VIVACOR

Package leaflet: Information for the user

Vivacor, 6.25 mg, tablets
Vivacor, 12.5 mg, tablets
Vivacor, 25 mg, tablets
Carvedilolum
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents

1. What Vivacor is and what it is used for
2. What you need to know before taking Vivacor
3. How to take Vivacor
4. Possible side effects
5. How to store Vivacor
6. Contents of the pack and other information

1. What Vivacor is and what it is used for

Vivacor 6.25 mg, 12.5 mg or 25 mg tablets contain carvedilol as the active substance.
Carvedilol is a beta-blocker and a vasodilator. It lowers high blood pressure and reduces the resistance the heart must overcome when pumping blood.
Vivacor is indicated for the treatment of:

• symptomatic chronic heart failure (stable mild, moderate or severe chronic heart failure), in addition to standard background therapy,
• arterial hypertension,
• stable angina pectoris,
• patients after myocardial infarction with documented left ventricular dysfunction (left ventricular ejection fraction (LVEF) ≤ 40%).

2. Important information before using Vivacor

When not to use Vivacor

• if the patient is allergic to carvedilol or any of the other ingredients of this medicine (listed in section 6);
• if the patient has unstable or decompensated heart failure;
• if the patient has overt clinical liver dysfunction (including severe cases);
• if the patient has second- or third-degree atrioventricular block (unless a permanent pacemaker is implanted);
• if the patient has bradycardia (severe slow heart rate < 50 beats per minute);
• if the patient has sick sinus syndrome (including sinoatrial block);
• if the patient has severe hypotension (severe low blood pressure with systolic blood pressure < 85 mmHg);
• if the patient has severe cardiac disorders (cardiogenic shock);
• if the patient has a respiratory disorder associated with bronchospasm or asthma;
• if the patient has significant fluid retention or cardiac overload requiring intravenous administration of drugs that increase myocardial contractility;
• if the patient has metabolic acidosis (a condition leading to acid-base imbalance in the blood);
• if the patient has a pheochromocytoma (a specific adrenal gland tumor associated with high blood pressure), unless symptoms are effectively controlled with alpha-adrenergic receptor-blocking drugs.

Warnings and precautions
Before starting treatment with Vivacor, discuss it with your doctor or pharmacist.
When to exercise special caution when using Vivacor

• if the patient has chronic heart failure, as this may worsen heart failure or cause fluid retention;
• if the patient has hypertension and chronic heart failure treated with cardiac glycosides, caution should be exercised when using Vivacor, as both cardiac glycosides and Vivacor slow atrioventricular conduction;
• if the patient has chronic heart failure and low blood pressure (systolic blood pressure < 100 mmHg), ischemic heart disease, generalized vascular disease, and/or coexisting renal dysfunction. During dose escalation of Vivacor in these patients, the doctor will monitor kidney function and, if worsening renal function is observed, may recommend discontinuation of treatment or dose reduction;
• if the patient has left ventricular dysfunction following acute myocardial infarction. Before initiating carvedilol treatment, the patient's condition must be stable and the patient must have been receiving an ACE inhibitor for at least 48 hours, at a stable dose for at least 24 hours;
• if the patient has chronic obstructive pulmonary disease (COPD) or is prone to bronchospasm but is not being treated for this with oral or inhaled medications. If any signs or symptoms of bronchospasm occur during Vivacor treatment, inform the doctor;
• if the patient has diabetes, as Vivacor may impair glucose regulation and may mask or weaken early symptoms and signs of hypoglycemia (low blood glucose). When initiating Vivacor or increasing its dose, regular monitoring of blood glucose levels and adjustment of antidiabetic medication doses are recommended, as Vivacor may lead to impaired glucose control;
• if the patient has peripheral circulatory disorders or Raynaud's syndrome, as beta-adrenergic receptor-blocking drugs may increase the risk of developing or worsening arterial dysfunction symptoms. However, the additional alpha-1 receptor blockade by Vivacor largely counteracts these effects;
• if the patient has hyperthyroidism, as Vivacor may mask signs and symptoms of hyperthyroidism;
• if heart rate is slower than 55 beats per minute, consult the treating physician, who may decide to reduce the dose;
• if the patient has ever experienced severe hypersensitivity reactions, or if the patient is undergoing allergen immunotherapy (like other drugs in this class, Vivacor may increase sensitivity to allergens and exacerbate anaphylactic reactions);
• if the patient experiences serious skin adverse reactions. Very rare cases of severe skin reactions such as toxic epidermal necrolysis or Stevens-Johnson syndrome have been reported during carvedilol treatment (see section 4 Possible side effects). Carvedilol must be completely discontinued if serious skin adverse reactions possibly related to carvedilol occur;
• if the patient has psoriasis associated with beta-adrenergic blocking agents. The doctor should weigh the potential risks and benefits of using Vivacor;
• if the patient is taking other medicines, such as digoxin, cyclosporine, rifampicin, anesthetics, or antiarrhythmics;
• if the patient has a pheochromocytoma, strict adherence to the doctor's instructions is required. Prior to administering Vivacor, the doctor will recommend treatment with an alpha-adrenergic blocking agent;
• if the patient is suspected of having Prinzmetal's angina, as using drugs that block only beta-adrenergic receptors may be associated with chest pain. However, the additional alpha-1-adrenergic receptor-blocking properties of Vivacor may prevent such effects;
• if the patient wears contact lenses, as reduced tear secretion may occur.

