sotalol

Sotalol is a medication used to treat certain heart rhythm disorders (arrhythmias) which cause the chambers of the heart, atria and ventricles, to beat out of synchronization and too rapidly. Sotalol is used to treat life-threatening rapid heart rate in the ventricles (ventricular tachycardia) and to maintain normal sinus rhythm in patients with symptomatic atrial fibrillation. Sotalol slows down the heart rate and helps maintain the normal rhythm of the heart.

Several mechanisms are involved in making the heart beat steadily in a coordinated manner for efficient pumping of blood. Specialized heart muscle tissue in the right atrium known as the sinoatrial (SA) node, the heart’s natural pacemaker, fires electrical impulses rhythmically to make the heart muscle (myocardium) contract. Stimulation of different types of protein molecules (receptors) in the heart muscle cells, results in rhythmic contraction and relaxation.

The electrical impulses from the nerve cells (neurons) in the SA node make the atria contract first and then travel to the atrioventricular (AV) node which delays the signal till the atrial blood empties into the ventricles before making the ventricles contract. Abnormal functioning of the cardiac electrical circuit generates irregular signals that result in uncoordinated contractions of the atria and ventricles.

Beta-1 receptors in the heart muscle cells increase the heart rate and force of contraction when stimulated by the neurohormones (catecholamines) epinephrine and norepinephrine. This further worsens the arrhythmia, overworks the heart, and impairs the flow of blood which can pool up increasing the risk for clot formation, stroke, heart failure or other life-threatening conditions.

Sotalol works in two ways to slow down the heart and make the heart rhythm regular:

• Blocks the beta-1 receptors to slow down the heart rate and contractility
• Inhibits the potassium channels in the neurons which slows down the sinus cycle and prolongs the refractory period and the action potential duration in both atrial and ventricular muscle fibers

Sotalol is approved by the FDA for the following conditions in both adult and pediatric patients:

• Treatment of life-threatening ventricular tachycardia. Point to note, antiarrhythmic drugs may not enhance survival in patients with ventricular arrhythmias.
• Maintenance of normal sinus rhythm in patients with highly symptomatic atrial fibrillation/flutter (AFIB/AFL) who are currently in sinus rhythm.

Off-label uses (adults) of sotalol include:

• Supraventricular tachycardia
• Hemodynamically stable sustained monomorphic ventricular tachycardia
• Sustained fetal tachycardia
• Symptomatic ventricular premature beats

• Do not use sotalol in patients with:
  • Known hypersensitivity to sotalol or any compound in the formulation
  • Heart rhythm disorders including:
    • Slow heart rate (sinus bradycardia - less than 50 bpm)
    • Sick sinus syndrome
    • Second or third degree AV block without a pacemaker
    • Congenital or acquired long QT syndromes, with QT interval longer than 450 msec
  • Cardiogenic shock or decompensated heart failure
  • Serum potassium less than 4 mEq/L
  • Bronchial asthma or related bronchospastic conditions (if sotalol must be used, use the lowest effective dose) 
• Creatinine clearance (CrCl) should be calculated before initiating sotalol therapy and dosing interval adjusted based on CrCl.
• When used to treat patients with atrial fibrillation/flutter, do not initiate oral sotalol if QT interval is longer than 450 msec or CrCl is less than 40 mL/minute
• Sotalol can cause life-threatening ventricular tachycardia associated with QT interval prolongation. Do not initiate if QT interval is longer than 450 msec, and if the QT interval prolongs to 500 msec or greater, reduce the dose, lengthen the dosing interval, or discontinue the drug.
• Initiate, reinitiate or uptitrate sotalol only in a facility that can provide cardiac resuscitation and continuous ECG monitoring to prevent drug-induced arrhythmia. The patient should be monitored for a minimum of 3 days.
• Sotalol can reduce blood pressure significantly. Monitor patients with marginal cardiac compensation.
• Sotalol may cause new-onset or exacerbation of heart failure. Monitor the patient and discontinue the drug if symptoms occur.
• Correct electrolyte imbalances such as low potassium (hypokalemia) or low magnesium (hypomagnesemia) before initiating sotalol.
• Use with caution in patients in the early phase of recovery from heart attack (myocardial infarction).
• Do not withdraw sotalol abruptly, it can lead to hypersensitivity to catecholamines which can cause chest pain (angina pectoris), arrhythmia and myocardial infarction.
• Exercise caution in patients with thyroid disease. Abrupt withdrawal may result in hyperthyroidism and thyroid storm.
• Patients with a history of severe allergic (anaphylactic) reactions to allergens may become more sensitive to repeated challenges and may not respond well to epinephrine.
• In patients taking sotalol who undergo major surgery, protracted severe hypotension and difficulty in restoring and maintaining normal cardiac rhythm after anesthesia have been reported.
• Use sotalol with caution in diabetic patients, it may mask signs of acute hypoglycemia.
• Use with extreme caution in patients with sick sinus syndrome associated with symptomatic arrhythmias, because it may cause sinus bradycardia, sinus pauses, or sinus arrest.
• Use with caution in patients with myasthenia gravis, as it may aggravate the condition.
• Can cause arterial insufficiency in patients with peripheral vascular disease or Raynaud’s disease. Use with caution and monitor the patient.

