Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Milpharm Limited, Ares, Odyssey Business Park, West End Road, South Ruislip HA4 6QD, United Kingdom
Sotalol should not be used where there is evidence of:
Hypersensitivity to catecholamines is observed in patients withdrawn from beta-blocker therapy. Occasional cases of exacerbation of angina pectoris, arrhythmias, and in some cases, myocardial infarction have been reported after abrupt discontinuation of therapy. Patients should be carefully monitored when discontinuing chronically administered sotalol, particularly those with ischaemic heart disease. If possible the dosage should be gradually reduced over a period of one to two weeks, if necessary at the same time initiating replacement therapy. Abrupt discontinuation may unmask latent coronary insufficiency. In addition, hypertension may develop.
The most dangerous adverse effect of Class III antiarrhythmic drugs (such as sotalol) is the aggravation of pre-existing arrhythmias or the provocation of new arrhythmias. 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, slow heart rate, reduction in serum potassium and magnesium, high plasma sotalol concentrations and with the concomitant use of sotalol and other medications which have been associated with torsades de pointes (see 4.5: Interactions). Females may be at increased risk of developing torsades de pointes.
Other risk factors for torsades de pointes were excessive prolongation of the QTc and history of cardiomegaly or congestive heart failure.
The incidence of torsades de pointes is dose dependent. Torsades de pointes usually occurs early after initiating therapy or escalation of the dose and can progress to ventricular fibrillation.
In clinical trials of patients with sustained VT/VF the incidence of severe proarrhythmia (torsades de pointes or new sustained VT/VF) was <2% at doses up to 320 mg. The incidence more than doubled at higher doses.
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. Initiating therapy at 80 mg with gradual upward dose titration thereafter reduces the risk of proarrhythmia. In patients already receiving sotalol caution should be used if the QTc exceeds 500msec whilst on therapy, and serious consideration should be given to reducing the dose or discontinuing therapy when the QTc-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.
Sotalol should not be used in patients with hypokalaemia or hypomagnesaemia prior to correction of imbalance; these conditions can exaggerate the degree of QT prolongation, and increase the potential for torsades de pointes. Special attention should be given to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhoea or patients receiving concomitant magnesium- and/or potassium-depleting drugs.
Beta-blockade may further depress myocardial contractility and precipitate more severe heart failure. 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.
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 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.
Excessive prolongation of the QT-interval, >500 msec, can be a sign of toxicity and should be avoided (see Proarrhythmias above). Sinus bradycardia has been observed very commonly in arrhythmia patients receiving sotalol in clinical trials. Bradycardia 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 2nd- or 3rd-degree AV block is approximately 1%.
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.
As with other beta-blocking agents, Sotalol 40mg Tablets should be used with caution in patients undergoing surgery and in association with anaesthetics that cause myocardial depression, such as cyclopropane or trichloroethylene.
Sotalol should be used with caution in patients with diabetes (especially labile diabetes) or with a history of episodes of spontaneous hypoglycaemia, since beta-blockade may mask some important signs of the onset of acute hypoglycaemia, e.g. tachycardia.
Beta-blockade may mask certain clinical signs of hyperthyroidism (e.g. tachycardia). Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-blockade which might be followed by an exacerbation of symptoms of hyperthyroidism, including thyroid storm.
As sotalol is mainly eliminated via the kidneys the dose should be adjusted in patients with renal impairment (see dosage-section 4.2).
Beta-blocking drugs have been reported rarely to exacerbate the symptoms of psoriasis vulgaris.
Class 1a antiarrhythmic drugs, such as disopyramide, quinidine and procainamide and other antiarrhythmic drugs such as amiodarone and bepridil are not recommended as concomitant therapy with sotalol, because of their potential to prolong refractoriness (see 4.4 Special Warnings and Precautions). The concomitant use of other beta-blocking agents with sotalol may result in additive Class II effects.
Sotalol 40mg Tablets should be given with extreme caution in conjunction with other drugs known to prolong the QT-interval such as phenothiazines, tricyclic antidepressants, terfenadine and astemizole. Other drugs that have been associated with an increased risk for torsades de pointes include erythromycin IV, halofantrine, pentamidine, and quinolone antibiotics.
Beta-adrenergic blocking agents may impede the compensatory cardiovascular reactions associated with hypotension or shock that may be induced by Floctafenine.
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 such as verapamil and diltiazem because of the additive effects on atrioventricular conduction, and ventricular function.
Hypokalaemia or hypomagnesaemia may occur, increasing the potential for torsade de pointes (see Special Warnings and Precautions for Use).
