental state, ataxia, orthostatic hypotension, xerostomia, and nausea, should be considered if amantadine is given with quinidine.
    Ambenonium Chloride: (Moderate) The anticholinergic properties of certain antiarrhythmic treatments may lessen the effectiveness of cholinomimetic agent treatment, such as therapy with ambenonium. Quinidine has some anticholinergic properties and should be used cautiously in patients with myasthenia gravis.
    Amiloride: (Severe) Seven of ten patients with inducible ventricular tachycardia developed adverse reactions including sustained ventricular tachycardia and other somatic complaints during concomitant amiloride and quinidine administration. The therapeutic antiarrhythmic actions of quinidine were antagonized by amiloride. In addition, quinidine exerts either direct or indirect (alpha-adrenergic blockade) peripheral vasodilatory effects, which can decrease blood pressure. Hypotension is more severe with parenteral quinidine. Until more data are available, this drug combination should be avoided whenever possible.
    Amiloride; Hydrochlorothiazide, HCTZ: (Severe) Seven of ten patients with inducible ventricular tachycardia developed adverse reactions including sustained ventricular tachycardia and other somatic complaints during concomitant amiloride and quinidine administration. The therapeutic antiarrhythmic actions of quinidine were antagonized by amiloride. In addition, quinidine exerts either direct or indirect (alpha-adrenergic blockade) peripheral vasodilatory effects, which can decrease blood pressure. Hypotension is more severe with parenteral quinidine. Until more data are available, this drug combination should be avoided whenever possible.
    Amiodarone: (Major) Amiodarone coadministration increases quinidine concentrations by about 33% after 2 days, by decreasing its renal clearance or by inhibiting its hepatic metabolism. Quinidine may also be displaced from tissue and protein binding sites. Prolongation of the QT interval is well documented with quinidine, and the addition of amiodarone may increase this effect, placing the patient at an increased risk for the development of torsade de pointes. Careful clinical observation of the patient as well as close monitoring of the ECG and serum quinidine concentrations are essential with adjustment of the quinidine dosing regimen performed as necessary to avoid enhanced toxicity or pharmacodynamic effects. An empiric reduction of the quinidine dose by 33-50% is suggested within 2 days following initiation of amiodarone therapy, with consideration given to immediately discontinuing of quinidine once amiodarone therapy is begun. Combination antiarrhythmic therapy is reserved for patients with refractory life-threatening arrhythmias. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Amitriptyline: (Severe) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
    Amitriptyline; Chlordiazepoxide: (Severe) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
    Amlodipine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Amlodipine; Atorvastatin: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Amlodipine; Benazepril: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Amlodipine; Olmesartan: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Amlodipine; Telmisartan: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Amlodipine; Valsartan: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Amobarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Amoxapine: (Major) Because most cyclic antidepressants are partially metabolized by CYP2D6, caution is advisable during co-administration of amoxapine and potent CYP2D6 inhibitors such as quinidine. Elevated plasma concentrations of amoxapine may result in more pronounced anticholinergic effects and the risk of seizures may be increased. Anti-arrhythmics that are less potent inhibitors of CYP2D6, such as propafenone, may similarly interact with amoxapine. CYP2D6 substrates including flecainide may compete with amoxapine for the same metabolic pathway.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Quinidine (including dextromethorphan; quinidine) and disopyramide are also associated with QT prolongation and TdP. There have been post-marketing reports of TdP occurring with the coadministration of clarithromycin and quinidine or disopyramide. If used concomitantly, monitor ECGs for QT prolongation and consider monitoring serum concentrations of quinidine or disopyramide.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Quinidine (including dextromethorphan; quinidine) and disopyramide are also associated with QT prolongation and TdP. There have been post-marketing reports of TdP occurring with the coadministration of clarithromycin and quinidine or disopyramide. If used concomitantly, monitor ECGs for QT prolongation and consider monitoring serum concentrations of quinidine or disopyramide.
    Amprenavir: (Major) Amprenavir can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is responsible for the metabolism of quinidine. The concurrent use of quinidine and amprenavir should be avoided or approached with great caution due to the potential for serious toxicity. Quinidine doses may require adjustment if amprenavir is added or discontinued during quinidine therapy.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include quinidine.
    Angiotensin II receptor antagonists: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Angiotensin-converting enzyme inhibitors: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Antacids: (Major) Alkalinizing agents such as antacids can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible.
    Apomorphine: (Major) Apomorphine should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Limited data indicate that QT prolongation is possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines. In one study, a single mean dose of 5.2 mg (range 2-10 mg) prolonged the QT interval by about 3 msec. However, large increases (> 60 msecs from pre-dose) have occurred in two patients receiving 6 mg doses. Doses <= 6 mg SC are associated with minimal increases in QTc; doses > 6 mg SC do not provide additional clinical benefit and are not recommended.
    Aprepitant, Fosaprepitant: (Major) Use caution if quinidine and aprepitant, fosaprepitant are used concurrently and monitor for an increase in quinidine-related adverse effects, including QT prolongation and torsade de pointes (TdP), for several days after administration of a multi-day aprepitant regimen. Quinidine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of quinidine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Arformoterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Aripiprazole: (Severe) According to the manufacturer of dextromethorphan; quinidine, the concurrent use of dextromethorphan; quinidine with drugs that are both 2D6 substrates and prolong the QT interval, such as aripiprazole, is contraindicated. Both quinidine and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP). During coadministration of aripiprazole and quinidine alone, there may be an increase in aripiprazole concentrations due to potent inhibition of CYP2D6 by quinidine, which can increase the risk for QT prolongation or other serious aripiprazole-related adverse effects. In one evaluation, concurrent use of quinidine and oral aripiprazole resulted in an increase in the AUC of aripiprazole of 112% and a decrease in the AUC of its active metabolite by 35%. The manufacturer of aripiprazole recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP2D6 such as quinidine. The manufacturer also recommends that the oral aripiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving a combination of CYP3A4 and CYP2D6 inhibitors. In adults receiving 300 mg or 400 mg of Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if a strong CYP2D6 inhibitor is used for more than 14 days. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP2D6 inhibitor for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 mg, combined use of a strong CYP2D6 inhibitor and a strong CYP3A4 inhibitor for more than 14 days should be avoided; no dose adjustment is needed in patients taking 441 mg, if tolerated.
    Arsenic Trioxide: (Major) If possible, quinidine should be discontinued prior to initiating arsenic trioxide therapy. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
    Asenapine: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Asenapine has been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect.
    Aspirin, ASA; Butalbital; Caffeine: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy. (Moderate) Quinidine is known to inhibit cytochrome P450 2D6. Codeine is metabolized via this pathway. By interfering with the hepatic conversion of codeine to morphine, quinidine reduces the amount of circulating morphine. The analgesic response to codeine is thus diminished.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of a potent CYP2D6 inhibitor like quinidine with dihydrocodeine-containing products may decrease the metabolism of dihydrocodeine to dihydromorphine. Although theoretical, patients may experience varying degrees of analgesia if they take dihydrocodeine with a CYP2D6 inhibitor.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Quinidine is known to inhibit cytochrome P450 2D6. Codeine is metabolized via this pathway. By interfering with the hepatic conversion of codeine to morphine, quinidine reduces the amount of circulating morphine. The analgesic response to codeine is thus diminished.
    Aspirin, ASA; Oxycodone: (Moderate) Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone, which represents < 15% of the total administered dose. Potent inhibitors of CYP2D6, such as quinidine, may potentially increase the effects of oxycodone; however, such blockade has not been shown to be of clinical significance during oxycodone treatment. Clinicians should be aware of this possible interaction.
    Atazanavir: (Major) Caution should be used in patients receiving atazanavir concurrently with drugs metabolized via CYP3A4 and known to cause QT prolongation like quinidine. Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of quinidine and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur between atazanavir and quinidine.
    Atazanavir; Cobicistat: (Major) Caution should be used in patients receiving atazanavir concurrently with drugs metabolized via CYP3A4 and known to cause QT prolongation like quinidine. Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of quinidine and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur between atazanavir and quinidine. (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of quinidine with cobicistat. Quinidine is a substrate for CYP3A4 and P-gp and an inhibitor of CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both these enzymes and an inhibitor of P-gp. Concurrent use may result in elevated plasma concentration of both drugs.
    Atenolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like atenolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure. Reduce the beta-blocker dosage if necessary.
    Atenolol; Chlorthalidone: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like atenolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure. Reduce the beta-blocker dosage if necessary.
    Atomoxetine: (Major) If possible, quinidine should be avoided in patients receiving medications that both prolong the QT interval and are CYP2D6 substrates such as atomoxetine. Quinidine may inhibit the metabolism of atomoxetine by CYP2D6 inhibition and increase the risk of adverse cardiac effects such as QT prolongation. In children and adolescents up to 70 kg receiving a strong CYP2D6 inhibitor or who are known CYP2D6 poor metabolizers (PMs), atomoxetine should be initiated at 0.5 mg/kg/day and only increased to the usual target dose of 1.2 mg/kg/day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated. In children and adolescents over 70 kg and adults receiving a strong CYP2D6 inhibitor or who are known CYP2D6 poor metabolizers, atomoxetine should be initiated at 40 mg/day and only increased to the usual target dose of 80 mg/day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated. If concurrent use is necessary, monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, QT prolongation).
    Atracurium: (Major) Quinidine can potentiate the effects of neuromuscular blockers. Neostigmine will not reverse these effects. Respiratory support may be necessary if quinidine is given concomitantly or shortly after a neuromuscular blocking agent.
    Atropine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs. (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Atropine; Difenoxin: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Atropine; Diphenoxylate: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Atropine; Edrophonium: (Major) Disopyramide possesses anticholinergic properties. It is unclear if disopyramide can interfere with the cholinomimetic activity of edrophonium. Procainamide and quinidine also have anticholinergic properties, albeit somewhat less than disopyramide. Edrophonium may not terminate paroxysmal supraventricular tachycardias in patients receiving quinidine, disopyramide or procainamide, although data are limited. These antiarrhythmics should be used cautiously in patients with myasthenia gravis. (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Major) Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs. (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy. (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics. (Moderate) The reduction in GI motility produced by scopolamine may increase the absorption of some drugs, including quinidine, resulting in increased anticholinergic effects. Increased monitoring is advised in patients receiving this combination.
    Azithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when coadministering quinidine with azithromycin. Quinidine is associated with QT prolongation and TdP, and rare cases of QT prolongation and TdP have been reported during the post-marketing use of azithromycin. In addition, both quinidine and azithromycin are P-glycoprotein (P-gp) substrates and inhibitors, which may lead to increased serum concentrations of either drug when given concomitantly.
    Barbiturates: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Basiliximab: (Moderate) Quinidine causes a dose-dependent QT prolongation and is metabolized via CYP3A4. Concurrent use of quinidine with CYP3A4 inhibitors such as basiliximab may result in elevated quinidine plasma concentrations with the potential for enhanced QT-prolonging effects.
    Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with quinidine or quinidine-containing products, such as dextromethorphan; quinidine. Both drugs have been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Bendroflumethiazide; Nadolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like nadolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs.
    Benztropine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Bepridil: (Severe) Bepridil is contraindicated for use with drugs that prolong the QT interval, including class 1A antiarrhythmic agents, due to the risk of torsade de pointes (TdP). Bepridil has Class I antiarrhythmic properties and is associated with a well-established risk of QT prolongation and TdP. Patients receiving other drugs which have the potential for QT prolongation, such as class 1A antiarrhythmics, have an increased risk of developing proarrhythmias during bepridil therapy.
    Betaxolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like betaxolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary. Ophthalmic betaxolol is not as likely to interact; however, bradycardia and heart block have been reported, and additive effects on conduction may be considered.
    Bethanechol: (Moderate) Drugs that possess antimuscarinic properties, such as quinidine, are pharmacologic opposites of bethanechol. These agents should not be used with bethanechol except when the specific intent is to counteract excessive actions of one or the other.
    Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving quinidine. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving quinidine. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; quinidine inhibits P-gp.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include quinidine, (including dextromethorphan; quinidine),
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include quinidine, (including dextromethorphan; quinidine),
    Bisoprolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like pindolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like pindolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary.
    Blinatumomab: (Moderate) No drug interaction studies have been performed with blinatumomab. The drug may cause a transient release of cytokines leading to an inhibition of CYP450 enzymes. The interaction risk with CYP450 substrates is likely the highest during the first 9 days of the first cycle and the first 2 days of the second cycle. Monitor patients receiving concurrent CYP450 substrates that have a narrow therapeutic index (NTI) such as quinidine. The dose of the concomitant drug may need to be adjusted.
    Boceprevir: (Major) Close clinical monitoring is advised when administering quinidine with boceprevir due to an increased potential for serious and/or life-threatening quinidine-related adverse events. If quinidine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of quinidine and boceprevir. Quinidine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Additionally, both quinidine and boceprevir are substrates and inhibitors of P-glycoprotein (PGP) drug efflux transporter. When used in combination, the plasma concentrations of both medications may be elevated.
    Bosentan: (Moderate) Bosentan is an inducer of cytochrome P450 enzymes, specifically the CYP2C9 and CYP3A4 isoenzymes, and may decrease concentrations of drugs metabolized by these enzymes, including quinidine.
    Brexpiprazole: (Major) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the brexpiprazole dose be reduced to one-half of the usual dose in patients receiving a strong CYP2D6 inhibitor and one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Quinidine is a strong inhibitor of CYP2D6. If these agents are used in combination, the patient should be carefully monitored for brexpiprazole-related adverse reactions. It should be noted that no dosage adjustment is needed in patients taking a strong CYP2D6 inhibitor who are receiving brexpiprazole as adjunct treatment for major depressive disorder because CYP2D6 considerations are already factored into general dosing recommendations.
    Brigatinib: (Moderate) Monitor for decreased efficacy of quinidine if coadministration with brigatinib is necessary. Quinidine is a CYP3A substrate and brigatinib induces CYP3A in vitro; plasma concentrations of quinidine may decrease.
    Brimonidine; Timolol: (Major) In general, patients receiving combined therapy with quinidine and beta-blockers should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects on cardiovascular parameters when used together with beta-blockers, such as timolol. Decreased heart rate (bradycardia) has been reported during combination timolol and quinidine therapy. Additive hypotension is also possible. Additionally, quinidine is a known inhibitor of CYP2D6, and may impair the hepatic clearance of timolol (CYP2D6 substrate). Patients should be monitored for excess beta-blockade. Quinidine has been reported to potentiate timolol-induced bradycardia even after use of ophthalmic timolol.
    Brompheniramine; Guaifenesin; Hydrocodone: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Budesonide; Formoterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Bupivacaine; Lidocaine: (Major) Avoid concurrent use of quinidine with other antiarrhythmics with Class I activities, such as lidocaine. Concurrent use may result in additive or antagonistic cardiac effects and additive toxicity.
