Document: leaflet MAH GENERIC_PL 11311-0481 change

• leaflet MAH GENERIC_PL 11311-0481
• leaflet MAH GENERIC_PL 40378-0137

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PATIENT INFORMATION LEAFLET

Carvedilol 3.125mg, 6.25mg, 12.5mg and 25mg Tablets

□ What Carvedilol is and what it is used for

Carvedilol belongs to a group of medicines called beta-blockers and works by slowing down the activity of the heart.

It does this by blocking tiny areas called receptors, which stops the heart from receiving messages sent by some nerves. As a result, the heart beats more slowly and with less force. The pressure of blood within the blood vessels is reduced and it is easier for the heart to pump blood around the body. Because the heart is using less energy, it also helps to reduce chest pain.

Carvedilol is used to treat the following:

■    High blood pressure (hypertension)

■    Chest pain (chronic stable angina pectoris)

■    Moderate to severe heart failure

□ What you need to know before you take Carvedilol

Do not take Carvedilol if:

■    You are allergic (hypersensitive) to Carvedilol, beta-blockers or any of the other ingredients of this medicine (see Section 6 "Contents of the pack and other information")

■    You suffer from unstable heart failure (attacks suddenly come on, are more frequent, are more uncomfortable or last longer) or decompensated heart failure (worsening of the symptoms) requiring intravenous inotropic support (medicine administered directly into a vein to alter the force or strength of the heartbeat)

■    You suffer from liver problems

■    You have a history of difficulty in breathing or wheezing (bronchospasm/asthma)

■    You suffer from a condition where the heart beats irregularly or much more slowly than normal, (2nd or 3rd degree heart block) unless you have a pacemaker

■    You have a very slow heart beat [less than 50 beats per minute whilst resting] (severe bradycardia)

■    You have a weakened heart that is unable to pump blood around the body (cardiogenic shock)

■    You have an irregular heart beat (sick sinus syndrome)

■    You suffer from very low blood pressure (severe hypotension)

■    You have an increased amount of acid in your blood (metabolic acidosis)

■    You have chest pains when at rest (prinzmetal's angina)

■    You have an untreated tumour of the adrenal gland (phaeochromocytoma)

■    You suffer from very poor circulation

■    You are taking verapamil or diltiazem, medicines used to treat high blood pressure, abnormal heart rhythms, chest pain [calcium channel blockers] (see "Other medicines and Carvedilol")

Warnings and precautions

Talk to your doctor before taking Carvedilol:

■    If you are due to have a surgical procedure. You should make sure that the anaesthetist is aware you are taking Carvedilol (see "Other medicines and Carvedilol")

■    If you suffer from severe heart failure

■    The following patients should be monitored for approximately 2 hours after the first dose or following a dose increase as low blood pressure (hypotension) may occur:

o patients with salt and/or fluid depletion o elderly patients

o patients with low basic blood pressure

■    If you are being treated for heart failure and suffer from any of the following conditions, as kidney function should be monitored during treatment with Carvedilol and if significant worsening of kidney function occurs (deterioration of kidney function is reversible for the following conditions), the dose of Carvedilol must be reduced or treatment must be discontinued:

o low blood pressure (hypotension) o reduced blood supply to the heart (ischaemic heart disease) o hardening and narrowing of the arteries restricting blood flow (diffuse vascular disease or atherosclerosis) o underlying kidney problems

■    If you suffer from heart failure following a heart attack as you must be clinically stable and have received an ACE inhibitor for at least 48 hours prior to starting treatment with Carvedilol (the dose of the ACE inhibitor should have been stable for at least the preceding 24 hours)

■    If you suffer from chronic obstructive pulmonary disease (collective group of lung diseases) unless the benefit outweighs the possible risks of use. You must be monitored carefully when starting treatment with Carvedilol and/or increasing the dose. The dose must be reduced if you display signs (difficulty in breathing or wheezing) of blockage/narrowing in the airways (bronchial obstruction or bronchospasm) during treatment with Carvedilol

