Consumer medicine information

SOTACOR [3408]

Sotalol hydrochloride

BRAND INFORMATION

Brand name

Sotacor Tablets

Active ingredient

Sotalol hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using SOTACOR [3408].

What is in this leaflet

This leaflet answers some common questions about SOTACOR. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits Your doctor has weighed the risks of you using SOTACOR against the benefits they expect it will have for you.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What SOTACOR is used for

SOTACOR contains sotalol hydrochloride as the active ingredient which belongs to the family of drugs known as beta-blockers.

SOTACOR is used to treat “arrhythmias”, which is a problem when the heart beats too quickly or with the wrong rhythm.

SOTACOR slows down and steadies the heart beat, reducing the effort the heart has to put into pumping blood.

Ask your doctor if you have any questions about why SOTACOR has been prescribed for you.

Your doctor may have prescribed it for another reason.

There is no evidence that this medicine is addictive.

SOTACOR is only available with a doctor’s prescription.

Before using it

When you must not use it

Do not use SOTACOR if you have an allergy to:

  • sotalol hydrochloride
  • any of the ingredients listed at the end of this leaflet

Some of the symptoms of an allergic reaction may include:

  • shortness of breath, wheezing or difficulty breathing
  • skin rash, itching or hives
  • swelling of the face, lips, tongue or any part of the body.

Do not take SOTACOR if you have asthma.

You should not take this medicine if you have allergies, or problems with your kidneys or thyroid gland, unless you have discussed it with your doctor.

You should not take this medicine if you are pregnant or are breast feeding, or if you intend to breast feed.

If you have any problems with your heart or circulation, discuss them with your doctor.

You should not take SOTACOR with any other medicines your doctor does not know about, particularly if they are to control high blood pressure, heart conditions, depression, hayfever, allergies, infections or diabetes.

Do not take it if the expiry (EXP) date printed on the pack has passed

Do not take it if the packaging is torn of shows signs of tampering.

Talk to you doctor if you are unsure whether you should start taking this medicine.

Before you start to take it

  • Make sure your doctor knows what other medicines you are already taking including ones you have bought yourself at the chemist or supermarket.
  • In particular remind your doctor if you have asthma, bronchitis or any allergies such as hay fever, food allergies or are allergic to bee or wasp stings.
  • Make sure your doctor is aware of any kind of heart disease, diabetes, phaeochromocytoma, kidney disease or thyroid disease that you have or have had, or if you have been told that your pulse is slow or irregular.
  • Tell your doctor if you have ever had trouble with the levels of salts like potassium or magnesium in your blood.
  • Remind your doctor if you are going to have surgery involving a general anaesthetic even if it is only minor.
  • Tell your doctor if you are pregnant, if you are planning to become pregnant, or if you are breast feeding.
  • Tell your doctor if you have been given SOTACOR (or any other beta-blocker) before and if you had any problems.
  • Remind your doctor if you have hardening of the arteries (cold fingers and toes or pain in the back of your legs when you walk).

Be careful driving or operating machinery until you know how SOTACOR affects you.

As with other medicines it may cause dizziness, light-headedness or drowsiness in some people. If this occurs do not drive or operate machinery or undertake any other activity that could be dangerous if you are dizzy, light-headed or drowsy.

Taking other medicines

Some medicines can affect the way SOTACOR works.

You should always tell your doctor about any other medicines you take, even those bought without a doctor’s prescription.

It is especially important that you tell your doctor if you are taking the following:

  • medicines which lower blood pressure (including other beta-blockers)
  • any other medicines used to treat irregular heart rhythm or beat
  • digoxin, a medicine used for heart failure
  • medicines used to treat angina or other heart conditions
  • antidepressants (medicines used to treat depression)
  • insulin or other drugs used to control diabetes
  • Medicines used to control or prevent asthma (inhalers or tablets) or to control allergies or which are used for other lung problems
  • Antihistamine medicine including terfenadine and astemizole that may be used to treat hayfever, allergies or to relive symptoms of cold and flu
  • quinolone antibiotics (medicines used to treat infections)
  • diuretics (water tablets)
  • some medicine used during surgery or emergency situations, such as anaesthetics.

If you are not sure whether you are taking any of these medicines, check with your doctor of pharmacist.

How to take it

Follow all directions given to you by your doctor or pharmacist carefully.

They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

How much to take

Your doctor will decide on the dose of SOTACOR tablets for you, and may need to change the dose a few times to get the best level for you.

