Brinavess - patient leaflet, side effects, dosage

1. What BRINAVESS is and what it is used for

BRINAVESS contains the active substance vernakalant hydrochloride. BRINAVESS works by changing your irregular or fast heart beat to a normal heart beat.

In adults it is used if you have a fast, irregular heart beat called atrial fibrillation which has started recently, less than or equivalent to 7 days, for non-surgery patients and less than or equivalent to 3 days for post-cardiac surgery patients.

2. What you need to know before you use BRINAVESS

Do not use BRINAVESS

• if you are allergic to vernakalant hydrochloride or any of the other ingredients of this medicine

(listed in section 6)

• if you have had new or worsening chest pain (angina) diagnosed by your doctor as an acute

coronary syndrome in the last 30 days or you have had a heart attack in the last 30 days

• if you have a very narrow heart valve, systolic blood pressure less than 100 mm Hg or advanced

heart failure with symptoms at minimal exertion or at rest

• if you have an abnormally slow heart rate or skipped heart beats and do not have a pacemaker,

or you have conduction disturbance called QT prolongation – which can be seen on an ECG by your doctor

• if you take certain other intravenous medicines (antiarrhythmics Class I and III) used to

normalise an abnormal heart rhythm, 4 hours before BRINAVESS is to be used

You must not use BRINAVESS if any of the above apply to you. If you are not sure, talk to your doctor before you use this medicine.

Warnings and precautions

Talk to your doctor before using BRINAVESS if you have:

• heart failure
• certain heart diseases involving the heart muscle, lining that surrounds the heart and a severe

narrowing of the heart valves

a disease of the heart valves

liver problems

you are taking other rhythm control medicines

If you have very low blood pressure or slow heart rate or certain changes in your ECG while using this medicine, your doctor will stop your treatment.

Your doctor will consider if you need additional rhythm control medicine 4 hours after using BRINAVESS.

BRINAVESS may not work in treating some other kinds of abnormal heart rhythms, however your doctor will be familiar with these.

Tell your doctor if you have a pacemaker.

If any of the above apply to you (or you are not sure), talk to your doctor. Detailed information on warnings and precautions relating to side effects that could occur are presented in section 4.

Blood tests

Before giving you this medicine, your doctor will decide whether to test your blood to see how well it clots and also to see your potassium level.

Children and adolescents

Do not give this medicine to children and adolescents less than 18 years of age because there is no experience on its use in this population.

Other medicines and BRINAVESS

Tell your doctor if you are taking, have recently taken or might take any other medicines.

Do not use BRINAVESS if you take certain other intravenous medicines (antiarrhythmics Class I and III) used to normalise an abnormal heart rhythm, 4 hours before BRINAVESS is to be used.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before using this medicine.

It is preferable to avoid the use of BRINAVESS during pregnancy.

It is not known whether BRINAVESS passes into the breast milk.

Driving and using machines

It should be taken into account that some people may get dizzy after receiving BRINAVESS, usually within the first 2 hours (see section “Possible side effects”). If you get dizzy, you should avoid driving or operating machinery after receiving BRINAVESS.

BRINAVESS contains sodium

This medicine contains 32 mg sodium (main component of cooking/table salt) in each 200 mg vial. This is equivalent to 1.6 % of the recommended maximum daily dietary intake of sodium for an adult.

This medicine contains 80 mg of sodium (main component of cooking/table salt) in each vial of 500 mg. This is equivalent to 4 % of the recommended maximum daily dietary intake of sodium for an adult.

3. How to use BRINAVESS

The amount of BRINAVESS you may be given will depend on your weight. The recommended initial dose is 3 mg/kg, with a maximum calculated dose based upon 113 kg. If you weigh more than 113 kg, you will receive a fixed dose of 339 mg. While you are being given BRINAVESS, your breathing, heart beat, blood pressure and the electrical activity of your heart will be checked.

If your heart beat has not returned to normal 15 minutes after the end of your first dose, you may be given a second dose. This will be a slightly lower dose of 2 mg/kg, with a maximum calculated dose based upon 113 kg. If you weigh more than 113 kg, you will receive a fixed dose of 226 mg. Total doses of greater than 5 mg/kg should not be administered within 24 hours.

BRINAVESS will be given to you by a health care professional. BRINAVESS will be diluted before being given to you. Information on how to prepare the solution is available at the end of this leaflet.

It will be given to you into your vein over 10 minutes.

If you are given more BRINAVESS than you should

If you think that you may have been given too much BRINAVESS, tell your doctor straight away.

If you have any further questions on the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Your doctor may decide to stop the infusion if he observes any of the following abnormal changes of:

• your heart beat (such as a very fast (uncommon) or very slow heart beat (common), a missed

beat (uncommon), or a short pause in the normal activity of your heart (uncommon))

• your blood pressure (such as a very low blood pressure causing a serious heart condition)

(uncommon)

• the electrical activity of your heart (uncommon)

Other side effects:

Very common (may affect more than 1 in 10 people)

• taste disturbances
• sneezing

Common (may affect up to 1 in 10 people)

• fast heart beat
• pain or numbness at the infusion site, numbness, decreased skin sensation, or tingling feelings
• nausea and vomiting
• feeling hot
• low blood pressure, slow heart beat, feeling dizzy
• coughing, sore nose
• excessive sweating, itching
• numbness or tingling that occurs in the mucosa or tissues of the oral cavity

Uncommon (may affect up to 1 in 100 people)

• certain kinds of heart beat problems, (such as an awareness of your heart beating (palpitations)

or an extra heart beat)

• decreased feeling or sensitivity
• eye irritation, watery eyes or changes in your vision
• a change in your sense of smell
• pain in your fingers and toes, a burning feeling
• cold sweats, hot flush
• urgency to have a bowel movement, diarrhoea
• shortness of breath or a tightness in the chest
• choking sensation
• pain in your mouth or throat
• irritation, itching at the infusion site
• high blood pressure
• feeling light-headed or fainting, generally feeling unwell, feeling drowsy or sleepy
• runny nose, sore throat
• stuffy nose
• dry mouth
• pale skin
• generalised itching
• fatigue
• decreased feeling or sensitivity of the mouth

These effects, seen within 24 hours of being given BRINAVESS, should pass quickly, however, if they do not you should consult your doctor.

