Colver

Package leaflet: Information for the patient

Colver 6.25 mg tablets, 25 mg tablets

Carvedilol
Equivalent medicine
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Colver is and what it is used for

Colver contains the active substance carvedilolo.
Carvedilolo belongs to a class of medicines called "α- and β-adrenergic receptor blockers", which relax and dilate blood vessels, lowering blood pressure and reducing the workload of the heart.
Colver is used for:

• the treatment of high blood pressure (essential arterial hypertension). It may be used alone or in combination with other antihypertensive medicines, especially thiazide diuretics;
• the treatment of a type of chest pain caused by heart problems (angina pectoris);
• the treatment of a condition characterized by inadequate heart function (heart failure).

2. What you should know before taking Colver

Do not take Colver

• if you are allergic to the active substance or to any of the other ingredients of this medicine listed in section 6;
• if you have severely impaired heart function (unstable/compensated heart failure, heart failure in NYHA Class IV);
• if you have a heart rhythm disorder (second- or third-degree atrioventricular block, unless a permanent pacemaker has been implanted, sick sinus syndrome, including sinoatrial block, cardiogenic shock);
• if you have respiratory problems due to a lung disease (chronic obstructive pulmonary disease (COPD) with bronchospastic component) or if you have previously suffered from asthma or other conditions involving airway narrowing (bronchospasm);
• if you have liver problems (clinically evident hepatic dysfunction);
• if you have a very slow heart rate (severe bradycardia) below 50 beats per minute;
• if you have very low blood pressure (severe hypotension, systolic or maximum pressure below 85 mm Hg);
• if you have a tumor of the adrenal glands (uncontrolled pheochromocytoma without alpha-blocker treatment);
• if your doctor has told you that your blood acidity level is higher than normal (metabolic acidosis);
• if you have a serious heart condition known as cardiogenic shock;
• if you are pregnant or breastfeeding (see section "Pregnancy and breastfeeding").

Warnings and precautions
Talk to your doctor or pharmacist before taking Colver.
Exercise particular caution with Colver:

• if you have diabetes. In this case, your doctor will prescribe Colver cautiously and will perform regular checks of your blood sugar levels (glycaemia), adjusting the dose of your diabetes medications (hypoglycaemic agents) accordingly. Taking carvedilol may be associated with worsening glycaemic control, or signs and symptoms of low blood sugar (hypoglycaemia) may be masked or diminished;
• if your heart function is impaired (chronic heart failure) and you have low blood pressure (maximum pressure below 100 mmHg), suffer from inadequate blood and oxygen supply to the heart (ischaemic heart disease), have circulatory problems (widespread vascular disease) and/or kidney problems (underlying renal insufficiency). In such cases, your kidney function may reversibly worsen. Your doctor will monitor you and may reduce the dose or discontinue treatment with Colver;
• if your heart function is impaired and you suffer from fluid retention (congestive heart failure);
• if you are taking other heart medications or drugs to lower blood pressure, such as digitalis glycosides, diuretics and/or ACE inhibitors, since both digoxin and carvedilol slow the heart rate;
• if you have left ventricular dysfunction following acute myocardial infarction;
• if you suffer from a disease characterized by irreversible airway obstruction (chronic obstructive pulmonary disease - COPD) and are not taking oral or inhaled medications. Your doctor will prescribe Colver cautiously and only if the potential benefits outweigh the potential risks. Your doctor will monitor you and adjust the dose of Colver;
• if you have thyroid problems (thyrotoxicosis), as Colver, like other beta-blockers, may mask the symptoms of thyrotoxicosis;
• if you are scheduled for surgery requiring anaesthetics, since carvedilol interacts with anaesthetics;
• if you have a very slow heart rate (bradycardia), below 55 beats per minute. Your doctor may reduce the dose;
• if you have previously experienced severe allergic reactions (anaphylactic reactions) or are undergoing desensitization therapy; if you have a skin condition called psoriasis;
• during treatment with carvedilol, very rare cases of serious skin adverse reactions such as toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) have been reported (see section 4 “Possible side effects”). In such cases, Colver must be discontinued immediately;
• if you have poor blood circulation in the limbs (peripheral vascular disease), or if you suffer from a condition called Raynaud's phenomenon, characterized by poor blood flow to the fingers or toes causing pain and whitening, as beta-blockers such as Colver may worsen these symptoms;
• if you are taking other blood pressure-lowering medications such as verapamil or diltiazem (“calcium antagonists”), or if you are taking other antiarrhythmic drugs;
• if you are taking other medications (see section “Other medicines and Colver”);
• if you have a tumor of the adrenal glands (pheochromocytoma);
• if you suffer from a condition called "Prinzmetal's variant angina";
• if you experience sudden blood pressure fluctuations (labile hypertension) or have high blood pressure due to other conditions (secondary hypertension);
• if you wear contact lenses, as carvedilol use may reduce tear production.

If, during treatment for heart failure, your condition worsens compared to the previous visit, your doctor will administer alternative therapy.
Do not stop treatment with carvedilol abruptly, especially if you suffer from ischaemic heart disease. Discontinuation of carvedilol should be gradual (over a two-week period).
Children and adolescents
The safety and efficacy of Colver in children and adolescents under 18 years of age have not yet been established.
For those engaged in sports
Using this medicine without therapeutic need constitutes doping and may lead to a positive anti-doping test.
Other medicines and Colver
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
The effects of Colver may be influenced by, or may influence, the following medicines:

• Agents that reduce catecholamines (e.g. reserpine and monoamine oxidase inhibitors). Hypotension (low blood pressure) and severe bradycardia (slow heart rate) may occur;
• Verapamil, diltiazem, or other antiarrhythmics. In combination with carvedilol, they may increase the risk of heart rhythm disorders (atrioventricular conduction disturbances - see section “Warnings and precautions”). Your doctor may ask you to monitor your blood pressure and perform an electrocardiogram (ECG);
• Digoxin and other digitalis glycosides. Concomitant administration may slow the heart rate;
• Insulin or oral hypoglycaemics (medicines for treating diabetes). Carvedilol may enhance their blood sugar-lowering effect (hypoglycaemic action). Signs of hypoglycaemia may be masked or diminished (especially tachycardia). If you are taking these medicines, regular monitoring of blood glucose is recommended (see section “Warnings and precautions”);
• Rifampicin (a medicine used to treat tuberculosis). It may reduce serum levels of carvedilol;
• Cimetidine (used to treat stomach problems). It may alter carvedilol blood levels;
• Cyclosporine (used to prevent transplant rejection). Carvedilol may increase cyclosporine blood concentration;
• Clonidine (a medicine used to treat high blood pressure). Concomitant administration of clonidine and carvedilol may enhance blood pressure- and heart rate-lowering effects. If both medicines are used together, clonidine should be tapered off gradually several days after stopping carvedilol;
• Amiodarone. It may reduce carvedilol elimination;
• Fluoxetine and paroxetine. They may inhibit carvedilol metabolism;
• Anaesthetic agents. A synergistic effect may occur between carvedilol and anaesthetics (see section “Warnings and precautions”);
• Non-steroidal anti-inflammatory drugs (NSAIDs). Concomitant use of NSAIDs and carvedilol may lead to increased blood pressure levels and reduced blood pressure control;
• Beta-agonist bronchodilators. Carvedilol may oppose the bronchodilator effects of these drugs;
• Antihypertensives. Carvedilol, when used in combination, may enhance the effect of other medicines used to treat high blood pressure (e.g. α1-receptor antagonists) or medicines for which hypotension is a known side effect.

The concomitant administration of carvedilol with inotropic agents has not been studied.
The bioavailability of carvedilol may be altered by P-glycoprotein inducers or inhibitors, and by inhibitors and inducers of CYP2D6 and CYP2C9.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not use carvedilol during pregnancy unless the potential benefits outweigh the potential risks.
Taking carvedilol during pregnancy may increase the risk of cardiac and pulmonary complications in the newborn during the postnatal period.
Breastfeeding
It is not known whether carvedilol is excreted in breast milk.
The use of carvedilol is not recommended during breastfeeding.
Driving and using machines
Due to variable individual reactions (e.g. dizziness, fatigue), your ability to drive, operate machinery, or work without secure support may be impaired. This is particularly relevant at the beginning of treatment, after dose increases, when switching products, and when combined with alcohol. Consider this if you need to drive or operate machinery requiring high attention.
Colver contains lactose and sucrose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

3. How to take Colver

Take this medicine exactly as directed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
Take the tablets with a sufficient amount of liquid.
It is not necessary to take the tablets with food; however, if you have heart failure,
you should take Colver with meals to slow its absorption and reduce
the incidence of effects due to a sudden drop in blood pressure upon rapidly
changing from a sitting or lying position to standing (orthostatic hypotension).
The recommended dose is:

• Essential arterial hypertension

Adults
Initial therapy: 12.5 mg once daily for the first two days.
Subsequently, 25 mg once daily.
If necessary, the dose may be gradually increased at intervals of no less than two
weeks, up to the maximum recommended dose of 50 mg daily, taken as a single dose or divided into 25 mg twice daily.
Use in the elderly
Initial therapy: 12.5 mg once daily. The dose may be increased at intervals
of no less than two weeks, up to the maximum recommended dose of 50 mg, to be taken as 25 mg twice daily.

• Angina pectoris

Adults
Initial therapy: 12.5 mg twice daily for the first two days.
Subsequently, 25 mg twice daily.
Do not exceed this dosage.
Use in the elderly
Initial therapy: 12.5 mg twice daily.
Subsequently, the dose may be increased, after an interval of at least two days, to 25 mg
twice daily (maximum dose not to be exceeded).

• Heart failure

The dose must be determined by your doctor specifically for you. Your doctor will monitor you and
assess the appropriate dosage for your condition.
Initial therapy: 3.125 mg (1/2 of a 6.25 mg tablet) twice daily for at least two
weeks.
If you tolerate this dose well, the dosage may subsequently be increased, at intervals of no
less than two weeks, first to 6.25 mg twice daily, then to 12.5 mg twice daily, and finally to 25 mg twice daily.
The dose should be increased up to the highest dose you can tolerate.
The maximum recommended dose is 25 mg twice daily in cases of severe heart failure and also in cases of mild or moderate heart failure when body weight is less than 85 kg.
In cases of mild or moderate heart failure with body weight greater than 85 kg, the maximum recommended dose is 50 mg twice daily.
Before each dose increase, your doctor will evaluate you for any signs of worsening heart failure or vasodilation.
If treatment with carvedilol is discontinued for more than two weeks, therapy should be restarted with 3.125 mg (1/2 of a 6.25 mg tablet) twice daily, and the dosage should then be increased according to the previous recommendations.
The tablet may be divided into equal parts.

If you take more Colver than you should
In case of accidental ingestion or overdose of Colver, contact your doctor immediately or go to the nearest hospital.
In case of overdose, the following may occur:

• severe drop in blood pressure (hypotension),
• slowing of the heart rate (bradycardia),
• heart problems (heart failure, cardiogenic shock, and cardiac arrest).

Additionally, the following may occur:

• breathing difficulties,
• narrowing of the airways (bronchospasm),
• vomiting,
• disturbances of consciousness and generalized seizures.

If you forget to take Colver
Do not take a double dose to make up for the missed dose.

If you stop taking Colver
Do not stop treatment with Colver abruptly.
Like other medicines with beta-blocking activity, treatment with carvedilol must not be stopped suddenly, especially if you have heart problems. Discontinuation of carvedilol should be gradual (over a period of two weeks).
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The side effects observed following administration of Colver are listed below:

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

• dizziness, headache (cephalalgia)
• heart problems (heart failure)
• low blood pressure (hypotension)
• tiredness (asthenia)

Common (may affect up to 1 in 10 people)

• bronchitis, pneumonia, upper respiratory tract infections (nose and throat)
• urinary tract infections
• reduced number of red blood cells (anaemia)
• weight gain
• increased cholesterol in the blood (hypercholesterolaemia)
• altered blood sugar levels (hyperglycaemia, hypoglycaemia) in diabetic patients
• depression, depressed mood
• visual disturbances, reduced tear production (dry eyes), eye irritation
• slow heartbeat (bradycardia), swelling (oedema, including generalised oedema, peripheral oedema, genital oedema, lower limb oedema), increased blood volume (hypervolaemia), fluid overload
• sudden drop in blood pressure upon rapidly changing from a sitting or lying position to standing (orthostatic hypotension)
• peripheral blood circulation disorders (cold extremities, peripheral vascular disease, worsening of intermittent claudication and Raynaud's phenomenon)
• increased blood pressure (hypertension)
• breathing difficulties (dyspnoea), accumulation of fluid in the lungs (pulmonary oedema), asthma in predisposed patients
• sensation of fainting and fainting (pre-syncope, syncope)
• nausea, diarrhoea, vomiting, digestive disturbances (dyspepsia), abdominal pain
• pain in the extremities
• kidney failure and changes in kidney function (in patients with diffuse vascular disease and/or pre-existing renal failure)
• pain

Uncommon (may affect up to 1 in 100 people)

• sleep disorders
• altered sensation (paraesthesia)
• heart problems (atrioventricular block, angina pectoris)
• constipation
• skin reactions (e.g., allergic rash, dermatitis, urticaria, pruritus, psoriasiform skin lesions and lichen planus-like lesions), hair loss (alopecia)
• erectile dysfunction

Rare (may affect up to 1 in 1,000 people)

• decreased number of blood cells called platelets (thrombocytopenia)
• nasal congestion (nasal congestion)
• dry mouth (xerostomia)
• problems with urination (urinary disorders)

Very rare (may affect up to 1 in 10,000 people)

• decreased white blood cells in the blood (leucopenia)
• allergic reaction (hypersensitivity)
• severe cutaneous adverse reactions (e.g., erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis)
• increased levels of certain substances produced by the liver (alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT))

The frequency of adverse reactions is not dose-dependent, except for dizziness, visual disturbances, and slow heartbeat (bradycardia).
The risk of most adverse reactions associated with carvedilol is similar across all indications.
Dizziness, fainting (syncope), headache, and tiredness (asthenia) are generally mild and are more likely to occur at the beginning of treatment.
Carvedilol may cause urinary incontinence in women, which resolves upon discontinuation of treatment.
Carvedilol may also trigger symptoms of diabetes in patients with a mild form of diabetes known as 'latent diabetes'.

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report adverse reactions directly via the national reporting system at the following website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. How to store Colver

Store below 25°C. Keep in the original packaging to protect the medicine from moisture and light.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "Exp.". The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Colver contains
Colver 6.25 mg tablets
The active substance is: carvedilolo. One tablet contains 6.25 mg of carvedilolo.
The other components are: sucrose, lactose, povidone, anhydrous colloidal silica, crospovidone,
magnesium stearate, yellow iron oxide (E 172).
Colver 25 mg tablets
The active substance is: carvedilolo. One tablet contains 25 mg of carvedilolo.
The other components are: sucrose, lactose, povidone, anhydrous colloidal silica, crospovidone,
magnesium stearate.

Description of the appearance of Colver and contents of the pack
Colver is available in tablet form.
Pack sizes: 28 tablets of 6.25 mg.
Pack sizes: 30 tablets of 25 mg.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
S.F. Group S.r.l.
Via Tiburtina, 1143
00156 Rome – Italy

Manufacturers:
Special Product’s Line S.p.A.
Via Fratta Rotonda Vado Largo, 1 - 03012 Anagni (FR)
Istituto Biochimico Italiano Giovanni Lorenzini S.p.A.
Via Fossignano, 2 - 04011 Aprilia (LT)