The usual dose is 80mg to 160mg twice a day. Your doctor may need to increase this as a very few patients may need up to three to four 160mg tablets spread over a day. The dosage may need to be different if you have a kidney problem.

How to take it

You should take your tablets with water one to two hours before meals. Do not take SOTACOR with milk or meals.

How long to take it for

If you have been prescribed SOTACOR you must be sure to follow your doctors instructions carefully.

Do not stop taking SOTACOR tablets suddenly.

The dose needs to be reduced gradually over 7 to 14 days.

If you forget to take it

It is important not to miss a dose but if you do, take your next dose at the normal time and with the normal amount.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much SOTACOR. Do this even if there are no signs of discomfort or poisoning.

You may need medical attention.

Too much of this medicine will cause your blood pressure and heart rate to drop to dangerous levels. Serious heart problems may develop and this could be fatal.

Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking SOTACOR.

SOTACOR helps most people with arrhythmia, but it may have unwanted side effects in some people. Rarely, serious heart problems can develop while you are taking normal doses but you must remember that you are taking this medicine because your heart already has a serious problem. It is very important that your doctor keeps a check on your progress.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • dizziness, lightheadedness or fainting, especially when you get up from a sitting or lying position. Getting up slowly may help.
  • tiredness, lack of energy, weakness
  • headache, fever
  • irritated eyes, blurred vision, worsening of eyesight, increased sensitivity of the eyes to sunlight
  • feeling sick, vomiting, stomach upset, diarrhoea, wind
  • change in taste sensation
  • anxiety, depression, mood changes
  • problems with sexual function
  • sleep problems, unusual dreams
  • worsening of psoriasis
  • hearing disturbances
  • tingling or numbness in the hands or feet, cold limbs

Tell your doctor immediately or go to casualty at the nearest hospital if you notice any of the following:

  • chest tightness, wheezing, shortness of breath
  • very slow heart beat
  • fast, irregular heart beat, palpitations
  • chest pain
  • any type of skin rash, itching
  • shortness of breath (sometimes with tiredness, weakness and reduced ability to exercise), which may occur together with swelling of the feet or legs due to fluid build up

This is not a complete list of all possible side effects. Others may occur in some people and there may be some side effects not yet known.

Tell your doctor if you notice anything that is making you feel unwell while you are taking, or soon after you have finished taking SOTOCOR, even if it is not on this list.

While you are taking it

Things you must do

Tell your doctor if you become pregnant while taking SOTACOR.

You doctor can discuss with the risks of taking it while you are pregnant.

If you are about to be started on any new medicine, remind your doctor or pharmacist that you are taking SOTACOR.

Tell any other doctor, dentist, or pharmacist who treats you that you are taking this medicine.

Things you must not do

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not take SOTACOR to treat any other complaints unless your doctor tells you to.

Do not let yourself run out of tablets over weekends or on holidays.

After taking it

Storage

Store your tablets safely in a cool dry place. Protect from light and moisture.

Do not store SOTACOR or any other medicine in the bathroom or near a sink.

Do not leave it in the car on hot days or on window sills.

Heat and dampness can destroy some medicines.

Keep your tablets in the original packaging they are provided in until it is time to take them.

If you take the tablets out of the blister they will not keep well.

Keep all medicines out of the reach of children.

A locked cupboard at least one-and-a-half meters above the ground is a good place to store medicines.

Product description

What it looks like

SOTACOR 80mg tablets are light blue, biconvex, capsule shaped tablets, plain on one side and engraved 'S', '80' and a break bar on the other side.

SOTACOR 160mg are light blue biconvex, capsule shaped tablets, plain on one side and engraved 'S', '160' and a break bar on the other side.

Active ingredients

SOTACOR 80mg tablets contain 80mg sotalol hydrochloride per tablets

SOTACOR 160mg tablets contain 160mg sotalol hydrochloride per tablet

The tablets also contain:

  • microcrystalline cellulose
  • magnesium stearate
  • maize starch
  • lactose (anhydrous)
  • stearic acid
  • colloidal anhydrous silica
  • indigo carmine (CI 73015)

BRAND INFORMATION

Brand name

Sotacor Tablets

Active ingredient

Sotalol hydrochloride

Schedule

S4

 

Name of the medicine

Sotalol hydrochloride.

Excipients.

Lactose, microcrystalline cellulose, maize starch, indigo carmine aluminium lake, anhydrous colloidal silica, stearic acid and magnesium stearate.