Reporting of side effects

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store BRINAVESS

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and vial label after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

BRINAVESS must be diluted before it is used. The diluted sterile concentrate is chemically and physically stable for 12 hours at or below 25 °C.

From a microbiological point of view, the medicine should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 °C to 8 °C, unless dilution has taken place in controlled and validated aseptic conditions.

Do not use this medicine if you notice particulate matter or discolouration.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What BRINAVESS contains

• The active substance is vernakalant hydrochloride. Each ml of concentrate contains 20 mg

vernakalant hydrochloride equivalent to 18.1 mg vernakalant.

Each vial of 200 mg vernakalant hydrochloride is equivalent to 181 mg vernakalant.

Each vial of 500 mg of vernakalant hydrochloride is equivalent to 452.5 mg of vernakalant.

• The other ingredients are citric acid, sodium chloride, sodium hydroxide (E524) and water for

injections (see section 2 “BRINAVESS contains sodium”).

What BRINAVESS looks like and contents of the pack

BRINAVESS is a concentrate for solution for infusion (sterile concentrate) which is clear and colourless to pale yellow.

For any information about this medicine, please Authorisation Holder.

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This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

.

The following information is intended for healthcare professionals only:

Please refer to the Summary of Product Characteristics and the educational material for additional information prior to the use of BRINAVESS

CLINICAL PARTICULARS

Therapeutic indications

Brinavess is indicated in adults for rapid conversion of recent onset atrial fibrillation to sinus rhythm -For non-surgery patients: atrial fibrillation < 7 days duration

-For post-cardiac surgery patients: atrial fibrillation < 3 days duration

Posology and method of administration

Vernakalant should be administered in a monitored clinical setting appropriate for cardioversion. Only a well-qualified healthcare professional should administer_it.

Posology

Vernakalant 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-minute period with a maximum initial dose of 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 2 mg/kg may be administered (maximum second infusion of 226 mg (56.5 ml of 4 mg/ml solution)). Cumulative doses of greater than 5 mg/kg should not be administered within 24 hours.

The initial infusion is administered as a 3 mg/kg dose over 10 minutes. During this period, the patient should be carefully monitored for any signs or symptoms of a sudden decrease in blood pressure or heart rate. If such signs develop, with or without symptomatic hypotension or bradycardia, the infusion should be stopped immediately.

If conversion to sinus rhythm has not occurred, the patient’s vital signs and cardiac rhythm should be observed for an additional 15 minutes.

If conversion to sinus rhythm did not occur with the initial infusion or within the 15 minute observation period, administer a 2 mg/kg second infusion over 10 minutes.

If conversion to sinus rhythm occurs during either the initial or second infusion, that infusion should be continued to completion. If haemodynamically stable atrial flutter is observed after the initial infusion, the second infusion may be administered as patients may convert to sinus rhythm (see “Special warnings and precautions for use” and “Undesirable effects”).

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.

Post-cardiac surgery

No dose adjustment necessary.

Renal impairment

No dose adjustment necessary (see “Pharmacokinetic properties”).

Hepatic impairment

No dose adjustment necessary (see “Special warnings and precautions for use” and “Pharmacokinetic properties”).

Elderly (> 65 years)

No dose adjustment necessary.

Paediatric population

There is no relevant use of vernakalant in children and adolescents < 18 years of age for rapid conversion of recent onset atrial fibrillation to sinus rhythm and therefore it should not be used in this population.

Method of administration

For intravenous use.

Vernakalant should not be administered as an intravenous push or bolus.

The vials are for single use only and must be diluted prior to administration.

For instructions on dilution of the medicinal product before administration, see section “Special precautions for disposal and other handling”.

Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in “List of excipients”.
• Patients with severe aortic stenosis, patients with systolic blood pressure < 100 mm Hg, and

patients with heart failure class NYHA III and NYHA IV.

• Patients with prolonged QT at baseline (uncorrected > 440 ms), or severe bradycardia, sinus

node dysfunction or second degree and third degree heart block in the absence of a pacemaker.

• Use of intravenous rhythm control antiarrhythmics (class I and class III) within 4 hours prior to,

as well as in the first 4 hours after, vernakalant administration.

• Acute coronary syndrome (including myocardial infarction) within the last 30 days.

Special warnings and precautions for use

Patient monitoring

Cases of serious hypotension have been reported during and immediately following vernakalant infusion. Patients should be carefully observed for the entire duration of the infusion and for at least 15 minutes after completion of the infusion with assessment of vital signs and continuous cardiac rhythm monitoring.

If any of the following signs or symptoms occurs, the administration of vernakalant should be discontinued and these patients should receive appropriate medical management:

• A sudden drop in blood pressure or heart rate, with or without symptomatic hypotension or

bradycardia

• Hypotension
• Bradycardia
• ECG changes (such as a clinically meaningful sinus pause, complete heart block, new bundle