Adverse reactions : תופעות לוואי

4.8   Undesirable effects
Summary of the safety profile
The most commonly reported adverse reactions (> 5%) seen in the first 24 hours after receiving vernakalant were dysgeusia (taste disturbance) (17.9%), sneezing (12.5%), and paraesthesia (6.9%). These reactions occurred around the time of infusion, were transient and were rarely treatment limiting.

Tabulated list of adverse reactions
The adverse reaction profile presented below is based on the analysis of pooled clinical trials, a post-authorisation safety study and spontaneous reporting. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000).

Table 1: Adverse reactions a


Nervous system            Very common: Dysgeusia disorders
Common: Paraesthesia, dizziness

Uncommon: Hypoaesthesia, burning sensation, parosmia,
syncope, somnolence
Eye disorders             Uncommon: Lacrimation increased, eye irritation, visual impairment
Cardiac disorders         Common: Bradycardiab, atrial flutterb

Uncommon: Sinus arrest, ventricular tachycardia, palpitations,
bundle branch block left, ventricular extrasystoles, AV block first degree, AV block complete, bundle branch block right, sinus bradycardia, ECG QRS complex prolonged, cardiogenic shock,
blood pressure diastolic increased

Rare: Atrial flutter with 1:1 atrioventricular conduction b, c

Vascular disorders        Common: Hypotension

Uncommon: Flushing, hot flush, pallor
Respiratory, thoracic     Very common: Sneezing and mediastinal disorders                 Common: Cough, nasal discomfort
Uncommon: Dyspnoea, throat irritation, oropharyngeal pain,
nasal congestion suffocation feeling,      choking sensation,
rhinorrhoea
Table 1: Adverse reactions a


Gastrointestinal        Common: Nausea, paraesthesia oral, vomiting disorders
Uncommon:       Dry mouth, diarrhoea,         hypoaesthesia     oral, defecation urgency
Skin and                Common: Pruritus, hyperhidrosis subcutaneous tissue disorders               Uncommon: Pruritus generalised, cold sweat
Musculoskeletal and     Uncommon: Pain in extremity connective tissue disorders
General disorders and   Common: Infusion site pain, feeling hot, infusion site paraesthesia administration site     Uncommon: Fatigue, Infusion site irritation, infusion site conditions              hypersensitivity, infusion site pruritus, malaise a
The adverse reactions included in the table occurred within 24 hours of administration of Vernakalant (see sections 4.2 and 5.2) with an incidence >0.1% of vernakalant patients and higher than placebo b
See subheadings atrial flutter and bradycardia below c
Identified in post-marketing experience

Description of selected adverse reactions:
Clinically significant adverse reactions observed in clinical trials included hypotension and ventricular arrhythmia. (see sections 4.4).

Bradycardia
Bradycardia was observed predominantly at the time of conversion to sinus rhythm. With a significantly higher conversion rate in patients treated with vernakalant, the incidence of bradycardia events was higher within the first 2 hours in vernakalant treated patients than in placebo-treated patients (1.6% versus 0%, respectively). Of the patients who did not convert to sinus rhythm, the incidence of bradycardia events in the first 2 hours postdose was similar in placebo and vernakalant treated groups (4.0% and 3.8%, respectively). In general, bradycardia responded well to discontinuation of treatment and/or administration of atropine.

Atrial flutter
Atrial fibrillation patients receiving vernakalant have a higher incidence of converting to atrial flutter within the first 2 hours postdose (10% versus 2.5% in placebo). With continuation of the infusion as recommended above, the majority of these patients continue to convert to sinus rhythm. In the remaining patients, electrical cardioversion can be recommended. In clinical studies to date, patients who developed atrial flutter following treatment with vernakalant did not develop 1:1 atrioventricular conduction. However, in post-marketing experience very rare cases of atrial flutter with 1:1 atrioventricular conduction are observed.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il/ In addition, you may report by sending an e-mail message to safety@tzamal-medical.co.il