    Buprenorphine: (Major) Buprenorphine should be avoided in combination with Class IA antiarrhythmics. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval.
    Buprenorphine; Naloxone: (Major) Buprenorphine should be avoided in combination with Class IA antiarrhythmics. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval.
    Butabarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Cabazitaxel: (Minor) Cabazitaxel is a substrate for P-glycoprotein (Pgp). No formal drug interaction studies have been conducted with Pgp inhibitors, such as quinidine. Use caution when cabazitaxel is administered concomitantly with Pgp inhibitors.
    Cabozantinib: (Moderate) Monitor for an increase in quinidine-related adverse events if concomitant use with cabozantinib is necessary, as plasma concentrations of quinidine may be increased. Cabozantinib is a P-glycoprotein (P-gp) inhibitor and quinidine is a substrate of P-gp; the clinical relevance of this finding is unknown.
    Calcium Carbonate: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
    Calcium Carbonate; Magnesium Hydroxide: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
    Calcium Carbonate; Risedronate: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
    Calcium; Vitamin D: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
    Canagliflozin: (Moderate) Canagliflozin is a substrate/weak inhibitor of drug transporter P glycoprotein (P-gp). Quinidine is a PGP inhibitor/substrate. Theoretically, concentrations of either drug may be increased. Patients should be monitored for changes in glycemic control and possible adverse reactions.
    Canagliflozin; Metformin: (Moderate) Canagliflozin is a substrate/weak inhibitor of drug transporter P glycoprotein (P-gp). Quinidine is a PGP inhibitor/substrate. Theoretically, concentrations of either drug may be increased. Patients should be monitored for changes in glycemic control and possible adverse reactions.
    Capreomycin: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Quinidine could potentiate the neuromuscular blocking effect of capreomycin by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Carbamazepine: (Moderate) Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Quinidine inhibits CYP3A4 and may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored closely if quinidine is added during carbamazepine therapy. It may be necessary to reduce the dose of carbamazepine in this situation.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Cardiac glycosides: (Major) Coadministration of quinidine and oral digoxin has resulted in a 100% increase in digoxin serum concentrations. When quinidine is coadministered with intravenous (IV) digoxin, the digoxin AUC is increased by 54 to 83%. Digoxin is a substrate for P-glycoprotein (P-gp). Quinidine inhibits P-gp, an energy-dependent cellular drug efflux pump. The inhibition of P-gp in the intestinal cell wall may lead to increased oral absorption of digoxin. It also has been shown that quinidine inhibits the secretion of digoxin by P-gp transporters in the kidney leading to decreased renal tubular elimination of digoxin and increased serum concentrations. Measure serum digoxin concentrations before initiating quinidine. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency and continue monitoring.
    Carteolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like carteololl. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure, Reduce the beta-blocker dosage if necessary. Carteolol is not as likely to interact as it is a nonselective beta-adrenoceptor antagonist with intrinsic sympathomimetic activity (ISA); however, additive effects on conduction may be considered, even with ophthalmic use.
    Carvedilol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with carvedilol, a beta-blocker. Altered concentrations of quinidine and/or carvedilol may occur during coadministration. Quinidine is a CYP2D6 inhibitor and P-glycoprotein (P-gp) inhibitor and substrate. Carvedilol is a P-gp inhibitor and substrate and a substrate of CYP2D6. Patients should be monitored for excess beta-blockade. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary.
    Central-acting adrenergic agents: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Ceritinib: (Major) Avoid coadministration of ceritinib with quinidine due to increased quinidine exposure; additive QT prolongation may also occur. If coadministration is unavoidable, monitor for quinidine-related adverse reactions and periodically monitor electrolytes and ECGs. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib is a CYP3A4 inhibitor that causes concentration-dependent prolongation of the QT interval. Quinidine is a CYP3A4 substrate with a narrow therapeutic index, and is also associated with QT prolongation and torsade de pointes (TdP).
    Cevimeline: (Moderate) Cevimeline is metabolized by cytochrome P450 3A4 and CYP2D6. Concurrent administration of inhibitors of these enzymes, such as quinidine, may lead to increased cevimeline plasma concentrations.
    Chlordiazepoxide; Clidinium: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics. Anticholinergic agents administered concurrently with quinidine may produce additive antivagal effects on AV nodal conduction.
    Chloroquine: (Major) Coadminister chloroquine with other drugs known to prolong the QT interval, such as quinidine, with caution. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); fatalities have been reported. The risk of QT prolongation is increased with higher chloroquine doses. Quinidine administration is also associated with QT prolongation and TdP.
    Chlorpheniramine; Codeine: (Moderate) Quinidine is known to inhibit cytochrome P450 2D6. Codeine is metabolized via this pathway. By interfering with the hepatic conversion of codeine to morphine, quinidine reduces the amount of circulating morphine. The analgesic response to codeine is thus diminished.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of a potent CYP2D6 inhibitor like quinidine with dihydrocodeine-containing products may decrease the metabolism of dihydrocodeine to dihydromorphine. Although theoretical, patients may experience varying degrees of analgesia if they take dihydrocodeine with a CYP2D6 inhibitor.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of a potent CYP2D6 inhibitor like quinidine with dihydrocodeine-containing products may decrease the metabolism of dihydrocodeine to dihydromorphine. Although theoretical, patients may experience varying degrees of analgesia if they take dihydrocodeine with a CYP2D6 inhibitor.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpheniramine; Hydrocodone: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpromazine: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include chlorpromazine.
    Cimetidine: (Major) Quinidine concentrations should be monitored closely after cimetidine is added; choose an alternate acid-reducing therapy if possible. Quinidine is eliminated primarily by the CYP3A4 isoenzyme. Cimetidine can inhibit quinidine metabolism and produce quinidine toxicity.
    Ciprofloxacin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering quinidine with ciprofloxacin. Quinidine is associated with QT prolongation and TdP. The manufacturer of dextromethorphan; quinidine recommends an ECG in patients taking it in combination with other drugs known to prolong the QTc, such as ciprofloxacin.
    Cisapride: (Severe) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Administration of Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) is associated with QT prolongation and TdP. Because of the potential for TdP, concurrent use of Class IA antiarrhythmics and cisapride is contraindicated.
    Cisatracurium: (Major) Quinidine can potentiate the effects of neuromuscular blockers. Neostigmine will not reverse these effects. Respiratory support may be necessary if quinidine is given concomitantly or shortly after a neuromuscular blocking agent.
    Citalopram: (Major) Because citalopram and quinidine are associated with QT prolongation, these combinations should be used cautiously and with close monitoring. The manufacturers of quinidine and citalopram recommend an ECG in patients taking either of these drugs in combination with other drugs known to cause QT prolongation.
    Citric Acid; Potassium Citrate: (Major) Alkalinizing agents such as potassium citrate can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible.
    Citric Acid; Potassium Citrate; Sodium Citrate: (Major) Alkalinizing agents such as potassium citrate can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible.
    Clarithromycin: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Quinidine (including dextromethorphan; quinidine) and disopyramide are also associated with QT prolongation and TdP. There have been post-marketing reports of TdP occurring with the coadministration of clarithromycin and quinidine or disopyramide. If used concomitantly, monitor ECGs for QT prolongation and consider monitoring serum concentrations of quinidine or disopyramide.
    Clofarabine: (Moderate) Concomitant use of clofarabine, a substrate of OCT1, and quinidine, an inhibitor of OCT1, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 inhibitors.
    Clomipramine: (Severe) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
    Clozapine: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include clozapine.
    Cobicistat: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of quinidine with cobicistat. Quinidine is a substrate for CYP3A4 and P-gp and an inhibitor of CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both these enzymes and an inhibitor of P-gp. Concurrent use may result in elevated plasma concentration of both drugs.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of quinidine with cobicistat. Quinidine is a substrate for CYP3A4 and P-gp and an inhibitor of CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both these enzymes and an inhibitor of P-gp. Concurrent use may result in elevated plasma concentration of both drugs.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of quinidine with cobicistat. Quinidine is a substrate for CYP3A4 and P-gp and an inhibitor of CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both these enzymes and an inhibitor of P-gp. Concurrent use may result in elevated plasma concentration of both drugs. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Cobimetinib: (Minor) If concurrent use of cobimetinib and quinidine is necessary, use caution and monitor for a possible increase in cobimetinib-related adverse effects. Cobimetinib is a P-glycoprotein (P-gp) substrate, and quinidine is a P-gp inhibitor; coadministration may result in increased cobimetinib exposure. However, coadministration of cobimetinib with another P-gp inhibitor, vemurafenib (960 mg twice daily), did not result in clinically relevant pharmacokinetic drug interactions.
    Codeine: (Moderate) Quinidine is known to inhibit cytochrome P450 2D6. Codeine is metabolized via this pathway. By interfering with the hepatic conversion of codeine to morphine, quinidine reduces the amount of circulating morphine. The analgesic response to codeine is thus diminished.
    Codeine; Guaifenesin: (Moderate) Quinidine is known to inhibit cytochrome P450 2D6. Codeine is metabolized via this pathway. By interfering with the hepatic conversion of codeine to morphine, quinidine reduces the amount of circulating morphine. The analgesic response to codeine is thus diminished.
    Codeine; Phenylephrine; Promethazine: (Severe) Quinidine (including dextromethorphan; quinidine) administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as promethazine, as the effects on the QT interval may be increased during concurrent use of these agents. (Moderate) Quinidine is known to inhibit cytochrome P450 2D6. Codeine is metabolized via this pathway. By interfering with the hepatic conversion of codeine to morphine, quinidine reduces the amount of circulating morphine. The analgesic response to codeine is thus diminished.
    Codeine; Promethazine: (Severe) Quinidine (including dextromethorphan; quinidine) administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as promethazine, as the effects on the QT interval may be increased during concurrent use of these agents. (Moderate) Quinidine is known to inhibit cytochrome P450 2D6. Codeine is metabolized via this pathway. By interfering with the hepatic conversion of codeine to morphine, quinidine reduces the amount of circulating morphine. The analgesic response to codeine is thus diminished.
    Colchicine: (Major) Coadministration of colchicine and quinidine should be avoided due to the potential for serious and life-threatening toxicity. Colchicine is a substrate of P-glycoprotein (P-gp) and quinidine is an inhibitor of P-gp; increased concentrations of colchicine are expected with concurrent use. Colchicine accumulation may be greater in patients with renal or hepatic impairment; therefore the manufacturer of Colcrys contraindicates the use of colchicine and P-gp inhibitors in this population. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine either by reducing the daily dose or reducing the dose frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations for coadministration with P-gp inhibitors are provided by the manufacturer of Colcrys.
    Colesevelam: (Moderate) Colesevelam may decrease the bioavailability of antiarrhythmics if coadministered. To minimize potential for interactions, consider administering oral antiarrhythmics at least 1 hour before or at least 4 hours after colesevelam.
    Conivaptan: (Major) Avoid coadministration of conivaptan, a CYP3A4/P-glycoprotein (P-gp) inhibitor and quinidine, a CYP3A4/P-gp substrate. Concurrent use may result in elevated quinidine serum concentrations. According to the manufacturer, concomitant use of conivaptan, a strong CYP3A4 inhibitor, and CYP3A substrates, such as quinidine, should be avoided. Coadministration of conivaptan with other CYP3A substrates has resulted in increased mean AUC values (2 to 3 times). Theoretically, similar pharmacokinetic effects could be seen with quinidine. Treatment with quinidine may be initiated no sooner than 1 week after completion of conivaptan therapy.
    Crizotinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving crizotinib concomitantly with quinidine; an increase in quinidine plasma concentrations may also occur. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Quinidine is a CYP3A4 substrate that is associated with QT prolongation and torsade de pointes (TdP). Crizotinib is a moderate CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation.
    Cyclobenzaprine: (Major) Cyclobenzaprine should be used cautiously and with close monitoring with Class IA antiarrhythics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Cyclobenzaprine is structurally similar to tricyclic antidepressants. Tricyclic antidepressants have been reported to prolong the QT interval, especially when given in excessive doses (or in overdosage settings). Cyclobenzaprine is associated with a possible risk of QT prolongation and torsades de pointes (TdP), particularly in the event of acute overdose.
    Dabigatran: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with quinidine, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like quinidine in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with quinidine, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. Coadministration of quinidine 200 mg every 2 hours up to a total dose of 1000 mg and dabigatran administered over 3 consecutive days, the last evening dose on Day 3 with or without quinidine pre-dosing, resulted in an increase in dabigatran AUC and Cmax of 53% and 56%, respectively. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
    Daclatasvir: (Major) Systemic exposure of quinidine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of quinidine; monitor patients for potential adverse effects.
    Dalfopristin; Quinupristin: (Moderate) Quinidine is metabolized by CYP3A4. Dalfopristin; quinupristin may decrease the elimination of quinidine by inhibiting CYP3A4.
    Danazol: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates including quinidine.
    Darifenacin: (Moderate) Clinicians should monitor patients for increased anticholinergic effects when CYP2D6 inhibitors, such as quinidine, are coadministered with darifenacin; the dosage of darifenacin should be adjusted, if necessary.
    Darunavir: (Major) Darunavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme should be expected with concurrent use. Coadministration of darunavir with quinidine should be done with extreme caution. Therapeutic monitoring of antiarrhythmic concentrations is recommended.
    Darunavir; Cobicistat: (Major) Darunavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme should be expected with concurrent use. Coadministration of darunavir with quinidine should be done with extreme caution. Therapeutic monitoring of antiarrhythmic concentrations is recommended. (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of quinidine with cobicistat. Quinidine is a substrate for CYP3A4 and P-gp and an inhibitor of CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both these enzymes and an inhibitor of P-gp. Concurrent use may result in elevated plasma concentration of both drugs.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Severe) The manufacturer of ombitasvir; paritaprevir; ritonavir recommends caution and therapeutic drug monitoring (when available) if administered concurrently with quinidine. However, since one of the components of the 3-drug combination is ritonavir, use of these drugs together is contraindicated. Both ritonavir and quinidine are associated with QT prolongation; concomitant use increases the risk for developing Torsade de Pointes (TdP). In addition, ritonavir is a potent CYP3A4 inhibitor, an enzyme partially responsible for the metabolism of quinidine. If administered together, serum concentration of quinidine may increase. (Major) Coadministration of HIV treatment doses of ritonavir and quinidine is contraindicated due to the potential for serious or life-threatening reactions, such as cardiac arrhythmias. Cautious consideration may be given to administering quinidine with boosting doses of ritonavir. Ritonavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as quinidine, should be expected with concurrent use. In addition, ritonavir is associated with QT prolongation and quinidine is associated with QT prolongation and torsade de pointes (TdP); concomitant use increases the risk of QT prolongation.
