Consumer medicine information

APO-Sotalol

Sotalol hydrochloride

BRAND INFORMATION

Brand name

APO-Sotalol

Active ingredient

Sotalol hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using APO-Sotalol.

What is in this leaflet

This leaflet answers some common questions about sotalol. 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 this medicine against the benefits they expect it will have for you.

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

Keep this leaflet with the medicine. You may want to read it again.

What this medicine is used for

Sotalol is used to prevent and treat an irregular heart rhythm or heartbeat, also known as an 'arrhythmia'.

Sotalol belongs to a group of medicines called beta-blockers.

How it works

Sotalol works by changing the body's response to some nervous impulses, especially in the heart. By doing so, sotalol helps the heart to beat more regularly and reduce the effort to which the heart has to pump blood.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed this medicine for another reason.

This medicine is available only with a doctor's prescription.

This medicine is not addictive.

There is not enough information to recommend the use of this medicine in children.

Before you take this medicine

When you must not take it

Do not take this medicine if you have an allergy to:

  • sotalol
  • 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
  • swelling of the face, lips, tongue, throat or other parts of the body
  • rash, itching or hives on the skin.

Do not take this medicine if you have or have had any of the following medical conditions:

  • bronchospasm (e.g. bronchial asthma or chronic obstructive airway disease)
  • allergic disorders, such as allergic rhinitis
  • severe kidney disease
  • certain cardiovascular conditions.

Ask your doctor if you have any cardiovascular conditions or diseases that would stop you from taking this medicine.

Do not take this medicine if you are going to receive certain anaesthetics. You must tell your doctor if you're going to receive an anaesthetic.

Do not take this medicine after the expiry date printed on the pack or the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • diabetes
  • kidney problems
  • an overactive thyroid
  • phaeochromocytoma, which is a rare tumour of the adrenal gland
  • any blood vessel disorders causing poor circulation in the arms and legs
  • a recent heart attack
  • certain types of angina (such as Prinzmetal angina or variant angina)
  • any other heart problems
  • problems with the levels of certain salts in your blood
  • psoriasis
  • eye or skin reactions, which were caused from using beta-blockers in the past.

Tell your doctor if you are pregnant or you plan to become pregnant.

Do not take this medicine whilst pregnant until you and your doctor have discussed the risks and benefits involved.

Tell your doctor if you are breastfeeding.

Do not take this medicine whilst breastfeeding.

  1. You are planning to have surgery or an anaesthetic.
  2. You are currently receiving or are planning to receive dental treatment.

If you have not told your doctor about any of the above, tell them before you start taking this medicine.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and sotalol may interfere with each other. These include:

  • other medicines used to treat an irregular heart rhythm or heartbeat
  • digoxin, a medicine used to treat heart failure
  • some medicines used to treat high blood pressure, angina or other heart conditions
  • insulin and other medicines used to treat diabetes
  • certain types of diuretics (fluid tablets)
  • some medicines used to treat depression
  • antihistamines such as terfenadine and astemizole, which are used to treat hay fever and allergies
  • some medicines used for asthma or other lung problems
  • some medicines used during surgery or emergency situations such as anaesthetics
  • some antibiotics.

These medicines may be affected by this medicine or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

Other interactions not listed above may also interact with sotalol.

How to take this medicine

Follow all directions given to you by your doctor or pharmacist carefully. They may differ to the information contained in this leaflet.

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

How much to take

Your doctor will tell you how much of this medicine you should take. This depends on your condition and whether you are taking any other medicines.

How to take it

Swallow the tablets whole with a full glass of water.

Do not take the tablets with any drinks that contains milk. Milk can interfere with the absorption of sotalol.

When to take it

Take your medicine on an empty stomach, at least half an hour (ideally 1-2 hours) before, or two hours after, a meal or milk-containing products.

Take this medicine at about the same time each day. Taking it at the same time each day will have the best effect and will also help you remember when to take it.

How long to take it for

Continue taking your medicine for as long as your doctor tells you.

Make sure you have enough to last over weekends and holidays.