Description

Chemical name: hydrochloride salt of 4'-(1-hydroxy -2-isopropylaminoethyl) methanesulfonanilide. Molecular formula: C12H20N2O3S.HCl. MW: 308.83. CAS: 959-24-0. Sotalol hydrochloride is a white crystalline solid, soluble in water (50% w/v). Melting point: 210°C.

Pharmacology

Pharmacological actions.

Sotalol is a nonselective beta-adrenergic receptor blocker without sympathomimetic activity or membrane stabilising activity. It causes a decrease in heart rate and a limited reduction in the force of contraction of the heart. There is a reduction in cardiac work and in myocardial oxygen demand. Sotalol does not decrease blood pressure in normotensive subjects.
Sotalol also possesses class III antiarrhythmic activity. Sotalol has no known effect on the upstroke velocity of the action potential, therefore no known effect on the depolarisation phase. Its major effects are prolongation of the atrial, ventricular and accessory pathway effective refractory periods. The effect on the ventricular myocardium may be reflected by a lengthening of the QTc interval on electrocardiographic recordings.
Like most other beta-blockers, sotalol inhibits renin release. This suppressive effect is significant both at rest and during exercise.

Pharmacokinetics.

Absorption.

Sotalol is well absorbed from the gastrointestinal tract. Peak plasma concentrations of 1.0 to 2.3 mg/L are reached at two to three hours after a 160 mg oral dose.

Distribution.

Total apparent volume of distribution of sotalol ranges from 1.6 to 2.4 L/kg. The volume of distribution at steady state is approximately halved in the elderly.

Protein binding.

Sotalol does not bind to plasma proteins and does not significantly cross the blood-brain barrier. However, it is excreted in breast milk and may cross the placental barrier.

Metabolism.

Sotalol is not metabolised by the liver and does not undergo biotransformation (no first-pass effect). There is a positive correlation between sotalol dose and plasma concentration.

Excretion.

Sotalol is excreted by glomerular filtration and to a small degree by tubular secretion. After oral administration, about 75% of the dose is excreted in the urine within 72 hours as unchanged sotalol. Less than 10% is excreted in the faeces. The mean elimination half-life of sotalol is 12.7 ± 1.6 (SE) hours.

Bioavailability.

The absolute bioavailability on oral administration is close to 100%. The bioavailability is decreased when Sotacor is administered with food, especially milk.

Clinical implications of pharmacokinetic data.

As sotalol is primarily excreted by the kidneys, dosage adjustment is necessary in patients with moderate renal impairment. Severe renal impairment (creatinine clearance < 10 mL/minute) is a contraindication.

Indications

Sotacor is indicated for use in the prevention and treatment of supraventricular and ventricular arrhythmias.

Contraindications

Bronchospasm (e.g. bronchial asthma or chronic obstructive airway disease).
Allergic disorders (including allergic rhinitis) which may suggest a predisposition to bronchospasm.
Right ventricular failure secondary to pulmonary hypertension.
Significant right ventricular hypertrophy.
Sinus bradycardia (less than 45 to 50 beats/minute).
Second and third degree A-V block or sick sinus syndrome unless a functioning pacemaker is present.
Shock (including cardiogenic and hypovolaemic shock).
Uncontrolled congestive heart failure.
Severe renal impairment (creatinine clearance < 10 mL/minute).
Congenital or acquired long QT syndromes.
Hypersensitivity to sotalol hydrochloride or the excipients.
Anaesthesia that produces myocardial depression.

Precautions

No antiarrhythmic drug has been shown to reduce the incidence of sudden death in patients with supraventricular or asymptomatic ventricular arrhythmias. Since most antiarrhythmic drugs have the potential to cause proarrhythmias or increase the incidence of sudden death, physicians should carefully consider the risks and benefits of antiarrhythmic therapy in these patients.

Proarrhythmia.

Postmarketing experience.

The most dangerous adverse effect of antiarrhythmic drugs is the aggravation of pre-existing arrhythmias or the provocation of new arrhythmias. The drugs that prolong the QT interval may cause torsades de pointes, a polymorphic ventricular tachycardia associated with prolongation of the QT interval. Experience to date indicates that the risk of torsades de pointes is associated with the prolongation of the QT interval, reduction in heart rate, reduction in serum potassium and magnesium (e.g. as a consequence of diuretic use), high plasma drug concentrations (e.g. as a consequence of overdosage or renal insufficiency), and with the concomitant use of sotalol and other medication such as antidepressants and class I antiarrhythmics which have been associated with torsades de pointes. Females appear to be at increased risk of developing torsades de pointes. ECG monitoring immediately prior to or following the episodes usually reveals a significantly prolonged QT interval and a significantly prolonged QTc interval. In clinical trials, sotalol generally has not been initiated to patients whose pretreatment QTc interval exceeded 450 milliseconds. Sotalol should be titrated very cautiously in patients with prolonged QT intervals.
Torsades de pointes is dose dependent, usually occurs early after initiating therapy or escalation of the dose, and terminates spontaneously in the majority of patients. Although most episodes of torsades de pointes are self limited or associated with symptoms (e.g. syncope), they can progress to ventricular fibrillation.