    Dasatinib: (Major) In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Cautious dasatinib administration is recommended to patients who have or may develop QT prolongation such as patients taking drugs that lead to QT prolongation. Quinidine is established to have a causal association with QT prolongation and torsade de pointes (TdP). Also, dasatinib is a time-dependent inhibitor of cytochrome P450 (CYP) isoenzyme 3A4, and cautious use of dasatinib with a CYP3A4 substrate with a narrow therapeutic index such as quinidine is recommended. For example, coadministration of a single 100 mg dasatinib dose and simvastatin, a CYP3A4 substrate, increased the mean systemic exposure of simvastatin by 20% and the mean maximum serum concentration by 37%.
    Daunorubicin: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP) and should be used cautiously with other drugs with a possible risk for QT prolongation and TdP including daunorubicin and doxorubicin. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Degarelix: (Major) Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) are associated with QT prolongation and torsades de pointes (TdP). Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking class IA antiarrhythmics.
    Delavirdine: (Major) Delavirdine is a potent inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as quinidine, should be expected with concurrent use. Increased quinidine concentrations may be associated with severe cardiovascular adverse reactions. Quinidine doses may require adjustment if delavirdine is added or discontinued during quinidine therapy.
    Desflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Desipramine: (Severe) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine and dextromethorphan; quinidine are contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
    Deutetrabenazine: (Severe) Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Clinically relevant QT prolongation may occur with deutetrabenazine. Additionally, quinidine is a strong CYP2D6 inhibitor, and the metabolites of deutetrabenazine, alpha- and beta-HTBZ, are CYP2D6 substrates. The systemic exposure of alpha- and beta-HTBZ may be increased resulting in an increase in deutetrabenazine-related adverse reactions.
    Dexamethasone: (Moderate) Quinidine is a substrate of the CYP3A4 isoenzyme. Inducers of CYP3A4 such as dexamethasone may increase hepatic elimination of quinidine with the potential for reduced efficacy of quinidine.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
    Dextromethorphan; Promethazine: (Severe) Quinidine (including dextromethorphan; quinidine) administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as promethazine, as the effects on the QT interval may be increased during concurrent use of these agents.
    Diazoxide: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Dicyclomine: (Moderate) Additive anticholinergic effects may be seen when dicyclomine is used concomitantly with other drugs that possess anticholinergic properties, such as quinidine. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Digitoxin: (Major) Coadministration of quinidine and oral digoxin has resulted in a 100% increase in digoxin serum concentrations. When quinidine is coadministered with intravenous (IV) digoxin, the digoxin AUC is increased by 54 to 83%. Digoxin is a substrate for P-glycoprotein (P-gp). Quinidine inhibits P-gp, an energy-dependent cellular drug efflux pump. The inhibition of P-gp in the intestinal cell wall may lead to increased oral absorption of digoxin. It also has been shown that quinidine inhibits the secretion of digoxin by P-gp transporters in the kidney leading to decreased renal tubular elimination of digoxin and increased serum concentrations. Measure serum digoxin concentrations before initiating quinidine. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency and continue monitoring.
    Digoxin: (Major) Coadministration of quinidine and oral digoxin has resulted in a 100% increase in digoxin serum concentrations. When quinidine is coadministered with intravenous (IV) digoxin, the digoxin AUC is increased by 54 to 83%. Digoxin is a substrate for P-glycoprotein (P-gp). Quinidine inhibits P-gp, an energy-dependent cellular drug efflux pump. The inhibition of P-gp in the intestinal cell wall may lead to increased oral absorption of digoxin. It also has been shown that quinidine inhibits the secretion of digoxin by P-gp transporters in the kidney leading to decreased renal tubular elimination of digoxin and increased serum concentrations. Measure serum digoxin concentrations before initiating quinidine. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency and continue monitoring.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of a potent CYP2D6 inhibitor like quinidine with dihydrocodeine-containing products may decrease the metabolism of dihydrocodeine to dihydromorphine. Although theoretical, patients may experience varying degrees of analgesia if they take dihydrocodeine with a CYP2D6 inhibitor.
    Diltiazem: (Major) Diltiazem significantly decreases the clearance and increases the half-life of quinidine. Quinidine does not alter the kinetics of diltiazem. Concurrent use of diltiazem and quinidine in some patients may cause additive hypotension. Due to the potential for additive effects, caution and careful titration are warranted in patients receiving diltiazem concomitantly with other agents known to affect cardiac contractility and/or conduction. Medications that possess negative inotropic effects and/or slow AV conduction, such as quinidine, should be administered with caution to patients receiving concomitant therapy with diltiazem due to the risk of additive effects. Diltiazem may increase serum quinidine concentrations (AUC increases by 51%) by reducing the oral clearance of quinidine by 33%. During diltiazem coadministration, monitor quinidine serum concentrations and therapeutic response; adjust quinidine dosage if needed.
    Diphenhydramine: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme. (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Diphenhydramine; Ibuprofen: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
    Diphenhydramine; Naproxen: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
    Diphenhydramine; Phenylephrine: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
    Disopyramide: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided.
    Dofetilide: (Severe) Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Before switching from another antiarrhythmic drug to dofetilide therapy, antiarrhythmics generally should be withheld for at least three half-lives prior to initiating dofetilide. According to the manufacturer, Class I (disopyramide, encainide, flecainide, lidocaine, mexiletine, moricizine, procainamide, propafenone, quinidine, and tocainide) and Class III (e.g., amiodarone, bretylium, ibutilide, and sotalol) antiarrhythmic agents are associated with QT prolongation and ventricular arrhythmias and concurrent exposure with dofetilide could increase the risk of dofetilide-induced proarrhythmias. Because of the unpredictable pharmacokinetics of amiodarone, dofetilide should not be initiated following a
    Dolasetron: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include dolasetron.
    Dolutegravir; Rilpivirine: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
    Donepezil: (Severe) Quinidine and combination products containing quinidine (e.g., dextromethorphan; quinidine) are contraindicated for use with medications that both prolong the QT interval and are CYP2D6 substrates, such as donepezil. Quinidine has QT prolonging actions and has been shown in vitro to inhibit the metabolism of donepezil by CYP2D6 inhibition; therefore, the effects on the QT interval may be increased during concurrent use of these agents. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy, and the drug is considered a drug with a known risk of TdP.
    Donepezil; Memantine: (Severe) Quinidine and combination products containing quinidine (e.g., dextromethorphan; quinidine) are contraindicated for use with medications that both prolong the QT interval and are CYP2D6 substrates, such as donepezil. Quinidine has QT prolonging actions and has been shown in vitro to inhibit the metabolism of donepezil by CYP2D6 inhibition; therefore, the effects on the QT interval may be increased during concurrent use of these agents. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy, and the drug is considered a drug with a known risk of TdP. (Major) Cationic drugs that are eliminated by renal tubular secretion, such as quinidine, may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or quinidine is recommended to assess for needed dosage adjustments. In selected individuals, quinidine serum concentration monitoring may be appropriate.
    Dorzolamide; Timolol: (Major) In general, patients receiving combined therapy with quinidine and beta-blockers should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects on cardiovascular parameters when used together with beta-blockers, such as timolol. Decreased heart rate (bradycardia) has been reported during combination timolol and quinidine therapy. Additive hypotension is also possible. Additionally, quinidine is a known inhibitor of CYP2D6, and may impair the hepatic clearance of timolol (CYP2D6 substrate). Patients should be monitored for excess beta-blockade. Quinidine has been reported to potentiate timolol-induced bradycardia even after use of ophthalmic timolol.
    Doxacurium: (Major) Quinidine can potentiate the effects of neuromuscular blockers. Neostigmine will not reverse these effects. Respiratory support may be necessary if quinidine is given concomitantly or shortly after a neuromuscular blocking agent.
    Doxazosin: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Doxepin: (Severe) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
    Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as quinidine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Doxorubicin: (Major) Avoid coadministration if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP) and should be used cautiously with other drugs with a possible risk for QT prolongation and TdP including daunorubicin, doxorubicin, epirubicin, and idarubicin. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. In addition, quinidine (including dextromethorphan; quinidine) is a potent CYP2D6 and moderate P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of both CYP2D6 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin.
    Dronedarone: (Severe) Concurrent use of dronedarone and quinidine is contraindicated. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Droperidol: (Major) Class IA antiarrhythmics (disopyramide, procainamide, quinidine) are associated with QT prolongation and torsades de pointes (TdP). Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). In December 2001, the FDA issued a black box warning regarding the use of droperidol and its association with QT prolongation and potential for cardiac arrhythmias based on post-marketing surveillance data. According to the revised 2001 labeling for droperidol, any drug known to have potential to prolong the QT interval should not be coadministered with droperidol.
    Dutasteride; Tamsulosin: (Moderate) Use caution when administering tamsulosin with a strong CYP2D6 inhibitor such as quinidine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure. If concomitant use in necessary, monitor patient closely for increased side effects.
    Edoxaban: (Major) Reduce the dose of edoxaban to 30 mg/day PO in patients being treated for deep venous thrombosis (DVT) or pulmonary embolism and receiving concomitant therapy with quinidine. No dosage adjustment is required in patients with atrial fibrillation. Edoxaban is a P-glycoprotein (P-gp) substrate and quinidine is a P-gp inhibitor. Increased concentrations of edoxaban may occur during concomitant use of quinidine; monitor for increased adverse effects of edoxaban. Similar interactions may occur with dextromethorphan; quinidine.
    Edrophonium: (Major) Disopyramide possesses anticholinergic properties. It is unclear if disopyramide can interfere with the cholinomimetic activity of edrophonium. Procainamide and quinidine also have anticholinergic properties, albeit somewhat less than disopyramide. Edrophonium may not terminate paroxysmal supraventricular tachycardias in patients receiving quinidine, disopyramide or procainamide, although data are limited. These antiarrhythmics should be used cautiously in patients with myasthenia gravis.
    Efavirenz: (Major) Coadministration of efavirenz and quinidine may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Quinidine administration is associated with QT prolongation and TdP. In addition, efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as quinidine.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Coadministration of efavirenz and quinidine may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Quinidine administration is associated with QT prolongation and TdP. In addition, efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as quinidine. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Elbasvir; Grazoprevir: (Moderate) Administering quinidine with elbasvir; grazoprevir may result in elevated quinidine plasma concentrations. Quinidine is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Eliglustat: (Severe) Coadministration of quinidine (including dextromethorphan; quinidine) and eliglustat is contraindicated. Quinidine is a P-glycoprotein (P-gp) substrate and strong CYP2D6 inhibitor associated with a well-established risk of QT prolongation and torsades de pointes (TdP); its use is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6. Eliglustat is a CYP2D6 substrate and P-gp inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of quinidine and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations of one or both drugs, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias).
    Eluxadoline: (Moderate) Although the CYP3A4 inhibitory effects of eluxadoline have not been definitively established, the manufacturer recommends caution when administering eluxadoline concurrently with CYP3A4 substrates that have a narrow therapeutic index, such as quinidine. Closely monitor for increased quinidine-related side effects (e.g., QT prolongation and torsade de pointes) when initiating or discontinuing eluxadoline therapy.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Emtricitabine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Enalapril; Felodipine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Enflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Entecavir: (Major) Both entecavir and quinidine are secreted by active tubular secretion. In theory, coadministration of entecavir with quinidine may increase the serum concentrations of either drug due to competition for the drug elimination pathway. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
    Enzalutamide: (Major) Avoid the concomitant use of enzalutamide, a strong CYP3A4 inducer, and quinidine, a CYP3A4 substrate with a narrow therapeutic index, as quinidine plasma exposure may be reduced.
    Epirubicin: (Major) Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP) and should be used cautiously with other drugs with a possible risk for QT prolongation and TdP including daunorubicin, doxorubicin, epirubicin, and idarubicin. Acute cardiotoxicity can occur during administration of anthracyclines; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Eplerenone: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Epoprostenol: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Eribulin: (Major) Eribulin has been associated with QT prolongation. Class IA antiarrhythmics (disopyramide, procainamide, quinidine) are associated with QT prolongation and torsades de pointes (TdP). If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Erythromycin: (Major) Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). In addition to potential pharmacokinetic interactions, erythromycin may cause QT prolongation and exhibit additive electrophysiologic effects with quinidine. Concurrent use of erythromycin with procainamide should be avoided. In addition, erythromycin may theoretically increase plasma concentrations of quinidine via inhibition of CYP3A4. Higher antiarrhythmic plasma concentrations increases the potential risk of QT prolongation, TdP or other proarrhythmias.
    Erythromycin; Sulfisoxazole: (Major) Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). In addition to potential pharmacokinetic interactions, erythromycin may cause QT prolongation and exhibit additive electrophysiologic effects with quinidine. Concurrent use of erythromycin with procainamide should be avoided. In addition, erythromycin may theoretically increase plasma concentrations of quinidine via inhibition of CYP3A4. Higher antiarrhythmic plasma concentrations increases the potential risk of QT prolongation, TdP or other proarrhythmias.
    Escitalopram: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as quinidine, should be done with caution and close monitoring.
    Esmolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like esmolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary.
    Etoposide, VP-16: (Major) Monitor for an increased incidence of etoposide-related adverse effects if used concomitantly with quinidine. Quinidine is an inhibitor of P-glycoprotein (P-gp) and etoposide, VP-16 is a P-gp substrate. Coadministration may increase etoposide concentrations.
    Etravirine: (Major) Etravirine is an inducer of CYP3A4; quinidine concentrations may be decreased with coadministration. Coadminister these drugs with caution. It is recommended to monitor quinidine concentrations when possible.
    Everolimus: (Major) Everolimus is an inhibitor and substrate of CYP3A4 and Pgp. Coadministration with inhibitors of Pgp, such as quinidine, is not recommended. Patients may experience an increase in systemic exposure to everolimus if these drugs are coadministered. In addition, quinidine is a substrate of CYP3A4 and Pgp. The effect of everolimus on quinidine pharmacokinetics has not been established; however, pharmacokinetic studies showed no significant impact of the coadministration of everolimus with the CYP3A4 and Pgp substrate atorvastatin.
    Ezogabine: (Major) Ezogabine has been associated with QT prolongation. The manufacturer of ezogabine recommends caution during concurrent use of medications known to increase the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with ezogabine include class IA antiarrhythmics (disopyramide, procainamide, quinidine).
    Felodipine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Fenoldopam: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Fentanyl: (Moderate) Quinidine increases fentanyl serum concentrations by inhibiting intestinal P-glycoprotein (P-gp). Receipt of fentanyl 2.5 mcg/kg orally 1 hour after a single dose of immediate-release quinidine 600 mg led to a fentanyl mean area under the plasma concentration-time curve (AUC) of 2.34 +/- 0.63 ng x hour/mL as compared with 0.9 +/- 0.47 ng x hour/mL with placebo. Elevated fentanyl serum concentrations can result in an increase in the pharmacologic effects of fentanyl, such as CNS or respiratory depression.