Common side effects of sotalol include:

• Shortness of breath (dyspnea)
• Slow heart rate (bradycardia)
• Chest pain
• Palpitation
• New onset or exacerbation of heart rhythm disorders (proarrhythmia) including:
  • Atrioventricular block
  • Ventricular tachycardia
  • Torsades de pointes
  • Sinus node dysfunction
  • Sinus pause
  • Sinoatrial arrest
• Abnormal ECG
• Low blood pressure (hypotension)
• Congestive heart failure
• Fatigue
• Dizziness
• Lightheadedness
• Headache
• Fainting (syncope)
• Shortness of breath (dyspnea)
• Fluid in lungs (pulmonary edema)
• Weakness (asthenia)
• Musculoskeletal pain
• Muscle pain (myalgia)
• Pain in extremities
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Visual disturbance
• Peripheral nerve damage (neuropathy)
• Peripheral vascular disorders
• Excessive sweating diaphoresis)
• Rash
• Itching (pruritus)
• Skin photosensitivity
• Hair loss (alopecia)
• Fever
• Blood disorders such as:
  • High count of eosinophil immune cells (eosinophilia)
  • Low count of leukocyte immune cells (leukopenia)
  • Low platelet count (thrombocytopenia)
• Sleep disturbances
• Altered mental status
• Mental confusion
• Anxiety
• Depression
• Mood swings (emotional lability)
• Vertigo
• Impaired coordination, balance and speech (ataxia)
• Paralysis
• Impotence
• Increased insulin requirement in diabetics
• Catecholamine hypersensitivity after abrupt withdrawal

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet (Betapace, Betapace AF, Sorine, generic)

• 80 mg
• 120 mg
• 160 mg

Oral Solution

• 5 mg/mL (Sotylize)

Injectable Solution

• 15 mg/mL

Adult:

Arrhythmias

Oral

• Life-threatening ventricular arrhythmias
  • 80 mg orally twice a day; may increase by increments of 80 mg/day every 3 days if QTc is lower than 500 msec
  • Monitor until steady state levels are achieved; therapeutic dose usually obtained at total daily dose of 160-320 mg/day divided twice or thrice daily
  • Doses of 480-640 mg/day have been utilized with refractory life-threatening arrhythmias
• Atrial fibrillation/flutter
  • 80 mg orally twice a day; may increase by increments of 80 mg/day every 3 days if QTc is lower than 500 msec
  • Monitor until steady state levels are achieved; the typical dose is 120 mg twice a day
  • Initiation of sotalol in patients with creatinine clearance less than 40 mL/minute or QTc higher than 450 msec is contraindicated

Use intravenous (IV) for substitution of oral

• To match the exposure to oral sotalol, use the same dosing frequency with IV administration and infuse the adjusted dose over 5 hours
• 80 mg PO: Substitute 75 mg IV
• 120 mg PO: Substitute 112.5 mg IV
• 160 mg PO: Substitute 150 mg IV

Use for IV loading dose

• Infuse loading dose over 1 hour
• IV sotalol initiation from 0 mg to 80 mg
  • CrCl higher than 90 mL/min: 60 mg IV; wait at least 4 hours for first oral dose (12 hour oral dose interval)
  • CrCl 60-90 mL/min: 82.5 mg IV; wait at least 4 hours for first oral dose (12 hour oral dose interval)
  • CrCl 30-60 mL/min: 75 mg IV; wait at least 6 hours for first oral dose (24 hour oral dose interval)
  • CrCl 10-30 mL/min: 75 mg IV; wait at least 12 hours for first oral dose (48 hours oral dose interval)
  • If the QTc interval prolongs to higher than 500 msec or increases 20% from baseline when initiating for an oral dose of 80 mg, discontinue drug
• IV sotalol initiation 0 to 120 mg
  • CrCl higher than 90 mL/min: 90 mg IV; wait at least 4 hours for first oral dose (12 hour oral dose interval)
  • CrCl 60-90 mL/min: 125 mg IV; wait at least 4 hours for first oral dose (12 hour oral dose interval)
  • CrCl 30-60 mL/min: 112.5 mg IV; wait at least 6 hours for first oral dose (24 hour oral dose interval)
  • CrCl 10-30 mL/min: 112.5 mg IV; wait at least 12 hours for first oral dose (48 hour oral dose interval)
• Reinitiating at lower dose from 120-mg to 80-mg
  • If the QTc interval prolongs to higher than 500 msec or increases 20% from baseline when initiating for an oral dose of 120-mg, discontinue drug and consider a lower dose
  • CrCL 60 or more mL/min: Wait at least 1 day to reinitiate
  • CrCL 30 to 60 mL/min: Wait at least 3 days to reinitiate
  • CrCL 10 to 30 mL/min: Wait at least 7 days to reinitiate
• IV sotalol escalation 80 to 120 mg
  • CrCl higher than 90 mL/min: 75 mg IV; wait at least 4 hours for first oral dose (12 hour PO dose interval)
  • CrCl 60-90 mL/min: 82.5 mg IV; wait at least 4 hours for first oral dose (12 hour oral dose interval)
  • CrCl 30-60 mL/min: 82.5 mg IV; wait at least 6 hours for first oral dose (24 hour oral dose interval)
  • CrCl 10-30 mL/min: 82.5 mg IV; wait at least 12 hours for first oral dose (48 hour oral dose interval)
• IV sotalol escalation 120 to 160 mg
  • CrCl higher than 90 mL/min: 90 mg IV; wait at least 4 hours for first oral dose (12 hour oral dose interval)
  • CrCl 60-90 mL/min: 105 mg IV; wait at least 4 hours for first oral dose (12 hour oral dose interval)
  • CrCl 30-60 mL/min: 105 mg IV; wait at least 6 hours for first oral dose (24 hour oral dose interval)
  • CrCl 10-30 mL/min: 105 mg IV; wait at least 12 hours for first oral dose (48 hour oral dose interval)

