Sotalol Hydrochloride - Indication, Dosage, Precautions, and Contraindications

Overview:

Sotalol hydrochloride is a medication that works as both a beta-blocker and a potassium channel blocker. It falls into a class of drugs used to treat heart rhythm problems. Sotalol is prescribed for various conditions, including certain types of irregular heartbeats, stabilizing heart rhythms, and managing heart issues after surgery. This medication is given based on specific medical conditions, and healthcare providers consider various factors to ensure its effectiveness and safety. It is crucial for healthcare teams to monitor patients closely when using Sotalol to achieve the best outcomes. The drug was approved by the Food and Drug Administration (FDA) in 1992. This drug has a black box warning from the FDA.

Drug Group:

The active ingredient of the medication is Sotalol hydrochloride, which also contains inactive substances like microcrystalline cellulose, lactose, starch, stearic acid, magnesium stearate, and colloidal silicon dioxide. These components are part of the formulation to make the medication into a tablet form for easy administration. It is a medication used to treat irregular heart rhythms. It has two main effects on the heart: it blocks beta-adrenergic receptors (Class II) and prolongs the duration of the cardiac action potential (Class III). Its chemical structure is described as d,l-N-[4-[1-hydroxy-2-[(1-methylethyl)amino]ethyl]phenyl]methanesulfonamide monohydrochloride.

Available Doses and Dosage Forms:

Sotalol hydrochloride comes in the form of white tablet pills that are taken by mouth. The medicine itself is a white, crystalline solid that dissolves well in water, propylene glycol, and ethanol but only slightly in chloroform.

Injection Form: 150 mg (milligram) Sotalol hydrochloride is available as a clear solution (15 milligram/milliliter) in 10mL clear, colorless single-dose vials.

For Patients:

What Is Sustained Ventricular Tachycardia?

Sustained ventricular tachycardia is defined as tachycardia that continues for more than 30 seconds or leads to hemodynamic compromise within 30 seconds and requires intervention. On the other hand, non-sustained ventricular tachycardia lasts less than 30 seconds and does not cause hemodynamic instability.

How Does Sotalol Hydrochloride Work?

Sotalol is a medication classified as a beta-blocker. It functions by altering the way the body reacts to certain nerve signals, particularly those affecting the heart. This medication helps in slowing down the heart rate and facilitating the pumping of blood throughout the body.

What Is the Dosage of Sotalol Hydrochloride?

Dosing and Administration in Adults:

• Initiation and Monitoring: Begin Sotalol hydrochloride in a monitored setting with continuous ECG (electrocardiogram) monitoring by trained personnel for at least three days. Patients should not be discharged within 12 hours of converting to normal sinus rhythm.

• QT Interval Monitoring: Baseline QT interval must be ≤ 450 msec (millisecond) to start Sotalol hydrochloride. During initiation, monitor the QT interval two to four hours after each dose. If the QT interval prolongs to 500 msec or more, adjust the dose or discontinue.

• Individualized Dosing: Adjust the dose based on calculated creatinine clearance. If creatinine clearance is >60 mL/min (milliliter/minute), then Sotalol hydrochloride is given twice daily (BID). If Creatinine clearance is 40 to 60 mL/min, then Sotalol hydrochloride is given once daily (QD). Contraindicated if creatinine clearance <40 mL/min. The recommended initial dose is 80 milligrams, titrating up to 120 milligrams if needed.

• Atrial Fibrillation and Hypokalemia: Anticoagulation as per standard practice for atrial fibrillation. Correct hypokalemia before starting Sotalol hydrochloride.

• Discharge Planning: Patients leaving the hospital on Sotalol hydrochloride should have a sufficient supply for uninterrupted therapy until they can fill a prescription.

Dosing and Administration in Children:

• Precautionary Measures: Initiate treatment in the hospital after clinical assessment. Individualized regimen, gradual dose increase if needed, and frequent monitoring of QTc interval and heart rate.

• Children (About 2 Years and Older): Doses normalized for body surface area. Initiated 30 mg/m² (milligram/meter square) three times a day, titrating up to a maximum of 60 mg/m².

• Children (About 2 Years or Younger): Dosage reduction based on age. Individualized dosing using age-dependent factors. Consideration for reduced doses if QTc exceeds 500 msec, and serious consideration if it exceeds 550 msec.

• Renal Impairment in Children: Use with caution in children with renal impairment. Lower doses or increased intervals between doses may be necessary. Monitoring heart rate and QTc is crucial, and reaching a steady state will take longer.

How Effective Is Sotalol Hydrochloride?