    Fingolimod: (Severe) Concurrent use of fingolimod with class Ia antiarrhythmics such as disopyramide, quinidine, and procainamide is contraindicated. Fingolimod initiation results in decreased heart rate, and class IA antiarrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia.
    Flavoxate: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Flecainide: (Severe) Class IC antiarrhythmic agents, such as flecainide, have proarrhythmic properties, and may have additive electrophysiologic effects with other Class I agents such as quinidine. In addition, quinidine should be considered contraindicated with flecainide. Quinidine and flecainide are associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; therefore, the effects on the QT interval may be increased during concurrent use of quinidine with flecainide or propafenone.
    Fluconazole: (Severe) The concomitant administration of fluconazole and quinidine is contraindicated. Fluconazole has been associated with QT prolongation and is contraindicated for use with other drugs that both prolong the QT interval and are CYP3A4 substrates, such as quinidine. Coadministration of fluconazole with quinidine may result in elevated plasma concentrations of quinidine, causing an increased risk for adverse events, such as QT prolongation.
    Fluoxetine: (Severe) Concurrent use of either quinidine or dextromethorphan; quinidine and fluoxetine is considered a contraindication. Quinidine and dextromethorphan; quinidine are contraindicated for use in patients taking drugs that prolong the QT interval and are metabolized by CYP2D6. Fluoxetine is a primary substrate of CYP2D6, and is associated with a risk of QT prolongation and torsade de pointes (TdP).
    Fluoxetine; Olanzapine: (Severe) Concurrent use of either quinidine or dextromethorphan; quinidine and fluoxetine is considered a contraindication. Quinidine and dextromethorphan; quinidine are contraindicated for use in patients taking drugs that prolong the QT interval and are metabolized by CYP2D6. Fluoxetine is a primary substrate of CYP2D6, and is associated with a risk of QT prolongation and torsade de pointes (TdP). (Major) Quinidine and dextromethorphan; quinidine cause dose-dependent QT prolongation. These drugs should be avoided in patients receiving drugs that may prolong the QT interval and are metabolized by CYP2D6, such as olanzapine. The manufacturer recommends an ECG in patients taking these drugs together.
    Fluphenazine: (Minor) Fluphenazine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Fluticasone; Salmeterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Fluticasone; Vilanterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Fluvoxamine: (Major) There may be an increased risk for QT prolongation, torsade de pointes (TdP), or elevated plasma concentrations of either quinidine or fluvoxamine during coadministration. Quinidine administration is associated with QT prolongation and TdP. QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. In addition, fluvoxamine is a moderate CYP3A4 inhibitor and the metabolism of CYP3A4 substrates such as quinidine may be reduced. In a small open-label study (n = 6), fluvoxamine 100 mg/day decreased the total oral clearance of quinidine by 29%. Conversely, quinidine is a CYP2D6 inhibitor and CYP2D6 is partially responsible for fluvoxamine metabolism, which may lead to elevated fluvoxamine concentrations.
    Formoterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Formoterol; Mometasone: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Fosamprenavir: (Major) Fosamprenavir can inhibit CYP3A4, an isoenzyme that is responsible for the metabolism of quinidine. Concurrent use should be avoided or approached with great caution due to the potential for serious toxicity. Quinidine doses may require adjustment if fosamprenavir is added or discontinued during quinidine therapy.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as quinidine. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Quinidine administration is also associated with QT prolongation and TdP. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Galantamine: (Moderate) A population pharmacokinetic analysis showed that the clearance of galantamine was decreased by 25% to 33% during coadministration of certain CYP2D6 inhibitors including quinidine. The CYP2D6 isoenzyme is partially involved in the metabolism of galantamine. The clinical relevance of this interaction is unknown; however, increased galantamine concentrations could potentially result in dose-related toxicity.
    Gefitinib: (Major) Monitor for an increased incidence of gefitinib-related adverse effects if gefitinib and quinidine are used concomitantly. Gefitinib is metabolized significantly by CYP3A4 and to a lesser extent by CYP2D6; quinidine is a strong CYP2D6 inhibitor. Coadministration may decrease the metabolism of gefitinib and increase gefitinib concentrations. While the manufacturer has provided no guidance regarding the use of gefitinib with CYP2D6 inhibitors, in patients with poor CYP2D6 metabolism, the mean exposure to gefitinib was 2-fold higher when compared to extensive metabolizers; the contribution of drugs that inhibit CYP2D6 on gefitinib exposure has not been evaluated.
    Gemifloxacin: (Major) According to the manufacturer, gemifloxacin should be avoided in patients receiving Class IA antiarrhythmics (such as disopyramide, quinidine and procainamide). Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5-10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
    Gemtuzumab Ozogamicin: (Major) Use gemtuzumab ozogamicin and quinidine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Quinidine administration is also associated with QT prolongation and TdP.
    Ginger, Zingiber officinale: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of antiarrhythmics, however, no clinical data are available.
    Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and quinidine as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and quinidine are both substrates and inhibitors of P-glycoprotein (P-gp). (Moderate) Caution is advised with the coadministration of pibrentasvir and quinidine as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Both pibrentasvir and quinidine are substrates and inhibitors of P-glycoprotein (P-gp).
    Glycerol Phenylbutyrate: (Moderate) Concomitant use of glycerol phenylbutyrate and quinidine may result in decreased exposure of quinidine. Quinidine is a CYP3A substrate; glycerol phenylbutyrate is a weak inducer of CYP3A4. Monitor for decreased efficacy of quinidine during coadministration.
    Glycopyrrolate: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Glycopyrrolate; Formoterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Goserelin: (Major) Quinidine should be used cautiously and with close monitoring with goserelin. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Granisetron: (Major) Granisetron should be used cautiously and with close monitoring with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
    Grapefruit juice: (Major) Grapefruit juice contains an unknown compound that inhibits cytochrome P-450 3A4 isozymes in the gut wall. Coadministration of quinidine with grapefruit juice to healthy volunteers delayed quinidine absorption and inhibited the conversion of quinidine to the major metabolite. Although the clinical significance of the interaction is unknown, concomitant administration with grapefruit juice should be avoided.
    Guaifenesin; Hydrocodone: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Halofantrine: (Severe) Halofantrine is considered to have a well-established risk for QT prolongation and torsades de pointes. Halofantrine should be avoided in patients receiving drugs which may induce QT prolongation; these drugs include class IA antiarrhythmics.
    Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Haloperidol: (Severe) Quinidine should be considered contraindicated with haloperidol. QT prolongation and torsade de pointes (TdP) have been observed during both haloperidol and quinidine treatment. Excessive doses (particularly in the overdose setting) of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval; however, quinidine is contraindicated for use with drugs that are CYP2D6 substrates that prolong the QT interval. Pretreatment with quinidine caused peak haloperidol serum concentrations and haloperidol AUC to increase.
    Halothane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Hawthorn, Crataegus laevigata: (Major) It would be prudent to avoid use of Hawthorn, Crataegus laevigata (also known as C. oxycantha) during therapy with antiarrhythmic agents whenever possible, due to the possibility of additive effects on cardiac conduction and the known effects of antiarrhythmic drugs on the heart. Following hawthorn administration to guinea pigs, the cardiac action potential duration was increased and the refractory period was prolonged. Hawthorn may also lower peripheral vascular resistance. Hawthorn could potentially interact with antiarrhythmics that have similar actions to hawthorn on cardiac electrophysiology. Use extreme caution with class IA antiarrhythmics, due to the potential for QT prolongation. However, no human clinical data are available. Patients should be advised to only use hawthorn with these antiarrhythmic agents after discussion with their prescriber. If co-use is advised, patients should receive periodic blood pressure and heart rate monitoring.
    Homatropine; Hydrocodone: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics. (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydantoins: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Inducers of CYP3A4, such as fosphenytoin or phenytoin, may increase hepatic elimination of quinidine and decrease its serum concentrations. Quinidine concentrations should be monitored closely after the anticonvulsant is added to the treatment regimen. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Hydralazine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Major) Patients receiving combined therapy with quinidine and metoprolol should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used with metoprolol. Quinidine is also a known inhibitor of CYP2D6 and metoprolol is a CYP2D6 substrate. In healthy subjects with CYP2D6 extensive metabolizer (normal metabolizer) phenotype, coadministration of quinidine 100 mg and immediate release metoprolol 200 mg tripled the concentration of S-metoprolol and doubled the metoprolol elimination half-life. This interaction may be more pronounced in poor CYP2D6 metabolizers. Patients should be monitored for excess beta-blockade.
    Hydrochlorothiazide, HCTZ; Propranolol: (Major) Patients receiving combined therapy with quinidine and propranolol should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, such as propranolol. Quinidine is a known inhibitor of CYP2D6, and may additionally impair the hepatic clearance of propanolol (CYP2D6 substrate); patients should be monitored for excess beta-blockade.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Hydrocodone: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Ibuprofen: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Phenylephrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Potassium Guaiacolsulfonate: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinidine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and quinidine. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes (TdP) have been reported with the use of hydroxychloroquine. Quinidine administration is associated with QT prolongation and TdP.
    Hydroxyzine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include quinidine.
    Hyoscyamine: (Major) Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs.
    Ibuprofen; Oxycodone: (Moderate) Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone, which represents < 15% of the total administered dose. Potent inhibitors of CYP2D6, such as quinidine, may potentially increase the effects of oxycodone; however, such blockade has not been shown to be of clinical significance during oxycodone treatment. Clinicians should be aware of this possible interaction.
    Ibutilide: (Severe) Combined use of antiarrhythmic drugs can have additive, antagonistic, or synergistic electrophysiologic, pharmacodynamic, or toxic effects. Because of their potential to prolong refractoriness, Class IA antiarrhythmics (e.g., disopyramide, quinidine, and procainamide) and other Class III antiarrhythmics (e.g., amiodarone, dofetilide and sotalol) are not recommended for use concurrently or within 4 hours after an infusion of ibutilide. In general, combination therapy with Class III antiarrhythmics has been reported to increase the risk of proarrhythmias. The manufacturer reported that during clinical trials, Class IA or other Class III antiarrhythmics were not given for at least 5 half-lives prior to ibutilide infusion or 4 hours after ibutilide dosing. Before switching from ibutilide to dofetilide therapy, ibutilide should generally be withheld for at least three half-lives prior to initiating dofetilide.
    Idarubicin: (Major) Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) are associated with QT prolongation and torsades de pointes (TdP) and should be used cautiously with other drugs with a possible risk for QT prolongation and TdP including daunorubicin, doxorubicin, epirubicin, and idarubicin. Acute cardiotoxicity can occur during administration of anthracyclines; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Idelalisib: (Severe) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with quinidine, a CYP3A substrate, as quinidine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Iloperidone: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include iloperidone.
    Imatinib: (Major) Imatinib, STI-571 is a potent inhibitor of cytochrome P450 3A4 and may inhibit quinidine metabolism leading to increased concentrations and risk of adverse reactions.
    Imipramine: (Severe) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
    Indacaterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Indacaterol; Glycopyrrolate: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Indinavir: (Moderate) Concurrent administration of indinavir and quinidine caused indinavir AUC to increase by about 10%. There were no effects on quinidine pharmacokinetics.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with quinidine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Quinidine administration is also associated with QT prolongation and TdP.
    Isavuconazonium: (Moderate) Caution and therapeutic drug concentration monitoring, if available, are recommended during coadministration of quinidine with isavuconazonium. Quinidine is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Concurrent use may result in elevated quinidine plasma concentrations.
    Isoflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Inducers of CYP3A4 may increase hepatic elimination of quinidine. Rifampin is a potent inducer of this isoenzyme. Quinidine concentrations should be monitored closely after rifampin is added to the treatment regimen. No special precautions appear necessary if rifampin is begun several weeks before quinidine is added but quinidine doses may require adjustment if it is added or discontinued during quinidine therapy.
    Isoniazid, INH; Rifampin: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Inducers of CYP3A4 may increase hepatic elimination of quinidine. Rifampin is a potent inducer of this isoenzyme. Quinidine concentrations should be monitored closely after rifampin is added to the treatment regimen. No special precautions appear necessary if rifampin is begun several weeks before quinidine is added but quinidine doses may require adjustment if it is added or discontinued during quinidine therapy.
    Isradipine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Itraconazole: (Severe) Quinidine is contraindicated for use during and for 2 weeks after itraconazole therapy. Serious cardiovascular events including EKG changes (i.e., QT prolongation) and cardiac arrhythmias, including ventricular arrhythmias and torsade de pointes, cardiac arrest, and/or sudden death have occurred when these drugs were administered together. Reports have documented cases in which substantial elevations in serum quinidine concentrations occurred after the addition of itraconazole. Quinidine is a CYP3A4 substrate; itraconazole is a strong CYP3A4 inhibitor. Transient or permanent hearing loss has also been reported in elderly patients receiving quinidine in combination with itraconazole.
    Ivacaftor: (Minor) Use caution when administering ivacaftor and quinidine concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (P-gp). Coadministration of ivacaftor with CYP3A and P-gp substrates, such as quinidine, can increase quinidine exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Ixabepilone: (Minor) Quinidine is an inhibitor of and substrate for P-glycoprotein (Pgp). Ixabepilone is a mild inhibitor of and substrate for Pgp. Concomitant use of these agents may cause an increase in ixabepilone concentrations and/or an increase in quinidine concentrations. Caution is recommended if ixabepilone is coadministered with a Pgp inhibitor.
    Ketoconazole: (Severe) Ketoconazole inhibits the hepatic CYP3A4 isoenzyme; quinidine is metabolized by this isoenzyme. Coadministration results in increased quinidine serum concentrations, with potential to result in proarrhythmias. A single case report has documented substantial elevations in serum quinidine concentrations after the addition of ketoconazole. The patient was receiving other drugs concomitantly and it is unclear if drug-induced arrhythmias occurred. Until more data are available, ketoconazole should be considered contraindicated in patients receiving quinidine.
    Labetalol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like labetalol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary.
    Lanreotide: (Major) Monitor ECGs for QT prolongation and watch for an increase in quinidine-related adverse reactions if coadministration with lanreotide is necessary. Quinidine is a CYP3A4 substrate with a narrow therapeutic range. Limited published data available indicate that somatostatin analogs may decrease the metabolic clearance of CYP3A4 substrates, which may be due to the suppression of growth hormone; it cannot be excluded that lanreotide has this effect.
    Lanthanum Carbonate: (Major) The manufacturer recommends that oral compounds known to interact with antacids should not be taken within 2 hours of dosing with lanthanum carbonate, including quinidine. If these agents are used concomitantly, space the dosing intervals appropriately; monitoring of serum concentrations and clinical condition may be prudent.