■    If you are diabetic as Carvedilol may mask or reduce the symptoms and signs of severely low blood sugar levels (acute hypoglycaemia)

■    If you suffer from peripheral vascular disease (buildup of fatty deposits in the arteries, causing narrowing of the arteries and restricting the blood supply to the limbs) as Carvedilol can aggravate symptoms of decreased blood flow or lack of blood flow through your arteries (arterial insufficiency)

■    If you suffer from poor circulation causing fingers and toes to be pale and numb (Raynaud's phenomenon)

■    If you suffer from high level of thyroid hormones in the blood (thyrotoxicosis)

■    You have a slow heart beat [less than 55 beats per minute whilst resting] (bradycardia) as your dose of Carvedilol may need to be reduced

■    If you suffer from or have a history of psoriasis (skin disease causing scaly pink patches) as Carvedilol may aggravate this condition. Your doctor should consider if the benefit of treatment outweighs the possible risks of use

■    You are taking amiodarone, a medicine used to treat irregular heart beats [antiarrhythmic] (see "Other medicines and Carvedilol")

■    If you are known to be a poor metaboliser (body unable to break down medicines well) of debrisoquine (an antihypertensive medicine used to treat high blood pressure [hypertension]) as you should be closely monitored during the start of treatment with Carvedilol (see "Other medicines and Carvedilol")

■    If you suffer from or are affected by the following (as there is limited clinical experience):

o high blood pressure that fluctuates abruptly and repeatedly (labile hypertension) o high blood pressure caused by a medical condition or medicine (secondary hypertension)

o low blood pressure causing dizziness or lightheadedness after a change in position i.e. when standing up from a lying or sitting position (orthostasis)

o severe inflammation of the heart muscles (acute inflammatory heart disease) o obstruction of the heart valves or outflow tract (a portion of the heart where blood passes through in order to enter the arteries) affecting blood circulation o end-stage peripheral arterial disease (major

body tissue loss due to restricted blood supply to the limbs)

o if you are also being treated with an alpha-1 adrenergic receptor antagonist such as doxazosin or an alpha-2 adrenergic receptor agonist such as clonidine, used to treat high blood pressure (hypertension) by widening the blood vessels allowing blood to flow more easily (see "Other medicines and Carvedilol")

■    If you suffer from 1st degree heart block (where the hearts electrical signals are slowed as they move from the upper chamber to the lower chamber)

■    If you wear contact lenses as Carvedilol can cause dry eyes

Other medicines and Carvedilol

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those obtained without a prescription. This includes herbal medicines.

Medicines which may interact with or be affected by Carvedilol:

■    Digoxin, a medicine used to treat heart failure (digitalis glycoside)

■    Rifampicin and erythromycin, medicines used to treat bacterial infections (antibiotics)

■    Barbiturates, medicines used to treat anxiety and sleep disorders e.g. phenobarbitone

■    Cimetidine, a medicine used to treat stomach ulcers (H2-receptor antagonist)

■    Ketoconazole, a medicine used to treat fungal skin infections (antifungal)

■    Fluoxetine, a medicine used to treat depression (Selective Serotonin Reuptake Inhibitor [SSRI])

■    Haloperidol, a medicine used to treat mental health problems (anti-psychotic)

■    Verapamil and diltiazem, medicines used to treat high blood pressure, abnormal heart rhythms, chest pain (calcium channel blockers). During treatment with Carvedilol, verapamil and diltiazem should not be administered intravenously (directly into a vein)

■    Cyclosporin, a medicine used to reduce the body's immunity when receiving organ transplant (immunosuppressant) as the dose of cyclosporin may have to be reduced whilst taking Carvedilol

■    Amiodarone, a medicine used to treat irregular heart beats (antiarrhythmic)

■    Medicines used to treat diabetes such as insulin (antidiabetics) (see "Talk to your doctor before taking Carvedilol")