If you forget to take it

If it is almost time to take your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember, and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose that you missed. This may increase the chance of you experiencing side effects.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

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 your nearest hospital, if you think that you or anyone else may have taken too much of this medicine. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are taking it

Things you must do

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

Tell any other doctors, dentists and pharmacists who are treating you that you take this medicine.

If you become pregnant while taking this medicine, tell your doctor immediately.

you are breastfeeding or are planning to breast-feed

you are about to have any blood tests

you are going to have surgery or an anaesthetic or are going into hospital.

If you have a history of allergies, there is a chance that sotalol may cause allergic reactions to be worse or harder to treat.

If you are being treated for diabetes, make sure you check your blood sugar levels regularly. Sotalol may affect how well your diabetes is controlled. It may also cover up some of the symptoms of low blood sugar (also called hypoglycaemia), such as a fast heartbeat. Sotalol may also make low blood sugar last longer. Your doctor may need to change the dose of diabetes medicines (such as insulin).

Keep all of your doctor's appointments so that your progress can be checked. Your doctor may occasionally do tests to make sure the medicine is working and to prevent side effects.

Things you must not do

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

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

Do not stop taking your medicine or change the dosage without checking with your doctor.

Things to be careful of

Be careful while driving or operating machinery until you know how medicine affects you. Sotalol may cause dizziness, light-headedness or drowsiness in some people. If this occurs do not drive or operate machinery or any other activity that could be dangerous if dizzy, light-headed or drowsy.

Dizziness, light-headedness or fainting may occur, especially when you get up from a sitting or lying position. Getting up slowly may help.

Make sure you drink enough water in hot weather and during exercise when you are taking sotalol, especially if you sweat a lot. If you do not drink enough water while taking sotalol, you may feel faint or light-headed or sick. This is because your blood pressure is dropping suddenly. If you continue to feel unwell, tell your doctor.

Side effects

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

This medicine helps most people, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

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

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

  • dizziness, light-headedness or fainting, especially when getting up quickly
  • tiredness, lack of energy, weakness
  • cramps
  • headache, fever
  • feeling sick, vomiting, stomach upset, diarrhoea, wind
  • change in taste sensation
  • problems with sexual function
  • sleep problems, unusual dreams
  • worsening of psoriasis

The above list includes the more common side effects of your medicine. They are usually mild.

Tell your doctor as soon as possible if you notice any of the following:

  • hearing disturbances
  • tingling or numbness in the hands or feet, cold limbs
  • irritated eyes, blurred vision, worsening of eyesight, increased sensitivity of the eyes to sunlight
  • anxiety, depression, mood changes

The above list includes serious side effects that may require medical attention.

If any of the following happen, stop taking your medicine and either tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • chest tightness, wheezing, shortness of breath
  • very slow heartbeat
  • fast, irregular heartbeat, palpitations
  • chest pain
  • any type of skin rash, itching
  • shortness of breath (sometimes with tiredness, weakness and a reduced ability to exercise), which may occur together with swelling of the feet or legs due to fluid build-up
  • shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue, throat or other parts of the body; rash, itching or hives on the skin (signs of an allergic reaction).

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may occur in some patients.

Storage and disposal

Storage

Keep your medicine in the bottle until it is time to take them. If you take the tablets out of the bottle they may not keep well.

Keep your medicine in a cool dry place where the temperature stays below 25°C. Protect from light.

Do not store your medicine or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep this medicine where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or it has passed its expiry date, ask your pharmacist what to do with any medicine that is left over.

Product description

What APO-Sotalol Tablets looks like

80 mg tablets:
Blue, capsule-shaped, biconvex tablets, engraved APO-80 on one side and scored on the other. AUST R 83094.

160 mg tablets:
Blue, capsule-shaped, biconvex tablets, engraved APO-160 on one side and scored on the other. AUST R 73846.

These tablets are packed in a bottle containing 60 tablets.

*Not all strengths, pack types and/or pack sizes may be available.

Ingredients

Each tablet contains 80mg or 160 mg of sotalol hydrochloride as the active ingredient.