    Lapatinib: (Major) Lapatinib is a CYP3A4 inhibitor at clinically relevant concentrations in vitro. Also, lapatinib is a substrate and inhibitor of the efflux transporter P-glycoprotein (P-gp, ABCB1). Quinidine is a CYP3A4 substrate and a P-gp inhibitor and substrate. If lapatinib will be coadministered with a CYP3A4 and P-gp substrate, such as quinidine, exercise caution and consider dose reduction of quinidine. Concurrent administration of lapatinib with a P-gp inhibitor, such as quinidine, is likely to cause elevated serum lapatinib concentrations, and caution is recommended. In addition to pharmacokinetic interactions, both lapatinib and quinidine can prolong the QT interval; therefore coadministration may further increase the risk for QT prolongation.
    Ledipasvir; Sofosbuvir: (Moderate) Caution and close monitoring of adverse reactions is advised with concomitant administration of quinidine and ledipasvir; sofosbuvir. Both ledipasvir and quinidine are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp); sofosbuvir is a P-gp substrate. Taking these drugs together may increase plasma concentrations of all three drugs. According to the manufacturer, no dosage adjustments are required when ledipasvir; sofosbuvir is administered concurrently with P-gp inhibitors.
    Lenvatinib: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with quinidine include lenvatinib. QT prolongation was reported in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) in a double-blind, randomized, placebo-controlled clinical trial after receiving lenvatinib daily at the recommended dose; the QT/QTc interval was not prolonged, however, after a single 32 mg dose (1.3 times the recommended daily dose) in healthy subjects.
    Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of quinidine; monitor for potential reduction in efficacy. Quinidine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of quinidine; monitor for potential reduction in efficacy. Quinidine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Leuprolide: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Quinidine is associated with QT prolongation and torsades de pointes (TdP).
    Leuprolide; Norethindrone: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Quinidine is associated with QT prolongation and torsades de pointes (TdP).
    Levalbuterol: (Minor) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Levobunolol: (Moderate) The concomitant use of ophthalmic beta-blockers, like levobunolol, in patients receiving antiarrhythmics which slow AV conduction (quinidine) may result in additive negative dromotropic effects, especially in patients with pre-existing cardiac disease or left ventricular dysfunction. Since ophthalmic levobunolol may be systemically absorbed, there is potential for enhanced hypotensive effects when it is given with beta-blockers.
    Levofloxacin: (Major) Levofloxacin should be avoided in combination with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Rare cases of TdP have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. According to the manufacturer, levofloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval.
    Levomethadyl: (Severe) Levomethadyl is contraindicated in combination with other agents that may prolong the QT interval, such as Class IA antiarrhythmics.
    Lidocaine: (Major) Avoid concurrent use of quinidine with other antiarrhythmics with Class I activities, such as lidocaine. Concurrent use may result in additive or antagonistic cardiac effects and additive toxicity.
    Lithium: (Major) Lithium should be used cautiously and with close monitoring with quinidine. Lithium has been associated with QT prolongation. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP).
    Lomefloxacin: (Severe) Lomefloxacin has been associated with QT prolongation and infrequent cases of arrhythmia. Lomefloxacin should be avoided in patients receiving Class IA Antiarrhythmics.
    Long-acting beta-agonists: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Loop diuretics: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Loperamide: (Major) Concurrent administration of loperamide and quinidine may increase the risk for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS events. Quinidine and high doses of loperamide are associated with QT prolongation and torsades de pointes (TdP). Additionally, loperamide is a substrate for CYP2D6 and the drug transporter P-glycoprotein (P-gp); quinidine is an inhibitor of both CYP2D6 and P-gp. Although the exact mechanism has not been determined, it is postulated that the P-glycoprotein (P-gp) pump acts to limit the oral absorption of drugs from the gastrointestinal tract as well as limit the concentration of drug in the central nervous system (CNS). In-vivo, single dose pharmacokinetic studies suggest that oral coadministration of loperamide (16 mg) and quinidine or ritonavir (600 mg), known P-gp inhibitors, lead to a 2 to 3 fold increase in loperamide plasma concentrations. Also, in the presence of a P-gp inhibitor, elevated CNS concentrations of loperamide lead to subsequent respiratory depression. The mechanism appears to be an effect on P-gp efflux transport across the blood-brain-barrier. Normally loperamide is efficiently removed from the CNS, however coadministration of a P-gp inhibitor hinders its transport out of the CNS. Monitor for depressed respiratory ventilation and adverse cardiac effects if these drugs are to be coadministered.
    Loperamide; Simethicone: (Major) Concurrent administration of loperamide and quinidine may increase the risk for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS events. Quinidine and high doses of loperamide are associated with QT prolongation and torsades de pointes (TdP). Additionally, loperamide is a substrate for CYP2D6 and the drug transporter P-glycoprotein (P-gp); quinidine is an inhibitor of both CYP2D6 and P-gp. Although the exact mechanism has not been determined, it is postulated that the P-glycoprotein (P-gp) pump acts to limit the oral absorption of drugs from the gastrointestinal tract as well as limit the concentration of drug in the central nervous system (CNS). In-vivo, single dose pharmacokinetic studies suggest that oral coadministration of loperamide (16 mg) and quinidine or ritonavir (600 mg), known P-gp inhibitors, lead to a 2 to 3 fold increase in loperamide plasma concentrations. Also, in the presence of a P-gp inhibitor, elevated CNS concentrations of loperamide lead to subsequent respiratory depression. The mechanism appears to be an effect on P-gp efflux transport across the blood-brain-barrier. Normally loperamide is efficiently removed from the CNS, however coadministration of a P-gp inhibitor hinders its transport out of the CNS. Monitor for depressed respiratory ventilation and adverse cardiac effects if these drugs are to be coadministered.
    Lopinavir; Ritonavir: (Severe) The use of ritonavir is considered contraindicated with quinidine due to the potential to induce quinidine toxicity. The manufacturer of dextromethorphan; quinidine recommends an initial ECG evaluation (baseline and 3 to 4 hours post-dose) in patients taking dextromethorphan; quinidine in combination with moderate or strong CYP3A4 inhibitors such as ritonavir. Quinidine causes a dose-dependent QT prolongation and is metabolized via CYP3A4. Concurrent use of dextromethorphan; quinidine with moderate or strong CYP3A4 inhibitors may result in elevated quinidine plasma concentrations with the potential for enhanced QT-prolonging effects. In addition, lopinavir; ritonavir is associated with a possible risk for QT prolongation; additive effects on QT prolongation are possible. (Major) Coadministration of HIV treatment doses of ritonavir and quinidine is contraindicated due to the potential for serious or life-threatening reactions, such as cardiac arrhythmias. Cautious consideration may be given to administering quinidine with boosting doses of ritonavir. Ritonavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as quinidine, should be expected with concurrent use. In addition, ritonavir is associated with QT prolongation and quinidine is associated with QT prolongation and torsade de pointes (TdP); concomitant use increases the risk of QT prolongation.
    Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may alter the therapeutic effects of quinidine. Use these agents together with caution; monitor quinidine concentrations and adjust the dosage as needed to attain antiarrhythmic efficacy endpoints. Quinidine is a substrate of CYP3A and the P-glycoprotein (P-gp) efflux transporter. Lumacaftor is a strong CYP3A inducer; in vitro data also suggest lumacaftor; ivacaftor may induce and/or inhibit P-gp. Although induction of quinidine metabolism through the CYP3A pathway may lead to decreased drug efficacy, the net effect of lumacaftor; ivacaftor on P-gp transport is not clear. Monitor the patient for decreased antiarrhythmic efficacy or increased or prolonged therapeutic effects and adverse events.
    Lumacaftor; Ivacaftor: (Minor) Use caution when administering ivacaftor and quinidine concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (P-gp). Coadministration of ivacaftor with CYP3A and P-gp substrates, such as quinidine, can increase quinidine exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Maprotiline: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include maprotiline.
    Maraviroc: (Moderate) Use caution and careful monitoring with the coadministration of maraviroc and quinidine as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); quinidine is an inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Mefloquine: (Severe) The use of mefloquine is contraindicated in patients receiving quinidine or quinidine containing drugs, including dextromethorphan; quinidine. Quinidine is a Class IA antiarrhythmic agent and is associated with a well-established risk of QT prolongation and torsade de pointes (TdP); using these drugs together could increase the risk of TdP.
    Memantine: (Major) Cationic drugs that are eliminated by renal tubular secretion, such as quinidine, may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or quinidine is recommended to assess for needed dosage adjustments. In selected individuals, quinidine serum concentration monitoring may be appropriate.
    Mepenzolate: (Moderate) The reduction in GI motility produced by mepenzolate may increase the absorption of some drugs, including quinidine. Increased monitoring is advised in patients receiving this combination.
    Meperidine; Promethazine: (Severe) Quinidine (including dextromethorphan; quinidine) administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as promethazine, as the effects on the QT interval may be increased during concurrent use of these agents.
    Mephobarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Mesoridazine: (Severe) Mesoridazine has been associated with orthostatic hypotension and a risk of QT prolongation and/or torsades de pointes, particularly at higher doses and is generally contraindicated in combination with other agents that prolong the QT interval including class IA antiarrhythmics.
    Metaproterenol: (Minor) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Methadone: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include methadone.
    Methamphetamine: (Minor) Quinidine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering quinidine with other CYP2D6 substrates, such as methamphetamine, that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions.
    Methazolamide: (Major) Methazolamide can decrease the urinary excretion and enhance the clinical effects of quinidine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized drug available for renal tubular reabsorption into the systemic circulation.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs.
    Methohexital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Methscopolamine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Metoprolol: (Major) Patients receiving combined therapy with quinidine and metoprolol should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used with metoprolol. Quinidine is also a known inhibitor of CYP2D6 and metoprolol is a CYP2D6 substrate. In healthy subjects with CYP2D6 extensive metabolizer (normal metabolizer) phenotype, coadministration of quinidine 100 mg and immediate release metoprolol 200 mg tripled the concentration of S-metoprolol and doubled the metoprolol elimination half-life. This interaction may be more pronounced in poor CYP2D6 metabolizers. Patients should be monitored for excess beta-blockade.
    Metreleptin: (Moderate) Upon initiation or discontinuation of metreleptin in a patient receiving quinidine, drug concentration monitoring should be performed and the quinidine dosage adjusted as needed. Leptin is a cytokine and may have the potential to alter the formation of cytochrome P450 (CYP450) enzymes. The effect of metreleptin on CYP450 enzymes may be clinically relevant for CYP450 substrates with a narrow therapeutic index, such as quinidine.
    Metronidazole: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include quinidine, (including dextromethorphan; quinidine),
    Mexiletine: (Moderate) Quinidine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering quinidine with other CYP2D6 substrates, such as mexiletine, that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions.
    Midodrine: (Minor) Although the exact mechanism is uncertain, midodrine may be excreted by the same base-secreting pathway of the kidneys responsible for secretion of other basic drugs like quinidine. By this pathway, midodrine may potentially interact with quinidine; however, no drug interactions of this kind have been reported.
    Midostaurin: (Major) The concomitant use of midostaurin and quinidine may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Quinidine is a Class IA antiarrhythmic agent; it is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Quinidine should be discontinued if significant QT prolongation or TdP occur during therapy.
    Mifepristone, RU-486: (Severe) Mifepristone, RU-486 inhibits CYP3A4 in vitro. Coadministration of mifepristone may lead to an increase in serum concentrations of drugs that are CYP3A4 substrates and that have a narrow therapeutic index. Drugs metabolized by CYP3A4 with narrow therapeutic ranges such as quinidine, are contraindicated for use with when mifepristone when the drug is used chronically, such as in the treatment of Cushing's syndrome. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. Discontinuation or dose reduction of other potentially interacting drugs may be necessary when mifepristone is used in the treatment of Cushing's syndrome.
    Minoxidil: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Mirtazapine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and quinidine. Coadminister with caution. Quinidine administration is associated with QT prolongation and TdP. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation.
    Mitotane: (Major) Use caution if mitotane and quinidine are used concomitantly, and monitor for decreased efficacy of quinidine and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and quinidine is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of quinidine. Quinidine concentrations should be monitored closely after mitotane is added to the treatment regimen.
    Mivacurium: (Major) Quinidine can potentiate the effects of neuromuscular blockers. Neostigmine will not reverse these effects. Respiratory support may be necessary if quinidine is given concomitantly or shortly after a neuromuscular blocking agent.
    Moricizine: (Severe) The effects of concomitant administration of Class IC antiarrhythmic agents with other antiarrhythmics can be synergistic, additive, or antagonistic, and adverse cardiac effects can be additive. Based on Class IC drug pharmacology, moricizine may have additive sodium channel blockade effects with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Additive Class I electrophysiologic effects can increase the risk for proarrhythmias. Although moricizine primarily is associated with Class IB and IC actions, it also is associated with quinidine-like (i.e, Class IA) features.
    Morphine: (Moderate) Morphine is a substrate for P-glycoprotein (P-gp), and quinidine is a P-gp substrate and inhibitor. Coadministration may lead to increased systemic exposure of morphine and morphine-related side effects.
    Morphine; Naltrexone: (Moderate) Morphine is a substrate for P-glycoprotein (P-gp), and quinidine is a P-gp substrate and inhibitor. Coadministration may lead to increased systemic exposure of morphine and morphine-related side effects.
    Moxifloxacin: (Major) Moxifloxacin should be avoided in combination with Class IA antiarrhythmics (disopyramide, quinidine, and procainamide). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Prolongation of the QT interval has been reported with administration of moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including torsade de pointes (TdP), usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. According to the manufacturer, moxifloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval.
    Nadolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like nadolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary.
    Nebivolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with nebivolol, a beta-blocker. Quinidine is a known inhibitor of CYP2D6 and nebivolol is metabolized by CYP2D6. Quinidine could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition. Patients should be monitored for excess beta-blockade. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary.
    Nebivolol; Valsartan: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with nebivolol, a beta-blocker. Quinidine is a known inhibitor of CYP2D6 and nebivolol is metabolized by CYP2D6. Quinidine could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition. Patients should be monitored for excess beta-blockade. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary.
    Nefazodone: (Moderate) Quinidine causes a dose-dependent QT prolongation and is metabolized via CYP3A4. Concurrent use of quinidine with moderate CYP3A4 inhibitors, such as nefazodone, may result in elevated quinidine plasma concentrations with the potential for enhanced QT-prolonging effects.
    Nelfinavir: (Severe) Coadministration of quinidine and nelfinavir is contraindicated. Nelfinavir inhibits the CYP3A4 metabolism of quinidine; concurrent use increases the potential for serious and/or life-threatening cardiac arrhythmias.
    Netupitant; Palonosetron: (Moderate) Coadminister with caution. Palonosetron is metabolized by CYP2D6, and quinidine is an inhibitor of this isoenzyme. Coadministration may result in elevated plasma concentrations of palonosetron, causing ain increased risk for serotonin-related adverse events.
