Sotagard 40

Sotagard 40 contains the salt Sotalol 40 mg which is a nonselective beta-adrenergic blocking agent belonging to the beta-blocker class and is approved for use in the following clinical indications:

Ventricular Tachycardia:

Sotagard 40 is indicated for the treatment of life-threatening ventricular tachycardia. Antiarrhythmic drugs may not enhance survival in patients with ventricular arrhythmias.

Atrial Fibrillation/Atrial Flutter:

Sotagard 40 is indicated for maintenance of the normal sinus rhythm [delay in time to recurrence of the atrial fibrillation/atrial flutter (AFIB/AFL)] in patients with symptomatic AFIB/AFL who are currently in sinus rhythm.

Although not approved, there have been certain off-label uses documented for Sotagard 40. These include:

• Premature ventricular contractions-Sotagard 40 has been superior to placebo for suppressing premature ventricular contractions.
• Pharmacological cardioversion of atrial fibrillation-less effective.
• Postoperative atrial fibrillation after cardiac surgery.
• Supraventricular tachycardia- especially when administered intravenously.
• Transplacental isolated Sotagard 40 or in conjunction with digoxin to treat fetal SVT and atrial fibrillation with 85% complete or partial resolution.

Sotagard 40 contains the salt Sotalol 40 mg which is a nonselective beta-adrenergic blocking agent belonging to the beta-blocker class and is available in the form of tablets.

For Oral Dosage:

Ventricular arrhythmias:

• 40 mg taken by mouth twice a day or once a day as per the medical practitioner and may increase by increments of 80 mg/day for every three days if QTc <500 msec.
• Monitor until steady-state levels are achieved; therapeutic dose is usually obtained at the total daily dose of 160-320 mg/day divided by twice a day or either three times a day.
• Doses of 480-640 mg/day have been utilized with refractory life-threatening arrhythmias.

Atrial fibrillation/flutter:

• 40 mg taken by mouth twice a day or once a day as per the medical practitioner and may increase by increments of 80 mg/day every 3 Days if QTc <500 msec.
• Monitor until steady-state levels are achieved; the typical dose is 120 mg twice a day.
• Initiation of Sotagard 40 in patients with creatinine clearance <40 mL/min or QTc >450 msec is contraindicated.

Use of IV for substitution of Oral dosage form:

• To match the exposure to oral Sotalol, use the same dosing frequency with IV administration and infuse the adjusted dose over 5 hr
• For 80 mg taken by mouth: Substitute 75 mg IV
• For 120 mg taken by mouth: Substitute 112.5 mg IV
• For 160 mg taken by mouth: Substitute 150 mg IV

Sotagard 40 can be administered orally before/ after meals. The dosage and the duration of treatment should be as per the clinical judgment of the treating physician.

Sotagard 40 contains the salt Sotalol 40 mg is approved for the treatment of hemodynamically stable ventricular tachycardia and paroxysmal atrial fibrillation.

• Ventricular tachycardia: It has been observed that the low-salt Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure. Sometimes after a few weeks, its effects on blood pressure become noticeable.

• Atrial Fibrillation: Some foods can negatively affect your heart health and have been shown to increase the risk of heart complications. Diets high in processed foods, such as fast food, and items high in added sugar, like soda and sugary baked goods, have been linked to increased heart disease risk They can also lead to other negative health outcomes like weight gain, and diabetes, cognitive decline, and certain cancers.

The dietary restriction should be individualized as per patient requirements.

Sotagard 40 contains the salt Sotalol 40 mg and may be contraindicated in the following:

Non-cardioselective Beta-blockade

• Bronchial asthma or other bronchospastic conditions
• Sinus bradycardia
• 2nd or 3^rd-degree AV block absent a functioning pacemaker
• Cardiogenic shock
• Decompensated heart failure due to a negative inotropic effect
• Sick sinus syndrome (without a pacemaker)
• Labile diabetes (due to hypoglycemia)
• Left ventricular hypertrophy (which also increases the risk of arrhythmia)

QTc Prolonging Effects

• CrCl < 40 ml/min when used for atrial fibrillation or flutter
• Acquired or congenital long QTc syndromes
• Uncorrected hypokalemia or hypomagnesemia (increased risk of prolonging QT and causing torsades de pointes)

Other Contraindications

• Previous evidence of Sotagard 40 hypersensitivity or allergy

The treating physician must closely monitor the patient and keep pharmacovigilance as follows:

• Proarrhythmia

Sotagard 40 can cause serious ventricular arrhythmias, primarily Torsade de Pointes (TdP) type ventricular tachycardia, a polymorphic ventricular tachycardia associated with QTc prolongation. QTc prolongation is directly related to the concentration of Sotagard 40. Factors such as decreased creatinine clearance, gender (female) and higher dose, bradycardia, history of sustained VT/VF, atrial fibrillation with sinus node dysfunction, and heart failure increase the risk of TdP. The risk of TdP can be reduced by the adjustment of the Sotagard 40 dose according to the creatinine clearance and by monitoring the ECG for excessive increases in QTc. Correct hypokalemia or hypomagnesemia prior to initiating Sotalol hydrochloride, as these conditions can exaggerate the degree of QT prolongation and increase the potential for TdP. Special attention should be given to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or patients receiving concomitant diuretic drugs. Avoid Sotagard 40 with other drugs known to cause QT prolongation.

