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  • CLASSES

    Anti-arrhythmics, Class II
    Anti-arrhythmics, Class III

    BOXED WARNING

    Alcoholism, AV block, bradycardia, cardiac arrhythmias, cardiac disease, cardiogenic shock, coronary artery disease, females, heart failure, hepatic disease, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, long QT syndrome, malnutrition, myocardial infarction, QT prolongation, renal disease, requires a specialized care setting, sick sinus syndrome, ventricular arrhythmias, ventricular dysfunction, ventricular fibrillation, ventricular tachycardia

    All formulations of sotalol are contraindicated in patients with sinus bradycardia, second or third degree AV block unless a functioning pacemaker is present, congenital long QT syndrome, acquired QT prolongation syndromes, cardiogenic shock, and/or uncontrolled heart failure. Betapace/Betapace AF, sotalol oral solution, and sotalol injection are also contraindicated in sick sinus syndrome unless a functioning pacemaker is present, hypokalemia (serum potassium less than 4 mEq/L), and/or a baseline QT interval more than 450 msec; for Betapace/Betapace AF, this contraindication only applies if used for the treatment of atrial fibrillation or atrial flutter. Use sotalol with caution in patients with heart failure controlled with digoxin and/or diuretics, particularly in those with left ventricular dysfunction, because the negative inotropic effect can further depress cardiac output. Sotalol has proarrhythmic effects and may induce or worsen cardiac arrhythmias, primarily ventricular arrhythmias. Use of the drug has been associated with QT prolongation which can lead to sustained ventricular fibrillation, sustained ventricular tachycardia, and/or torsade de pointes (TdP). Higher sotalol doses are associated with more pronounced QTc prolongation and, thus, a greater incidence of TdP. Use sotalol with caution and consider dose reduction or drug discontinuation if the QTc prolongs more than 500 msec; serious consideration to dose reduction or drug discontinuance should occur in patients with a QTc more than 550 msec. Although it is sometimes difficult to distinguish between a patient's underlying malignant arrhythmia and a drug-induced arrhythmia, patients with an initially normal QT interval who subsequently suffer a proarrhythmic event generally do so as the result of antiarrhythmic therapy. Use of antiarrhythmic drugs has been associated with sudden death, and patients are at risk throughout the duration of therapy. Use sotalol 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, patients with diabetes, thyroid impairment, malnutrition, alcoholism, or hepatic disease may also be at increased risk for QT prolongation. Due to elimination of the drug primarily via renal processes, patients with renal disease may also be at risk for sotalol-induced arrhythmias. To minimize the risk of proarrhythmias, a patient initiated or reinitiated on sotalol requires a specialized care setting and should be placed for a minimum of 3 days (on their maintenance dose) in a facility that can provide cardiac resuscitation and continuous electrocardiographic (ECG) monitoring. Calculate creatinine clearance and correct electrolyte imbalances prior to initiating sotalol.

    DEA CLASS

    Rx

    DESCRIPTION

    Nonselective beta-adrenergic blocking agent and class III antiarrhythmic
    Used for the treatment of atrial fibrillation, atrial flutter, and life-threatening ventricular arrhythmias
    May induce QT prolongation and torsade de pointes

    COMMON BRAND NAMES

    BETAPACE, BETAPACE AF, Sorine, SOTYLIZE

    HOW SUPPLIED

    BETAPACE/BETAPACE AF/Sorine/Sotalol/Sotalol Hydrochloride Oral Tab: 80mg, 120mg, 160mg, 240mg
    Sotalol/Sotalol Hydrochloride Intravenous Inj Sol: 1mL, 15mg
    SOTYLIZE Oral Sol: 1mL, 5mg

    DOSAGE & INDICATIONS

    For the maintenance of normal sinus rhythm in patients with highly symptomatic atrial fibrillation or atrial flutter who are currently in sinus rhythm.
    Oral dosage
    Adults

    Initially, 80 mg PO twice daily. The dose may be increased in increments of 80 mg/day every 3 days if QTc is less than 500 msec. Continually monitor patients until steady state blood concentrations are achieved. If the QTc prolongs to 500 msec or more, reduce the dose, lengthen the dosing interval, or discontinue therapy. Most patients reach a therapeutic response at a total daily dose of 240 mg/day PO. Do not exceed 320 mg/day PO.

    Children and Adolescents 6 to 17 years†

    Initially, 30 mg/m2/dose PO 3 times daily titrated up as needed at intervals of 36 hours or more (Max: 60 mg/m2/dose PO 3 times daily) is recommended by FDA-approved labeling based on pharmacokinetic data. Alternatively, initial doses of 1 to 2 mg/kg/day PO given in 2 to 3 divided doses have been studied in pediatric patients with various tachyarrhythmias (combined n from 3 studies = 213). The dose was increased as needed by 1 to 2 mg/kg/day PO every 3 days (Max: 10 mg/kg/day PO). A target dose of 4 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study. An absolute maximum dose for pediatric patients has not been specified; FDA-approved labeling recommends a maximum dose of 320 mg/day PO for adult patients.

    Children 2 to 5 years†

    Initially, 30 mg/m2/dose PO 3 times daily titrated up as needed at intervals of 36 hours or more (Max: 60 mg/m2/dose PO 3 times daily) is recommended by FDA-approved labeling based on pharmacokinetic data. Alternatively, initial doses of 1 to 2 mg/kg/day PO given in 2 to 3 divided doses have been studied in pediatric patients with various tachyarrhythmias (combined n from 3 studies = 213). The dose was increased as needed by 1 to 2 mg/kg/day PO every 3 days (Max: 10 mg/kg/day PO). A target dose of 6 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study. An absolute maximum dose for pediatric patients has not been specified; FDA-approved labeling recommends a maximum dose of 320 mg/day PO for adult patients.

    Infants and Children younger than 2 years†

    The FDA-approved product label recommends decreasing the usual starting dose recommended for a 2-year-old child (30 mg/m2/dose PO 3 times daily) by an age-specific reduction factor, which is determined by plotting the child's age on the manufacturer-provided logarithmic scale (see complete prescribing information). Alternatively, initial doses of 1 to 2 mg/kg/day PO given in 2 to 3 divided doses have been studied in pediatric patients with various tachyarrhythmias (combined n from 3 studies = 213). The dose was increased as needed by 1 to 2 mg/kg/day PO every 3 days (Max: 10 mg/kg/day PO). A target dose of 6 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study.

    Neonates†

    The FDA-approved product label recommends decreasing the usual starting dose recommended for a 2-year-old child (30 mg/m2/dose PO 3 times daily) by an age-specific reduction factor, which is determined by plotting the child's age on the manufacturer-provided logarithmic scale (see complete prescribing information). Alternatively, initial doses of 1 to 2 mg/kg/day PO given in 2 to 3 divided doses have been studied in pediatric patients with various tachyarrhythmias (combined n from 3 studies = 213). The dose was increased as needed by 1 to 2 mg/kg/day PO every 3 days (Max: 10 mg/kg/day PO). A target dose of 4 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study.

    Intravenous dosage

    NOTE: The concomitant use of sotalol with other drugs that prolong the QT interval has not been studied and is not recommended. Withhold Class I (e.g., disopyramide, procainamide, quinidine) or Class III antiarrhythmics (e.g., amiodarone, dofetilide) for at least three half-lives prior to initiating sotalol. In clinical trials, sotalol was not administered to patients previously treated with oral amiodarone for more than 1 month duration within the previous three months.
    NOTE: Intravenous sotalol should only be used in patients who are unable to tolerate oral sotalol. The corresponding doses are 80 mg PO = 75 mg IV, 120 mg PO = 112.5 mg IV, 160 mg PO = 150 mg IV.

    Adults

    Initially, 75 mg IV twice daily. The dose may be increased in increments of 75 mg/day every 3 days IV if the QTc is less than 500 msec. Continue to monitor QTc during dose escalations. If the QTc prolongs to 500 msec or more, reduce the dose, lengthen the infusion duration, or discontinue therapy. Most patients reach a therapeutic response at a total daily dose of 225 mg/day IV. Do not exceed 300 mg/day IV.

    For the treatment of ventricular arrhythmias, such as sustained ventricular tachycardia that are deemed to be life-threatening.
    Oral dosage
    Adults

    Initially, 80 mg PO twice daily. The dose may be increased in increments of 80 mg/day every 3 days if the QTc is less than 500 msec. Continually monitor patients until steady state blood concentrations are achieved. If the QTc prolongs to 500 msec or more, reduce the dose, lengthen the dosing interval, or discontinue therapy. Most patients reach a therapeutic response at a total daily dose of 160 to 320 mg/day PO. Doses as high as 480 to 640 mg/day PO have been used in refractory life-threatening arrhythmias.

    Children and Adolescents 6 to 17 years†

    Initially, 30 mg/m2/dose PO 3 times daily titrated up as needed at intervals of 36 hours or more (Max: 60 mg/m2/dose PO 3 times daily) is recommended by FDA-approved labeling based on pharmacokinetic data. Alternatively, initial doses of 1 to 2 mg/kg/day PO given in 2 to 3 divided doses have been studied in pediatric patients with various tachyarrhythmias (combined n from 3 studies = 213). The dose was increased as needed by 1 to 2 mg/kg/day PO every 3 days (Max: 10 mg/kg/day PO). A target dose of 4 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study. An absolute maximum dose for pediatric patients has not been specified; FDA-approved labeling recommends a maximum dose of 640 mg/day PO for adult patients.

    Children 2 to 5 years†

    Initially, 30 mg/m2/dose PO 3 times daily titrated up as needed at intervals of 36 hours or more (Max: 60 mg/m2/dose PO 3 times daily) is recommended by FDA-approved labeling based on pharmacokinetic data. Alternatively, initial doses of 1 to 2 mg/kg/day PO given in 2 to 3 divided doses have been studied in pediatric patients with various tachyarrhythmias (combined n from 3 studies = 213). The dose was increased as needed by 1 to 2 mg/kg/day PO every 3 days (Max: 10 mg/kg/day PO). A target dose of 6 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study. An absolute maximum dose for pediatric patients has not been specified; FDA-approved labeling recommends a maximum dose of 640 mg/day PO for adult patients.

    Infants and Children younger than 2 years†

    The FDA-approved product label recommends decreasing the usual starting dose recommended for a 2-year-old child (30 mg/m2/dose PO 3 times daily) by an age-specific reduction factor, which is determined by plotting the child's age on the manufacturer-provided logarithmic scale (see complete prescribing information). Alternatively, initial doses of 1 to 2 mg/kg/day PO given in 2 to 3 divided doses have been studied in pediatric patients with various tachyarrhythmias (combined n from 3 studies = 213). The dose was increased as needed by 1 to 2 mg/kg/day PO every 3 days (Max: 10 mg/kg/day). A target dose of 6 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study.

    Neonates†

    The FDA-approved product label recommends decreasing the usual starting dose recommended for a 2-year-old child (30 mg/m2/dose PO 3 times daily) by an age-specific reduction factor, which is determined by plotting the child's age on the manufacturer-provided logarithmic scale (see complete prescribing information). Alternatively, initial doses of 1 to 2 mg/kg/day PO given in 2 to 3 divided doses have been studied in pediatric patients with various tachyarrhythmias (combined n from 3 studies = 213). The dose was increased as needed by 1 to 2 mg/kg/day PO every 3 days (Max: 10 mg/kg/day). A target dose of 4 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study.