    Neuromuscular blockers: (Major) Quinidine can potentiate the effects of neuromuscular blockers. Neostigmine will not reverse these effects. Respiratory support may be necessary if quinidine is given concomitantly or shortly after a neuromuscular blocking agent.
    Nevirapine: (Moderate) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, such as quinidine, may require dosage adjustments as the concentration may be decreased.
    Nicardipine: (Moderate) Quinidine concentrations decrease by 20 to 40% when nicardipine is added and rise after nicardipine is withdrawn. Although this appears to be an idiosyncratic reaction, quinidine doses may need to be adjusted when nicardipine is added or withdrawn. Careful monitoring of serum quinidine concentrations is prudent following the addition or discontinuation of nicardipine.
    Nifedipine: (Moderate) Nifedipine has been reported to rarely decrease quinidine serum concentrations. Quinidine concentrations may decrease by 20% to 40% when nifedipine is added, and potentially increase after nifedipine is withdrawn. There have also been reports of no significant change in quinidine concentrations or effect. In addition, both drugs can cause hypotension, and these effects can be additive. Careful monitoring of serum quinidine concentrations is prudent following the addition or discontinuation of nifedipine, with dose adjustment as clinically warranted. Monitor heart rate, blood pressure, and cardiac response.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib with other agents that prolong the QT interval such as quinidine. Additionally, nilotinib is a moderate CYP3A4 inhibitor and P-glycoprotein (P-gp) inhibitor and quinidine is a CYP3A4 and P-gp substrate with a narrow therapeutic range; administering these drugs together may result in increased quinidine exposure. If the use of quinidine is required, hold nilotinib therapy. If the use of both nilotinib and quinidine cannot be avoided, a quinidine dose reduction may be necessary; close monitoring of the QT interval is recommended.
    Nintedanib: (Moderate) Quinidine is a moderate inhibitor of P-glycoprotein (P-gp) and nintedanib is a P-gp substrate. Coadministration may increase the concentration and clinical effect of nintedanib. If concomitant use of quinidine and nintedanib is necessary, closely monitor for increased nintedanib side effects including gastrointestinal toxicity, elevated liver enzymes, and hypertension. A dose reduction, interruption of therapy, or discontinuation of therapy may be necessary.
    Nisoldipine: (Moderate) Quinidine may decrease the bioavailability of nisoldipine by 26% without affecting the peak concentration. Monitoring serum quinidine concentrations is prudent following the addition or discontinuation of nisoldipine.
    Nitroglycerin: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as quinidine.Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with quinidine.
    Nitroprusside: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Norfloxacin: (Major) Class IA antiarrhythmics (disopyramide, procainamide, quinidine) should be used cautiously with norfloxacin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Quinolones have been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, torsade de pointes has been reported during post-marketing surveillance of norfloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Nortriptyline: (Severe) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
    Octreotide: (Major) Limited data indicate that somatostatin analogs may inhibit the clearance of drugs metabolized by CYP isoenzymes; this may be due to the suppression of growth hormones. Coadminister octreotide cautiously with drugs that have a narrow therapeutic index and are metabolized by CYP3A4, such as quinidine, as octreotide may inhibit drug metabolism. In addition, until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval, such as quinidine. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ofloxacin: (Major) Class IA antiarrhythmics (such as disopyramide, quinidine, and procainamide) should be used cautiously and with close monitoring with ofloxacin. Class IA antiarrhythmics (such as disopyramide, quinidine, and procainamide) are associated with QT prolongation and torsades de pointes (TdP). Some quinolones, including ofloxacin, have been associated with QT prolongation and infrequent cases of arrhythmia. Post-marketing surveillance for ofloxacin has identified very rare cases of torsades de pointes (TdP).
    Olanzapine: (Major) Quinidine and dextromethorphan; quinidine cause dose-dependent QT prolongation. These drugs should be avoided in patients receiving drugs that may prolong the QT interval and are metabolized by CYP2D6, such as olanzapine. The manufacturer recommends an ECG in patients taking these drugs together.
    Olodaterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Ombitasvir; Paritaprevir; Ritonavir: (Severe) The manufacturer of ombitasvir; paritaprevir; ritonavir recommends caution and therapeutic drug monitoring (when available) if administered concurrently with quinidine. However, since one of the components of the 3-drug combination is ritonavir, use of these drugs together is contraindicated. Both ritonavir and quinidine are associated with QT prolongation; concomitant use increases the risk for developing Torsade de Pointes (TdP). In addition, ritonavir is a potent CYP3A4 inhibitor, an enzyme partially responsible for the metabolism of quinidine. If administered together, serum concentration of quinidine may increase. (Major) Coadministration of HIV treatment doses of ritonavir and quinidine is contraindicated due to the potential for serious or life-threatening reactions, such as cardiac arrhythmias. Cautious consideration may be given to administering quinidine with boosting doses of ritonavir. Ritonavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as quinidine, should be expected with concurrent use. In addition, ritonavir is associated with QT prolongation and quinidine is associated with QT prolongation and torsade de pointes (TdP); concomitant use increases the risk of QT prolongation.
    Ondansetron: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include ondansetron.
    Oritavancin: (Moderate) Quinidine is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of quinidine may be reduced if these drugs are administered concurrently. Quinidine concentrations should be monitored closely after oritavancin is added to the treatment regimen. No special precautions appear necessary if oritavancin is begun several weeks before quinidine is added but quinidine doses may require adjustment if oritavancin is added or discontinued during quinidine therapy.
    Osimertinib: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of quinidine with osimertinib is necessary; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Quinidine administration is also associated with QT prolongation and torsade de pointes (TdP).
    Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of quinidine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Oxcarbazepine: (Moderate) Quinidine is a substrate of the CYP3A4 isoenzyme. Inducers of CYP3A4 such as oxcarbazepine may increase hepatic elimination of quinidine with the potential for reduced efficacy of quinidine.
    Oxybutynin: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Oxycodone: (Moderate) Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone, which represents < 15% of the total administered dose. Potent inhibitors of CYP2D6, such as quinidine, may potentially increase the effects of oxycodone; however, such blockade has not been shown to be of clinical significance during oxycodone treatment. Clinicians should be aware of this possible interaction.
    Palbociclib: (Moderate) Monitor for an increase in quinidine-related adverse reactions if coadministration with palbociclib is necessary. A quinidine dose reduction may be necessary. Palbociclib is a weak time-dependent inhibitor of CYP3A and quinidine is a sensitive CYP3A4 substrate with a narrow therapeutic index.
    Paliperidone: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include paliperidone.
    Palonosetron: (Moderate) Coadminister with caution. Palonosetron is metabolized by CYP2D6, and quinidine is an inhibitor of this isoenzyme. Coadministration may result in elevated plasma concentrations of palonosetron, causing ain increased risk for serotonin-related adverse events.
    Pancuronium: (Major) Quinidine can potentiate the effects of neuromuscular blockers. Neostigmine will not reverse these effects. Respiratory support may be necessary if quinidine is given concomitantly or shortly after a neuromuscular blocking agent.
    Panobinostat: (Severe) Because of the potential for torsade de pointes, avoid the use of quinidine or dextromethorphan; quinidine with panobinostat. Panobinostat is a CYP2D6 inhibitor and quinidine is a CYP2D6 substrate. When a single 60-mg dose of dextromethorphan was administered after 3 doses of panobinostat (20 mg given on days 3, 5, and 8), the CYP2D6 substrate Cmax increased by 20% to 200% and the AUC value increased by 20% to 130% in 14 patients with advanced cancer; exposure was highly variable (coefficient of variance > 150%).
    Paroxetine: (Moderate) Quinidine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering quinidine with CYP2D6 substrates, including paroxetine.
    Pasireotide: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Cautious use of pasireotide and drugs that prolong the QT interval is needed, as coadministration may have additive effects on the prolongation of the QT interval.
    Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and quinidine (including dextromethorphan; quinidine have been reported to prolong the QT interval. If pazopanib and quinidine must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4 and a substrate for P-glycoprotein (P-gp). Quinidine is a substrate for CYP3A4 and an inhibitor of P-gp. Concurrent administration of quinidine and pazopanib may result in increased pazopanib and/or quinidine concentrations. Use caution when concurrent administration is necessary.
    Penbutolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like penbutolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary.
    Pentamidine: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include systemic pentamidine.
    Pentobarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Perindopril; Amlodipine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Perphenazine: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include perphenazine.
    Perphenazine; Amitriptyline: (Severe) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6. (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include perphenazine.
    Phenobarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Phenoxybenzamine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Phentolamine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Phenylephrine; Promethazine: (Severe) Quinidine (including dextromethorphan; quinidine) administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as promethazine, as the effects on the QT interval may be increased during concurrent use of these agents.
    Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP).
    Pimozide: (Severe) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of quinidine with pimozide is contraindicated.
    Pindolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like pindolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary.
    Pirbuterol: (Minor) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Polymyxins: (Moderate) Quinidine can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
    Posaconazole: (Severe) The concurrent use of posaconazole and quinidine (or products containing quinidine such as dextromethorphan; quinidine) is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of quinidine. Further, both posaconazole and quinidine are inhibitors and substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of either drug. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and quinidine. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as quinidine.
    Potassium Citrate: (Major) Alkalinizing agents such as potassium citrate can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible.
    Potassium Salts: (Major) Alkalinizing agents such as potassium citrate can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible.
    Pramipexole: (Moderate) Population pharmacokinetics suggest that coadministration of drugs secreted by the cationic transport system, such as quinidine, decreases the clearance of pramipexole by about 20 percent. An increase in pramipexole levels secondary to the use of quinidine, may result in an increased risk of somnolence, postural hypotension, or other clinically significant events.
    Prazosin: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include quinidine.
    Primidone: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Procainamide: (Major) According to the manufacturer of procainamide, use with other Class 1A agents, such as quinidine, is contraindicated; however, the manufacturer also states such use may be reserved for patients with serious arrhythmias unresponsive to a single drug if under close observation. Quinidine should only be used with extreme caution with procainamide, due to the potential for QT prolongation and similar effects on the cardiac action potential. Coadministration of quinidine may increase serum concentrations of procainamide, possibly by competing for pathways of renal clearance.
    Prochlorperazine: (Minor) Prochlorperazine is associated with a possible risk for QT prolongation.] Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with prochlorperazine include: quinidine (including dextromethorphan; quinidine),
    Promethazine: (Severe) Quinidine (including dextromethorphan; quinidine) administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as promethazine, as the effects on the QT interval may be increased during concurrent use of these agents.
    Propafenone: (Severe) Class IA antiarrhythmics are associated with QT prolongation and ventricular arrhythmias including torsades de pointes (TdP), and concurrent use with propafenone is not recommended by the manufacturer. Before switching from another antiarrhythmic drug to propafenone therapy, Class IA antiarrhythmics and Class III antiarrhythmics generally should be withheld for at least five half-lives prior to initiating propafenone. Quinidine is a CYP2D6 inhibitor with potential to inhibit propafenone metabolism, and coadministration is contraindicated. Small doses of quinidine completely inhibit the CYP2D6 hydroxylation metabolic pathway, with the result that extensive metabolizers become poor metabolizers. Coadministration with quinidine markedly decreases propafenone clearance in extensive metabolizers, and increases plasma propafenone concentrations by 2 to 3-fold at steady-state. Steady-state plasma concentrations increased more than 2-fold for propafenone, and decreased 50% for 5-OH-propafenone.
    Propantheline: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Propoxyphene: (Moderate) Propoxyphene is a substrate and an inhibitor of CYP2D6. Increased serum concentrations of propoxyphene would be expected from concurrent use of a CYP2D6 inhibitor like quinidine.
    Propranolol: (Major) Patients receiving combined therapy with quinidine and propranolol should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, such as propranolol. Quinidine is a known inhibitor of CYP2D6, and may additionally impair the hepatic clearance of propanolol (CYP2D6 substrate); patients should be monitored for excess beta-blockade.
    Protriptyline: (Major) TCAs should be used cautiously and with close monitoring with cardiac drugs known to prolong the QT interval such as quinidine. The need to coadminister TCAs with protriptyline should be done with a careful assessment of risk versus benefit; consider alternative therapy to the TCA. The dosage of protriptyline may need to be reduced if these drugs are coadministered. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). This pharmacologic property of the TCAs is of concern in patients with significant cardiac histories or treated with selected cardiac agents. Cases of long QT syndrome and torsade de pointes tachycardia have been described with TCA use, but rarely occur when TCAs are used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of the combined therapies. Certain cardiac drugs prolong repolarization at therapeutic or elevated plasma concentrations, and the addition of other drugs may increase the risk of QT prolongation and torsades de pointes via pharmacokinetic or pharmacodynamic interactions.
    Pyridostigmine: (Moderate) Quinidine can potentiate the effects of depolarizing and nondepolarizing neuromuscular blockers. Recurrent paralysis may occur if quinidine injection is administered during recovery from use of nondepolarizing muscle relaxants. Consider the possible effect from quinidine when administering anticholinesterase agents such as pyridostigmine to antagonize neuromuscular blockade induced by nondepolarizing muscle relaxants
    Quetiapine: (Major) Class IA antiarrhythmics (disopyramide, procainamide, quinidine) should be used cautiously with quetiapine. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval.
    Quinine: (Severe) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP3A4. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP3A4 substrates, such as quinidine. Coadministration may result in an elevated quinidine plasma concentration, causing an increased risk for adverse events, such as QT prolongation. Further, both quinine and quinidine are cinchona alkaloids; the possibility of cinchonism is increased if these drugs are administered concomitantly
    Ranolazine: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include ranolazine.
    Rapacuronium: (Major) Quinidine can potentiate the effects of neuromuscular blockers. Neostigmine will not reverse these effects. Respiratory support may be necessary if quinidine is given concomitantly or shortly after a neuromuscular blocking agent.
    Regadenoson: (Major) Regadenoson should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP) and regadenoson has been associated with QT prolongation.
    Reserpine: (Moderate) Reserpine-induced arrhythmias are more likely to occur during concomitant administration of quinidine. Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Ribociclib: (Major) Avoid coadministration of ribociclib with quinidine due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of quinidine may be increased resulting in an increase in quinidine-related adverse reactions. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Quinidine has also been associated with QT prolongation and torsade de pointes (TdP). Concomitant use may increase the risk for QT prolongation. Ribociclib is also a moderate CYP3A4 inhibitor and quinidine is a CYP3A4 substrate with a narrow therapeutic window.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with quinidine due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of quinidine may be increased resulting in an increase in quinidine-related adverse reactions. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Quinidine has also been associated with QT prolongation and torsade de pointes (TdP). Concomitant use may increase the risk for QT prolongation. Ribociclib is also a moderate CYP3A4 inhibitor and quinidine is a CYP3A4 substrate with a narrow therapeutic window.