As with all beta-adrenergic blocking agents, carvedilol should not be abruptly discontinued.
This is particularly important for patients with coronary artery disease. The carvedilol dose should be gradually reduced (over 2 weeks).

Children and adolescents
The safety and efficacy of carvedilol in children and adolescents under 18 years of age have not been established; therefore, it should not be used in this age group.

Vivacor and other medicines
Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines planned for use.
It is especially important to inform the doctor if the patient is taking the following medicines:

• medicines containing digoxin (used in the treatment of heart failure), as the doctor may recommend dose adjustments during concomitant use with Vivacor;
• oral cyclosporine and tacrolimus (immunosuppressive drugs used to prevent organ transplant rejection), as Vivacor may enhance the effects of cyclosporine and tacrolimus;
• rifampicin (an antibiotic used in the treatment of tuberculosis), as it may reduce the effectiveness of Vivacor;
• fluoxetine and paroxetine (medicines used in the treatment of depression);
• insulin and oral antidiabetic drugs, as Vivacor may enhance the effects of these drugs. The doctor may recommend more frequent monitoring of blood glucose levels;
• reserpine (a medicine affecting blood pressure) and monoamine oxidase inhibitors (a type of antidepressant), as these medicines may additionally slow heart rate and/or lower blood pressure;
• calcium channel blockers not belonging to the dihydropyridine class, amiodarone, and other medicines used in cardiac rhythm disorders. The doctor will monitor ECG and blood pressure;
• clonidine (a medicine used to lower blood pressure and treat migraines);
• other medicines that lower blood pressure. Vivacor may enhance the effects of concomitantly administered antihypertensive drugs (e.g., alpha-adrenergic receptor antagonists) and medicines whose side effect may include lowering blood pressure (e.g., barbiturates used in epilepsy treatment, phenothiazine derivatives used in psychosis treatment, tricyclic antidepressants used in depression treatment, vasodilators), as well as alcohol;
• anesthetics;
• non-steroidal anti-inflammatory drugs (NSAIDs), which may reduce the effectiveness of Vivacor;
• bronchodilators.

Taking Vivacor with food and alcohol
Avoid drinking grapefruit juice at the same time or immediately after taking Vivacor.
Grapefruit or its juice may increase the blood concentration of the active substance carvedilol and cause unexpected adverse effects.
Alcohol should not be consumed during treatment, as alcohol affects the action of Vivacor.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor or pharmacist before using this medicine.
Animal studies have shown harmful effects on fertility. The potential risk in humans is unknown.
Vivacor should not be used during pregnancy unless the expected benefits outweigh the potential risks.
Vivacor should not be used during breastfeeding.

Driving and operating machinery
As with many other medicines used to treat hypertension, if dizziness or other similar adverse symptoms occur, the patient should not drive or operate machinery. This is particularly important at the beginning of treatment, when changes in therapy are made, when the dose is increased, or when the medicine is taken together with alcohol.

All Vivacor tablets contain lactose, and Vivacor 6.25 mg contains sucrose.
Each tablet of Vivacor 6.25 mg contains lactose (as 50 mg of monohydrate lactose) and 12.5 mg of sucrose.
Each tablet of Vivacor 12.5 mg contains lactose (as 62.5 mg of monohydrate lactose).
Each tablet of Vivacor 25 mg contains lactose (as 125 mg of monohydrate lactose).
If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult a doctor before taking this medicine.

Each tablet of Vivacor 12.5 mg and Vivacor 25 mg contains sodium.
The medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to take Vivacor

This medicine should always be taken exactly as directed by your doctor or pharmacist. If you are unsure,
you should consult your doctor or pharmacist. If you feel that the effect of Vivacor is too strong or too weak,
you should consult your doctor or pharmacist. The tablets should be swallowed with at least half a glass of water;
do not chew the tablets.
Vivacor tablets should be taken with sufficient fluid. Patients with chronic heart failure should take the tablets
with food (during a meal).
Vivacor tablets are available in the following strengths:
6.25 mg, 12.5 mg and 25 mg

Symptomatic chronic heart failure
Your doctor will adjust the dose of this medicine individually for each patient.
Treatment with Vivacor will be initiated under the supervision of a physician experienced in managing
heart failure and preceded by an assessment of the patient's clinical condition. Depending on the outcome
of this assessment, the medicine will be administered either on an outpatient or inpatient basis.

Adults
The recommended starting dose is 3.125 mg twice daily for 2 weeks. The 3.125 mg dose can be obtained
by dividing the 6.25 mg tablet in half. If the medicine is well tolerated, your doctor will increase the dose
at intervals of at least 2 weeks, according to the following schedule: to 6.25 mg twice daily, then to 12.5 mg
twice daily, and finally to 25 mg twice daily. The goal is to reach the highest dose tolerated by the patient.
The maximum recommended dose for all patients with severe chronic heart failure and for patients with mild
or moderate heart failure weighing less than 85 kg is 25 mg twice daily. For patients with mild or moderate
heart failure weighing more than 85 kg, the maximum recommended dose is 50 mg twice daily.
In patients with systolic blood pressure < 100 mmHg, increasing the dose of Vivacor may lead to worsening
renal function and/or worsening of heart failure. Therefore, before each dose increase, your doctor will monitor
kidney function and assess the severity of subjective and objective symptoms of heart failure and vasodilation.
If treatment with Vivacor is interrupted for longer than 2 weeks, re-initiation of therapy should begin with
a dose of 3.125 mg twice daily, and this dose should be gradually increased according to the dosing
recommendations outlined above.

Elderly patients
Dosage is the same as for adults.

Children and adolescents
The safety and efficacy of the medicine have not been established in children and adolescents (under 18 years of age).

Hypertension
Once-daily dosing is recommended.

Adults
The recommended starting dose is 12.5 mg once daily for the first 2 days. This should then be increased to
25 mg once daily. This dose is sufficient for most patients, but if necessary, your doctor may increase the dose
up to a maximum of 50 mg, administered as a single dose or in divided doses.
Dose increases should be made at intervals of no less than 2 weeks.

Elderly patients
The recommended starting dose is 12.5 mg per day. This dose provides adequate blood pressure control
in many cases. If the antihypertensive effect is insufficient, your doctor may gradually increase the dose
up to the maximum recommended dose of 50 mg, administered as a single dose or in divided doses.

Children and adolescents
The safety and efficacy of the medicine have not been established in children and adolescents (under 18 years of age).

Coronary artery disease

Adults
The recommended starting dose is 12.5 mg twice daily for the first 2 days. This should then be increased
to 25 mg twice daily.

Elderly patients
The maximum recommended daily dose is 50 mg in divided doses.

Children and adolescents
The safety and efficacy of the medicine have not been established in children and adolescents (under 18 years of age).

Left ventricular dysfunction after acute myocardial infarction
For patients with left ventricular dysfunction following myocardial infarction, the recommended starting dose
is 6.25 mg twice daily. The patient will be monitored for 3 hours after the first dose. Your doctor will increase
the dose every 3–10 days to 12.5 mg twice daily, and then to 25 mg twice daily.
For patients who do not tolerate a dose of 6.25 mg twice daily, your doctor will reduce the dose to
3.125 mg twice daily and continue this dose for 3–10 days. The 3.125 mg dose can be obtained by dividing
the 6.25 mg tablet in half.
If this dose is well tolerated, it will be increased to 6.25 mg twice daily, and then gradually to 25 mg twice daily.
The goal is to reach the highest dose tolerated by the patient.

Patients with concomitant liver disease
Administration of Vivacor is contraindicated in patients with concomitant hepatic impairment.

Patients with concomitant renal impairment
In patients with systolic blood pressure > 100 mmHg, no dose adjustment is necessary.

Taking more Vivacor than recommended
If you take more than the recommended dose, contact your doctor immediately or go to the nearest hospital.
Significant overdose may cause hypotension (too low blood pressure), bradycardia (too slow heart rate),
heart failure, sinus arrest, cardiogenic shock (inadequate blood supply to tissues and organs due to heart failure),
and circulatory arrest. Respiratory depression, bronchospasm, vomiting, impaired consciousness, and generalized
seizures have also been observed.

Missing a dose of Vivacor
Do not take a double dose to make up for a missed dose. If you miss a dose (or several doses), do not increase
the next dose. Take the next dose at your usual time. Continue treatment as directed by your doctor.

Stopping Vivacor
Treatment with Vivacor is intended for long-term use. Stopping treatment suddenly may lead to chest pain
and increased blood pressure, especially in patients with angina pectoris. The medicine should be discontinued
gradually, according to your doctor's instructions.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Frequency of possible adverse effects:

Very common (occurring in more than 1 in 10 patients):

• dizziness, headache, usually mild and occurring at the beginning of treatment
• heart failure
• low blood pressure
• fatigue (weakness)

Common (occurring in 1 in 10 patients):

• bronchitis, pneumonia, upper respiratory tract infection
• urinary tract infection
• anaemia
• increased body weight
• hypercholesterolaemia (increased blood cholesterol levels)
• in diabetic patients, reduced effectiveness of glucose regulation, which may lead to hyperglycaemia (excessively high blood glucose levels) or hypoglycaemia (too low blood glucose levels)
• depression, low mood
• pre-syncope, fainting
• visual disturbances
• reduced tear secretion (dry eye syndrome), eye irritation
• bradycardia (slow heart rate)
• hypervolaemia (increased circulating blood volume) and fluid overload
• oedema (including generalised, peripheral, orthostatic and localised in the genital area and lower limbs)
• orthostatic hypotension (sudden drop in blood pressure upon changing position)
• peripheral circulation disorders (cold extremities, peripheral vascular disease, worsening of intermittent claudication – calf muscle pain during walking, Raynaud's syndrome – pallor and blueness of fingers and toes, nose or ears caused by constriction of blood vessels)
• high blood pressure
• shortness of breath, pulmonary oedema, asthma in susceptible patients
• gastrointestinal disorders (including nausea, diarrhoea, vomiting, dyspepsia, abdominal pain)
• limb pain
• renal failure and worsening of kidney function in patients with generalized vascular disease and/or pre-existing kidney function disorders
• pain

Uncommon (occurring in 1 in 100 patients):

• sleep disorders
• paraesthesia (tingling and numbness of limbs)
• atrioventricular block (impaired conduction of electrical impulses in the heart muscle)
• angina pectoris (chest pain)
• constipation
• skin reactions (e.g. allergic rash, dermatitis, urticaria, pruritus, psoriasiform or lichen planus-like skin lesions)
• erectile dysfunction, impotence

Rare (occurring in 1 in 1000 patients):

• low platelet count (thrombocytopenia)
• nasal mucosal congestion (swelling of nasal mucosa)
• dryness of the oral mucosa
• urinary disorders

Very rare (occurring in no more than 1 in 10,000 patients):

• low white blood cell count (leukopenia)
• hypersensitivity (allergic reaction)
• abnormal liver function test results (increased alanine aminotransferase (AlAT), aspartate aminotransferase (AspAT), and gamma-glutamyl transferase activity)
• urinary incontinence in women

In patients with congestive heart failure, increasing the dose of carvedilol may lead to worsening of heart failure and fluid retention.

In patients with chronic heart failure and low blood pressure, ischaemic heart disease, generalized vascular disease, and/or coexisting kidney function disorders, reversible worsening of renal function has been observed during treatment with carvedilol.

The frequency of adverse effects does not depend on dose, except for dizziness, visual disturbances, and bradycardia.

The adverse effect profile observed in patients with hypertension and angina pectoris treated with Vivacor is consistent with that observed in patients with heart failure, although the frequency of these effects is lower.

Since Vivacor has beta-adrenolytic activity, treatment may unmask latent diabetes, worsen glucose control, and impair glucose regulation.

Isolated cases of urinary incontinence in women, resolving after discontinuation of treatment, have been reported.

In addition, hallucinations may occur during treatment with Vivacor.

Hair loss (alopecia) may occur (uncommon), excessive sweating (hyperhidrosis), and (very rare) severe skin reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis).

Sinus blockade may occur, meaning the heart may beat very slowly or stop beating altogether. These symptoms may be particularly observed in patients over 65 years of age or patients with other heart-related problems.

Other adverse effects not listed above may occur in some patients treated with Vivacor.

Reporting of adverse effects

If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to:

Department of Monitoring Adverse Drug Reactions
Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl

Adverse effects can also be reported to the marketing authorization holder.

Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Vivacor

Store at a temperature below 25°C.
Vivacor 6.25 mg tablets: Store in the original packaging to protect from light and moisture.
Vivacor 12.5 mg, 25 mg tablets: Store in the original packaging to protect from light.
Keep out of sight and reach of children.
Do not use this medicine after the expiry date (EXP) stated on the packaging. The expiry date refers to the last day of the month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Vivacor contains
The active substance is carvedilol.
Each tablet contains 6.25 mg, 12.5 mg or 25 mg of carvedilol.
Other ingredients are:
Vivacor 6.25 mg tablets – monohydrate lactose, crospovidone, sucrose, colloidal silicon dioxide anhydrous, polyvinylpyrrolidone K-25, magnesium stearate, quinoline yellow (E-104).
Vivacor 12.5 mg tablets – potato starch, monohydrate lactose, sodium lauryl sulfate, magnesium stearate, sodium croscarmellose, colloidal silicon dioxide anhydrous.
Vivacor 25 mg tablets – potato starch, monohydrate lactose, sodium lauryl sulfate, magnesium stearate, sodium croscarmellose, colloidal silicon dioxide anhydrous.

What Vivacor looks like and contents of the pack
Vivacor 6.25 mg tablets
Light yellow, elongated tablets marked with "E 341" on one side and a division line on the other side.

Vivacor 12.5 mg tablets
White or almost white, elongated, biconvex tablets with a division line on one side.

Vivacor 25 mg tablets
White or almost white, round, biconvex tablets with a division line on one side.
The tablets can be divided into equal doses.

Vivacor 6.25 mg tablets are available in packs containing 30 or 60 tablets in blisters made of OPA/Al/PVC/Al foil, packed in cardboard boxes.

Vivacor 12.5 mg and 25 mg tablets are available in packs containing 30 or 60 tablets in blisters made of PVC/Aluminium foil, packed in cardboard boxes.

Marketing Authorisation Holder
PROTERAPIA Spółka z o.o.
ul. Komitetu Obrony Robotników 45 D
02-146 Warsaw
Poland

Manufacturer
EGIS Pharmaceuticals PLC
1165 Budapest, Bökényföldi út 118-120.
Hungary

For further information, please contact the marketing authorisation holder:
PROTERAPIA Spółka z o.o.
ul. Komitetu Obrony Robotników 45 D
02-146 Warsaw
Poland
Tel. (22) 417 92 00