Sotalol is a medication known as a beta-blocker. Similar to other beta-blockers, it affects how the body reacts to nerve signals, particularly in the heart. It helps in reducing the heart rate, making it simpler for the heart to effectively pump blood throughout the body.

What Are the Things to Inform the Doctor Before Taking Sotalol Hydrochloride?

Before a person begins to take Sotalol, inform the doctor to ensure it is suitable for the person if they have:

• Experienced an allergic reaction to Sotalol or any other medication.

• Low blood pressure or a slow heart rate.

• Heart failure that is worsening, heart disease, or if the person recently had a heart attack.

What Are the Side Effects of Sotalol Hydrochloride?

• Side effects associated with Sotalol hydrochloride are mainly connected to its impact on heart function (Class II) and the duration of cardiac action potential (Class III).

• Common side effects include slow heart rate (bradycardia), difficulty breathing (dyspnea), and fatigue.

• The Class III effects involve prolongation of the QT interval, a measure of the electrical activity of the heart.

• The likelihood of experiencing these side effects is influenced by the dosage, with higher doses leading to an increased risk.

• In a combined analysis of four placebo-controlled studies involving 275 patients with atrial fibrillation/flutter, treated with doses ranging from 160 to 320 milligrams of Sotalol hydrochloride.

• Adverse events were reported at a rate of two percent or more in patients taking 160 to 240 mg.

• The incidence of these events was higher compared to those on a placebo.

• The data categorize events based on the body system and daily dose in both the Sotalol hydrochloride and placebo groups.

• No irreversible non-cardiac toxicity, and there were no significant long-term side effects unrelated to the heart observed.

Dietary Considerations: It has to be followed according to the doctor's advice; until then, continue a normal diet.

Missed Dose: If an individual misses a dose, they should take it as soon as they remember it. But if it is almost time for the next dosage, skip the missed dose and continue the regular dosing schedule. Avoid taking double doses to make up for the missed dose.

Overdose: Taking too much Sotalol, whether intentional or accidental, has rarely resulted in death.

Common Symptoms of Overdose:

• Slow heart rate (bradycardia).

• Congestive heart failure.

• Low blood pressure (hypotension).

• Bronchospasm (breathing difficulties).

• Low blood sugar (hypoglycemia).

Severe Overdose Effects (2 to 16 grams):

• Extremely low blood pressure.

• Cardiac asystole (heart stoppage).

• Prolonged QT interval.

• Torsade de Pointes (a specific type of abnormal heart rhythm).

• Ventricular tachycardia.

• Premature ventricular complexes.

Response to Overdose:

• Stop taking Sotalol hydrochloride.

• Close observation of the patient is essential.

• Hemodialysis is effective in reducing Sotalol levels due to its lack of protein binding.

Recovery Measures:

• Patient monitoring until QT intervals return to normal and heart rate surpasses 50 beats per minute.

Specific Therapeutic Measures Based on Symptoms:

• Bradycardia or Cardiac Asystole: Atropine, beta-adrenergic agonist, or transvenous cardiac pacing.

• Heart Block (Second and Third Degree): Transvenous cardiac pacemaker.

• Hypotension: Epinephrine may be useful, depending on associated factors.

• Bronchospasm: Aminophylline or aerosol beta-2-receptor stimulant.

• Torsade de Pointes: DC cardioversion, transvenous cardiac pacing, epinephrine, magnesium sulfate.

Storage and Disposal:

Store this medication in its original container, keeping it tightly closed and away from children. Keep it at room temperature, avoiding exposure to excessive heat and moisture (do not store it in the bathroom). Ensure that all medications are out of children's sight and reach, as some containers are not child-resistant. Use safety caps and store the medication in a secure place – high up and out of sight. For additional safety, consider using lockable safety caps.

Dispose of any unused medication in a way that prevents accidental ingestion by pets, children, or others. Do not flush the medication down the toilet. The recommended method is through a medicine take-back program. Consult the pharmacist or contact the local garbage/recycling department to learn about take-back programs in the area.

For Doctors:

Indication:

• Sotalol is used to help people with a certain heart condition called atrial fibrillation or atrial flutter stay in normal heart rhythm for a longer time, delaying the recurrence of these irregular heartbeats.

• It is prescribed for individuals facing a serious condition known as life-threatening ventricular tachycardia, a dangerous type of heart rhythm disorder.

• It is important to note that using antiarrhythmic drugs like Sotalol may not necessarily improve the chances of survival in patients with these ventricular arrhythmias.

