Brinavess 20 mg/ml concentrate for solution for infusion

The SPC have also been updated following approval of the renewal

Date changed to state:

31 October 2019

Date of revision changed to state:

10/2019

Only the paragraphs that have been amended are indicated here

Product name “BRINAVESS” has been deleted from some sections in the SPC, in most instances this has been replaced with “vernakalant”.

The following sections of the SPC have also been updated following approval of variation 0035 (update to the product information in line with the CCDS)

4.2     Posology and method of administration

4.3       Contraindications

4.4       Special warnings and precautions for use

4.5       Interaction with other medicinal products and other forms of interaction

4.6       Fertility, pregnancy and lactation

4.7       Effects on ability to drive and use machines

4.8       Undesirable effects

4.9       Overdose

5.1     Pharmacodynamic properties

5.2     Pharmacokinetic properties

5.3     Preclinical safety data

6.4     Special precautions for storage

6.6     Special precautions for disposal and other handling

10.       DATE OF REVISION OF THE TEXT

11 December 2019

Only the paragraphs that have been amended are indicated here

Product name “BRINAVESS” has been deleted from some sections in the SPC, in most instances this has been replaced with “vernakalant”.

The following sections of the SPC have also been updated following approval of variation 0035 (update to the product information in line with the CCDS)

4.2     Posology and method of administration

4.3       Contraindications

4.4       Special warnings and precautions for use

4.5       Interaction with other medicinal products and other forms of interaction

4.6       Fertility, pregnancy and lactation

4.7       Effects on ability to drive and use machines

4.8       Undesirable effects

4.9       Overdose

5.1     Pharmacodynamic properties

5.2     Pharmacokinetic properties

5.3     Preclinical safety data

6.4     Special precautions for storage

6.6     Special precautions for disposal and other handling

10.       DATE OF REVISION OF THE TEXT

11 December 2019

Only the paragraphs that have been amended are indicated here

New text highlighted in blue

Deleted text highlighted in red

4.2     Posology and method of administration

Posology

BRINAVESS is dosed by patient body weight, with a maximum calculated dose based upon 113 kg.

The recommended initial infusion is 3 mg/kg to be infused over a 10 10-minute period For patients weighing ≥ 113 kg, the with a maximum initial dose of 339 mg (84.7 ml of 4 mg/ml solution) should not be exceeded. If conversion to sinus rhythm does not occur within 15 minutes after the end of the initial infusion, a second 10 minute infusion of 2 mg/kg may be administered. For patients weighing ≥ 113 kg, the (maximum second infusion of 226 mg (56.5 ml of 4 mg/ml solution)) should not be exceeded. Cumulative doses of greater than 5 mg/kg should not be administered within 24 hours.

Patients with body weight > 113 kg:

For patients above 113 kg, vernakalant has a fixed dose. The initial dose is 339 mg (84.7 ml of 4 mg/ml solution). If conversion to sinus rhythm does not occur within 15 minutes after the end of the initial infusion, a second 10 minute infusion of 226 mg (56.5 ml of 4 mg/ml solution) may be administered. Cumulative doses above 565 mg have not been evaluated.

5.       PHARMACOLOGICAL PROPERTIES

5.1     Pharmacodynamic properties

Efficacy from Post-Marketing Observational Study

In the post-approval safety study SPECTRUM that included 1,778 patients with 2,009 BRINAVESS treatment episodes, effectiveness was assessed as the proportion of patients who converted to sinus rhythm for at least one (1) minute within 90 minutes from the start of BRINAVESS infusion, excluding patients who received electrical cardioversion or intravenous Class I/III antiarrhythmics for cardioversion within the 90-minute window. Overall, BRINAVESS was effective in 70.2% (1,359/1,936) of these patients. Median time to conversion to SR as reported among all patients who, as per the investigator judgement, converted to SR was 12 minutes and in most of the treatment episodes (60.4%) only one infusion was administered. The higher cardioversion rate in SPECTRUM as compared to clinical phase 3 studies (70.2% vs 47% to 51%) is correlated with a shorter duration of the duration of the index atrial fibrillation period (median duration of 11.1 hours in SPECTRUM vs 17.7 to 28.2 hours in clinical studies).

If patients who received electrical cardioversion, intravenous antiarrhythmics or oral propafenone/flecainide within 90 minutes from the start of BRINAVESS infusion are regarded as treatment failures in addition to patients who did not convert for one minute within 90 minutes, the conversion rate among the 2,009 patients who received BRINAVESS was 67.3 % (1,352/2,009). There was no meaningful difference when stratifying the analysis by therapeutic indication (i.e. non‑surgery and post-cardiac surgery patients).

10.       DATE OF REVISION OF THE TEXT

19 September 2019