Clinical studies for arrhythmia.

During clinical trials, 4.3% of 3257 patients with arrhythmias experienced a new or worsened ventricular arrhythmia, including sustained ventricular tachycardia (approximately 1%) and torsades de pointes (2.4%). In addition, in approximately 1% of patients, deaths were considered possibly drug related. In patients with other, less serious, ventricular arrhythmias and supraventricular arrhythmias, the incidence of torsades de pointes was 1% and 1.4% respectively.
Serious proarrhythmias including torsades de pointes were dose related as indicated in Table 1.
Other risk factors for torsades de pointes were excessive prolongation of the QTc and history of cardiomegaly or congestive heart failure. Patients with sustained ventricular tachycardia and a history of congestive heart failure have the highest risk of serious proarrhythmia (.7%). Proarrhythmic events must be anticipated not only on initiating therapy but with every upward dose adjustment; events tend to occur within seven days of initiating therapy or with an increase in dose. Initiating therapy at 80 mg twice daily with gradual upward dose titration thereafter reduces the risk of proarrhythmia (see Dosage and Administration). Sotalol should be used with caution if the QTc is greater than 500 msec on therapy, and serious consideration should be given to reducing the dose or discontinuing therapy when the QT interval exceeds 550 msec. Due to the multiple risk factors associated with torsades de pointes, however, caution should be exercised regardless of the QTc interval.

Cardiac failure.

Beta-blockade depresses myocardial contractility and may precipitate cardiac failure in some patients with a history of cardiac failure, chronic myocardial insufficiency or unsuspected cardiomyopathy. In patients without a history of cardiac failure, continuing depression of the myocardium may lead to cardiac failure. If cardiac failure persists, Sotacor should be discontinued (see Abrupt withdrawal).
Caution is advised when initiating therapy in patients with left ventricular dysfunction controlled by therapy (i.e. ACE inhibitors, diuretics, digitalis, etc); a low initial dose and careful dose titration is appropriate.

Note.

Although congestive heart failure has been considered to be a contraindication to the use of beta-blockers, there is growing literature on the experimental use of beta-adrenergic blocking drugs in heart failure. As further trials are needed to identify which patients are most likely to respond to which drugs, beta-blockers should not normally be prescribed for heart failure outside specialist centres.

Recent myocardial infarction.

In postinfarction patients with impaired left ventricular function, the risk versus benefit of sotalol administration must be considered. Careful monitoring and dose titration are critical during initiation and follow-up of therapy. The adverse results of clinical trials involving antiarrhythmic drugs (i.e. apparent increase in mortality) suggest that sotalol should be avoided in patients with left ventricular ejection fractions ≤ 40% without serious ventricular arrhythmias.
In a large controlled trial in patients with a recent myocardial infarction without heart failure, who did not necessarily have ventricular arrhythmias, oral sotalol hydrochloride treatment was associated with a nonstatistically significant risk reduction in mortality compared to the placebo group (18%). In this postinfarction study using a fixed dose of 320 mg once daily and in a second small randomised trial in high risk postinfarction patients with left ventricular ejection fractions ≤ 40% treated with high doses (640 mg/day), there were suggestions of an excess of early sudden deaths.

Abrupt withdrawal.

Care should be taken if beta-blockers have to be discontinued abruptly in patients with coronary artery disease. Severe exacerbation of angina and precipitation of myocardial infarction and ventricular arrhythmias have occurred following abrupt discontinuation of beta-blockade in patients with ischaemic heart disease. Therefore, it is recommended that the dosage be reduced gradually over a period of 8 to 14 days during which time the patient's progress should be assessed. Sotalol should be temporarily reinstituted if the angina worsens.
If the drug must be withdrawn abruptly in these patients, close observation is required since latent coronary insufficiency may be unmasked. In the perioperative period, sotalol should not be withdrawn unless indicated.

Concomitant therapy with calcium channel blocking drugs.