Dose and Dosing Considerations:

• When transitioning from oral to intravenous Sotalol, maintain the same dosing frequency and administer the adjusted dose over a five-hour infusion.

• Initiate or adjust intravenous Sotalol in a facility with continuous ECG (electrocardiogram) monitoring and cardiac resuscitation capabilities. Staff should be proficient in managing severe ventricular arrhythmias.

• Discontinue other antiarrhythmic medications before starting Sotalol hydrochloride.

• Before initiation, ensure serum potassium and magnesium levels are measured and normalized. If baseline QTc is >450 ms (JT >330 ms with QRS over 100 ms), Sotalol is not recommended.

• Administer the loading dose over one hour, monitoring the QTc interval every 15 minutes during infusion.

• Continue monitoring QTc around Tmax (two or four hours post-dose) after the first oral dose (for all patients) and the second oral dose (for patients with CrCL ≥ 60 mL/min).

• Discontinue the drug if QTc prolongs to >500 ms or increases by 20 percent from baseline when initiating an oral dose of 80 mg. Consider discontinuation and a lower dose if initiating an oral dose of 120 milligrams (mg).

• If re-initiating at a lower dose of 80 mg is desired, wait at least one day (for patients with CrCL ≥60 mL/min) or at least three days (for patients with CrCL ≥30 to <60 mL/min), or seven days (for patients with CrCL ≥10 to <30 mL/min).

• Intravenous loading dose depends on the target oral dose and creatinine clearance; the dosing interval and minimum delay between the end of infusion and the first oral dose also depend on renal function.

Clinical Pharmacology Pharmacodynamics:

Sotalol acts as a competitive inhibitor of rapid potassium channels, prolonging action potentials and refractory periods in the heart. The inhibition intensifies as the heart rate decreases, increasing the risk of adverse effects like torsades de pointes, especially at lower heart rates. L-Sotalol exhibits beta-adrenergic receptor-blocking activity above plasma concentrations of 800ng/L, further extending action potentials. D-Sotalol, lacking beta-blocking activity, reduces heart rate during standing or exercise, collectively resulting in a negative inotropic effect, diminishing the strength of heart muscle contraction. This, along with QT interval prolongation, is associated with arrhythmia induction in patients.

In terms of glucose regulation, hyperglycemia poses a higher risk for non-insulin-dependent diabetics compared to insulin-dependent diabetics. Beta-blockers, like Sotalol, hinder insulin secretion, potentially causing hyperglycemia in type II diabetes mellitus. Conversely, insulin-dependent diabetes carries a greater risk of hypoglycemia with beta-blockers, as these medications reduce insulin secretion, masking symptoms of low blood sugar. Additionally, beta blockers enhance glucose uptake into cells, potentially extending or intensifying episodes of hypoglycemia.

Mechanism of Action:

Sotalol hydrochloride is a medication that works in two ways to manage irregular heart rhythms. It has both beta-blocker properties, which help control heart rate, and it prolongs the duration of the heart's action potential, assisting in rhythm regulation. Sotalol hydrochloride contains two forms of Sotalol, and while both contribute to the regulation of heart rhythm, one of them is primarily responsible for beta-blocking activity.

The beta-blocker aspect of Sotalol is not selective to any specific part of the heart, becoming effective at around 80 mg/day and reaching maximum impact between 320 and 640 mg/day. Sotalol does not exhibit partial agonist or membrane-stabilizing effects. While beta-blockade starts at doses as low as 25 mg, significant antiarrhythmic effects are noticeable only at daily doses of 160 mg and higher.

In children, a Class III antiarrhythmic effect is observed at daily doses of 210 mg/m2 of body surface area, and a decrease in resting heart rate due to beta-blockade is seen at daily doses equal to or greater than 90 mg/m2.

Pharmacokinetics:

Sotalol, when taken orally, is well-absorbed in healthy individuals (90 to 100 percent). Peak concentration in the blood occurs two and a half to four hours after intake, and steady levels are reached after two to three days of twice-daily use (160 to 640 mg/day). It distributes throughout the body and blood, with a 12-hour elimination half-life. Maintaining consistent levels is achieved by taking it every 12 hours. Sotalol does not bind to blood proteins, undergo metabolism, or involve the liver significantly. Kidneys primarily remove it, requiring lower doses for those with kidney issues. Aging does not impact processing, but older adults with kidney problems may eliminate it more slowly. Taking Sotalol with food slightly reduces absorption. In children, a study found consistent absorption and elimination. Body surface area (BSA), not age, is crucial in how Sotalol behaves. Smaller children may have higher exposure, with natural variation in drug clearance.