    Rifabutin: (Moderate) Rifabutin is an inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of quinidine.
    Rifampin: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Inducers of CYP3A4 may increase hepatic elimination of quinidine. Rifampin is a potent inducer of this isoenzyme. Quinidine concentrations should be monitored closely after rifampin is added to the treatment regimen. No special precautions appear necessary if rifampin is begun several weeks before quinidine is added but quinidine doses may require adjustment if it is added or discontinued during quinidine therapy.
    Rifapentine: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Inducers of CYP3A4, such as rifapentine, may increase hepatic elimination of quinidine and decrease its serum concentrations. Quinidine concentrations should be monitored closely after rifapentine is added to the treatment regimen. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Rifaximin: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and quinidine, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
    Rilpivirine: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
    Risperidone: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include risperidone.
    Ritonavir: (Major) Coadministration of HIV treatment doses of ritonavir and quinidine is contraindicated due to the potential for serious or life-threatening reactions, such as cardiac arrhythmias. Cautious consideration may be given to administering quinidine with boosting doses of ritonavir. Ritonavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as quinidine, should be expected with concurrent use. In addition, ritonavir is associated with QT prolongation and quinidine is associated with QT prolongation and torsade de pointes (TdP); concomitant use increases the risk of QT prolongation.
    Rivaroxaban: (Minor) Coadministration of rivaroxaban and quinidine may result in increases in rivaroxaban exposure and may increase bleeding risk. Quinidine is an inhibitor of P-glycoprotein (P-gp), and rivaroxaban is a substrate of P-gp. If these drugs are administered concurrently, monitor the patient for signs and symptoms of bleeding.
    Rocuronium: (Major) Quinidine can potentiate the effects of neuromuscular blockers. Neostigmine will not reverse these effects. Respiratory support may be necessary if quinidine is given concomitantly or shortly after a neuromuscular blocking agent.
    Rolapitant: (Moderate) Use caution if quinidine and rolapitant are used concurrently, and monitor for quinidine-related adverse effects, including QT prolongation. Quinidine is a P-glycoprotein (P-gp) substrate, where an increase in exposure may significantly increase adverse effects; rolapitant is a P-gp inhibitor. When rolapitant was administered with another P-gp substrate, digoxin, the day 1 Cmax and AUC were increased by 70% and 30%, respectively; the Cmax and AUC on day 8 were not studied.
    Romidepsin: (Major) Romidepsin is a substrate for P-glycoprotein (P-gp). Quinidine is an inhibitor of P-gp. Concurrent administration of romidepsin with an inhibitor of P-gp may cause an increase in systemic romidepsin concentrations. Use caution when concomitant administration of these agents is necessary. In addition, romidepsin has been reported to prolong the QT interval. Quinidine also prolongs the QT interval. If romidepsin and quinidine must be coadministered, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.
    Rufinamide: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as quinidine, may occur during concurrent use with rufinamide.
    Salmeterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Sapropterin: (Moderate) Caution is advised with the concomitant use of sapropterin and quinidine as coadministration may result in increased systemic exposure of quinidine. Quinidine is a substrate for the drug transporter P-glycoprotein (P-gp); in vitro data show that sapropterin may inhibit P-gp. If these drugs are used together, closely monitor for increased side effects of quinidine.
    Saquinavir: (Severe) Concurrent use of quinidine or quinidine-containing products (e.g., dextromethorphan; quinidine) and saquinavir boosted with ritonavir is contraindicated due to the risk of life threatening cardiac arrhythmias such as torsade de pointes (TdP). Saquinavir boosted with ritonavir is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of quinidine. Concurrent administration may result in large increases in quinidine serum concentrations, which could cause fatal cardiac arrhythmias. Additionally, saquinavir boosted with ritonavir causes dose-dependent QT and PR prolongation; avoid use with other drugs that may prolong the QT or PR interval, such quinidine.
    Scopolamine: (Moderate) The reduction in GI motility produced by scopolamine may increase the absorption of some drugs, including quinidine, resulting in increased anticholinergic effects. Increased monitoring is advised in patients receiving this combination.
    Secobarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Sertraline: (Major) There have been post-marketing reports of QT prolongation and Torsade de Pointes (TdP) during treatment with sertraline; therefore, caution is advisable when using sertraline in patients with risk factors for QT prolongation, including concurrent use of other drugs that prolong the QTc interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sertraline include quinidine (including dextromethorphan; quinidine),
    Sevoflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Short-acting beta-agonists: (Minor) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Sildenafil: (Moderate) Sildenafil is metabolized principally by the hepatic isoenzymes CYP3A4 and CYP2C9. Inhibitors of these isoenzymes, such as quinidine, may reduce sildenafil clearance. Increased systemic exposure to sildenafil may result in an increase in sildenafil-induced adverse effects.
    Simeprevir: (Moderate) Use of orally administered quinidine with simeprevir, an intestinal CYP3A4 inhibitor, may result in mild increases in quinidine plasma concentrations. If these drugs are administered together, monitoring of quinidine plasma concentrations (if available) is recommended.
    Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with quinidine. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp).
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of quinidine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently. (Moderate) Use caution when administering velpatasvir with quinidine. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp).
    Solifenacin: (Moderate) Class IA antiarrhythmics (disopymide, procainamide, and quinidine) should be used cautiously and with close monitoring with solifenacin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval.Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation. In addition, coadministration may result in additive anticholinergic effects. Anticholinergic agents administered concurrently with disopyramide, procainamide, or quinidine may produce additive antivagal effects on AV nodal conduction.
    Sorafenib: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering sorafenib with quinidine. If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Sorafenib has been associated with QT prolongation. Quinidine and quinidine-containing products (e.g., dextromethorphan; quinidine) have also been associated with QT prolongation and TdP.
    Sotalol: (Major) Sotalol administration is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Drugs that prolong the QT interval should be used with extreme caution in combination with sotalol. Ventricular tachycardia, including torsade de pointes and monomorphic ventricular tachycardia can occur with excessive prolongation of the QT interval. Examples of agents that may prolong the QT interval include: Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Before initiating sotalol, the previous Class I antiarrhythmic therapy should be withdrawn under careful monitoring for a minimum of (2-3) plasma half-lives for the discontinued drug.
    Sparfloxacin: (Severe) Sparfloxacin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Increases in QTc interval have been observed in healthy volunteers treated with sparfloxacin, and torsade de pointes has been reported in patients receiving sparfloxacin with disopyramide and amiodarone. Therefore, sparfloxacin is contraindicated in patients receiving these drugs. The use of sparfloxacin in conjunction with other drugs known to prolong the QT interval has not been studied and is not recommended due to the potential risk for torsade de pointes. Drugs which have been established to have a causal association with QT prolongation and TdP include: Class IA antiarrhythmics (disopyramide, procainamide, quinidine).
    Spironolactone: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    St. John's Wort, Hypericum perforatum: (Major) St. John's Wort appears to induce several isoenzymes of the hepatic cytochrome P450 enzyme system, including CYP3A4. Coadministration of St. John's wort could decrease the efficacy of some medications metabolized by this enzyme, such as quinidine. Clinicians should observe patients closely if St. John's wort is used.
    Streptogramins: (Moderate) Quinidine is metabolized by CYP3A4. Dalfopristin; quinupristin may decrease the elimination of quinidine by inhibiting CYP3A4.
    Succinylcholine: (Major) Quinidine can potentiate the effects of neuromuscular blockers. Neostigmine will not reverse these effects. Respiratory support may be necessary if quinidine is given concomitantly or shortly after a neuromuscular blocking agent.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include quinidine.
    Sunitinib: (Major) Class IA antiarrhythmics (disopyramide, procainamide, quinidine) should be used cautiously with sunitinib. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP) and sunitinib can prolong the QT interval.
    Tacrolimus: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). As the risk of TdP is increased with greater QT prolongation, avoid use of quinidine with another drug that prolongs the QT interval such as tacrolimus. It should be noted that the manufacturer of tacrolimus recommends reducing the tacrolimus dose, close monitoring of tacrolimus whole blood concentrations, and monitoring for QT prolongation when coadministrating tacrolimus with other substrates and/or inhibitors of CYP3A4 that also have the potential to prolong the QT interval such as quinidine. Tacrolimus and quinidine are both metabolized by cytochrome P450 3A4.
    Tadalafil: (Moderate) Tadalafil is metabolized predominantly by the hepatic isoenzyme CYP3A4. Inhibitors of CYP3A4, such as quinidine, may reduce tadalafil clearance. Increased systemic exposure to tadalafil may result in an increase in tadalafil-induced adverse effects, including hypotension.
    Tamoxifen: (Severe) The concomitant use of quinidine, a strong CYP2D6 inhibitor, with drugs that are associated with QT prolongation and are also CYP2D6 substrates, such as tamoxifen, is contraindicated. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses.
    Tamsulosin: (Moderate) Use caution when administering tamsulosin with a strong CYP2D6 inhibitor such as quinidine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure. If concomitant use in necessary, monitor patient closely for increased side effects.
    Teduglutide: (Moderate) Teduglutide may increase absorption of quinidine because of it's pharmacodynamic effect of improving intestinal absorption. Careful monitoring and possible dose adjustment of quinidine is recommended.
    Telaprevir: (Major) Close clinical monitoring is advised when administering quinidine with telaprevir due to an increased potential for serious and/or life-threatening quinidine-related adverse events. If quinidine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of quinidine and telaprevir. Quinidine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Additionally, both quinidine and telaprevir are substrates and inhibitors of P-glycoprotein (P-gp) drug efflux transporter. When used in combination, the plasma concentrations of both medications may be elevated.
    Telavancin: (Major) Class IA antiarrhythmics (disopyramide, procainamide, quinidine) should be used cautiously with telavancin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP) and telavancin has been associated with QT prolongation.
    Telithromycin: (Major) Concurrent use of quinidine and/or quinidine-containing products (e.g., dextromethorphan; quinidinne) with telithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). The manufacturer of dextromethorphan; quinidine recommends an initial ECG evaluation (baseline and 3 to 4 hours post-dose) in patients taking dextromethorphan; quinidine in combination with moderate or strong CYP3A4 inhibitors such as telithromycin. The quinidine component of dextromethorphan; quinidine causes a dose-dependent QT prolongation and is metabolized via CYP3A4. Concurrent use of dextromethorphan; quinidine with moderate or strong CYP3A4 inhibitors may result in elevated quinidine plasma concentrations with the potential for enhanced QT-prolonging effects. In addition, telithromycin has the potential to prolong the QTc interval in some patients.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and quinidine is necessary, as the systemic exposure of quinidine may be decreased resulting in reduced efficacy; exposure to telotristat ethyl may also be increased. If these drugs are used together, monitor patients for suboptimal efficacy of quinidine as well as an increase in adverse reactions related to telotristat ethyl. Consider increasing the dose of quinidine if necessary. Quinidine is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate. Additionally, the active metabolite of telotristat ethyl, telotristat, is a substrate of P-glycoprotein (P-gp) and quinidine is a P-gp inhibitor. Exposure to telotristat ethyl may increase.
    Temsirolimus: (Moderate) Use caution if coadministration of temsirolimus with quinidine is necessary, and monitor for an increase in temsirolimus- and quinidine-related adverse reactions. Temsirolimus is a P-glycoprotein (P-gp) substrate/inhibitor in vitro, while quinidine is also a P-gp substrate/inhibitor. Pharmacokinetic data are not available for concomitant use of temsirolimus with P-gp inhibitors or substrates, but exposure to both quinidine and temsirolimus (and active metabolite, sirolimus) is likely to increase.
    Tenofovir, PMPA: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Terazosin: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Terbutaline: (Minor) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Terfenadine: (Severe) Use together is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Terfenadine has a well-established risk for QT prolongation and torsade de pointes (TdP). Other drugs that have also been independently associated with prolonged QT syndrome and/or TdP, such as quinidine, should not be used concomitantly with terfenadine.
    Tetrabenazine: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include tetrabenazine.
    Thiazide diuretics: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Thiopental: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Thioridazine: (Severe) Because of the potential for torsades de pointes (TdP), use of a Class IA antiarrhythmic (disopyramide, procainamide, and quinidine) with thioridazine is contraindicated. Class IA antiarrhythmics and thioridazine are associated with a well-established risk of QT prolongation and TdP. Thioridazine is associated with a well-established risk of QT prolongation and TdP and is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Ticagrelor: (Moderate) Coadministration of ticagrelor and quinidine may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and quinidine is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding.
    Timolol: (Major) In general, patients receiving combined therapy with quinidine and beta-blockers should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects on cardiovascular parameters when used together with beta-blockers, such as timolol. Decreased heart rate (bradycardia) has been reported during combination timolol and quinidine therapy. Additive hypotension is also possible. Additionally, quinidine is a known inhibitor of CYP2D6, and may impair the hepatic clearance of timolol (CYP2D6 substrate). Patients should be monitored for excess beta-blockade. Quinidine has been reported to potentiate timolol-induced bradycardia even after use of ophthalmic timolol.
    Tiotropium; Olodaterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Tipranavir: (Severe) Concurrent use of quinidine and tipranavir is contraindicated due to the potential for serious and/or life-threatening cardiac arrhythmias. Tipranavir inhibits the CYP3A4 metabolism of quinidine, resulting in elevated quinidine serum concentrations.
    Tizanidine: (Major) Quinidine and dextromethorphan; quinidine should be used cautiously and with close monitoring with tizanidine. Tizanidine administration may result in QT prolongation. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Coadministration increases the risk for QT prolongation and torsade de pointes.
    Tolterodine: (Major) Use tolterodine and quinidine concomitantly with caution and close monitoring. Quinidine can inhibit the hepatic CYP2D6 isoenzyme, which may decrease the metabolism of tolterodine. It is not known if dosage adjustments in tolterodine would be needed as the result of this interaction. In addition, tolterodine is associated with dose-dependent prolongation of the QT interval, especially in poor metabolizers of CYP2D6, and quinidine (including dextromethorphan; quinidine) is associated with an established risk of QT prolongation. In addition, the anticholinergic effects of quinidine may be significant and may be enhanced when combined with tolterodine. Anticholinergic agents administered concurrently with quinidine may produce additive antivagal effects on AV nodal conduction.
    Tolvaptan: (Major) Tolvaptan is a substrate for P-gp. Quinidine is an inhibitor of P-gp. Coadministration may result in increased exposure of tolvaptan; a reduction in the dose of tolvaptan may be required.