Concurrent administration of beta-blocking agents and calcium channel blockers has resulted in hypotension, bradycardia, conduction defects and cardiac failure. Beta-blockers should be avoided in combination with cardiodepressant calcium channel blockers because of the additive effect on atrioventricular conduction and ventricular function.

Peripheral circulation.

Beta-blockade may impair the peripheral circulation and exacerbate the symptoms of peripheral vascular disease.

Antiarrhythmic drugs.

Interactions have been reported during concomitant beta-blocker therapy with the class IA agents disopyramide and, less frequently, quinidine; the class IB agents tocainide, mexiletine and lignocaine; the class IC agents flecainide and propafenone (not available in Australia); the class III agent amiodarone; and the class IV antiarrhythmic agents. Concomitant use of sotalol with these agents, and with other beta-blocking drugs, is not recommended.

Prinzmetal angina.

There is a risk of exacerbating coronary artery spasm if patients with Prinzmetal or variant angina are treated with a beta-blocker. If this treatment is essential, it should only be undertaken in a coronary or intensive care unit.

Euthyroid hyperthyroxinaemia.

The effects of beta-blockers on thyroid hormone metabolism may result in elevations of serum free thyroxine (T4) levels. In the absence of any signs or symptoms of hyperthyroidism, additional investigation is necessary before a diagnosis of thyrotoxicosis can be made.

Anaphylaxis.

Patients with a history of anaphylactic reaction to a variety of allergens may have a more severe reaction on repeated challenge while taking beta-blockers. Such patients may be unresponsive to the usual doses of adrenaline used to treat the allergic reaction.

Anaesthesia and the perioperative period.

Beta-blockade may have beneficial effects in decreasing the incidence of arrhythmias and myocardial ischaemia during anaesthesia and the postoperative period. It is currently recommended that maintenance beta-blockade be continued perioperatively. The anaesthetist must be made aware of beta-blockade because of the potential for interactions with other drugs, resulting in severe bradyarrhythmias and hypotension, the decreased reflex ability to compensate for blood loss, hypovolaemia and regional sympathetic blockade, and the increased propensity for vagal induced bradycardia. Incidents of protracted severe hypotension or difficulty restoring normal cardiac rhythm during anaesthesia have been reported.
Modern inhalational anaesthetic agents are generally well tolerated, although older agents (ether, cyclopropane, methoxyflurane, trichloroethylene) were sometimes associated with severe circulatory depression in the presence of beta-blockade.

Diabetes.

Beta-blockers affect glucose metabolism and may mask some important premonitory signs of acute hypoglycaemia, such as tachycardia.
In patients with insulin or noninsulin dependent diabetes, especially labile diabetes, or with a history of spontaneous hypoglycaemia, beta-blockade may result in the loss of diabetic control and delayed recovery from hypoglycaemia. The dose of insulin or oral hypoglycaemic agent may need to be adjusted.

Other metabolic effects.

Beta-adrenoreceptors are involved in the regulation of lipid as well as carbohydrate metabolism. Some drugs affect the lipid profile adversely although the long-term clinical significance of this change is unknown and the effect appears to be less for drugs with intrinsic sympathomimetic activity.

Renal disease.

In patients with severe renal disease, haemodynamic changes following beta-blockade may impair renal function further. Beta-blockers which are excreted mainly by the kidney may require dose adjustment in patients with renal impairment. Sotalol excretion is reduced in patients with renal impairment. Dosage should therefore be adjusted accordingly. Sotalol is contraindicated in patients with severe renal impairment (creatinine clearance < 10 mL/minute).

Use of catecholamine depleting agents.

Concomitant use of drugs such as reserpine and guanethidine requires careful monitoring since the added effect of a beta-blocker may produce an excessive reduction of the resting sympathetic nervous tone.

Clonidine.

Concurrent use of beta-blockers and clonidine should be avoided because of the risk of adverse interaction and severe withdrawal symptoms. If administered concomitantly, the clonidine should not be discontinued until several days after the withdrawal of the beta-blocker.

Phaeochromocytoma.

In patients with this condition, an α-blocking drug (e.g. phentolamine/ phenoxybenzamine) should be administered before the beta-blocker to avoid exacerbation of hypertension.

Eye and skin reactions.

Various skin rashes and conjunctival xerosis have been reported with beta-blocking agents. Cross reactions may occur between beta-blockers, therefore substitutions within the group may not necessarily preclude occurrence of symptoms.

Allergic conditions.