Toxicity:

• Carcinogenicity: Rats in a 24-month study showed no signs of carcinogenic potential at doses ranging from 137 to 275 mg/kg/day (milligram/kilogram/day). Mice also did not exhibit carcinogenic effects during a 24-month study at doses of 4141 to 7122 mg/kg/day.

• Mutagenicity and Clastogenicity: Sotalol has not undergone specific assessments for mutagenic or clastogenic potential.

• Impairment of Fertility: Rats administered oral doses of 1000 mg/kg/day did not experience a significant reduction in fertility before mating, with a minor decrease noted in the number of offspring per litter. Reproduction studies in rats and rabbits during organogenesis at doses of 100 and 22 times the maximum recommended human oral dose as mg/kg (nine and seven times the MRHD as mg/m2), respectively, did not reveal teratogenic potential associated with Sotalol hydrochloride. In rabbits, a high dose of Sotalol HCl (160 mg/kg/day) at 16 times the MRHD as mg/kg (six times the MRHD as mg/m2) resulted in a slight increase in fetal death, likely due to maternal toxicity. Eight times the maximum dose (80 mg/kg/day or three times the MRHD as mg/m2) did not lead to an increased incidence of fetal deaths. In rats, Sotalol HCl at 1000 mg/kg/day, 100 times the MRHD (18 times the MRHD as mg/m2), increased the number of early resorptions, while at 14 times the maximum dose (2.5 times the MRHD as mg/m2), no increase in early resorptions was observed.

Clinical Studies:

Sotalol hydrochloride was studied in two trials for symptomatic atrial fibrillation or flutter (AFIB/AFL). The first trial, focusing on occasional episodes, compared different Sotalol hydrochloride doses to placebo in patients with reduced kidney function. Results showed the 120 mg (milligrams) dose was more effective than 80 mg, but 160 mg had no added benefits. Adverse events leading to discontinuation were dose-related.

The second trial involved chronic AFIB patients, gradually increasing Sotalol hydrochloride from 80 mg/day to 320 mg/day over six months. Results indicated a longer time before AFIB recurrence and reduced risk at six months compared to a placebo.

In another study post-heart attack, Sotalol 320 mg once daily was compared to a placebo, showing no significant difference in mortality rates. In essence, Sotalol hydrochloride delays symptomatic AFIB/AFL recurrence in both occasional and chronic cases, offering a potential treatment for those with irregular heart rhythms.

Contraindications of Sotalol Hydrochloride:

Sotalol hydrochloride should not be used in individuals with:

• Slow heart rate (<50 beats per minute while awake).

• Certain heart rhythm disorders (sick sinus syndrome or second and third-degree AV (Atrioventricular) block, unless a pacemaker is in place).

• Specific types of prolonged QT interval conditions.

• Very low blood potassium levels.

• Severely reduced kidney function (creatinine clearance <40 mL/min).

• Serious heart conditions like cardiogenic shock or uncontrolled heart failure.

• Bronchial asthma.

• Previous evidence of hypersensitivity to Sotalol.

Warnings and Precautions:

1. Proarrhythmia (Sotalol-Induced Ventricular Arrhythmias) - Sotalol has the potential to induce serious ventricular arrhythmias, notably Torsade de Pointes (TdP). TdP is associated with QTc prolongation, which correlates directly with Sotalol concentration. Factors like reduced creatinine clearance, female gender, higher doses, bradycardia, history of sustained VT/VF, atrial fibrillation with sinus node dysfunction, and heart failure elevate TdP risk. Risk mitigation involves Sotalol dose adjustment based on creatinine clearance and vigilant ECG monitoring for excessive QTc prolongation. Correcting hypokalemia or hypomagnesemia before Sotalol initiation is crucial due to their potential to amplify QT prolongation and TdP risk. Special attention is required for electrolyte and acid-base balance, particularly in patients with severe or prolonged diarrhea or those on concomitant diuretics. Caution against combining Sotalol with other drugs known to cause QT prolongation.

2. Bradycardia or Heart Block (Sotalol-Induced Bradyarrhythmias) - Sotalol may induce bradycardia, sinus pauses, or sinus arrest, increasing the risk of Torsade de Pointe, especially post-cardioversion. ECG monitoring is essential in patients with concomitant negative chronotropes.

3. Sick Sinus Syndrome (Sick Sinus Syndrome and Sotalol) - Generally discouraged in symptomatic sick sinus syndrome due to their potential to cause sinus bradycardia, pauses, or arrest. Caution is exercised in AFIB/AFL patients with sick sinus syndrome who have a pacemaker for bradycardia control.