• Bradycardia/Heart Block

Sotagard 40 can cause bradycardia, sinus pauses, or sinus arrest. Sotagard 40-induced bradycardia increases the risk of Torsade de Pointe, particularly the following cardioversion. Monitor the ECG in patients receiving concomitant negative chronotropes

• Sick Sinus Syndrome

In general, Sotagard 40 is not recommended in patients with sick sinus syndrome associated with symptomatic arrhythmias, because it may cause sinus bradycardia, sinus pauses, or sinus arrest. Sotagard 40 augments bradycardia and QTc prolongation following cardioversion. Patients with AFIB/AFL associated with sick sinus syndrome may be treated with Sotagard 40 if they have an implanted pacemaker for control of bradycardia symptoms.

• Hypotension

Sotagard 40 produces significant reductions in both systolic and diastolic blood pressures. Monitor hemodynamics during administration.

• Heart Failure

New onset or worsening heart failure may occur during initiation or up-titration of Sotagard 40 because of its beta-blocking effects. Monitor for signs and symptoms of heart failure and discontinue treatment if symptoms occur.

• Bronchospasm

Avoid beta-blockers, like Sotagard 40, in patients with bronchospastic diseases. If Sotagard 40 is required, use the smallest effective dose.

• Masked Signs of Hypoglycemia in Diabetics

Beta-blockade may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected. Diabetic patients may experience elevated blood glucose levels and increased insulin requirements.

• Thyroid Abnormalities

Avoid abrupt withdrawal of beta-blockade which might be followed by an exacerbation of symptoms of hyperthyroidism, including thyroid storm. Beta-blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism.

• Anaphylaxis

While taking beta-blockers, patients with a history of anaphylactic reactions to a variety of allergens may have a more severe reaction to repeated challenges, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat the allergic reaction.

• Anesthesia

The impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.

There are some food warnings mentioned below for the drug Sotagard 40:

Potassium-Rich Foods: Bananas, sweet potatoes, nuts, and other foods rich in potassium when taken along with Sotagard 40, can be led to an increase in blood potassium levels.

Pleurisy Root: Pleurisy roots are not recommended with most heart medications due to the cardiac glycoside content of the root.

The adverse reactions related to the molecule Sotagard 40 contains the salt Sotalol 40 mg and can be categorized as

• Common Adverse effects:

Bradycardia, headache, Dizziness, fatigue, etc.

• Less Common adverse effects:

Nervousness, Elevated liver enzymes, joint paint, edema, vivid dreams, abdominal discomfort, nausea, muscle cramps, paresthesias, bradycardia, cold extremities, hypotension, palpitations, syncope, Anxiety, lethargy, diarrhea, vomiting, Impotence/reduced libido.

• Rare adverse effects:

Heart failure, tachyarrhythmia, bronchospasm, depression, decreased exercise tolerance, Raynaud's phenomenon, etc.

The clinically relevant drug interactions of Sotagard 40 which contains the salt Sotalol 40 mg are briefly summarized here:

• Negative Chronotropes

Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

• Calcium Blocking Drugs

Sotagard 40 and calcium blocking drugs can be expected to have additive effects on atrioventricular conduction, ventricular function, and blood pressure.

• Catecholamine-Depleting Agents

Concomitant use of catecholamine-depleting drugs, such as reserpine and guanethidine, with a beta-blocker may produce an excessive reduction of resting sympathetic nervous tone. Monitor such patients for hypotension and marked bradycardia which may produce syncope.

• Insulin and Oral Antidiabetics

Hyperglycemia may occur, and the dosage of insulin or antidiabetic drugs may require adjustment. Symptoms of hypoglycemia may be masked.

• Beta-2-Receptor Stimulants

Beta-agonists such as albuterol, terbutaline, and isoproterenol may have to be administered in increased dosages when used concomitantly with Sotagard 40.

• Clonidine

Concomitant use with Sotagard 40 increases the risk of bradycardia. Because beta-blockers may potentiate the rebound hypertension sometimes observed after clonidine discontinuation, withdraw Sotagard 40 several days before the gradual withdrawal of clonidine to reduce the risk of rebound hypertension.

The use of Sotagard 40 which contains the salt Sotalol 40 mg should be prudent in the following group of special populations:

• Patients with Renal Impairment: Sotagard 40 is excreted mainly through the kidneys. Therefore, dose adjustment is required if the eGFR is less than 60 ml/min. The recommended initial dose of Sotagard 40 is 80 mg given twice daily if GFR is more than 60 ml/min, with the dose increased (generally allowing 2 to 3 days between dosing increments), up to 320 mg, given in 2 or 3 divided doses. Sotagard 40 should be prescribed once daily if the creatinine clearance is between 40 to 60 ml/min. Data suggest that the patient population with heart failure also needs a dose adjustment. The most effective dosage for preventing atrial fibrillation is 120 mg twice daily, depending on renal function.