    Intravenous dosage
    Adults

    Initially, 75 mg IV twice daily. The dose may be increased in increments of 75 mg/day every 3 days if the QTc is less than 500 msec. Continue to monitor QTc during dose escalations. If the QTc prolongs to 500 msec or more, reduce the dose, lengthen the infusion duration, or discontinue therapy. Most patients reach a therapeutic response at a total daily dose of 150 to 300 mg/day IV. Doses as high as 550 to 600 mg/day IV have been used in refractory life-threatening arrhythmias.

    For the maintenance of sinus rhythm in patients with supraventricular arrhythmias†, including paroxysmal supraventricular tachycardia (PSVT)†, Wolff-Parkinson-White (WPW) syndrome†, junctional ectopic tachycardia†, paroxysmal atrial tachycardia†, and atrioventricular node reentrant tachycardia†.
    Oral dosage
    Children and Adolescents 6 to 17 years

    Initially, 30 mg/m2/dose PO 3 times daily titrated up as needed at intervals of 36 hours or more (Max: 60 mg/m2/dose PO 3 times daily) is recommended by FDA-approved labeling based on pharmacokinetic data. Alternatively, initial doses of 1 to 2 mg/kg/day PO given in 2 to 3 divided doses have been studied in pediatric patients with various tachyarrhythmias (combined n from 3 studies = 213). The dose was increased as needed by 1 to 2 mg/kg/day PO every 3 days (Max: 10 mg/kg/day PO). A target dose of 4 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study. An absolute maximum dose for pediatric patients has not been specified; FDA-approved labeling recommends a maximum dose of 320 mg/day PO for adult patients treated for atrial fibrillation/atrial flutter and 640 mg/day PO for adult patients treated for ventricular arrhythmias.

    Children 2 to 5 years

    Initially, 30 mg/m2/dose PO 3 times daily titrated up as needed at intervals of 36 hours or more (Max: 60 mg/m2/dose PO 3 times daily) is recommended by FDA-approved labeling based on pharmacokinetic data. Alternatively, initial doses of 1 to 2 mg/kg/day PO given in 2 to 3 divided doses have been studied in pediatric patients with various tachyarrhythmias (combined n from 3 studies = 213). The dose was increased as needed by 1 to 2 mg/kg/day PO every 3 days (Max: 10 mg/kg/day PO). A target dose of 6 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study. An absolute maximum dose for pediatric patients has not been specified; FDA-approved labeling recommends a maximum dose of 320 mg/day PO for adult patients treated for atrial fibrillation/atrial flutter and 640 mg/day PO for adult patients treated for ventricular arrhythmias.

    Infants and Children younger than 2 years

    The FDA-approved product label recommends decreasing the usual starting dose recommended for a 2-year-old child (30 mg/m2/dose PO 3 times daily) by an age-specific reduction factor, which is determined by plotting the child's age on the manufacturer-provided logarithmic scale (see complete prescribing information). Alternatively, initial doses of 1 to 2 mg/kg/day PO given in 2 to 3 divided doses have been studied in pediatric patients with various tachyarrhythmias (combined n from 3 studies = 213). The dose was increased as needed by 1 to 2 mg/kg/day PO every 3 days (Max: 10 mg/kg/day). A target dose of 6 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study.

    Neonates

    The FDA-approved product label recommends decreasing the usual starting dose recommended for a 2-year-old child (30 mg/m2/dose PO 3 times daily) by an age-specific reduction factor, which is determined by plotting the child's age on the manufacturer-provided logarithmic scale (see complete prescribing information). Alternatively, initial doses of 1 to 2 mg/kg/day PO given in 2 to 3 divided doses have been studied in pediatric patients with various tachyarrhythmias (combined n from 3 studies = 213). The dose was increased as needed by 1 to 2 mg/kg/day PO every 3 days (Max: 10 mg/kg/day). A target dose of 4 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study.

    For primary atrial fibrillation prophylaxis† in patients undergoing cardiac surgery†.
    Oral dosage
    Adults

    80 mg PO twice daily; duration of treatment varies. Dose should be individualized based on CrCl, QTc, and clinical response. Per clinical practice guidelines, prophylactic administration of sotalol may be considered for patients at risk of developing atrial fibrillation following cardiac surgery.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    320 mg/day PO or 300 mg/day IV for atrial fibrillation/atrial flutter; up to 640 mg/day PO or 600 mg/day IV for life-threatening ventricular arrhythmias.

    Geriatric

    320 mg/day PO or 300 mg/day IV for atrial fibrillation/atrial flutter; up to 640 mg/day PO or 600 mg/day IV for life-threatening ventricular arrhythmias.

    Adolescents

    Safety and efficacy have not been established; 180 mg/m2/day PO is the maximum dosage recommended by FDA-approved labeling; alternatively, doses up to 10 mg/kg/day PO have been used for the management of various tachyarrhythmias.

    Children

    2 to 12 years: Safety and efficacy have not been established; 180 mg/m2/day PO is the maximum dosage recommended by FDA-approved labeling; alternatively, doses up to 10 mg/kg/day PO have been used for the management of various tachyarrhythmias.
    1 year: Safety and efficacy have not been established; see full prescribing information for age-specific dosing chart; doses up to 10 mg/kg/day PO have been used for the management of various tachyarrhythmias.

    Infants

    Safety and efficacy have not been established; see full prescribing information for age-specific dosing chart; doses up to 10 mg/kg/day PO have been used for the management of various tachyarrhythmias.

    Neonates

    Safety and efficacy have not been established; see full prescribing information for age-specific dosing chart; doses up to 10 mg/kg/day PO have been used for the management of various tachyarrhythmias.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Sotalol has not been studied in pediatric patients with renal impairment; although lower doses or increased dosing intervals are recommended, specific dosage adjustments are not available. It will take longer to reach steady state in pediatric patients with renal impairment; closely monitor heart rate and QTc. Recommended dose adjustments for adult patients are dependent on the formulation and/or indication:
     
    Betapace/Betapace AF and Sorine (both for ventricular arrhythmias):
    CrCl 60 mL/minute or more: No dosage adjustment needed.
    CrCl 30 to 59 mL/minute: Extend dosage interval to every 24 hours. Dose may be titrated after at least 5 doses.
    CrCl 10 to 29 mL/minute: Extend dosage interval to every 36 to 48 hours according to clinical response. Dose may be titrated after at least 5 doses.
    CrCl less than 10 mL/minute: Individualize dosage.
     
    Betapace/Betapace AF (for atrial fibrillation/atrial flutter), Sotylize, and intravenous (IV) sotalol:
    CrCl 60 mL/minute or more: No dosage adjustment needed.
    CrCl 40 to 59 mL/minute: Extend dosage interval to every 24 hours. Dose may be titrated after at least 5 doses.
    CrCl less than 40 mL/minute: Use is contraindicated.
     
    Intermittent hemodialysis
    The use of Betapace/Betapace AF (for atrial fibrillation/atrial flutter), Sotylize, and IV sotalol are contraindicated in patients with CrCl less than 40 mL/minute. Use other formulations of sotalol with extreme caution in patients on hemodialysis; the half-life of sotalol is prolonged up to 69 hours in anuric patients. While sotalol is partially removed by hemodialysis, subsequent partial rebound in sotalol concentrations will occur once the dialysis session is completed. Both heart rate and QT interval, as well as efficacy (arrhythmia control) must be carefully monitored.

    ADMINISTRATION

    Oral Administration

    May administer without regard to meals.

    Oral Liquid Formulations

    Measure dosage with calibrated measuring device.
    Extemporaneous Oral Suspension: Shake well prior to use.

    Extemporaneous Compounding-Oral

    Extemporaneous 5 mg/mL Sotalol Oral Suspension Preparation
     
    NOTE: A 5 mg/mL oral solution is commercially available.
    Measure 120 mL of Simple Syrup containing 0.1% sodium benzoate (Syrup, NF).
    Transfer the syrup to a 6-ounce amber plastic bottle.
    Add five 120 mg sotalol tablets to the bottle. The tablets may be added intact or they may be crushed.
    If the tablets are crushed, carefully transfer the entire amount of powder to the bottle and shake the bottle until dispersion of the fine particles in the syrup is obtained.
    If the tablets are intact, shake the bottle to wet the entire surface of the tablet and allow to hydrate for approximately 2 hours. The tablets may also be hydrated overnight to allow for easier disintegration.
    Shake the bottle intermittently over the next 2 hours until the tablets are completely disintegrated and a dispersion of fine particles in the syrup is achieved.
    Storage: The resulting suspension is stable for 3 months at 15 to 30 degrees Celsius (59 to 86 degrees Farenheit).

    Injectable Administration
    Intravenous Administration

    Sotalol injection is available in vials containing 150 mg sotalol hydrochloride in 10 mL (15 mg/mL).
    Dilution:
    Must be diluted prior to use to a volume of either 120 mL or 300 mL. Appropriate diluents are 0.9% Sodium Chloride Injection, Dextrose 5% Injection, or Lactated Ringer's Injection.
    The solution prepared will contain more drug than is prescribed to account for drug remaining in the infusion set (i.e., total volume prepared will be either 120 mL or 300 mL but the volume to be infused will be either 100 mL or 250 mL). Therefore, it is imperative that healthcare personnel administering sotalol injection program the volumetric infusion pump to deliver either 100 mL or 250 mL.
    75 mg dose: Withdraw 6 mL sotalol injection (90 mg) and add 114 mL diluent for a total volume of 120 mL (final concentration: 0.75 mg/mL), or withdraw 6 mL sotalol injection (90 mg) and add 294 mL diluent for a total volume of 300 mL (final concentration: 0.3 mg/mL).
    112.5 mg dose: Withdraw 9 mL sotalol injection (135 mg) and add 111 mL diluent for a total volume of 120 mL (final concentration: 1.125 mg/mL), or withdraw 9 mL sotalol injection (135 mg) and add 291 mL diluent for a total volume of 300 mL (final concentration: 0.45 mg/mL).
    150 mg dose: Withdraw 12 mL sotalol injection (180 mg) and add 108 mL diluent for a total volume of 120 mL (final concentration: 1.5 mg/mL), or withdraw 12 mL sotalol injection (180 mg) and add 288 mL diluent for a total volume of 300 mL (final concentration: 0.6 mg/mL).
     
    Intermittent IV Infusion:
    Program a volumetric infusion pump to administer a total volume of either 100 mL or 250 mL. Some solution may remain in the infusion set. Discard any remaining drug in the infusion set and bag.
    Infuse 100 mL or 250 mL over 5 hours at a constant infusion rate. A significantly shorter administration rate of over 5 minutes has been described for 100 mg doses in emergent situations.

    STORAGE

    Generic:
    - Protect from freezing
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in carton until time of use
    BETAPACE:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    BETAPACE AF:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Sorine :
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    SOTYLIZE:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Sotalol is contraindicated in patients with a known hypersensitivity to sotalol. Use sotalol with caution in patients with a history of anaphylactic reactions. These patients may have a more severe reaction if rechallenge to the allergen occurs while receiving a beta-blocker, such as sotalol. The patient also may be unresponsive to the usual doses of epinephrine used to treat the reaction.

    Abrupt discontinuation

    Abrupt discontinuation of beta-blockers can precipitate arrhythmias and possibly a heart attack. Although not included in the black box warnings for sotalol, many oral beta-blockers include a black box warning within the prescribing information advising against abrupt discontinuation of beta-blockers. When discontinuing chronically administered sotalol, gradually reduce the dose over 1 to 2 weeks and monitor the patient. If sotalol must be discontinued abruptly or if angina or acute coronary ischemia develops during dose reduction, the temporary use of an alternative beta-blocker may be considered.