Amphotericin B (IV route), corticosteroids (systemic administration), and some laxatives may also be associated with hypokalaemia; potassium levels should be monitored and corrected appropriately during concomitant administration with sotalol.
Beta-blocking drugs may potentiate the rebound hypertension sometimes observed after discontinuation of clonidine; therefore, the beta-blocker should be discontinued slowly several days before the gradual withdrawal of clonidine.
Single and multiple doses of sotalol do not significantly affect serum digoxin levels. Proarrhythmic events were more common in sotalol treated patients also receiving digitalis glycosides; however, this may be related to the presence of CHF, a known risk factor for proarrhythmia, in patients receiving digitalis glycosides. Association of digitalis glycosides with beta-blockers may increase auriculo-ventricular conduction time.
Concomitant use of catecholamine-depleting drugs, such as reserpine, guanethidine, or alpha methyldopa, 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.
Hyperglycaemia may occur, and the dosage of antidiabetic drugs may require adjustment. Symptoms of hypoglycaemia (tachycardia) may be masked by beta-blocking agents
The neuromuscular blockade is prolonged by beta-blocking agents
Patients in need of beta-agonists should not normally receive sotalol. However, if concomitant therapy is necessary beta-agonists may have to be administered in increased dosages.
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 HPLC assay with solid phase extraction.
Animal studies with sotalol hydrochloride have shown no evidence of teratogenicity or other harmful effects on the foetus. Although there are no adequate and well-controlled studies in pregnant women, sotalol hydrochloride has been shown to cross the placenta and is found in amniotic fluid. Beta-blockers reduce placental perfusion, which may result in intrauterine foetal death, immature and premature deliveries. In addition, adverse effects (especially hypoglycaemia and bradycardia) may occur in foetus and neonate. There is an increased risk of cardiac and pulmonary complications in the neonate in the postnatal period. Therefore, sotalol should be used in pregnancy only if the potential benefits outweigh the possible risk to the foetus. The neonate should be monitored very carefully for 48-72 hours after delivery if it was not possible to interrupt maternal therapy with sotalol 2-3 days before the birthdate.
Most beta-blockers, particularly lipophilic compounds, will pass into breast milk although to a variable extent. Breast-feeding is therefore not recommended during administration of these compounds.
There are no data available, but the occasional occurrence of side effects such as dizziness and fatigue should be taken into account (see 4.8 Undesirable effects).
Sotalol is well tolerated in the majority of patients, with the most frequent adverse effects arising from its beta-blockade properties. Adverse effects 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, they usually disappear when the dosage is reduced. The most significant adverse effects, however, are those due to proarrhythmia, including torsades de pointes (see section 4.4).
Frequency is defines using the following convention: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000) including isolated reports
The following are adverse events considered related to therapy, occurring in 1% or more of patients treated with sotalol.
Common: Bradycardia, dyspnoea, chest pain, palpitations, oedema, ECG abnormalities, hypotension, arrhythmia, syncope, heart failure, presyncope
Common: Rash
Common: Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, flatulence
Common: Muscle spasms
Common: Fatigue, dizziness, asthenia, lightheadedness, headache, paresthesia, dysgeusia
Common: Sleep disorder, mood altered, depression, anxiety
Common: Sexual dysfunction
Common: Visual disturbances
Common: Hearing disturbances
Common: Pyrexia
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 2 weeks.
The most significant adverse events were torsade de pointes and other serious new ventricular arrhythmias (see section 4.4), which occurred at the following rates:
| Patient Populations | |||
|---|---|---|---|
| VT/VF (n=1,363) | NSVT/PVC (n=946) | SVA (n=947) | |
| Torsade de Pointes | 4.1% | 1.0% | 1.4% |
| Sustained VT/VF | 1.2% | 0.7% | 0.3% |
VT = ventricular tachycardia; VF = ventricular fibrillation; NSVT = nonsustained ventricular tachycardia; PVC = premature ventricular contractions; SVA = supraventricular arrhythmia.
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 are listed in the table below:
| Fatigue | 4% |
| Bradycardia (<50 bpm) | 3% |
| Dyspnoea | 3% |
| Proarrythmia | 2% |
| Asthenia | 2% |
| Dizziness | 2% |
Cold and cyanotic extremities, Raynaud’s phenomenon, increase in existing intermittent claudication and dry eyes have been seen in association with other beta-blockers.
Reporting suspected adverse reactions after authorisation of the medicinal products 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 via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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