Allergic reactions may be exaggerated by beta-blockade (e.g. allergic rhinitis during the pollen season and allergic reactions to bee and wasp stings). Beta-blockers should be avoided if there is a risk of bronchospasm.

Hyperthyroidism.

Because beta-blockers may mask the clinical signs of developing or continuing hyperthyroidism, resulting in symptomatic improvement without any change in thyroid status, special care should be exercised in hyperthyroid patients who are also receiving beta-blockers. Abrupt withdrawal of beta-blockade in hyperthyroid patients may be followed by an exacerbation of symptoms of hyperthyroidism, including thyroid storm, and should be avoided in these patients.

Electrocardiographic monitoring.

Regular electrocardiographic monitoring should be carried out during sotalol therapy because of prolongation of the QT interval (see Proarrhythmia, Postmarketing experience). Excessive prolongation of the QT interval (> 550 milliseconds) can be a sign of toxicity and should be avoided. Sinus bradycardia (heart rate < 50 beats/minute) occurred at a frequency of 13% in arrhythmia patients receiving sotalol in clinical trials. Bradycardia itself increases the risk of torsades de pointes. Sinus pause, sinus arrest and sinus node dysfunction occur in less than 1% of patients. The incidence of second or third degree atrioventricular block is approximately 1%.

Electrolyte disturbances.

Prior to starting treatment with sotalol, serum electrolytes should be obtained and any electrolyte imbalance corrected. Hypokalaemia and hypomagnesaemia can exaggerate the degree of QT prolongation, and increase the potential for torsades de pointes. Throughout treatment, it is important to monitor electrolyte balance at regular intervals and correct any imbalance. When significant diarrhoea or other intercurrent illness associated with electrolyte losses occurs during treatment with sotalol, patients should be instructed to contact their doctor so that they can be closely monitored with frequent checks of plasma electrolytes and receive replacement therapy as appropriate. (See Proarrhythmia, Postmarketing experience.)

Excessive bradycardia.

If excessive bradycardia occurs alone or with hypotension, atropine 0.5 to 2.0 mg should be given intravenously and immediately followed, if necessary, by a beta-receptor stimulating agent such as isoprenaline (see Overdosage, Treatment).
Patients experiencing this effect on initial administration of sotalol should be removed temporarily from therapy. Sotacor may be later reintroduced at a lower dosage level.
A reduction in dosage by 80 or 160 mg/day may be advisable to alleviate symptoms of weakness and dizziness in cases where the blood pressure continues to fall after a month or two of sotalol administration.

Psoriasis.

Beta-blocking drugs have been reported rarely to exacerbate the symptoms of psoriasis vulgaris.

Hepatic impairment.

Since sotalol is not subject to first-pass metabolism, patients with hepatic impairment show no alteration in clearance of sotalol.

Use in pregnancy.

(Category C)
Beta-blockers may cause bradycardia in the fetus and newborn. Sotalol has been shown to cross the placental barrier and cause bradycardia in the newborn.
During the late stages of pregnancy these drugs should only be given after weighing the needs of the mother against the risk to the fetus.

Use in lactation.

Sotalol is actively excreted in breast milk (milk/plasma ratio = 5.4/1) and therefore should not be administered to nursing mothers.

Paediatric use.

The safety and effectiveness of Sotacor in children under 18 has not been established.

Interactions

Alcohol.

The plasma clearance of sotalol is reduced after alcohol ingestion.

Insulin and oral hypoglycaemics.

Beta-blocking drugs may prolong the hypoglycaemic action of these drugs especially in conditions where glucose mobilisation may be compromised, e.g. labile diabetes, diabetic ketoacidosis and fasting diabetic patients. Symptoms of hypoglycaemia may be masked by sotalol. Hyperglycaemia may occur and the dosage of antidiabetic drugs may require adjustment. (See Precautions, Diabetes.)

Anaesthetics.

Agents such as ether, chloroform and cyclopropane are contraindicated with sotalol (see Precautions, Anaesthesia and the perioperative period).

Beta2-receptor stimulants.

Beta-agonists such as salbutamol, terbutaline and isoprenaline may have to be administered in increased dosages when used concomitantly with sotalol.

Calcium channel blocking drugs.

Concurrent administration of beta-blocking agents and calcium channel blockers has resulted in hypotension, bradycardia, conduction defects and cardiac failure. Beta-blockers should be avoided in combination with cardiodepressant calcium channel blockers because of the additive effects on atrioventricular conduction and ventricular function. (See Precautions, Concomitant therapy with calcium channel blocking drugs.)

Catecholamine depleting agents.

Concomitant use of catecholamine depleting drugs, e.g. reserpine and guanethidine, with a beta-blocker may produce an excessive reduction of resting sympathetic nervous tone. Patients should be closely monitored for evidence of hypotension and/or marked bradycardia which may produce syncope.

Clonidine.

An antagonistic effect between clonidine and sotalol has been observed. Concurrent administration of clonidine and sotalol has caused increased blood pressure compared with clonidine or sotalol alone. The combination of beta-adrenoreceptor antagonists and clonidine should be avoided (see Precautions, Clonidine).

Drugs prolonging the QT interval.

Drugs known to prolong the QT interval and/or to be associated with atypical ventricular tachycardia (AVT, torsades de pointes), especially quinidine, disopyramide, tricyclic antidepressants, terfenadine, astemizole and certain quinolone antibiotics, should be avoided (see Precautions, Proarrhythmia, Postmarketing experience).

Antiarrhythmic agents.

Interactions have been reported during concomitant beta-blocker therapy with the class IA agents disopyramide and, less frequently, quinidine; the class IB agents tocainide, mexiletine and lignocaine; the class IC agents flecainide and propafenone (not available in Australia); the class III agent amiodarone; and the class IV antiarrhythmic agents. Concomitant use of sotalol with these agents, and with other beta-blocking drugs is not recommended.

Potassium depleting diuretics.

Hypokalaemia or hypomagnesaemia may occur, increasing the potential for torsades de pointes (see Precautions, Electrolyte disturbances).

Digoxin.

Single and multiple doses of sotalol do not significantly affect serum digoxin levels. Proarrhythmic events were more common in sotalol treated patients also receiving digoxin, however this may be related to the presence of congestive heart failure, a known risk factor for proarrhythmia, in the patient receiving digoxin.

Drug/ laboratory interaction.

The presence of sotalol in the urine may result in falsely elevated levels of urinary metanephrine when measured by photometric methods. Patients suspected of having phaeochromocytoma and who are treated with sotalol should have their urine screened utilising the high performance liquid chromatographic assay with solid phase extraction.

Adverse Effects

Sotalol is well tolerated in the majority of patients, with the most frequent adverse events arising from its beta-blockade properties. Adverse events are usually transient in nature and rarely necessitate interruption of, or withdrawal from, treatment. These include dyspnoea, fatigue, dizziness, headache, fever, excessive bradycardia and/or hypotension. If they do occur, these side effects usually disappear when the dosage is reduced. The most significant adverse events, however, are those due to proarrhythmia, including torsades de pointes.
In clinical trials, 3256 patients with cardiac arrhythmias (1363 with sustained ventricular tachycardia) received oral Sotacor, of whom 2,451 received the drug for at least two weeks. The most significant adverse events were torsades de pointes and other serious new ventricular arrhythmias (see Precautions, Proarrhythmia, Postmarketing experience), which occurred at rates outlined in Table 2.
Overall, discontinuation because of unacceptable adverse events was necessary in 18% of all patients in cardiac arrhythmia trials. The most common adverse events leading to discontinuation of sotalol were fatigue 4%, bradycardia (< 50 beats/minute) 3%, dyspnoea 3%, proarrhythmia 2%, asthenia 2% and dizziness 2%.

More common reactions (> 1%).

Biochemical abnormalities.

Changes in plasma lipid concentrations (see Precautions, Other metabolic effects).

Cardiovascular.

Ventricular tachyarrhythmias, torsades de pointes, chest pain, bradycardia, hypotension, cold extremities, dyspnoea, palpitations, oedema, ECG abnormalities, proarrhythmia, syncope, heart failure, presyncope. Hypotension and bradycardia are more frequent after intravenous administration.

Dermatological.

Rash.

Gastrointestinal.

Diarrhoea, nausea/ vomiting, flatulence, dyspepsia, abdominal pain.

General.

Headache, tiredness, fever.

Musculoskeletal.

Cramps.

Nervous system.

Dizziness, drowsiness, lethargy, weakness, vertigo, lightheadedness, headache, sleep disturbances, depression, paraesthesia, mood changes, anxiety.

Special senses.

Visual disturbances (including eye irritation, deterioration of eyesight, blurred vision, photophobia), taste abnormalities, hearing disturbances.

Urogenital.

Sexual dysfunction.

Respiratory.

Shortness of breath.

Less common reactions (< 1%).

Biochemical abnormalities.