■    Reserpine, a medicine used to treat high blood pressure and mental disorders (antihypertensive)

■    Monoamine-oxidase inhibitors, medicines used to treat depression e.g. moclobemide

■    Clonidine, a medicine used to treat high blood pressure and migraine (alpha-2 adrenergic receptor agonist). When combination treatment with Carvedilol and clonidine is discontinued, Carvedilol should be withdrawn several days before gradually decreasing the dose of clonidine

■    Alpha-1 adrenergic receptor antagonists, medicines used to treat high blood pressure e.g. doxazosin

■    Phenothiazines, medicines used to treat serious mental and emotional disorders and also severe nausea (feeling sick) and vomiting (being sick) e.g. chlorpromazine

■    Tricyclic antidepressants, medicines used to treat depression e.g. clomipramine

■    Vasodilators, medicines used to treat poor circulation e.g. nifedipine

■    Guanethidine, methyldopa, guanfacin, medicines used to treat high blood pressure (antihypertensives)

■    Dihydropyridines, medicines used to treat high blood pressure e.g. amlodipine, felodipine, nicardipine (calcium channel blockers)

■    Nitrates, medicines used to prevent chest pain (angina) e.g. isosorbide mononitrate

■    Neuromuscular blocking agents, medicines used to induce muscle relaxation such as anaesthetics. If you are due to have a surgical procedure. You should make sure that the anaesthetist is aware you are taking Carvedilol (see "Talk to your doctor before taking Carvedilol")

■    Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), medicines used to treat certain rheumatic disorders e.g. ibuprofen

■    Female hormones e.g. oestrogen

■    Corticosteroids, medicines used to relieve inflammation e.g. prednisolone

■    Sympathomimetics, medicines used to treat severe allergic reactions e.g. epinephrine (adrenaline)

■    Ergotamine, a medicine used to treat migraines (ergot alkaloids)

■    Beta-agonist bronchodilators, medicines used to treat asthma e.g. salbutamol

■    Debrisoquine, a medicine used to treat high blood pressure (antihypertensive) (see "Talk to your doctor before taking Carvedilol")

■    Diuretics, medicines used to increase frequency of urination e.g. hydrochlorothiazide (dosing must be stabilised for at least 4 weeks prior to starting treatment with Carvedilol) (see Section 3 "Treatment of heart failure")

■    ACE inhibitors, medicines used to treat high blood pressure or heart failure e.g. lisinopril (dosing must be stabilised for at least 4 weeks prior to starting treatment with Carvedilol) (see Section 3 "Treatment of heart failure") be stabilised for at least 4 weeks prior to starting treatment with Carvedilol) (see Section 3 "Treatment of heart failure")

Taking Carvedilol with food and drink and alcohol

■    Carvedilol should be taken with sufficient fluid

■    Carvedilol can be taken before, with or after meals, but should be taken with food when used for the treatment of heart failure (see Section 3 "How to take Carvedilol")

■    It is not recommended to drink alcohol whilst taking Carvedilol (see "Driving and using machinery")

Pregnancy and Breastfeeding

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 taking this medicine.

Pregnancy

Carvedilol should only be used for pregnant women, if the benefit for the mother outweighs the potential risk to the baby.

Treatment with Carvedilol should be stopped 2-3 days before expected birth date. If this is not possible, the new-born must be monitored for the first 2-3 days of life.

Breast-feeding

If you are breast-feeding, Carvedilol should not be taken as it is not known whether Carvedilol is passed into breast milk.

Driving and using machinery

Carvedilol may cause dizziness or tiredness. This is more likely to occur at the start of treatment, after a dose increase, on changing medicines or if you drink alcohol (see "Taking Carvedilol with food and drink and alcohol"). If either of these symptoms are experienced, it may be necessary to avoid driving or operating machinery or pursuing any activity in which full attention is required.

Carvedilol contains lactose

If you have been told by your doctor that you have intolerance to some sugars, contact your doctor before taking this medicine.

continued....