    Hyperthyroidism, thyroid disease, thyrotoxicosis

    Use sotalol with caution in patients with hyperthyroidism or thyrotoxicosis because the drug can mask tachycardia, which is a useful monitoring parameter in thyroid disease. Abrupt withdrawal of beta-blockers in a patient with hyperthyroidism can precipitate thyroid storm. However, certain beta-blockers are generally useful in the symptomatic treatment of hyperthyroid-related states, like thyrotoxicosis. While sotalol may be helpful in controlling the heart rate in atrial fibrillation associated with thyrotoxicosis, such use has not been evaluated.

    Alcoholism, AV block, bradycardia, cardiac arrhythmias, cardiac disease, cardiogenic shock, coronary artery disease, females, heart failure, hepatic disease, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, long QT syndrome, malnutrition, myocardial infarction, QT prolongation, renal disease, requires a specialized care setting, sick sinus syndrome, ventricular arrhythmias, ventricular dysfunction, ventricular fibrillation, ventricular tachycardia

    All formulations of sotalol are contraindicated in patients with sinus bradycardia, second or third degree AV block unless a functioning pacemaker is present, congenital long QT syndrome, acquired QT prolongation syndromes, cardiogenic shock, and/or uncontrolled heart failure. Betapace/Betapace AF, sotalol oral solution, and sotalol injection are also contraindicated in sick sinus syndrome unless a functioning pacemaker is present, hypokalemia (serum potassium less than 4 mEq/L), and/or a baseline QT interval more than 450 msec; for Betapace/Betapace AF, this contraindication only applies if used for the treatment of atrial fibrillation or atrial flutter. Use sotalol with caution in patients with heart failure controlled with digoxin and/or diuretics, particularly in those with left ventricular dysfunction, because the negative inotropic effect can further depress cardiac output. Sotalol has proarrhythmic effects and may induce or worsen cardiac arrhythmias, primarily ventricular arrhythmias. Use of the drug has been associated with QT prolongation which can lead to sustained ventricular fibrillation, sustained ventricular tachycardia, and/or torsade de pointes (TdP). Higher sotalol doses are associated with more pronounced QTc prolongation and, thus, a greater incidence of TdP. Use sotalol with caution and consider dose reduction or drug discontinuation if the QTc prolongs more than 500 msec; serious consideration to dose reduction or drug discontinuance should occur in patients with a QTc more than 550 msec. Although it is sometimes difficult to distinguish between a patient's underlying malignant arrhythmia and a drug-induced arrhythmia, patients with an initially normal QT interval who subsequently suffer a proarrhythmic event generally do so as the result of antiarrhythmic therapy. Use of antiarrhythmic drugs has been associated with sudden death, and patients are at risk throughout the duration of therapy. Use sotalol 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, patients with diabetes, thyroid impairment, malnutrition, alcoholism, or hepatic disease may also be at increased risk for QT prolongation. Due to elimination of the drug primarily via renal processes, patients with renal disease may also be at risk for sotalol-induced arrhythmias. To minimize the risk of proarrhythmias, a patient initiated or reinitiated on sotalol requires a specialized care setting and should be placed for a minimum of 3 days (on their maintenance dose) in a facility that can provide cardiac resuscitation and continuous electrocardiographic (ECG) monitoring. Calculate creatinine clearance and correct electrolyte imbalances prior to initiating sotalol.

    Hypotension

    Hypotension may occur with sotalol use as a result of significant reductions in both systolic and diastolic blood pressure. Because sotalol exhibits beta-adrenergic blocking activity, effects on both blood pressure and pulse are possible. Although sotalol is usually well-tolerated, monitor patients with marginal cardiac compensation closely for deterioration in cardiac performance.

    Dialysis, renal failure, renal impairment

    Use sotalol with caution in patients with renal impairment. Betapace/Betapace AF, sotalol oral solution, and sotalol injection are contraindicated in patients with renal failure or renal impairment (creatinine clearance (CrCl) less than 40 mL/minute); for Betapace/Betapace AF, this contraindication only applies if used for the treatment of atrial fibrillation or atrial flutter. Dosage adjustment of sotalol is recommended when the CrCl is less than 60 mL/minute. Use extreme caution in patients on hemodialysis, the half-life of sotalol is prolonged up to 69 hours in anuric patients. While sotalol is partially removed by hemodialysis, subsequent partial rebound in sotalol concentrations will occur once the dialysis session is completed. Both heart rate and QT interval, as well as efficacy (arrhythmia control) must be carefully monitored.

    Pheochromocytoma, vasospastic angina

    Use sotalol monotherapy with caution in patients with a pheochromocytoma or vasospastic angina (Prinzmetal's angina) because of the risk of hypertension secondary to unopposed alpha-receptor stimulation. In patients with pheochromocytoma, use an alpha-blocking agent prior to the initiation of any beta-blocker. The presence of sotalol in the urine may cause falsely elevated concentrations of urinary metanephrine when measured by fluorimetric or photometric methods, which may interfere with screening of patients for pheochromocytoma. A more specific method, such as a high performance liquid chromatographic assay with solid phase extraction, is recommended to determine catecholamine concentrations.

    Surgery

    The necessity or desirability of withdrawing beta-blockers, such as sotalol, prior to major surgery is controversial; evaluate the risks versus benefits in individual patients. Because beta-blocker therapy reduces the ability of the heart to respond to beta-adrenergically mediated sympathetic reflex stimuli, the risks of general anesthesia and surgical procedures may be augmented in patients receiving sotalol. Although gradual withdrawal of beta-blockers is sometimes recommended prior to general anesthesia to limit the potential for hypotension and heart failure, the manufacturer does not recommend withdrawal of chronically-administered sotalol prior to major surgery. The risk of precipitating adverse cardiac events (e.g., myocardial infarction, tachycardia) following preoperative withdrawal of beta-blockers may outweigh the risks of ongoing beta-blocker therapy, particularly in patients with coexisting cardiovascular disease. Monitor patients receiving sotalol before or during surgery involving the use of general anesthetics with negative inotropic effects (e.g., ether, cyclopropane, or trichloroethylene) closely for signs of heart failure. Severe, protracted hypotension and difficulty in restarting the heart have been reported after surgery in patients receiving beta-blockers. Consider the type of surgery (e.g., cardiac vs. noncardiac), anesthetic strategy, and coexisting health conditions. The anesthetic technique may be modified to reduce the risk of concurrent beta-blocker therapy. If needed, the negative inotropic effects of beta-blockers may be cautiously reversed by sufficient doses of adrenergic agonists such as isoproterenol, dopamine, dobutamine, or norepinephrine. Vagal dominance, if it occurs, may be corrected with atropine.

    Acute bronchospasm, asthma, bronchitis, chronic lung disease (CLD), pulmonary disease

    Sotalol (a non-specific beta-blocker) is contraindicated in patients with bronchial asthma or related bronchospastic conditions. Avoid sotalol or use with great caution at the lowest effective dose in patients with pulmonary disease, including acute bronchospasm, chronic lung disease (CLD), bronchitis, or pneumonia.

    Diabetes mellitus

    Beta-blockers prolong or enhance hypoglycemia by interfering with catecholamine-induced glycogenolysis, glyconeogenesis, and lipolysis. Additionally, they can mask signs of hypoglycemia, including tachycardia, palpitations, and tremors. In addition to acute blood glucose effects, beta-blockers have been shown to increase the risk of developing diabetes mellitus in adult hypertensive patients. The risk in pediatric patients is undefined.

    Pregnancy

    Sotalol is classified as FDA pregnancy category B. Adequate evaluation of the use of sotalol during pregnancy has not been completed. Sotalol has been shown to cross the placenta and can be found in amniotic fluid. When administered to animals at 18 times the maximum recommended human dose, there was no increase in congenital anomalies, but an increase in early resorptions occurred. One case of subnormal birth weight was reported with use of sotalol in a pregnant woman. All beta-blockers have the potential for causing fetal bradycardia. Thus, sotalol should be used during pregnancy only when the benefits outweigh the potential risk to the fetus.

    Breast-feeding

    Breast-feeding should be discontinued during sotalol therapy. Sotalol is secreted into breast milk in high concentrations. In 5 mothers whose mean sotalol dose was 433 mg/day, sotalol concentrations in milk ranged from 4.8 to 20.2 mg/L (mean = 10.5 mg/L), with a milk:plasma ratio of 5.5:1 (range 2.2 to 8.8). The calculated infant dose was 0.8 to 3.4 mg/kg, which is similar to recommended therapeutic doses in neonates. Two other case reports showed similar findings.

    Activities requiring coordination and concentration, driving or operating machinery

    Sotalol may be associated with dizziness or drowsiness in some patients. Advise patients to use caution when driving or operating machinery or performing activities requiring coordination and concentration (e.g., riding a bicycle) until the response is known.

    Peripheral vascular disease, Raynaud's phenomenon

    Avoid sotalol in patients with Raynaud's phenomenon or peripheral vascular disease because reduced cardiac output and the relative increase in alpha stimulation can exacerbate symptoms.

    Acute myocardial infarction

    Use sotalol with caution and careful dosage titration in the first 2 weeks after acute myocardial infarction, especially in patients with markedly impaired ventricular function. Sotalol (320 mg/day PO; non-titrated) did not significantly affect mortality in a large double-blind, placebo-controlled secondary prevention (post-infarction) trial including 1,456 adults; however, there was a suggestion of early (within the first 10 days of treatment) excess mortality in sotalol-treated patients. In a second smaller trial (n = 17 randomized to sotalol), 4 fatalities and 3 serious hemodynamic/electrical events occurred within 2 weeks of sotalol initiation in high-risk post-infarction patients (ejection fraction < 40% and either > 10 VPC/hour or VT on Holter) receiving high dose sotalol (320 mg PO twice daily). During investigation of the d-isomer of sotalol (virtually devoid of beta-blocking activity and considered a pure Class III antiarrhythmic) as an antiarrhythmic in high-risk patients post-MI, a higher mortality rate was observed with d-sotalol versus placebo, presumably due to increased arrhythmic deaths (SWORD trial).