    Topotecan: (Major) Avoid the concomitant use of quinidine, a P-glycoprotein (P-gp) inhibitor, with oral topotecan, a P-gp substrate; P-gp inhibitors have less of an effect on intravenous topotecan and these may be coadministered with caution. If coadministration of quinidine and oral topotecan is necessary, carefully monitor for increased toxicity of topotecan, including severe myelosuppression and diarrhea; this also applies to combination products containing quinidine, such as dextromethorphan; quinidine. In a pharmacokinetic cohort study, coadministration of oral topotecan with a potent P-gp inhibitor (n = 8) increased the Cmax and AUC of topotecan by 2 to 3 fold (p = 0.008); coadministration with intravenous topotecan (n = 8) increased total topotecan exposure by 1.2-fold (p = 0.02) and topotecan lactone by 1.1-fold (not significant).
    Toremifene: (Major) Class IA Antiarrhythmics (disopyramide, procainamide, and quinidine) should be used cautiously with toremifene. Class IA Antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP) and toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner.
    Tramadol: (Moderate) As quinidine is a potent inhibitor of CYP2D6 and tramadol is partially metabolized by CYP2D6, concurrent therapy may decrease tramadol metabolism. This interaction may result in decreased tramadol efficacy and/or increased tramadol-induced risks of serotonin syndrome or seizures. The analgesic activity of tramadol is due to the activity of both the parent drug and the O-desmethyltramadol metabolite (M1), and M1 formation is dependent on CYP2D6. Therefore, use of tramadol with a CYP2D6-inhibitor may alter tramadol efficacy. In addition, inhibition of CYP2D6 metabolism is expected to result in reduced metabolic clearance of tramadol. This in turn may increase the risk of tramadol-related adverse events including serotonin syndrome and seizures. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Trandolapril; Verapamil: (Major) Pharmacokinetic and pharmacodynamic interactions exist between quinidine and verapamil. Oral verapamil has been shown to reduce the clearance and metabolism of oral quinidine. Quinidine half-life increased and plasma concentrations were higher after verapamil. No changes in quinidine protein binding were observed. In addition to the pharmacokinetic interaction which may potentiate quinidine's clinical effects, both quinidine and verapamil can cause hypotension. When quinidine and verapamil are coadministered in doses that are each well tolerated as monotherapy, hypotension attributable to additive peripheral (alpha)-blockade is sometimes reported. Concurrent use of verapamil and quinidine in patients with hypertrophic cardiomyopathy or arrhythmias can cause significant hypotension. It is recommended to avoid combined therapy with verapamil and quinidine in patients with hypertrophic cardiomyopathy. Quinidine and verapamil may also have additive negative inotropic effects. Concurrent use of verapamil and quinidine should be monitored carefully for electrophysiologic and hemodynamic effects.
    Trazodone: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include trazodone.
    Treprostinil: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Triamterene: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Trifluoperazine: (Minor) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with Class IA antiarrhythmics.
    Trihexyphenidyl: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Trimipramine: (Severe) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
    Triptorelin: (Major) Androgen deprivation therapy (e.g., triptorelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with triptorelin include quinidine (including dextromethorphan; quinidine.
    Trospium: (Major) Trospium is eliminated by active tubular secretion and has the potential for pharmacokinetic interactions with other drugs that are eliminated by active tubular secretion, such as quinidine. In theory, coadministration of trospium with quinidine may increase the serum concentrations of trospium or quinidine due to competition for the drug elimination pathway.
    Tubocurarine: (Major) Quinidine can potentiate the effects of neuromuscular blockers. Neostigmine will not reverse these effects. Respiratory support may be necessary if quinidine is given concomitantly or shortly after a neuromuscular blocking agent.
    Ulipristal: (Minor) In vitro data indicate that ulipristal may be an inhibitor of P-glycoprotein (P-gp) at clinically relevant concentrations. Thus, co-administration of ulipristal and P-gp substrates such as quinidine may increase quinidine concentrations; use caution. In the absence of clinical data, co-administration of ulipristal (when given daily) and P-gp substrates is not recommended.
    Umeclidinium; Vilanterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Valbenazine: (Major) Consider reducing the dose of valbenazine, based on tolerability, during co-administration with a strong CYP2D6 inhibitor, such as quinidine. QT prolongation is not clinically significant at valbenazine concentrations expected with recommended dosing; however, concentrations of the active metabolite of valbenazine may be higher in patients taking a strong CYP2D6 inhibitor and QT prolongation may become clinically significant.
    Vandetanib: (Major) The manufacturer of vandetanib recommends avoiding coadministration with other drugs that prolong the QT interval due to an increased risk of QT prolongation and torsade de pointes (TdP); an increase in quinidine-related adverse reactions is also possible. Vandetanib can prolong the QT interval in a concentration-dependent manner. TdP and sudden death have also been reported in patients receiving vandetanib; quinidine also has a possible risk for QT prolongation and TdP. If coadministration is necessary, an ECG is needed, as well as more frequent monitoring of the QT interval. If QTcF is greater than 500 msec, interrupt vandetanib dosing until the QTcF is less than 450 msec; then, vandetanib may be resumed at a reduced dose. Additionally, quinidine is a substrate of P-glycoprotein (P-gp). Coadministration with vandetanib increased the Cmax and AUC of another P-gp substrate by 29% and 23%, respectively.
    Vardenafil: (Major) The manufacturer recommends that vardenafil be avoided in patients taking Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produces an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction) The effect of vardenafil on the QT interval should be considered when prescribing the drug.
    Vecuronium: (Major) Quinidine can potentiate the effects of neuromuscular blockers. Neostigmine will not reverse these effects. Respiratory support may be necessary if quinidine is given concomitantly or shortly after a neuromuscular blocking agent.
    Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). If vemurafenib and quinidine must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Also, quinidine is also a CYP3A4 substrate and a P-glycoprotein (P-gp) substrate/inhibitor. Vemurafenib is a CYP3A4 substrate/inducer, and a P-gp substrate/inhibitor. Quinidine concentrations may be increased or decreased and vemurafenib concentrations may be increased during concurrent use.
    Venetoclax: (Major) Avoid the concomitant use of venetoclax and quinidine; venetoclax is a substrate of P-glycoprotein (P-gp) and quinidine is an inhibitor of P-gp. Consider alternative agents. If concomitant use of these drugs is required, reduce the venetoclax dosage by at least 50% (maximum dose of 200 mg/day). If quinidine is discontinued, wait 2 to 3 days and then resume the recommended venetoclax dosage (or prior dosage if less). Monitor patients for signs and symptoms of venetoclax toxicity such as hematologic toxicity, GI toxicity, and tumor lysis syndrome. In a drug interaction study (n = 11), the venetoclax Cmax and AUC values were increased by 106% and 78%, respectively, when a P-gp inhibitor was co-administered in healthy subjects.
    Venlafaxine: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine includes venlafaxine.
    Verapamil: (Major) Pharmacokinetic and pharmacodynamic interactions exist between quinidine and verapamil. Oral verapamil has been shown to reduce the clearance and metabolism of oral quinidine. Quinidine half-life increased and plasma concentrations were higher after verapamil. No changes in quinidine protein binding were observed. In addition to the pharmacokinetic interaction which may potentiate quinidine's clinical effects, both quinidine and verapamil can cause hypotension. When quinidine and verapamil are coadministered in doses that are each well tolerated as monotherapy, hypotension attributable to additive peripheral (alpha)-blockade is sometimes reported. Concurrent use of verapamil and quinidine in patients with hypertrophic cardiomyopathy or arrhythmias can cause significant hypotension. It is recommended to avoid combined therapy with verapamil and quinidine in patients with hypertrophic cardiomyopathy. Quinidine and verapamil may also have additive negative inotropic effects. Concurrent use of verapamil and quinidine should be monitored carefully for electrophysiologic and hemodynamic effects.
    Vinblastine: (Minor) Quinidine is an inhibitor of the efflux transporter P-glycoprotein. Vinblastine is a P-glycoprotein substrate. Increased concentrations of vinblastine are likely if it is coadministered with quinidine; exercise caution.
    Vincristine Liposomal: (Major) Quinidine inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
    Vincristine: (Major) Quinidine inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
    Vinorelbine: (Moderate) Caution is warranted when quinidine is administered with vinorelbine as there is a potential for elevated vinorelbine concentrations; this may also apply to combination drugs containing quinidine, such as dextromethorphan; quinidine. Monitor patients for an earlier onset and/or an increased severity of adverse effects including neurotoxicity and myelosuppression. Vinorelbine is a substrate of P-glycoprotein (P-gp) and quinidine is an inhibitor of P-gp.
    Voriconazole: (Severe) Quinidine (including dextromethorphan; quinidine) use is contraindicated with voriconazole according to recommendations made by the manufacturer of voriconazole. Voriconazole inhibits the CYP3A4 enzyme that is responsible for quinidine metabolism; elevated and toxic levels of quinidine may occur potentiating the risk for QT prolongation and cardiac arrhythmias (e.g., torsade de pointes).
    Vorinostat: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with quinidine.
    Vortioxetine: (Major) The primary isoenzyme involved in the metabolim of vortioxetine is CYP2D6; therefore, the manufacturer recommends a reduction in the vortioxetine dose by one-half during co-administration with strong inhibitors of CYP2D6 such as quinidine. The vortioxetine dose should be increased to the original level when the CYP2D6 inhibitor is discontinued.
    Warfarin: (Moderate) Quinidine may potentiate the anticoagulation effects of warfarin; bleeding has been reported. This interaction is probably due to additive hypoprothrombinemia associated with concomitant administration of warfarin and quinine or quinidine. Close monitoring of the INR is required when either of these agents is added to warfarin therapy.
    Zafirlukast: (Minor) Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as quinidine.
    Zileuton: (Moderate) Zileuton is metabolized by the hepatic isoenzyme CYP3A4 and may inhibit CYP3A4 isoenzymes. Zileuton could potentially compete with other CYP3A4 substrates, including quinidine.
    Ziprasidone: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including Class IA antiarrhythmics.
    Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and quinidine is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.

    PREGNANCY AND LACTATION

    Pregnancy

    Quinidine is excreted in human milk at concentrations slightly lower than those found in maternal serum. According to the manufacturer, breast-feeding infants would be expected to develop serum quinidine concentrations at least an order of magnitude lower than those of the mother. However, the pharmacokinetics and pharmacodynamics of quinidine in human infants have not been adequately studied. The reduced protein binding of quinidine in neonates may increase their risk of toxicity at low total serum concentrations. The manufacturer recommends that quinidine be avoided if possible in lactating women. However, if pharmacotherapy is necessary in a nursing woman, the American Academy of Pediatrics considers quinidine, as well as procainamide and disopyramide, to be usually compatible with breast-feeding. If quinidine is administered to a breast-feeding mother, monitor the infant carefully for signs and symptoms of quinidine exposure. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Mechanism of Action: Quinidine has properties similar to those of other class Ia antiarrhythmics (disopyramide and procainamide). These drugs decrease myocardial conduction velocity, excitability, and contractility by inhibiting the influx of sodium through "fast" channels of the myocardial cell membrane, thereby increasing the recovery period after repolarization. Quinidine suppresses atrial flutter or fibrillation by increasing the effective refractory period and the action potential duration in the atria, ventricles, and His-Purkinje system. The effective refractory period is increased more than the action potential duration, so the myocardium remains refractory even after the resting membrane potential has been restored. Quinidine decreases automaticity in the His-Purkinje system and decreases conduction velocity in the atria and ventricles. Quinidine prolongs the QRS and QT intervals in both normal sinus rhythm and atrial arrhythmias, and measurement of these intervals can be used to monitor therapy.Quinidine also exhibits anticholinergic properties that may modify its myocardial effects. When using quinidine to treat atrial flutter or fibrillation, ventricular rate can accelerate due to vagolytic effects on the AV node.

    PHARMACOKINETICS

    All quinidine salts can be administered orally. Only quinidine gluconate can be administered intravenously. Quinidine is commercially available as quinidine sulfate or quinidine gluconate, which contain 83% or 62% of anhydrous quinidine alkaloid, respectively. Quinidine distributes rapidly into all tissues except the brain, concentrating mainly in the heart, skeletal muscle, liver, and kidneys. The therapeutic range for quinidine serum concentrations ranges from 2—6 mcg/ml. The drug is 80—90% plasma protein-bound, with alpha-1-acid glycoprotein accounting for the majority of binding. 
     
    Quinidine is metabolized by a series of hydroxylations in the liver to form two active derivatives. Approximately 60—80% of a dose is metabolized via the cytochrome P450 enzyme system in the liver. Quinidine is primarily metabolized by the CYP3A4 enzyme and drugs that affect this enzyme may theoretically alter its' metabolism. Quinidine is an inhibitor of CYP2D6. There are several different hydroxylated metabolites, including some with antiarrhythmic activity. The most important active metabolite is 3-hydroxy-quinidine (3HQ). As measured by antiarrhythmic effects in animals, by QTc prolongation in human volunteers, or by various in vitro techniques, 3HQ has at least half the antiarrhythmic activity of the parent compound, so it may be responsible for a substantial fraction of the therapeutic response. Serum concentrations of 3HQ can approach those of quinidine in patients receiving conventional doses of oral quinidine. The volume of distribution of 3HQ appears to be larger than that of quinidine, and the elimination half-life of 3HQ is about 12 hours. 
     
    The elimination half-life of quinidine is 6—8 hours in adults. Roughly 10% is excreted unchanged in the urine, and 5% is excreted in the feces within 24 hours. Alkalinization of the urine can decrease renal elimination, while acidification will enhance excretion. 
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP2D6, CYP3A4, P-gp
    Quinidine is an inhibitor but not a substrate of the CYP2D6 cytochrome P450 enzyme and theoretically may interact with drugs that are metabolized by this enzyme. It also inhibits P-glycoprotein (P-gp) transport and is a substrate for P-gp. Quinidine is primarily metabolized by the CYP3A4 enzyme and drugs that affect this enzyme may theoretically alter the metabolism of quinidine.

    Oral Route

    Quinidine is readily absorbed from the GI tract, but interpatient variation in bioavailability, distribution, and elimination of the drug causes serum levels to differ greatly among individuals. The absolute bioavailability of the drug ranges 45—100%. Peak plasma concentrations and peak therapeutic effects are reached within 1—3 hours for quinidine sulfate regular-release capsules and tablets. Elimination half-life for quinidine averages 6.3—7.3 hours, although this varies considerably. Therapeutic effects usually last 6—8 hours. Quinidine sulfate regular-release capsules and tablets require three to four doses per day. Absorption of the extended-release quinidine sulfate or quinidine gluconate tablets is slower and more prolonged, and the duration of action for these formulations is about 12 hours. The presence of food in the stomach can decrease the absorption rate of regular-release quinidine sulfate capsules and tablets but not of extended-release preparations. Food does not affect the extent of absorption of these oral dosage forms. Administration with grapefruit juice delays the absorption of quinidine and inhibits CYP3A4 metabolism of quinidine to 3-hydroxyquinidine. The absorption of oral quinidine preparations can be decreased if antacids (except aluminum hydroxide gel) or antidiarrheals are administered concomitantly.