4. Hypotension (Sotalol-Induced Blood Pressure Reduction) - Sotalol induces significant reductions in both systolic and diastolic blood pressures. Continuous hemodynamic monitoring is recommended during administration.

5. Heart Failure (Sotalol and Heart Failure) - Initiation or up-titration of Sotalol may lead to new onset or worsening heart failure due to its beta-blocking effects. Monitoring for heart failure signs and symptoms is crucial, with treatment discontinuation if symptoms occur.

6. Bronchospasm (Sotalol and Bronchospastic Diseases) - Beta-blockers like Sotalol is to be avoided in patients with bronchospastic diseases. If necessary, use the smallest effective dose.

7. Masked Signs of Hypoglycemia in Diabetics - Beta-blockade by Sotalol may obscure tachycardia during hypoglycemia in diabetics.

8. Thyroid Abnormalities - Abrupt withdrawal of beta-blockade may exacerbate hyperthyroidism symptoms, with beta-blockade potentially masking certain clinical signs.

9. Anaphylaxis - Patients with a history of anaphylactic reactions may experience more severe reactions during beta-blocker therapy.

10. Anesthesia - The impaired response of the heart to reflex adrenergic stimuli under beta-blockade increases the risks associated with general anesthesia and surgical procedures.

Drug Interactions of Sotalol Hydrochloride:

• Negative Chronotropes: Digitalis glycosides and beta-blockers: Both digitalis glycosides and beta-blockers exert effects of slowing atrioventricular conduction and reducing heart rate. Concurrent usage increases the susceptibility to bradycardia.

• Calcium Blocking Drugs: Sotalol and Calcium Blocking Drugs: Sotalol and calcium blocking drugs exhibit cumulative impacts on atrioventricular conduction, ventricular function, and blood pressure.

• Catecholamine-Depleting Agents: Catecholamine-Depleting Agents with Beta-Blockers: Combining beta-blockers with catecholamine-depleting drugs like reserpine and guanethidine can excessively diminish resting sympathetic nervous tone. Monitoring for hypotension and pronounced bradycardia, potentially leading to syncope, is advisable.

• Insulin and Oral Antidiabetics: Concurrent use of Sotalol may induce hyperglycemia, necessitating adjustments in insulin or oral antidiabetic drug dosages. Symptoms of hypoglycemia may be obscured.

• Beta-2-Receptor Stimulants: Beta-agonists such as Albuterol, Terbutaline, and Isoproterenol may require increased dosages when used alongside Sotalol.

• Clonidine: Co-administration with Sotalol elevates the risk of bradycardia. Withdrawal of Sotalol several days prior to gradually discontinuing Clonidine is recommended to mitigate the risk of rebound hypertension.

• Drug or Laboratory Test Interactions: The presence of Sotalol in urine may lead to falsely elevated levels of urinary metanephrine when assessed using fluorimetric or photometric methods.

Specific Considerations:

1. Pregnancy: Both untreated maternal conditions and Sotalol use during pregnancy pose risks to the mother and fetus. Animal studies indicate increased early resorptions and fetal death at higher doses but show no teratogenic potential. Incidence of ventricular tachycardia (VT) may rise during pregnancy, potentially leading to symptomatic episodes. Arrhythmia occurrences may increase, and therapeutic levels may be challenging to maintain due to pregnancy-related changes.

2. Fetal or Neonatal Adverse Reactions: Sotalol crosses the placenta, impacting fetal outcomes. Potential effects include growth restriction, transient fetal bradycardia, hyperbilirubinemia, hypoglycemia, uterine contractions, and intrauterine death. Increased risk of serious fetal arrhythmia or intrauterine death due to heightened QT prolongation.

3. Labor or Delivery: Due to heightened arrhythmia risk, continuous monitoring is recommended during labor and delivery.

4. Data: Animal studies indicate no teratogenic potential, but highlight increased early resorptions and fetal death at higher doses.

5. Lactation: Sotalol is present in human milk at levels similar to neonatal therapeutic dosage. Potential adverse effects in breastfed infants include bradycardia and beta-blockade symptoms. Advisable to avoid breastfeeding during Sotalol treatment. Sotalol concentrations in breast milk are high, and the estimated daily infant dose aligns with neonatal therapeutic dosage.

6. Females and Males of Reproductive Potential: Beta-blockers, including Sotalol, may cause erectile dysfunction.

7. Pediatric Use: Safety and effectiveness in children not established. Evaluation in children aged three days to 12 years indicates Class III electrophysiologic and beta-blocking effects.