    Geriatric

    In general, geriatric patients may be at increased risk for QT prolongation from drugs such as sotalol. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) 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

    bradycardia / Rapid / 1.0-16.0
    heart failure / Delayed / 1.2-10.0
    visual impairment / Early / 0-5.0
    torsade de pointes / Rapid / 0.6-4.0
    AV block / Early / 1.0-1.0
    pulmonary edema / Early / 0-1.0
    stroke / Early / 1.0-1.0
    ventricular fibrillation / Early / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    arrhythmia exacerbation / Early / Incidence not known
    muscle paralysis / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known

    Moderate

    dyspnea / Early / 9.0-20.0
    palpitations / Early / 5.0-14.0
    QT prolongation / Rapid / 4.0-12.0
    edema / Delayed / 8.0-8.0
    hypotension / Rapid / 6.0-6.0
    chest pain (unspecified) / Early / 2.5-4.6
    depression / Delayed / 2.0-4.0
    hypertension / Early / 2.0-2.0
    bleeding / Early / 2.0-2.0
    angina / Early / 2.0-2.0
    elevated hepatic enzymes / Delayed / 0-1.0
    peripheral neuropathy / Delayed / 0-1.0
    hyperglycemia / Delayed / Incidence not known
    hypoglycemia / Early / Incidence not known
    diabetes mellitus / Delayed / Incidence not known
    confusion / Early / Incidence not known
    withdrawal / Early / Incidence not known
    eosinophilia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    hyperlipidemia / Delayed / Incidence not known