• Patients with Hepatic Impairment: There is no alteration in the clearance of Sotagard 40 in patients with hepatic impairment.

• Pregnancy Considerations: Half-life decreases to 10 hours in pregnancy due to the increased glomerular filtration rate. Data show that Sotagard 40 should be avoided in pregnancy. Sotagard 40 can be teratogenic and hence, is not often the first choice in pregnant females. Close fetal monitoring is necessary when used.

• Breastfeeding Considerations: Sotagard 40 is extensively excreted into breastmilk and has minimal safety data in breastfed infants. Other drugs are preferred to Sotagard 40, especially while nursing a newborn or preterm infant.

Overdosage with Sotagard 40 which contains the salt Sotalol 40 mg may be fatal.

Symptoms and Treatment of Overdosage:

The most common signs to be expected are bradycardia, congestive heart failure, hypotension, bronchospasm, and hypoglycemia. In cases of massive intentional overdosage (2-16 grams) of Sotalol, the following clinical findings were seen: hypotension, bradycardia, cardiac asystole, prolongation of QT interval, Torsade de Pointes, ventricular tachycardia, premature ventricular complexes. If overdosage occurs, therapy with Sotalol should be discontinued and the patient observed closely. Because of the lack of protein binding, hemodialysis is useful for reducing Sotalol plasma concentrations. Patients should be carefully observed until QT intervals are normalized and the heart rate returns to levels >50 bpm. The occurrence of hypotension following an overdose may be associated with an initial slow drug elimination phase (half-life of 30 hours) thought to be due to a temporary reduction of renal function caused by the hypotension. In addition, if required, the following therapeutic measures are suggested:

• Bradycardia or Cardiac Asystole: Atropine, another anticholinergic drug, a beta-adrenergic agonist or transvenous cardiac pacing.
• Heart Block: (second and third degree) transvenous cardiac pacemaker.
• Hypotension: (depending on associated factors) epinephrine rather than isoproterenol or norepinephrine may be useful.
• Bronchospasm: Aminophylline or aerosol beta-2-receptor stimulant. Higher than normal doses of beta-2 stimulus may be required.
• Torsade de Pointes: DC cardioversion, magnesium sulfate, potassium replacement. Once Torsade de Pointes is terminated, transvenous cardiac pacing or an isoproterenol infusion to increase heart rate can be employed.

Pharmacodynamics:

• Electrophysiology:

Sotagard 40 prolongs the plateau phase of the cardiac action potential in the isolated myocyte, as well as in isolated tissue preparations of ventricular or atrial muscle (Class III activity). In intact animals, it slows heart rate, decreases AV nodal conduction, and increases the refractory periods of atrial and ventricular muscle and conduction tissue.

• Hemodynamics:

In a study of systemic hemodynamic function measured invasively in 12 patients with a mean LV ejection fraction of 37% and ventricular tachycardia (9 sustained and 3 non-sustained), a median dose of 160 mg twice daily of Sotagard 40 produced a 28% reduction in heart rate and a 24% decrease in the cardiac index at 2 hours post-dosing at steady state. Concurrently, systemic vascular resistance and stroke volume showed non-significant increases of 25% and 8%, respectively.

Pulmonary capillary wedge pressure increased significantly from 6 to 12 mmHg in the 11 patients who completed the study. Mean arterial pressure, mean pulmonary artery pressure and stroke work index did not significantly change. Exercise and isoproterenol-induced tachycardia are antagonized by Sotagard 40, and total peripheral resistance increases by a small amount. In hypertensive patients, Sotagard 40 produces significant reductions in both systolic and diastolic blood pressures. Although Sotagard 40 is usually well-tolerated hemodynamically, in patients with marginal cardiac compensation, deterioration in cardiac performance may occur.

Pharmacokinetics:

• Absorption:

In healthy subjects, the oral bioavailability of Sotagard 40 is >90%. After oral administration, peak plasma concentrations are reached in 2.5 to 4 hours, and steady-state plasma concentrations are attained within 2-3 days (i.e., after 5-6 doses when administered twice daily). Over the oral dosage range of 160-640 mg/day, Sotagard 40 displays dose proportionality with respect to plasma concentrations. When administered with a standard meal, the absorption of Sotagard 40 was reduced by approximately 20% compared to administration in the fasting state.

• Distribution:

Distribution occurs to a central (plasma) and to a peripheral compartment, with a mean elimination half-life of 12 hours. Dosing every 12 hours result in trough plasma concentrations which are approximately one-half of those at peak. Sotagard 40 does not bind to plasma proteins and is not metabolized. Sotagard 40 shows very little intersubject variability in plasma levels. Sotagard 40 crosses the blood-brain barrier poorly.

• Metabolism:

Sotagard 40 is not metabolized and is not expected to inhibit or induce any CYP 450 enzymes.

• Excretion:

Excretion is predominantly via the kidney in the unchanged form, and therefore lower doses are necessary for conditions of renal impairment. Dosing every 12 hours result in trough plasma concentration which is approximately one-half of that at peak concentration.