Dosing Modifications

Renal impairment

• Ventricular arrhythmia (oral)
  • CrCl higher than 60 mL/min: Give every 12 hours
  • CrCl 30-59 mL/min: Give every 24 hours
  • CrCl 10-29 mL/min: Give every 36-48 hours
  • CrCl lower than 10 mL/min: Individualize dose
• Atrial fibrillation/flutter (oral)
  • CrCl higher than 60 mL/min: Give every 12 hours
  • CrCl 40-59 mL/min: Give every 24 hours
  • CrCl lower than 40 mL/min: Contraindicated

Dosing Considerations

Monitoring before initiating or re-initiating

• Perform baseline ECG to determine QT interval and measure and normalize serum potassium and magnesium levels before initiating therapy
• Measure serum creatinine and calculate estimated CrCl to establish appropriate dosing interval (if CrCl 60 mL/min or lower, dosing interval adjustment necessary)
• Continue ECG monitoring with each uptitration in dose, until steady state reached
• Determine QTc 2-4 hours after every dose; proarrhythmic event may occur after initiation of therapy and with each upward dosage adjustment

Limitations of use

• AFIB/AFL: Because therapy with sotalol can cause life-threatening ventricular arrhythmias, reserve use for patients in whom AFIB/AFL is highly symptomatic; patients with paroxysmal AFIB that is easily reversed (by Valsalva maneuver, for example) should usually not be treated

Pediatric:

Arrhythmias

2 years or older

• Normal renal function: 30 mg/m2 orally thrice daily initially (90 mg/m2 total daily dose) is approximately equivalent to the initial 160 mg total daily dose for adults  
• Subsequent titration to maximum 60 mg/m² twice daily (approximately equivalent to the 320 mg total daily dose for adults) can then occur
• Guide titration by clinical response, heart rate and QTc, with increased dosing preferably carried out in-hospital
• Allow at least 36 hours between dose increments to attain steady-state plasma concentrations of drug in patients with age-adjusted normal renal function

Younger than 2 years

• Pediatric dosage should be reduced by a factor that depends heavily upon age
• Use the graph in prescribing information where age in months is plotted on a logarithmic scale; see manufacturer's package insert for details
• Examples
  • Child aged 20 months: Dosing suggested for children with normal renal function aged 2 or older, which is about 30 mg should be multiplied by about 0.97, which is the age factor (30 X 0.97) for a dose of 29.1 mg/m²
  • Child aged 1 week: Initial starting dose (30 mg) should be multiplied by age factor 0.3; the starting dose would be (30 X 0.3) for a dose of 9 mg/m²

Sotalol overdose has rarely resulted in death. Most common symptoms of overdose include slow heart rate (bradycardia), congestive heart failure, low blood pressure (hypotension), bronchospasm and low blood sugar (hypoglycemia). Severe overdose can cause life-threatening abnormal heart rhythms. Sotalol overdose is treated with symptomatic and supportive care.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Sotalol has severe interactions with at least 49 different drugs.
• Sotalol has serious interactions with at least 100 different drugs.
• Sotalol has moderate interactions with at least 205 different drugs.
• Sotalol has mild interactions with at least 30 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Both sotalol and untreated arrhythmia in pregnancy can cause adverse outcomes in the mother and fetus/newborn. Use sotalol in pregnant women if potential benefits outweigh maternal and fetal risks.
• If sotalol is administered in pregnancy or during labor and delivery, monitor the mother and newborn infant closely. 
• Sotalol is present in breast milk. Discontinue the drug or nursing, taking into account the importance of treatment to the mother.

• Take sotalol exactly as prescribed. Do not interrupt or discontinue without your physician’s advice.
• In case of overdose, seek immediate medical help or contact Poison Control.
• Store sotalol safely out of reach of children.