    Mild

    fatigue / Early / 2.0-26.0
    dizziness / Early / 3.0-20.0
    asthenia / Delayed / 10.0-20.0
    headache / Early / 2.0-12.0
    vomiting / Early / 6.0-10.0
    nausea / Early / 6.0-10.0
    diarrhea / Early / 5.0-7.0
    abdominal pain / Early / 2.5-7.0
    dyspepsia / Early / 2.0-6.0
    pyrosis (heartburn) / Early / 2.0-6.0
    hyperhidrosis / Delayed / 5.0-6.0
    syncope / Early / 5.0-5.0
    weakness / Early / 5.0-5.0
    rash / Early / 5.0-5.0
    insomnia / Early / 3.0-4.0
    anxiety / Delayed / 4.0-4.0
    paresthesias / Delayed / 4.0-4.0
    infection / Delayed / 4.0-4.0
    musculoskeletal pain / Early / 2.0-4.0
    fever / Early / 0.7-4.0
    back pain / Delayed / 3.0-3.0
    cough / Delayed / 3.0-3.0
    flatulence / Early / 2.0-2.0
    anorexia / Delayed / 2.0-2.0
    influenza / Delayed / 0.8-2.0
    vertigo / Early / Incidence not known
    emotional lability / Early / Incidence not known
    myalgia / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    photosensitivity / Delayed / Incidence not known
    alopecia / 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, including sotalol.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Aclidinium; Formoterol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Albiglutide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Albuterol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Albuterol; Ipratropium: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Aldesleukin, IL-2: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
    Alfentanil: (Moderate) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers.
    Alfuzosin: (Major) Use caution during concurrent administration. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. 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) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
    Alogliptin; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Alpha-blockers: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
    Alpha-glucosidase Inhibitors: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Ambrisentan: (Moderate) Although no specific interactions have been documented, ambrisentan has vasodilatory effects and may contribute additive hypotensive effects when given with other antihypertensive agents. Patients receiving ambrisentan in combination with other antihypertensive agents should be monitored for decreases in blood pressure.
    Amifostine: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
    Amiodarone: (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. Before initiating sotalol, the previous Class I and Class III antiarrhythmic therapy should be withdrawn under careful monitoring for a minimum of (2-3) plasma half-lives for the discontinued drug. Class III antiarrhythmics (e.g., amiodarone, dofetilide) are associated with QT prolongation and ventricular arrhythmias; concurrent exposure with sotalol could increase the risk of drug-induced proarrhythmias. Because of unpredictable pharmacokinetics with amiodarone, sotalol should not be initiated following discontinuation of amiodarone therapy until the QTc interval has normalized. In clinical trials, patients were not allowed to receive sotalol if they had received amiodarone for > 1 month in the previous 3 months.
    Amitriptyline: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sotalol include tricyclic antidepressants (TCAs). 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 (TdP) have been described, 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.
    Amitriptyline; Chlordiazepoxide: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sotalol include tricyclic antidepressants (TCAs). 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 (TdP) have been described, 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.
    Amlodipine: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
    Amlodipine; Atorvastatin: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
    Amlodipine; Benazepril: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
    Amlodipine; Olmesartan: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
    Amlodipine; Telmisartan: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
    Amlodipine; Valsartan: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Use caution if coadministering clarithromycin and sotalol. Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Use caution if coadministering clarithromycin and sotalol. Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    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 sotalol.
    Antacids: (Major) Coadministration of antacids with sotalol reduces the Cmax and AUC of sotalol by 26% and 20%, respectively. This interaction results in a 25% reduction in the bradycardic effect of sotalol (measured at rest). Antacid administration two hours after the sotalol dose does not alter sotalol pharmacokinetics or pharmacodynamics. Instruct patients to avoid using antacids containing aluminum hydroxide or magnesium hydroxide within 2 hours of taking sotalol.
    Antithyroid agents: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
    Apomorphine: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP should be used cautiously with sotalol. 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.
    Apraclonidine: (Moderate) Theoretically, additive blood pressure reductions could occur when apraclonidine is combined with antihypertensive agents.
    Arformoterol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Aripiprazole: (Major) QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Aripiprazole should be used cautiously and with close monitoring with sotalol.
    Arsenic Trioxide: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Artemether; Lumefantrine: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. 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. Consider ECG monitoring if sotalol must be used with or after artemether; lumefantrine treatment.
    Asenapine: (Major) 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. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Aspirin, ASA: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Aspirin, ASA; Carisoprodol: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Coadministration of antacids with sotalol reduces the Cmax and AUC of sotalol by 26% and 20%, respectively. This interaction results in a 25% reduction in the bradycardic effect of sotalol (measured at rest). Administer magnesium hydroxide two hours after the sotalol dose to avoid altering sotalol pharmacokinetics or pharmacodynamics. (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Aspirin, ASA; Dipyridamole: (Major) Beta-blockers should generally be withheld before dipyridamole-stress testing. Monitor the heart rate carefully following the dipyridamole injection. (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Aspirin, ASA; Omeprazole: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Aspirin, ASA; Oxycodone: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Aspirin, ASA; Pravastatin: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Atomoxetine: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with atomoxetine include sotalol.
    Azithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), cautious use of sotalol with azithromycin is advised. Azithromycin has been associated with post-marketing reports of QT prolongation and TdP. Sotalol administration is also associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of sotalol therapy and after each upward dosage adjustment.
    Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with sotalol. Bedaquiline has 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. Sotalol administration is also associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Concurrent use of beta-blockers and ergot alkaloids should be approached with caution. Concomitant administration with beta-blockers may enhance the vasoconstrictive action of certain ergot alkaloids including dihydroergotamine, ergotamine, methylergonovine, and methysergide. The risk of peripheral ischemia, resulting in cold extremities or gangrene, has been reported to be increased when ergotamine or dihydroergotamine is coadministered with selected beta-blockers, including propranolol, a beta-blocker commonly used for migraine prophylaxis. However, the precise mechanism of these interactions remains elusive. Additionally, because of the potential to cause coronary vasospasm, these ergot alkaloids could antagonize the therapeutic effects of anti-anginal agents including beta-blockers; clinicians should keep in mind that ergot alkaloids are contraindicated for use in patients with coronary heart disease or hypertension.
    Bepridil: (Severe) Bepridil is contraindicated for use with drugs that prolong the QT interval due to the risk of torsade de pointes (TdP), including Class III antiarrhythmic agents. 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 III antiarrhythmics, have an increased risk of developing proarrhythmias during bepridil therapy.
    Betaxolol: (Severe) Using sotalol with other beta-blockers would be illogical as it would represent duplicate therapy; additive effects on AV nodal conduction and blood pressure would be expected. The risk of additive inhibition of AV conduction is symptomatic bradycardia with hypotension or advanced AV block; whereas additive negative inotropic effects could precipitate overt heart failure in some patients.
    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 sotalol.
    Bismuth Subsalicylate: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    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 sotalol. (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Bosentan: (Moderate) Although no specific interactions have been documented, bosentan has vasodilatory effects and may contribute additive hypotensive effects when given with beta-blockers.
    Bretylium: (Severe) Sotalol administration is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Before initiating sotalol, the previous Class III antiarrhythmic therapy (Bretylium) should be withdrawn under careful monitoring for a minimum of (23) plasma half-lives for the discontinued drug. Class III antiarrhythmics are associated with QT prolongation and ventricular arrhythmias; concurrent exposure with sotalol could increase the risk of drug-induced proarrhythmias.
    Budesonide; Formoterol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Buprenorphine: (Major) Buprenorphine should be avoided in combination with sotalol. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Sotalol, a class III antiarrhythmic, has an established risk for QT prolongation and TdP and caution is recommended if concurrent use with buprenorphine is required. 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 sotalol. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Sotalol, a class III antiarrhythmic, has an established risk for QT prolongation and TdP and caution is recommended if concurrent use with buprenorphine is required. 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.
    Cabergoline: (Major) Because of its potential to cause coronary vasospasm, ergot alkaloids could theoretically antagonize the therapeutic effects of beta-blockers.
    Caffeine; Ergotamine: (Moderate) Concurrent use of beta-blockers and ergot alkaloids should be approached with caution. Concomitant administration with beta-blockers may enhance the vasoconstrictive action of certain ergot alkaloids including dihydroergotamine, ergotamine, methylergonovine, and methysergide. The risk of peripheral ischemia, resulting in cold extremities or gangrene, has been reported to be increased when ergotamine or dihydroergotamine is coadministered with selected beta-blockers, including propranolol, a beta-blocker commonly used for migraine prophylaxis. However, the precise mechanism of these interactions remains elusive. Additionally, because of the potential to cause coronary vasospasm, these ergot alkaloids could antagonize the therapeutic effects of anti-anginal agents including beta-blockers; clinicians should keep in mind that ergot alkaloids are contraindicated for use in patients with coronary heart disease or hypertension.
    Calcium Carbonate: (Major) Coadministration of antacids with sotalol reduces the Cmax and AUC of sotalol by 26% and 20%, respectively. This interaction results in a 25% reduction in the bradycardic effect of sotalol (measured at rest). Administer antacids two hours after the sotalol dose to avoid altering sotalol pharmacokinetics or pharmacodynamics.
    Calcium Carbonate; Magnesium Hydroxide: (Major) Coadministration of antacids with sotalol reduces the Cmax and AUC of sotalol by 26% and 20%, respectively. This interaction results in a 25% reduction in the bradycardic effect of sotalol (measured at rest). Administer antacids two hours after the sotalol dose to avoid altering sotalol pharmacokinetics or pharmacodynamics.
    Calcium Carbonate; Risedronate: (Major) Coadministration of antacids with sotalol reduces the Cmax and AUC of sotalol by 26% and 20%, respectively. This interaction results in a 25% reduction in the bradycardic effect of sotalol (measured at rest). Administer antacids two hours after the sotalol dose to avoid altering sotalol pharmacokinetics or pharmacodynamics.
    Calcium Carbonate; Simethicone: (Major) Coadministration of antacids with sotalol reduces the Cmax and AUC of sotalol by 26% and 20%, respectively. This interaction results in a 25% reduction in the bradycardic effect of sotalol (measured at rest). Administer antacids two hours after the sotalol dose to avoid altering sotalol pharmacokinetics or pharmacodynamics.
    Canagliflozin; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Carbidopa; Levodopa: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
    Carbidopa; Levodopa; Entacapone: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
    Carbonic anhydrase inhibitors: (Major) Diuretics should be used cautiously with sotalol and should be accompanied by close monitoring of electrolyte balance because hypokalemia and hypomagnesemia have been associated with an increased risk of proarrhythmia.
    Cardiac glycosides: (Moderate) Sotalol and digoxin should be used together cautiously. Digoxin and sotalol slow AV conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. In addition, digoxin used concomitantly with sotalol can increase the possibility of proarrhythmia. Proarrhythmic events were more common in sotalol-treated patients also receiving digoxin; it is not clear whether this represents an interaction or is related to the presence of CHF, a known risk factor for proarrhythmia. Single and multiple doses of sotalol do not appear to interfere substantially with digoxin serum concentrations.
    Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
    Ceritinib: (Major) Avoid coadministration of ceritinib with sotalol if possible due to the risk of additive bradycardia; QT prolongation may also occur. If unavoidable, monitor heart rate and blood pressure regularly; periodically monitor electrolytes and ECGs. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation or bradycardia occurs. Ceritinib causes concentration-dependent prolongation of the QT interval and bradycardia. Sotalol is also associated with bradycardia, QT prolongation, and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Cevimeline: (Moderate) Cevimeline may alter cardiac conduction and/or heart rate. Conduction disturbances are possible with concurrent use of beta-blockers and cevimeline.
    Charcoal: (Major) Charcoal exerts a nonspecific effect, and many medications can be adsorbed by activated charcoal. While the reduction in absorption is beneficial in treating overdoses of drugs and toxins, activated charcoal dietary supplements used for flatulence or other purposes may reduce the effectiveness of certain beta-blocking agents (e.g., atenolol, sotalol, nadolol, pindolol). Use together is best limited to situations of drug overdose. Activated charcoal (single dose, 50-gram) reduced the absorption of therapeutic doses of atenolol, pindolol, and sotalol by > 90%. Repeat charcoal doses may decrease the entero-hepatic recycling of some of these agents. Repeated doses increased the elimination of sotalol and nadolol.
    Chloroquine: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Chloroquine administration is associated with an increased risk of QT prolongation and TdP. The need to coadminister chloroquine with drugs known to prolong the QT interval should be done with a careful assessment of risks versus benefits and should be avoided when possible.
    Chlorpromazine: (Major) Use caution during concurrent administration of chlorpromazine and sotalol. Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Chlorthalidone; Clonidine: (Major) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
    Choline Salicylate; Magnesium Salicylate: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Ciprofloxacin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering sotalol with ciprofloxacin. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Ciprofloxacin has a possible risk for QT prolongation and TdP and should be used cautiously with sotalol.
    Cisapride: (Severe) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. QT prolongation and ventricular arrhythmias, including TdP and death, have been reported with cisapride. Because of the potential for TdP, concurrent use is contraindicated.
    Citalopram: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Clarithromycin: (Major) Use caution if coadministering clarithromycin and sotalol. Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Class IA Antiarrhythmics: (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.
    Clevidipine: (Moderate) Calcium-channel blockers, like clevidipine, and beta-blockers frequently are used together with no adverse reactions. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension if these drugs are given together.
    Clofazimine: (Major) Monitor ECGs for QT prolongation when clofazimine is administered with sotalol. QT prolongation and torsade de pointes (TdP) have been reported in patients receiving clofazimine in combination with QT prolonging medications. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Clomipramine: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sotalol include tricyclic antidepressants (TCAs). 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 (TdP) have been described, 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.
    Clonidine: (Major) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
    Clozapine: (Major) Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause QT prolongation. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Codeine; Phenylephrine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include sotalol.
    Codeine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include sotalol.
    Colesevelam: (Moderate) Colesevelam may decrease the absorption of oral antiarrhythmics. To minimize potential for interactions, consider administering oral antiarrhythmics at least 1 hour before or at least 4 hours after colesevelam.
    Conivaptan: (Major) Conivaptan has been associated with hypokalemia (9.8%). Drug-induced hypokalemia increases the potential for proarrhythmic effects (e.g., torsade de pointes) due to sotalol. Coadministration of conivaptan with sotalol should be undertaken with extreme caution. Sotalol is contraindicated in patients with uncorrected hypokalemia (< 4 mEq/ml).
    Crizotinib: (Major) Avoid coadministration of crizotinib with sotalol due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Dapagliflozin; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include sotalol.
    Dasatinib: (Minor) Use caution during concurrent use of sotalol and dasatinib. 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. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Degarelix: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sotalol include degarelix.
    Desflurane: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension. Severe, protracted hypotension and difficulty in restarting the heart have been reported after surgery on patients receiving beta-blockers. In addition, sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP, such as halogenated anesthetics, should be used cautiously with sotalol.
    Desipramine: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sotalol include tricyclic antidepressants (TCAs). 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 (TdP) have been described, 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.
    Deutetrabenazine: (Major) For patients taking a deutetrabenazine dosage more than 24 mg/day with sotalol, assess the QTc interval before and after increasing the dosage of either medication. Clinically relevant QTc prolongation may occur with deutetrabenazine. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Dexmedetomidine: (Major) In general, the concomitant administration of dexmedetomidine with antihypertensive agents could lead to additive hypotensive effects. Dexmedetomidine can produce bradycardia or AV block and should be used cautiously in patients who are receiving antihypertensive drugs that lower the heart rate such as beta-blockers.
    Dextromethorphan; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include sotalol.
    Dextromethorphan; Quinidine: (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.
    Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agent. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving beta-blockers.
    Dihydroergotamine: (Moderate) Concurrent use of beta-blockers and ergot alkaloids should be approached with caution. Concomitant administration with beta-blockers may enhance the vasoconstrictive action of certain ergot alkaloids including dihydroergotamine, ergotamine, methylergonovine, and methysergide. The risk of peripheral ischemia, resulting in cold extremities or gangrene, has been reported to be increased when ergotamine or dihydroergotamine is coadministered with selected beta-blockers, including propranolol, a beta-blocker commonly used for migraine prophylaxis. However, the precise mechanism of these interactions remains elusive. Additionally, because of the potential to cause coronary vasospasm, these ergot alkaloids could antagonize the therapeutic effects of anti-anginal agents including beta-blockers; clinicians should keep in mind that ergot alkaloids are contraindicated for use in patients with coronary heart disease or hypertension.
    Diltiazem: (Moderate) The combination of diltiazem and a beta-blocker, like sotalol, is usually well tolerated; the combination is often used for their combined therapeutic benefits to reduce angina and improve exercise tolerance. However, because beta-blockers and diltiazem are negative inotropes and chronotropes, the combination of beta-blockers and diltiazem may cause heart failure, excessive bradycardia, hypotension, cardiac conduction abnormalities, or heart block.
    Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Dipyridamole: (Major) Beta-blockers should generally be withheld before dipyridamole-stress testing. Monitor the heart rate carefully following the dipyridamole injection.
    Disopyramide: (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.
    Dofetilide: (Major) Coadministration of dofetilide and sotalol is not recommended as concurrent use may increase the risk of QT prolongation. Class III antiarrhythmic agents, such as sotalol, should be withheld for at least 3 half-lives prior to initiating dofetilide therapy. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Dolasetron: (Major) Use caution during concurrent use of dolasetron and sotalol. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised.
    Dolutegravir; Rilpivirine: (Major) 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. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Donepezil: (Major) Monitor for evidence of QT prolongation and torsade de pointes (TdP) if concurrent use of donepezil and sotalol is necessary. Both drugs are associated with a risk of QT prolongation and TdP; these effects may be additive during coadministration. In addition, the increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may be increased when given with other medications known to cause bradycardia such as beta-blockers. These interactions are pharmacodynamic in nature rather than pharmacokinetic.
    Donepezil; Memantine: (Major) Monitor for evidence of QT prolongation and torsade de pointes (TdP) if concurrent use of donepezil and sotalol is necessary. Both drugs are associated with a risk of QT prolongation and TdP; these effects may be additive during coadministration. In addition, the increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may be increased when given with other medications known to cause bradycardia such as beta-blockers. These interactions are pharmacodynamic in nature rather than pharmacokinetic.
    Doxazosin: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
    Doxepin: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sotalol include tricyclic antidepressants (TCAs). 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 (TdP) have been described, 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.
    Dronedarone: (Severe) Concurrent use of dronedarone and sotalol is contraindicated. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. 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. The concomitant use of dronedarone with other drugs that prolong the QTc may induce TdP and is contraindicated.
    Droperidol: (Major) Use caution during concurrent use of droperidol and sotalol. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.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 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.
    Dulaglutide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Dutasteride; Tamsulosin: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Efavirenz: (Major) Coadministration of efavirenz and sotalol 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. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Coadministration of efavirenz and sotalol 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. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of efavirenz and sotalol 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. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Eliglustat: (Major) Coadministration of sotalol and eliglustat is not recommended. If coadministration is necessary, use extreme caution and close monitoring. Sotalol is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration may result in additive effects on the QT interval, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias).