3| How to take Carvedilol

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

■    These tablets are to be taken orally and with sufficient fluid.

■    These tablets can be taken before, with or after meals. (See Section 2 "Taking Carvedilol with food and drink and alcohol" and Section 3 "Treatment of heart failure").

■    The score line on the tablet is only to facilitate breaking for ease of swallowing and not to divide the tablet into equal doses.

Treatment of high blood pressure (hypertension)

Carvedilol may be used for the treatment of high blood pressure (hypertension) alone or in combination with other medicines used to treat high blood pressure.

Once daily dosing is recommended. The recommended maximum daily dose is 50mg (given once a day or in divided doses).

Adults

The recommended starting dose is 12.5mg once a day for 2 days. Thereafter, the treatment is continued at a daily dose of 25mg. If necessary, the dose may be increased gradually (at intervals of at least 2 weeks or more) to a recommended maximum daily dose of 50mg given once a day or in divided doses.

Elderly

The recommended starting dose is 12.5mg once a day, which may be sufficient for continued treatment. If necessary, the dose may be increased gradually (at intervals of at least 2 weeks or more) to a recommended maximum daily dose of 50mg given once a day or in divided doses.

Elderly patients may be more susceptible to the effects of Carvedilol and should be monitored carefully.

Treatment of chest pain (chronic stable angina pectoris)

Adults

The recommended starting dose is 12.5mg twice daily for 2 days. Thereafter, the treatment is continued at a dose of 25mg twice daily. If necessary, the dose may be increased gradually (at intervals of at least 2 weeks or more) to a recommended maximum daily dose of 100mg given in divided doses (twice daily).

Elderly

The recommended starting dose is 12.5mg twice daily for 2 days. Thereafter, the treatment is continued at a dose of 25mg twice daily, which is the recommended maximum daily dose.

Elderly patients may be more susceptible to the effects of Carvedilol and should be monitored carefully.

Treatment of heart failure

Dosing of the following medicines must be stabilised for at least 4 weeks prior to starting treatment with Carvedilol (see Section 2 "Other medicines and Carvedilol"):

■    Diuretics, medicines used to increase frequency of urination e.g. hydrochlorothiazide

■    Digoxin, a medicine used to treat heart failure (digitalis glycosides)

■    ACE inhibitors, medicines used to treat high blood pressure or heart failure e.g. lisinopril

■    Vasodilators, medicines used to treat poor circulation e.g. nifedipine

The recommended starting dose is 3.125mg twice daily for 2 weeks. If this dose is well tolerated, the dose can be increased gradually (at intervals of at least 2 weeks or more), first to 6.25mg twice daily, then 12.5mg twice daily, followed by 25mg twice daily. It is recommended that the dose is increased to the highest level tolerated by the patient.

Provided that the heart failure is not severe:

■    The recommended maximum dose in patients weighing less than 85kg is 25mg given twice daily.

■    The recommended maximum dose in patients weighing more than 85kg is 50mg twice daily. A dose increase to 50mg twice daily should be performed carefully under close medical supervision.

Short-term worsening of symptoms of heart failure may occur at the beginning of treatment or due to a dose increase, especially in patients with severe heart failure and/or under high dose diuretic treatment. Discontinuation of treatment is not usually necessary, but the dose should not be increased. The patient should be carefully monitored after starting treatment or increasing the dose.

If treatment with Carvedilol is discontinued for more than 2 weeks, it should be re-started at 3.125mg twice daily and increased gradually in accordance with the above recommendations.

Carvedilol should be taken with food (when used for the treatment of heart failure) to slow the rate of absorption and reduce the incidence of dizziness or lightheadedness occurring after a change in position i.e. when standing up from a lying or sitting position.

Patients with kidney problems

Dosage must be determined for each patient individually, but it is unlikely that dose adjustment of Carvedilol will be necessary.

Patients with moderate liver problems

Dosage must be determined for each patient individually, but dose adjustment of Carvedilol may be necessary.