Changes in antinuclear factor (ANF) titres have been reported but the clinical significance of this is not clear.

Cardiovascular.

Congestive heart failure, prolonged QT interval. Increased ventricular ectopic beat frequency, cardiogenic shock and first degree atrioventricular block have been observed after intravenous administration.

Dermatological.

Cutaneous thickening, pruritus.

Psychiatric.

Unusual dreams.

Others.

Retroperitoneal fibrosis, facial atrophy.

Serious or life threatening reactions.

Myocardial insufficiency may require treatment with digitalis and diuretics. Bradycardia may respond to atropine (see Precautions, Excessive bradycardia). Bronchospasm may be reversed with a beta2-stimulant. Hypotension, if severe, may require use of a vasopressor. Cardiac infarction following too abrupt a withdrawal of the beta-blocker from patients with ischaemic heart disease can be avoided by gradual reduction of dose. Temporary overdrive pacing is suggested as treatment of ventricular arrhythmias in association with prolonged QT interval.

Dosage and Administration

Sotacor is administered orally for the prevention and treatment of arrhythmias.
An intravenous formulation is useful for the management of acute arrhythmias.
As with other antiarrhythmic agents, Sotacor should be initiated and doses increased in a facility capable of monitoring and assessing cardiac rhythm. The dosage must be individualised for each patient on the basis of therapeutic response and tolerance. Proarrhythmic events can occur not only at initiation of therapy, but also with each upward dosage adjustment.

Oral.

Sotacor should be taken preferably one to two hours before meals.
Oral dosage of Sotacor should be adjusted gradually allowing two to three days between dosing increments in order to attain steady state, and to allow monitoring of QT intervals. Graded dose adjustment will help prevent the use of doses which are higher than necessary to control the arrhythmia. The recommended initial oral dosing schedule is 160 mg daily, given in two divided doses at approximately twelve hour intervals. This dose may be increased, if necessary, after appropriate evaluation, to 240 or 320 mg/day. In most patients, a therapeutic response is obtained at a total daily dose of 160 to 320 mg/day, given in two divided doses. Some patients with life threatening refractory ventricular arrhythmias may require doses as high as 480 to 640 mg/day, however these doses should only be prescribed when the potential benefit outweighs the increased risk of adverse events, particularly proarrhythmias.
Because of the long elimination half-life of Sotacor, dosing on more than a twice daily regimen is not usually necessary.

With impaired renal function.

As sotalol is primarily excreted by the kidneys, a dosage adjustment should be made.

Overdosage

Several cases, one fatal, of sotalol intoxication have been reported. Clinical features include asystole, severe bradycardia, congestive heart failure, hypotension, prolongation of QT interval, premature ventricular complex, ventricular tachyarrhythmias, torsades de pointes, hypoglycaemia and bronchospasm.
Close monitoring of the electrocardiogram in patients with suspected sotalol intoxication is recommended. Every effort should be made to correct promptly metabolic and electrolyte imbalances which might contribute to the initiation of ventricular arrhythmias.
Gastric lavage and activated charcoal should be administered when an overdose of Sotacor tablets is suspected. Bradycardia and hypotension should be corrected prior to gastric lavage or endotracheal intubation as these procedures may increase vagal tone.
Depending on the symptoms, the following therapeutic measures are suggested.

Severe bradycardia.

Atropine 1 to 2 mg intravenously may be used to induce vagal blockade. If bradycardia persists, intravenous isoprenaline may be given. An appropriate regimen would be a 5 microgram bolus followed by an infusion of 0.5 to 10 microgram per minute, titrated to achieve the desired effect. In refractory cases, the use of a cardiac pacemaker should be considered.

Heart block (second and third degree).

Transvenous cardiac pacing.

Hypotension.

Severe hypotension should respond to a sympathomimetic amine, such as isoprenaline or noradrenaline. In refractory cases, the use of glucagon hydrochloride should be considered.

Torsades de pointes.

DC cardioversion, transvenous cardiac pacing, adrenaline and/or intravenous magnesium sulfate.

Dialysis.

Dialysis lowers the plasma sotalol concentration by approximately 20%.

Bronchospasm.

A beta2-agonist and/or aminophylline.

Presentation

Tablets (light blue, biconvex, capsule shaped, plain on reverse), 80 mg (marked S 80 with score); 160 mg (marked S 160 with score): 60's (Al/PVC/PVDC blister packs).

Storage

Store below 30°C. Protect from light and moisture.

Poison Schedule

S4.