It also contains the following:

  • dextrates
  • methylcellulose
  • magnesium stearate
  • colloidal anhydrous silica
  • indigo carmine aluminium lake.

This medicine contains sugars as dextrose

This medicine does not contain gluten, lactose, sucrose, tartrazine and other azo dyes.

Sponsor

Apotex Pty Ltd
16 Giffnock Avenue
Macquarie Park NSW 2113

APO- and APOTEX are registered trademarks of Apotex Inc.

This leaflet was prepared in September 2018.

Published by MIMS March 2019

BRAND INFORMATION

Brand name

APO-Sotalol

Active ingredient

Sotalol hydrochloride

Schedule

S4

 

1 Name of Medicine

Sotalol hydrochloride.

2 Qualitative and Quantitative Composition

Each tablet contains sotalol hydrochloride as the active ingredient.
For the full list of excipients see Section 6.1 List of Excipients.

3 Pharmaceutical Form

80 mg tablets.

Blue capsule shaped, biconvex tablets, engraved APO-80 on one side and scored on the other.

160 mg tablets.

Blue, capsule-shaped, biconvex tablets, engraved APO-160 on one side and scored on the other.

4 Clinical Particulars

4.1 Therapeutic Indications

Prevention and treatment of supraventricular and ventricular arrhythmias.

4.2 Dose and Method of Administration

APO-Sotalol tablets are intended for oral administration.

Dosage.

Sotalol is administered orally for the prevention and treatment of arrhythmias.
As with other antiarrhythmic agents, sotalol 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 commencement of therapy, but also with each upward dosage adjustment.
Sotalol should be taken preferably 1 to 2 hours before meals.
Oral dosage of sotalol should be adjusted gradually allowing 2 to 3 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/day, given in two divided doses at approximately 12 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 2 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 long elimination half-life of sotalol, dosing on more than a twice daily regimen is not usually necessary.

Renal impairment.

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

4.3 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 45-50 beats/minute).
Second and third degree atrioventricular 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/min).
Congenital or acquired long QT syndromes.
Hypersensitivity to sotalol hydrochloride or the excipients.
Anaesthesia that produces myocardial depression.

4.4 Special Warnings and Precautions for Use

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.

Post-marketing experience.

The most dangerous adverse effect of antiarrhythmic agents is the aggravation of pre-existing arrhythmias or the provocation of new arrhythmias. Agents that prolong the QT interval may cause torsade de pointes, a polymorphic ventricular tachycardia associated with prolongation of the QT interval. Experience to date indicates that the risk of torsade 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 torsade de pointes. Females appear to be at increased risk of developing torsade 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 administered to patients whose pretreatment QTc interval exceeded 450 msec. Sotalol should be titrated very cautiously in patients with prolonged QT intervals.
Torsade de pointes is dose dependent, usually occurs early after commencing therapy or increasing the dose, and terminates spontaneously in the majority of patients. Although most episodes of torsade 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 torsade 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 torsade de pointes was 1% and 1.4% respectively.
Serious proarrhythmias including torsade de pointes were dose related as indicated in Table 1.
Other risk factors for torsade 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 (approximately 7%). Proarrhythmic events must be anticipated not only on initiating therapy, but with every upward dose adjustment; events tend to occur within 7 days of initiating therapy or with an increase in dose. Initiating therapy at 80 mg twice a day with gradual upward dose titration thereafter decreases the risk of proarrhythmia (see Section 4.2 Dose and Method of 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 torsade 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 develops, sotalol tablets should be withdrawn (see Section 4.4 Special Warnings and Precautions for Use, Abrupt withdrawal).
Caution is advised when initiating therapy in patients with left ventricular dysfunction controlled by therapy (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 a 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 of specialist centres.

Recent myocardial infarction.

In post-infarction 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 treatment. 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 non-statistically significant risk reduction in mortality compared to the placebo group (18%). In this post-infarction study using a fixed dose of 320 mg once a day and in a second small randomised trial in high risk post-infarction 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 withdrawn 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 reinstituted temporarily 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 peri-operative period, sotalol should not be withdrawn, unless indicated.