    Empagliflozin; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) 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. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) 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. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Enalapril; Felodipine: (Moderate) The concomitant use of felodipine and sotalol can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
    Encainide: (Major) There is limited experience when using class 1C antiarrhythmics, like encainide, in combination with sotalol. Pharmacologically, sotalol causes AV nodal conduction depression and additive effects are possible when used in combination with encainide. Patients should be monitored closely if encainide used in combination with sotalol, and the dose should be adjusted according to clinical response. In addition, sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Encorafenib: (Major) Avoid coadministration of encorafenib and sotalol due to the potential for additive QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Enflurane: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension. Severe, protracted hypotension and difficulty in restarting the heart have been reported after surgery on patients receiving beta-blockers. In addition, sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP, such as halogenated anesthetics, should be used cautiously with sotalol.
    Entrectinib: (Major) Avoid coadministration of entrectinib with sotalol due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Epoprostenol: (Moderate) Epoprostenol can have additive effects when administered with other antihypertensive agents, including beta-blockers. These effects can be used to therapeutic advantage, but dosage adjustments may be necessary.
    Ergonovine: (Major) Whenever possible, concomitant use of beta-blockers and ergot alkaloids should be avoided, since propranolol has been reported to potentiate the vasoconstrictive action of ergotamine. The risk of peripheral ischemia, resulting in cold extremities or gangrene, has been reported to be increased when ergot alkaloids are coadministered with selected beta-blockers, including propranolol, a beta-blocker commonly used for migraine prophylaxis. However, the precise mechanism of these interactions remains elusive. Additionally, because of the potential to cause coronary vasospasm, ergot alkaloids could antagonize the therapeutic effects of anti-anginal agents including beta-blockers; clinicians should keep in mind that ergot alkaloids are contraindicated for use in patients with coronary heart disease or hypertension.
    Ergotamine: (Moderate) Concurrent use of beta-blockers and ergot alkaloids should be approached with caution. Concomitant administration with beta-blockers may enhance the vasoconstrictive action of certain ergot alkaloids including dihydroergotamine, ergotamine, methylergonovine, and methysergide. The risk of peripheral ischemia, resulting in cold extremities or gangrene, has been reported to be increased when ergotamine or dihydroergotamine is coadministered with selected beta-blockers, including propranolol, a beta-blocker commonly used for migraine prophylaxis. However, the precise mechanism of these interactions remains elusive. Additionally, because of the potential to cause coronary vasospasm, these ergot alkaloids could antagonize the therapeutic effects of anti-anginal agents including beta-blockers; clinicians should keep in mind that ergot alkaloids are contraindicated for use in patients with coronary heart disease or hypertension.
    Eribulin: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sotalol include eribulin. If eribulin and sotalol must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Ertugliflozin; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Erythromycin: (Major) Concurrent use of erythromycin with Class III (amiodarone, ibutilide, sotalol) antiarrhythmic agents should be avoided. 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 Class III antiarrhythmics. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Erythromycin; Sulfisoxazole: (Major) Concurrent use of erythromycin with Class III (amiodarone, ibutilide, sotalol) antiarrhythmic agents should be avoided. 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 Class III antiarrhythmics. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    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 sotalol, should be done with caution and close monitoring.
    Estradiol Cypionate; Medroxyprogesterone: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormonal contraceptives should be monitored for antihypertensive effectiveness.
    Estradiol: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormonal contraceptives should be monitored for antihypertensive effectiveness.
    Etomidate: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension.
    Exenatide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Ezogabine: (Major) Ezogabine has been associated with QT prolongation. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Use caution during concurrent use of medications known to increase the QT interval.
    Felodipine: (Moderate) The concomitant use of felodipine and sotalol can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
    Fingolimod: (Severe) Fingolimod is contraindicated in patients with cardiac arrhythmias requiring anti-arrhythmic treatment with Class III antiarrhythmics due to an increase in the risk of QT prolongation. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Class III antiarrhythmics are known to prolong the QT interval.
    Flecainide: (Major) There is limited experience when using Class IC antiarrhythmics in combination with sotalol. Pharmacologically, sotalol causes AV nodal conduction depression, and additive effects are possible when used in combination with class 1C antiarrhythmic drugs including flecainide. Patients should be monitored closely if class IC antiarrhythmic drugs are used in combination with sotalol, and the dose should be adjusted according to clinical response. In a small trial of ten pediatric infants (aged < 1 year), flecainide and sotalol combination therapy has been reported to effectively treat refractory supraventricular arrhythmias without development of proarrhythmias. Sotalol is associated with a causal risk for QT prolongation and torsades de pointes (TdP), and should be used cautiously with drugs that may prolong the QT interval. Flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, rare cases of QT prolongation and torsades de pointes (TdP) have been reported during flecainide therapy.
    Fluconazole: (Major) Use caution during concurrent use of fluconazole and sotalol. Fluconazole has been associated with QT prolongation and rare cases of torsades de pointes (TdP). Sotalol administration is also associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Fluorescein: (Moderate) Patients on beta-blockers are at an increased risk of adverse reaction when administered fluorescein injection. It is thought that beta-blockers may worsen anaphylaxis severity by exacerbating bronchospasm or by increasing the release of anaphylaxis mediators; alternately, beta-blocker therapy may make the patient more pharmacodynamically resistance to epinephrine rescue treatment.
    Fluoxetine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include sotalol.
    Fluoxetine; Olanzapine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include sotalol. (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP, such as olanzapine, should be used cautiously with sotalol. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Fluphenazine: (Minor) Use caution during concurrent administration of fluphenazine and sotalol. Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Fluticasone; Salmeterol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Fluticasone; Vilanterol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Fluvoxamine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and sotalol. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. Sotalol is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Food: (Major) Avoid administering marijuana and beta-blockers together as concurrent use may result in decreased beta-blocker efficacy. Marijuana is known to produce significant increases in heart rate and cardiac output lasting for 2-3 hours. Further, rare case reports of myocardial infarction and cardiac arrhythmias have been associated with marijuana use. These marijuana-induced cardiovascular effects may be detrimental to patients requiring treatment with beta-blockers; thus, coadministration of beta-blockers and marijuana should be avoided.
    Formoterol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Formoterol; Mometasone: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as sotalol. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Sotalol administration is also associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Galantamine: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors such as galantamine may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Gallium Ga 68 Dotatate: (Major) Diuretics should be used cautiously with sotalol and should be accompanied by close monitoring of electrolyte balance because hypokalemia and hypomagnesemia have been associated with an increased risk of proarrhythmia.
    Gemifloxacin: (Major) Concurrent use of sotalol and gemifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Gemifloxacin may also prolong the QT interval in some patients, with the maximal change in the QTc interval occurring approximately 5 to 10 hours following oral administration. The likelihood of QTc prolongation may increase with increasing dose of gemifloxacin; 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 sotalol 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. Sotalol administration is also associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of sotalol and after each upward dosage adjustment.
    Gilteritinib: (Major) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and sotalol is necessary. Gilteritinib has been associated with QT prolongation. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    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 human data are available.
    Glasdegib: (Major) Avoid coadministration of glasdegib with sotalol due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Glipizide; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Glucagon: (Minor) A temporary increase in both blood pressure and pulse rate may occur following the administration of glucagon. Patients taking beta-blockers might be expected to have a greater increase in both pulse and blood pressure. Glucagon exerts positive inotropic and chronotropic effects and may, therefore, cause tachycardia and hypertension in some patients. The increase in blood pressure and pulse rate may require therapy in some patients with coronary artery disease.
    Glyburide; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Glycopyrrolate; Formoterol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Goserelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving sotalol. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Granisetron: (Major) 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. Drugs with a possible risk for QT prolongation and TdP, such as granisetron, should be used cautiously with sotalol. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Guanabenz: (Moderate) Guanabenz can have additive effects when administered with other antihypertensive agents, including beta-blockers. These effects can be used to therapeutic advantage, but dosage adjustments may be necessary.
    Guanfacine: (Moderate) Guanfacine can have additive effects when administered with other antihypertensive agents, including beta-blockers. These effects can be used to therapeutic advantage, but dosage adjustments may be necessary.
    Halofantrine: (Severe) Halofantrine should be avoided in patients receiving drugs which may induce QT prolongation; these drugs include class III antiarrhythmics.
    Halogenated Anesthetics: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension. Severe, protracted hypotension and difficulty in restarting the heart have been reported after surgery on patients receiving beta-blockers. In addition, sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP, such as halogenated anesthetics, should be used cautiously with sotalol.
    Haloperidol: (Major) QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration 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. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Halothane: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension. Severe, protracted hypotension and difficulty in restarting the heart have been reported after surgery on patients receiving beta-blockers. In addition, sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP, such as halogenated anesthetics, should be used cautiously with sotalol.
    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 is increased and the refractory period is prolonged. Hawthorn may also lower peripheral vascular resistance. Hawthorn thus has effects similar to the class III antiarrhythmics and would theoretically interact with drugs with similar cardiac electrophysiology (e.g., amiodarone, bretylium, dofetilide, ibutilide, sotalol). 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.
    Histrelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving sotalol. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and sotalol. 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. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of sotalol therapy and after each upward dosage adjustment.
    Hydroxyzine: (Major) Caution is recommended if hydroxyzine is administered with sotalol due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    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, 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, other Class III antiarrhythmics were not given for at least 5 half-lives prior to ibutilide infusion or 4 hours after ibutilide dosing. If sotalol is to be initiated in a patient previously receiving ibutilide, ibutilide should be withdrawn under careful monitoring for a minimum of (2-3) plasma half-lives.
    Iloperidone: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. loperidone has been associated with QT prolongation; however, TdP has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect.
    Iloprost: (Moderate) Additive reductions in blood pressure may occur when inhaled iloprost is administered to patients receiving other antihypertensive agents.
    Imipramine: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sotalol include tricyclic antidepressants (TCAs). 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 (TdP) have been described, 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.
    Incretin Mimetics: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Indacaterol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Indacaterol; Glycopyrrolate: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with sotalol 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. Sotalol administration is also associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of sotalol and after each upward dosage adjustment.
    Insulin Degludec; Liraglutide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Insulin Glargine; Lixisenatide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Insulins: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Isoflurane: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension. Severe, protracted hypotension and difficulty in restarting the heart have been reported after surgery on patients receiving beta-blockers. In addition, sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP, such as halogenated anesthetics, should be used cautiously with sotalol.
    Isradipine: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Itraconazole: (Major) Itraconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with itraconazole include sotalol.
    Ivabradine: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with sotalol due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Ketamine: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension.
    Ketoconazole: (Major) Ketoconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ketoconazole include sotalol.
    Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class III antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
    Lanreotide: (Moderate) Concomitant administration of bradycardia-inducing drugs such as sotalol may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the dose of sotalol if necessary.
    Lapatinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of lapatinib with sotalol is necessary; correct electrolyte abnormalities prior to treatment. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Sotalol administration is also associated with QT prolongation and TdP; proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Lefamulin: (Major) Avoid coadministration of lefamulin with sotalol as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with sotalol due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Sotalol administration is also associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of sotalol therapy and after each upward dosage adjustment.
    Leuprolide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving sotalol. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Leuprolide; Norethindrone: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving sotalol. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Levalbuterol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Levodopa: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
    Levofloxacin: (Major) Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Rare cases of torsade de pointes (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. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Levomethadyl: (Severe) Levomethadyl is associated with an established risk of QT prolongation and/or torsades de pointes and is contraindicated in combination with other agents that may prolong the QT interval, such as Class III antiarrhythmics.
    Levothyroxine: (Minor) Because thyroid hormones cause cardiac stimulation including increased heart rate and increased contractility, the effects of beta-blockers may be reduced by thyroid hormones. The reduction of effects may be especially evident when a patient goes from a hypothyroid to a euthyroid state or when excessive amounts of thyroid hormone is given to the patient.
    Levothyroxine; Liothyronine (Porcine): (Minor) Because thyroid hormones cause cardiac stimulation including increased heart rate and increased contractility, the effects of beta-blockers may be reduced by thyroid hormones. The reduction of effects may be especially evident when a patient goes from a hypothyroid to a euthyroid state or when excessive amounts of thyroid hormone is given to the patient.
    Levothyroxine; Liothyronine (Synthetic): (Minor) Because thyroid hormones cause cardiac stimulation including increased heart rate and increased contractility, the effects of beta-blockers may be reduced by thyroid hormones. The reduction of effects may be especially evident when a patient goes from a hypothyroid to a euthyroid state or when excessive amounts of thyroid hormone is given to the patient.
    Linagliptin; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Liothyronine: (Minor) Because thyroid hormones cause cardiac stimulation including increased heart rate and increased contractility, the effects of beta-blockers may be reduced by thyroid hormones. The reduction of effects may be especially evident when a patient goes from a hypothyroid to a euthyroid state or when excessive amounts of thyroid hormone is given to the patient.
    Liraglutide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Lithium: (Major) Sotalol and lithium are associated with QT prolongation. Coadministration may increase the risk of QT prolongation; therefore, sotalol and lithium should be coadministered with caution and close monitoring. Beta-blockers have been used to treat lithium-induced tremor, however, sotalol is not one of the beta-blockers used in this fashion. Tremor may be a sign of lithium toxicity and may be masked by the coadministration of beta-blockers including sotalol, so patients should be monitored for other clinical signs of lithium toxicity if these medications are taken concurrently. Other clinical signs of toxicity include: anorexia; visual impairment; drowsiness; muscular weakness; fasciculations or myoclonia; ataxia; dysarthria or slurred speech; stupor or coma; confusion or impaired cognition; seizures; and arrhythmias. Limited data suggest that using propranolol, even in low doses, with lithium can lead to bradycardia and syncope. In addition, lithium renal clearance has been shown to be lower when propranolol was coadministered. It is not clear if these effects are unique for propranolol or hold true for all beta-blockers. Until more data are known, clinicians should use all beta-blockers with caution in patients receiving lithium.
    Lixisenatide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Lofexidine: (Major) Because both lofexidine and sotalol can cause hypotension and bradycardia, concurrent use should be avoided if possible. In addition, both drugs have been associated with QT prolongation and torsade de pointes (TdP) and additive effects are possible. If coadministration is necessary, monitor the ECG during treatment. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Patients being given lofexidine in an outpatient setting should be capable of and instructed on self-monitoring for hypotension, orthostasis, bradycardia, and associated symptoms. If clinically significant or symptomatic hypotension and/or bradycardia occur, the next dose of lofexidine should be reduced in amount, delayed, or skipped.
    Lomefloxacin: (Severe) Lomefloxacin has been associated with QT prolongation and infrequent cases of arrhythmia. Lomefloxacin should be avoided in patients receiving Class III Antiarrhythmics.
    Long-acting beta-agonists: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Loperamide: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like sotalol, should be used cautiously and with close monitoring with loperamide.
    Loperamide; Simethicone: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like sotalol, should be used cautiously and with close monitoring with loperamide.
    Lopinavir; Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include sotalol. (Major) Use caution during coadministration of sotalol and lopinavir; ritonavir. Lopinavir; ritonavir is associated with QT prolongation. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Coadministration of lopinavir; ritonavir with sotalol may result in additive QT prolongation.
    Lovastatin; Niacin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as sotalol. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Magnesium Salicylate: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Mannitol: (Major) Diuretics should be used cautiously with sotalol and should be accompanied by close monitoring of electrolyte balance because hypokalemia and hypomagnesemia have been associated with an increased risk of proarrhythmia.
    Maprotiline: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP should be used cautiously with sotalol. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is 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 maprotiline in combination with other QT-prolonging drugs.
    Mefloquine: (Moderate) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Mefloquine is associated with a possible risk for QT prolongation and TdP and should be used cautiously with sotalol. In addition, the concurrent use of mefloquine and beta-blockers can result in ECG abnormalities or cardiac arrest.
    Meglitinides: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Meperidine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include sotalol.
    Metaproterenol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Metformin; Pioglitazone: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Metformin; Repaglinide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Metformin; Rosiglitazone: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Metformin; Saxagliptin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Metformin; Sitagliptin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Methacholine: (Moderate) Beta-blockers may impair reversal of methacholine-induced bronchoconstriction with an inhaled rapid-acting beta-agonist.
    Methadone: (Major) The need to coadminister methadone with sotalol should be done with extreme caution and a careful assessment of treatment risks versus benefits. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Methadone is considered to be associated with an increased risk for QT prolongation and TdP, especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
    Methohexital: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension.
    Methylergonovine: (Moderate) Concurrent use of beta-blockers and ergot alkaloids should be approached with caution. Concomitant administration with beta-blockers may enhance the vasoconstrictive action of certain ergot alkaloids including dihydroergotamine, ergotamine, methylergonovine, and methysergide. The risk of peripheral ischemia, resulting in cold extremities or gangrene, has been reported to be increased when ergotamine or dihydroergotamine is coadministered with selected beta-blockers, including propranolol, a beta-blocker commonly used for migraine prophylaxis. However, the precise mechanism of these interactions remains elusive. Additionally, because of the potential to cause coronary vasospasm, these ergot alkaloids could antagonize the therapeutic effects of anti-anginal agents including beta-blockers; clinicians should keep in mind that ergot alkaloids are contraindicated for use in patients with coronary heart disease or hypertension.
    Methysergide: (Moderate) Concurrent use of beta-blockers and ergot alkaloids should be approached with caution. Concomitant administration with beta-blockers may enhance the vasoconstrictive action of certain ergot alkaloids including dihydroergotamine, ergotamine, methylergonovine, and methysergide. The risk of peripheral ischemia, resulting in cold extremities or gangrene, has been reported to be increased when ergotamine or dihydroergotamine is coadministered with selected beta-blockers, including propranolol, a beta-blocker commonly used for migraine prophylaxis. However, the precise mechanism of these interactions remains elusive. Additionally, because of the potential to cause coronary vasospasm, these ergot alkaloids could antagonize the therapeutic effects of anti-anginal agents including beta-blockers; clinicians should keep in mind that ergot alkaloids are contraindicated for use in patients with coronary heart disease or hypertension.
    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 sotalol.
    Midostaurin: (Major) The concomitant use of midostaurin and sotalol may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. Consider sotalol dose reduction or discontinuation if the QTc interval is greater than 500 milliseconds (msec); serious consideration to dose reduction or drug discontinuation should occur in patients with a QTc interval greater than 550 msec. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. QT prolongation and torsade de pointes have been reported with sotalol in clinical trials.
    Mifepristone: (Major) Mifepristone should be used cautiously and with close monitoring with sotalol. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used.
    Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
    Mirtazapine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and sotalol. Coadminister with caution. Sotalol is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. 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.
    Moxifloxacin: (Major) 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, such as sotalol. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Nebivolol: (Severe) Coadministration would be illogical as both are beta-blockers and would represent duplicate therapy; additive effects on AV nodal conduction and blood pressure would be expected.
    Nebivolol; Valsartan: (Severe) Coadministration would be illogical as both are beta-blockers and would represent duplicate therapy; additive effects on AV nodal conduction and blood pressure would be expected.
    Nefazodone: (Minor) Although relatively infrequent, nefazodone may cause orthostatic hypotension in some patients; this effect may be additive with antihypertensive agents. Blood pressure monitoring and dosage adjustments of either drug may be necessary.
    Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Niacin; Simvastatin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Nicardipine: (Moderate) Although concomitant therapy with nicardipine and sotalol generally is well tolerated and can even be beneficial in some cases (by inhibiting reflex tachycardia induced by nicardipine), sotalol can induce excessive bradycardia or hypotension. This combination also can cause additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nicardipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nicardipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with verapamil or diltiazem than with nicardipine.
    Nifedipine: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib and sotalol; significant prolongation of the QT interval may occur. Sudden death and QT prolongation have occurred in patients who received nilotinib therapy. Sotalol administration is associated with QT prolongation and torsades de pointes. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Nimodipine: (Moderate) Nimodipine, a selective calcium-channel blocker, can enhance the antihypertensive effects of beta-blockers. Although often used together, concurrent use of calcium-channel blockers and beta-blockers may result in additive hypotensive, negative inotropic, and/or bradycardic effects in some patients.
    Nisoldipine: (Moderate) Concurrent use of nisoldipine with sotalol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
    Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Non-Ionic Contrast Media: (Moderate) Some clinicians consider patients taking beta-blockers to be at increased risk for anaphylactoid reactions and administer prophylactic corticosteroids/antihistamines prior to the administration of radiopaque contrast agents.
    Nonsteroidal antiinflammatory drugs: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Norfloxacin: (Major) 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. Norfloxacin should be used cautiously with other agents that may prolong the QT interval or increase the risk of TdP, such as sotalol. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Nortriptyline: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sotalol include tricyclic antidepressants (TCAs). 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 (TdP) have been described, 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.
    Octreotide: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Octreotide should be used cautiously with sotalol. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. 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) 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). Drugs with a possible risk for QT prolongation and TdP should be used cautiously with ofloxacin. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Olanzapine: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP, such as olanzapine, should be used cautiously with sotalol. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Olodaterol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include sotalol.
    Omeprazole; Sodium Bicarbonate: (Major) Coadministration of antacids with sotalol reduces the Cmax and AUC of sotalol by 26% and 20%, respectively. This interaction results in a 25% reduction in the bradycardic effect of sotalol (measured at rest). Administer magnesium hydroxide two hours after the sotalol dose to avoid altering sotalol pharmacokinetics or pharmacodynamics.
    Ondansetron: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP, such as ondansetron, should be used cautiously with sotalol. Ondansetron has been associated with QT prolongation and post-marketing reports of TdP. Among 42 patients receiving a 4 mg bolus dose of intravenous ondansetron for the treatment of postoperative nausea and vomiting, the mean maximal QTc interval prolongation was 20 +/- 13 msec at the third minute after antiemetic administration (p < 0.0001). If ondansetron and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended.
    Osimertinib: (Major) Avoid coadministration of sotalol with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Sotalol administration is associated with QT prolongation and TdP; proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of sotalol with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by beta-blockers. If these drugs are used together, closely monitor for changes in blood pressure.
    Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
    Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Antiarrhythmic medicines with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include sotalol.
    Pasireotide: (Major) 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. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. In addition, pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
    Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as sotalol, is not advised; pazopanib has been reported to prolong the QT interval. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. If pazopanib and sotalol must be continued, closely monitor the patient for QT interval prolongation.
    Pentamidine: (Major) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP), such as sotalol, should be used cautiously with pentamidine. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Perindopril; Amlodipine: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
    Perphenazine: (Minor) Use caution during concurrent administration of perphenazine and sotalol. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Perphenazine; Amitriptyline: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sotalol include tricyclic antidepressants (TCAs). 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 (TdP) have been described, 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. (Minor) Use caution during concurrent administration of perphenazine and sotalol. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Phenoxybenzamine: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
    Phentolamine: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
    Phenylephrine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include sotalol.
    Pilocarpine: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    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 sotalol. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    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 sotalol with pimozide is contraindicated.
    Pirbuterol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Pitolisant: (Major) Avoid coadministration of pitolisant with sotalol as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Posaconazole: (Major) Use caution during concurrent administration of sotalol and posaconazole. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes.
    Pramlintide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Prazosin: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
    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 sotalol.
    Procainamide: (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.
    Prochlorperazine: (Minor) Phenothiazines have been reported to prolong the QT interval. Concurrent use of drugs that are associated with a possible risk for QT prolongation and torsade de pointes (TdP), such as sotalol, with prochlorperazine should be approached with caution. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential.
    Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include sotalol.
    Propafenone: (Major) Concurrent use of propafenone and Class III agents is not recommended. Propafenone and sotalol are both associated with QT prolongation. The effects of concomitant administration of antiarrhythmics can be synergistic, additive, or antagonistic, and adverse cardiac effects can be additive. There is limited experience when using class 1C antiarrhythmics in combination with sotalol, a Class III antiarrhythmic. Pharmacologically, sotalol cause AV nodal conduction depression and additive effects are possible when used in combination with class 1C antiarrhythmic drugs such as propafenone. Patients should be monitored closely if class IC antiarrhythmic drugs are used in combination with sotalol, and the dose should be adjusted according to clinical response. Before switching from another antiarrhythmic drug to propafenone therapy, Class III antiarrhythmics generally should be withheld for at least five half-lives prior to initiating propafenone.
    Propofol: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension.
    Protriptyline: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sotalol include tricyclic antidepressants (TCAs). 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 (TdP) have been described, 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.
    Quetiapine: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. 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.
    Quinidine: (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.
    Quinine: (Major) Concurrent use of quinine and sotalol should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Sotalol administration is also associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of sotalol therapy and after each upward dosage adjustment.
    Ranolazine: (Major) Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. The mean increase in QTc is about 6 milliseconds, measured at the tmax of the maximum dosage (1000 mg PO twice daily). However, in 5% of the population studied, increases in the QTc of at least 15 milliseconds have been reported. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, such as sotalol, coadministration may result in additive QT prolongation. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Rasagiline: (Moderate) Limited data suggest that bradycardia is worsened when monoamine oxidase inhibitors (MAOIs) are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers.
    Remifentanil: (Moderate) The risk of significant hypotension and/or bradycardia during therapy with remifentanil may be increased in patients receiving beta-blockers or calcium-channel blockers due to additive hypotensive effects.
    Reserpine: (Major) Use caution when adminstering sotalol together with catecholamine-depleting agents, such as reserpine or other rauwolfia alkaloids, as concomitant use may cause excessive reductions in resting sympathetic tone can produce hypotension or bradycardia, precipitating a syncopal episode.
    Ribociclib: (Major) Avoid coadministration of ribociclib with sotalol due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Sotalol administration is also associated with QT prolongation and TdP, with proarrhythmic events anticipated after initiation of therapy and after each upward dosage adjustment. Concomitant use may increase the risk for QT prolongation.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with sotalol due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Sotalol administration is also associated with QT prolongation and TdP, with proarrhythmic events anticipated after initiation of therapy and after each upward dosage adjustment. Concomitant use may increase the risk for QT prolongation.
    Rilpivirine: (Major) 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. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Risperidone: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, such as sotalol, taking into account the patient's underlying disease state(s) and additional potential risk factors. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
    Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include sotalol.
    Rivastigmine: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Romidepsin: (Major) Romidepsin has been reported to prolong the QT interval. Sotalol also prolongs the QT interval. If romidepsin and sotalol must be continued, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.
    Salmeterol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Salsalate: (Moderate) Concurrent use of beta-blockers with salsalate and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
    Saquinavir: (Major) Concurrent use of saquinavir boosted with ritonavir and sotalol should be avoided if possible due to the risk of life threatening cardiac arrhythmias such as torsade de pointes (TdP). Saquinavir boosted with ritonavir causes dose-dependent QT and PR prolongation; if possible, avoid use with other drugs that may prolong the QT or PR interval, such as all Class III antiarrhythmics. If no alternative therapy is acceptable, perform a baseline ECG prior to initiation of concomitant therapy and follow recommended ECG monitoring.
    Selegiline: (Moderate) Limited data suggest that bradycardia is worsened when monoamine oxidase inhibitors (MAOIs) are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers.
    Semaglutide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Sertraline: (Major) Use caution and monitor patients for QT prolongation when administering sotalol with sertraline. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. QTc prolongation and TdP have been reported during postmarketing use of sertraline; most cases had confounding risk factors. The risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
    Sevoflurane: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension. Severe, protracted hypotension and difficulty in restarting the heart have been reported after surgery on patients receiving beta-blockers. In addition, sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP, such as halogenated anesthetics, should be used cautiously with sotalol.
    SGLT2 Inhibitors: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Short-acting beta-agonists: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving sotalol due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Sotalol administration is associated with QT prolongation and torsade de pointes. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Sodium Bicarbonate: (Major) Coadministration of antacids with sotalol reduces the Cmax and AUC of sotalol by 26% and 20%, respectively. This interaction results in a 25% reduction in the bradycardic effect of sotalol (measured at rest). Administer magnesium hydroxide two hours after the sotalol dose to avoid altering sotalol pharmacokinetics or pharmacodynamics.
    Solifenacin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering solifenacin with sotalol. Solifenacin has been associated with dose-dependent prolongation of the QT interval; TdP has been reported during post-marketing use, although causality was not determined. Sotalol administration is also associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Sorafenib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of sorafenib with sotalol is necessary; correct any electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib has been associated with QT prolongation. Sotalol administration is also associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Sparfloxacin: (Severe) Sparfloxacin is associated with an established risk for QT prolongation and torsades de pointes. 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 or other drugs that can cause QT prolongation, such as class III antiarrhythmics.
    Succinylcholine: (Moderate) Beta-blockers can enhance the neuromuscular blocking activity of succinylcholine.
    Sufentanil: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
    Sulfonylureas: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Sunitinib: (Major) Monitor patients for QT prolongation if coadministration of sotalol with sunitinib is necessary. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Sunitinib can also cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
    Sympathomimetics: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Tacrine: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope in some patients. The vagotonic effect of these drugs may be increased when given with other medications known to cause bradycardia such as beta-blockers. These interactions are pharmacodynamic in nature rather than pharmacokinetic.
    Tacrolimus: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Tacrolimus causes QT prolongation and should be used cautiously with sotalol.
    Tamoxifen: (Major) Caution is advised with the concomitant use of tamoxifen and sotalol due to an increased risk of 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. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Tamsulosin: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Tasimelteon: (Major) The efficacy of tasimelteon in treating circadian rhythm disruptions may be reduced in patients receiving beta-blockers. Because the circadian rhythm of melatonin is regulated by the sympathetic nervous system, administration of beta-blockers may result in a clinically relevant blockade of melatonin secretion.
    Telavancin: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Telavancin has been associated with QT prolongation. Use caution and close monitoring during concurrent administration.
    Telithromycin: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Telithromycin is associated with QT prolongation and TdP. Use caution and close monitoring during concurrent administration.
    Terazosin: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
    Terbutaline: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Terfenadine: (Severe) Terfenadine has an established association with QT prolongation and torsade de pointes (tdP). Other drugs that have also been independently associated with prolonged QT syndrome and/or TdP should not be used concomitantly with terfenadine, such as Class III antiarrythmics.
    Tetrabenazine: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc.
    Thalidomide: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Thiazolidinediones: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
    Thiopental: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension.
    Thioridazine: (Severe) Because of the potential for torsades de pointes (TdP), use of thioridazine with sotalol is contraindicated. 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. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Thyroid hormones: (Minor) Because thyroid hormones cause cardiac stimulation including increased heart rate and increased contractility, the effects of beta-blockers may be reduced by thyroid hormones. The reduction of effects may be especially evident when a patient goes from a hypothyroid to a euthyroid state or when excessive amounts of thyroid hormone is given to the patient.
    Tiotropium; Olodaterol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Tolterodine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering tolterodine with sotalol. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Sotalol administration is also associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Toremifene: (Major) Avoid coadministration of sotalol with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Sotalol administration is also associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Trandolapril; Verapamil: (Moderate) Oral calcium-channel blockers and beta-blockers like sotalol are used together for their therapeutic benefits to reduce angina and improve exercise tolerance. However, concomitant administration of beta-adrenergic blocking agents and verapamil can lead to significant AV nodal blockade. This can manifest as heart block, bradycardia, cardiac conduction abnormalities and/or prolonged PR interval. Congestive heart failure or severe hypotension also can occur. The combination of beta-blockers and verapamil should be avoided in patients with poor ventricular function due to increased negative inotropic effects.
    Tranylcypromine: (Severe) The use of hypotensive agents and tranylcypromine is contraindicated by the manufacturer of tranylcypromine because the effects of hypotensive agents may be markedly potentiated. In addition, limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers.
    Trazodone: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are post-marketing reports of torsade de pointes (TdP). Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval.
    Tricyclic antidepressants: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sotalol include tricyclic antidepressants (TCAs). 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 (TdP) have been described, 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.
    Trifluoperazine: (Minor) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation and should be used cautiously with sotalol. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Trimipramine: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sotalol include tricyclic antidepressants (TCAs). 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 (TdP) have been described, 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.
    Triptorelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving sotalol. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Umeclidinium; Vilanterol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Urea: (Major) Diuretics should be used cautiously with sotalol and should be accompanied by close monitoring of electrolyte balance because hypokalemia and hypomagnesemia have been associated with an increased risk of proarrhythmia.
    Vandetanib: (Major) Avoid coadministration of vandetanib with sotalol due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Sotalol administration is also associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Vardenafil: (Major) 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. The manufacturer recommends that vardenafil be avoided in patients taking sotalol. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. If vemurafenib and sotalol must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Venlafaxine: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Venlafaxine administration is associated with a possible risk of QT prolongation; TdP has been reported with post-marketing use and should be used cautiously with sotalol.
    Verapamil: (Moderate) Oral calcium-channel blockers and beta-blockers like sotalol are used together for their therapeutic benefits to reduce angina and improve exercise tolerance. However, concomitant administration of beta-adrenergic blocking agents and verapamil can lead to significant AV nodal blockade. This can manifest as heart block, bradycardia, cardiac conduction abnormalities and/or prolonged PR interval. Congestive heart failure or severe hypotension also can occur. The combination of beta-blockers and verapamil should be avoided in patients with poor ventricular function due to increased negative inotropic effects.
    Voriconazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering voriconazole with sotalol. Voriconazole has been associated with prolongation of the QT interval and rare cases of arrhythmias, including TdP. Sotalol is also associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of sotalol therapy and after each upward dosage adjustment.
    Vorinostat: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with sotalol.
    Yohimbine: (Moderate) Yohimbine can increase blood pressure and therefore can antagonize the therapeutic action of antihypertensive agents. Use with particular caution in hypertensive patients with high or uncontrolled blood pressure.
    Ziprasidone: (Severe) Concomitant use of ziprasidone and class III antiarrhythmics, such as sotalol, is contraindicated by the manufacturer of ziprasidone due to the potential for additive QT prolongation and torsade de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of TdP in patients with multiple confounding factors. Class III antiarrhythmics are associated with a well-established risk of QT prolongation and TdP.