Use in children

Carvedilol tablets are not recommended for use in children under 18 years of age.

If you take more Carvedilol than you should

If you accidentally take too many tablets, contact your doctor or nearest hospital emergency department immediately for advice. Remember to take this leaflet or any remaining tablets with you.

The symptoms of overdose are: severely low blood pressure (hypotension), slow heart beat (bradycardia), heart failure, weakened heart (cardiogenic shock), heart suddenly and unexpectedly stops beating (cardiac arrest), difficulty in breathing or wheezing (bronchospasm), being sick (vomiting), disturbed consciousness and fits (convulsions).

If you forget to take Carvedilol:

Take it as soon as you remember, unless it is time for your next dose. If you miss a dose do not take a double dose to make up for a forgotten dose.

If you stop taking Carvedilol:

It is important that you keep taking Carvedilol for as long as your doctor has told you to.

As with other beta-blockers and especially in patients suffering from heart problems, the discontinuation of Carvedilol should be done gradually over a 2 week period e.g. by reducing the daily dose to half every 3 days.

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

Possible side effects

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

Seek medical advice immediately if you develop the following symptoms:

■    Allergic reactions: swelling of the face, throat or tongue, fever, difficulty in breathing, dizziness

■    Swelling of parts of the body (oedema)

■    Allergic skin rashes (exanthema)

■    Fever, general ill feeling, itching, joint aches, multiple skin lesions (erythema multiforme)

■    Severe blistering of the skin, mouth, eyes and genitals (Stevens-Johnson syndrome, toxic epidermal necrolysis)

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

■    Dizziness (usually mild and most likely to occur at the beginning of treatment)

■    Headache (usually mild and most likely to occur at the beginning of treatment)

■    Heart failure

■    Low blood pressure (hypotension)

■    General weakness (asthenia) (usually mild and most likely to occur at the beginning of treatment)

■    Tiredness, weakness or lack energy (fatigue)

Common side effects (may affect up to 1 in 10 people)

■    Infection causing inflammation and irritation to the

main airways of the lungs (bronchitis)

■    Inflammation of the lungs (pneumonia)

■    Infection of the nose, sinuses and throat (upper respiratory tract infection)

■    Infection of the bladder causing pain and discomfort (urinary tract infection)

■    Looking pale and feeling tired (anaemia)

■    Weight gain

■    Very high levels of cholesterol in the blood (hypercholesterolaemia)

■    Increased (hyperglycaemia) or low (hypoglycaemia) blood sugar levels in patients with diabetes

■    Depression or low mood

■    Visual impairment, dry eyes, eye irritation

■    Slower heartbeat (bradycardia)

■    An abnormal increase in the volume of blood plasma in the body (hypervolaemia or fluid overload)

■    Low blood pressure causing dizziness or lightheadedness after a change in position i.e. when standing up from a lying or sitting position (orthostatic hypotension)

■    Disturbances of blood flow that reaches the upper and lower extremities of the body (arms and legs) and the surface of the skin (peripheral circulation)

■    Build-up of fatty deposits in the arteries causing narrowing of the arteries and restricting the blood supply to the limbs (peripheral vascular disease)

■    Cramp-like pain felt in the calf, thigh or buttock during walking or other exercise (intermittent claudication)

■    Poor circulation causing fingers and toes to be pale and numb (Raynaud's phenomenon)

■    Difficulty in breathing (dyspnoea)

■    Excess collection of watery fluid in the lungs (pulmonary oedema)

■    Asthma in susceptible patients Feeling (nausea) or being (vomiting) sick

■    Diarrhoea

■    Indigestion (dyspepsia)

■    Stomach pain

■    Pain in the extremities of the body (arms and legs)

■    Kidney failure and/or kidney problems in patients suffering from diffuse vascular disease (damage/disease in the coronary arteries, the major blood vessels that supply the heart) and/or underlying poor kidney function

■    Urination disorders

Uncommon side effects (may affect up to 1 in 100 people)

■    Sleep disorders

■    Lightheadedness, muscular weakness, blurred vision, and feeling faint (presyncope)

■    Fainting (syncope) (usually mild and most likely to occur at the beginning of treatment)

■    Tingling or numbness in the hands or feet (paraesthesia)

■    The hearts electrical signals are slowed as they move from the upper chamber to the lower chamber (atrioventricular [AV] block)

■    Chest pain (angina)

■    Skin rash or inflammation (dermatitis)

■    Skin rashes with the formation of wheals (urticaria)

■    Severe itching (pruritus)

■    Psoriatic skin lesions (skin disease causing scaly pink patches) may occur or existing lesions may be aggravated

■    Non-infectious, itchy rash that can affect many areas of the body (lichen planus-like skin lesions)

■    Hair loss (alopecia)

■    Inability to maintain an erection (erectile dysfunction)

Rare side effects (may affect up to 1 in 1000 people)

■    Reduction in blood platelets, which increases risk of bleeding or bruising (thrombocytopaenia)

■    Blocked nose

■    Flu-like symptoms

■    Constipation

■    Increase in liver enzyme levels (detected by blood test)

■    The hearts ability to contract may be decreased during dose adjustment

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

■    A reduction in white blood cells (leukopenia)

■    Dry mouth

■    Increase in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma-Glutamyl Transferase (GGT), blood tests typically used to detect liver disorders/diseases

■    Urinary incontinence in women (should resolve when treatment is stopped)

Other side effects (frequency not known)

During treatment with Carvedilol latent diabetes mellitus (slow-onset diabetes) may occur, existing diabetes may be aggravated, and blood sugar levels may become disturbed.

Reporting of side effects

If you get any side effects talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the internet at

www.mhra.gsi.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

How to store Carvedilol

■    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/blister/bottle after EXP. The expiry date refers to the last date of that month.

■    Store in the original package.

■    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 to protect the environment.

Contents of the pack and other information

What Carvedilol contains:

■    Each 3.125mg tablet contains 3.125mg of Carvedilol

■    Each 6.25mg tablet contains 6.25mg of Carvedilol

■    Each 12.5mg tablet contains 12.5mg of Carvedilol

■    Each 25mg tablet contains 25mg of Carvedilol

The other ingredients are: lactose monohydrate, microcrystalline cellulose, crospovidone, povidone K30, colloidal anhydrous silica, magnesium stearate. 3.125mg and 12.5mg tablets also contain ferric oxide red (E172).

6.25mg and 12.5mg tablets also contain ferric oxide yellow (E172).

What Carvedilol looks like and contents of the pack:

■    Carvedilol 3.125mg are light red, round, convex, scored tablets encoded "C1" on one side with an approximate size of 7mm

■    Carvedilol 6.25mg are yellow, round, convex, scored tablets encoded "C2" on one side with an approximate size of 7mm

■    Carvedilol 12.5mg are red/brown, round, convex, scored tablets encoded "C3" on one side with an approximate size of 7mm

■    Carvedilol 25mg are white, round, convex, scored tablets encoded "C4" on one side with an approximate size of 9mm

Carvedilol is available in:

Carvedilol tablets are available in packs of 14, 20, 28, 30, 50, 56, 60, 98, 100, 250 or 500 tablets.

Not all pack sizes may be marketed.

Product Licence Numbers:

Carvedilol 3.125mg - PL 11311/0480 Carvedilol 6.25mg - PL 11311/0481 Carvedilol 12.5mg - PL 11311/0482 Carvedilol 25mg - PL 11311/0483

Marketing Authorisation Holder

Tillomed Laboratories Ltd 3 Howard Road, Eaton Socon, St. Neots Cambridgeshire PE19 8ET, UK

Manufacturer

Salutas Pharma GmbH Otto-Von-Guericke-Allee 1 D-39179 Barleben Germany

This leaflet was last revised in June 2014

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