Concomitant therapy with calcium channel blocking drugs.

Concomitant administration of beta-blocking agents and calcium channel blockers has resulted in hypotension, bradycardia, conduction defects and cardiac failure. Beta-blocking agents 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-blocking agents. Such patients may be unresponsive to the usual doses of adrenaline used to treat the allergic reaction.

Anaesthesia and the peri-operative period.

Beta-blockade may have beneficial effects in decreasing the incidence of arrhythmias and myocardial ischaemia during anaesthesia and the post-operative period. It is currently recommended that maintenance beta-blockade be continued peri-operatively. 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 non-insulin 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 adjustment.

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/min) (see Section 4.3 Contraindications).

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, clonidine should not be discontinued until several days after the withdrawal of the beta-blocker.

Phaeochromocytoma.

In patients with this condition, an alpha-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 hormone status, special care should be exercised in those patients who are hyperthyroid and 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 Section 4.4 Special Warnings and Precautions for Use, Proarrhythmia, Post-marketing experience). Excessive prolongation of the QT interval (> 550 msec) can be a sign of toxicity and should be avoided. Sinus bradycardia (heart rate < 50 bpm) occurred at a frequency of 13% in arrhythmia patients receiving sotalol in clinical trials. Bradycardia itself increases the rate of torsade de pointes. Sinus pause, sinus arrest and sinus node dysfunction occur in less than 1% of patients. The incidence of 2nd or 3rd 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 torsade de pointes. It is important to monitor electrolyte balance at regular intervals and correct any imbalance throughout therapy. 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 Section 4.4 Special Warnings and Precautions for Use, Proarrhythmia, Post-marketing experience).

Excessive bradycardia.

If excessive bradycardia occurs alone or with hypotension, atropine 0.5 to 2 mg should be given intravenously and immediately followed, if necessary, by a beta-receptor stimulating agent such as isoprenaline (see Section 4.9 Overdose).
Patients experiencing this effect on initial administration of sotalol should be removed temporarily from therapy. Sotalol may be reintroduced later 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-blockers have been reported rarely to exacerbate the symptoms of psoriasis vulgaris.

Use in the elderly.

No data available.

Paediatric use.

The safety and effectiveness of sotalol in children under 18 years of age has not been established.

Effects on laboratory tests.

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 (HPLC) assay with solid phase extraction.

4.5 Interactions with Other Medicines and Other Forms of 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 Section 4.4 Special Warnings and Precautions for Use, Diabetes).

Anaesthetics.

Agents such as ether, chloroform and cyclopropane are contraindicated with sotalol (see Section 4.4 Special Warnings and Precautions for Use, Anaesthesia and the peri-operative 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 tablets.

Calcium channel blocking drugs.

Concurrent use of beta-blocking drugs 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 blocking agents because of the additive effects on atrioventricular conduction and ventricular function (see Section 4.4 Special Warnings and Precautions for Use, Concomitant therapy with calcium channel blocking drugs).

Catecholamine-depleting agents.

Concomitant use of catecholamine-depleting drugs, such as reserpine and guanethidine, with a beta-blocking agent 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 Section 4.4 Special Warnings and Precautions for Use, Clonidine).

Drugs prolonging the QT interval.

Drugs known to prolong the QT interval and/or to be associated with atypical ventricular tachycardia (AVT, torsade de pointes) especially quinidine, disopyramide and tricyclic antidepressants, terfenadine, astemizole and certain quinolone antibiotics should be avoided (see Section 4.4 Special Warnings and Precautions for Use, Proarrhythmia, Post-marketing experience).

Antiarrhythmic agents.

Interactions have been reported during concomitant use of beta-blockers 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 torsade de pointes (see Section 4.4 Special Warnings and Precautions for Use, Electrolyte disturbances).

Digoxin.

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

Food and milk interaction.

Since the bioavailability of sotalol is decreased when sotalol is administered with food or milk, the tablets should be taken on an empty stomach, i.e. at least half an hour (ideally 1-2 hours) before, or two hours after, meals or milk containing products.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Beta-blocking agents may cause pharmacological effects such as bradycardia in the foetus and newborn infant. 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 foetus.
 Sotalol is actively excreted in breast milk (milk:plasma ratio = 5.4:1) and therefore should not be administered to nursing mothers.