    PREGNANCY AND LACTATION

    Pregnancy

    Sotalol is classified as FDA pregnancy category B. Adequate evaluation of the use of sotalol during pregnancy has not been completed. Sotalol has been shown to cross the placenta and can be found in amniotic fluid. When administered to animals at 18 times the maximum recommended human dose, there was no increase in congenital anomalies, but an increase in early resorptions occurred. One case of subnormal birth weight was reported with use of sotalol in a pregnant woman. All beta-blockers have the potential for causing fetal bradycardia. Thus, sotalol should be used during pregnancy only when the benefits outweigh the potential risk to the fetus.

    Breast-feeding should be discontinued during sotalol therapy. Sotalol is secreted into breast milk in high concentrations. In 5 mothers whose mean sotalol dose was 433 mg/day, sotalol concentrations in milk ranged from 4.8 to 20.2 mg/L (mean = 10.5 mg/L), with a milk:plasma ratio of 5.5:1 (range 2.2 to 8.8). The calculated infant dose was 0.8 to 3.4 mg/kg, which is similar to recommended therapeutic doses in neonates. Two other case reports showed similar findings.

    MECHANISM OF ACTION

    Sotalol is a racemic mixture of isomers. The levorotatory isomer has all of the beta-blocking activity and both the levorotatory and dextrorotatory isomers possess Class III antiarrhythmic activity. Significant beta-blockade occurs with oral doses as low as 25 mg; the half maximal beta-blocking effect of sotalol is seen with daily doses of 80 mg, and maximal beta-blocking effects are observed with daily doses between 320 mg and 640 mg. Significant class III antiarrhythmic effects are observed with daily doses of 160 mg and more.
     
    The beta-blocker activity of sotalol increases sinus cycle length, decreases AV nodal conduction, and increases AV nodal refractoriness. Hemodynamic effects of sotalol include reduced heart rate and cardiac index as well as increased systemic vascular resistance, stroke volume, and pulmonary capillary wedge pressure. Significant reductions in systolic and diastolic blood pressure are also seen in hypertensive patients. In general, beta-blockers without intrinsic sympathomimetic activity (ISA), like sotalol, exert detrimental effects on left ventricular hypertrophy and the lipid profile.
     
    The antiarrhythmic activity is exerted by a combination of Class II activity and Class III activity, which lengthens repolarization or the plateau phase of the action potential and lengthens the refractory period in all cardiac tissues. In addition, sotalol prolongs the QT interval (a Class III effect), which must be carefully monitored to avoid predisposing patients to proarrhythmic events.

    PHARMACOKINETICS

    Sotalol is administered orally or intravenously. Distribution occurs to a central (plasma) and peripheral compartment. Sotalol does not bind to plasma proteins and has poor penetration of the blood brain barrier. Sotalol is not metabolized and is excreted primarily unchanged by the kidneys via glomerular filtration and tubular secretion. The plasma half-life in patients with normal renal function is 12 hours.
     
    Affected cytochrome P450 isoenzymes: none

    Oral Route

    After oral administration, bioavailability is 90% to 100%. Food reduces the rate of absorption by approximately 20%, but sotalol may be taken with or without food. In healthy patients, peak plasma concentrations are reached within 2.5 to 4 hours of oral administration, and steady-state plasma concentrations are reached within 2 to 3 days.