4.7 Effects on Ability to Drive and Use Machines

No specific studies have been conducted to assess the direct effect of sotalol on the ability to drive and use machines. However, adverse effects of sotalol include dizziness, drowsiness and visual disturbances, which could affect the ability to drive or use machines. See Section 4.8 Adverse Effects (Undesirable Effects).

4.8 Adverse Effects (Undesirable 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 lowered. The most significant adverse events, however, are those due to proarrhythmia, including torsade de pointes.
In clinical trials, 3256 patients with cardiac arrhythmias (1363 with sustained ventricular tachycardia) received oral sotalol, of whom 2451 received the drug for at least two weeks. The most significant adverse events were torsade de pointes and other serious new ventricular arrhythmias (see Section 4.4 Special Warnings and Precautions for Use, Proarrhythmia, Post-marketing experience), which occurred at the following rates as seen in Table 2.
Overall, discontinuation of sotalol due to 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 bpm) 3%, dyspnoea 3%, proarrhythmia 2%, asthenia 2% and dizziness 2%.

More common reactions > 1%.

Biochemical abnormalities.

Changes in plasma lipid concentrations (see Section 4.4 Special Warnings and Precautions for Use, Other metabolic effects).

Cardiovascular.

Ventricular tachyarrhythmias, torsade 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 Section 4.4 Special Warnings and Precautions for Use, 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.

Not known: (frequency cannot be estimated on the basis of available data).

Blood and lymphatic system disorders.

Thrombocytopenia - frequency unknown.

Skin and subcutaneous tissue disorders.

Alopecia and hyperhidrosis - frequency unknown.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems and contact Apotex Medical Information Enquiries/Adverse Drug Reaction Reporting on 1800 195 055.

4.9 Overdose

Symptoms.

Several cases, one fatal, of sotalol intoxication have been reported. Clinical features include: asystole, severe bradycardia, congestive heart failure, hypotension, prolongation of QT interval, ventricular tachyarrhythmias, torsade de pointes, hypoglycaemia and bronchospasm.

Treatment.

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 sotalol 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 regime would be 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.

Torsade de pointes.

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

Dialysis.

Dialysis lowers the plasma sotalol concentration by approximately 20%.

Bronchospasm.

A beta2-agonist and/or aminophylline.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Sotalol is a nonselective beta-adrenoreceptor antagonist 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 and 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 (QT interval corrected for heart rate) on electrocardiographic recordings.
Like most other beta-blockers, sotalol inhibits renin release. This suppressive effect is significant both at rest and during exercise.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Sotalol is well absorbed from the gastrointestinal tract. Peak plasma concentrations of 1.0 to 1.9 mg/L are reached at 1.5 to 5 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.

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.

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.

Bioavailability.

The absolute bioavailability on oral administration is close to 100%. The bioavailability is decreased when sotalol 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/min) is a contraindication.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Dextrates, methylcellulose, magnesium stearate, colloidal anhydrous silica, Indigo carmine aluminium lake.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

80 mg tablets.

Bottle (white, round HDPE bottle with white PP SS/L and P Child resistant Cap) of 60 tablets (AUST R 83094).

160 mg tablets.

Bottle (white, round HDPE bottle with white PP SS/L and P Child resistant Cap) of 60 tablets (AUST R 73846).
APO- and APOTEX- are registered trademarks of Apotex Inc.
Not all strengths may be available.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Sotalol hydrochloride is a white crystalline solid, freely soluble in water (50% w/v) and has a melting point of 210°C.

Chemical structure.


Chemical Name: The active ingredient sotalol hydrochloride is the hydrochloride salt of (RS)- 4'-(1-hydroxy-2-isopropylaminoethyl)-methanesulfonanilide.
Molecular Formula: C12H20N2O3S.HCl.
Molecular Weight: 308.83.

CAS number.

959-24-0.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes