MercuryPharma

PACKAGE LEAFLET: INFORMATION FOR THE USER

Clarithromycin 500mg, powder for concentrate for solution for infusion

_Clarithromycin_

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, ask your doctor or pharmacist or nurse.

•    This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

•    If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

The name of your medicine is Clarithromycin 500mg, powder for concentrate for solution for infusion, which will be referred to as Clarithromycin throughout this leaflet.

What is in this leaflet

1    What Clarithromycin is and what it is used for

2    What you need to know before you use Clarithromycin

3    How to use Clarithromycin

4    Possible side effects

5    How to store Clarithromycin

6    Contents of the pack and other information

1 .WHAT CLARITHROMYCIN IS AND WHAT IT IS USED FOR

Clarithromycin is an antibiotic that belongs to a group of medicines called macrolides. Antibiotics stop the growth of bacteria which cause infections. Clarithromycin is used whenever an intravenous (injection into the vein) antibiotic is required to treat severe infections or, alternatively, if a patient cannot swallow Clarithromycin tablets.

It is used to treat infections caused by bacteria such as:

•    Chest infections like acute bronchitis and pneumonia

•    Throat and sinus infections

•    Skin and tissue infections.

2. WHAT YOU NEED TO KNOW BEFORE YOU USE CLARITHROMYCIN Do not use Clarithromycin:

•    If you (or your child) are allergic to clarithromycin, other macrolides (similar antibiotics such as erythromycin, azithromycin), or any of the other ingredients of this medicine (listed in Section 6). An allergic reaction may include rash, itching, difficulty in breathing or swelling of the face, lips, throat or tongue

•    If you are taking ergotamine like drugs or dihydroergotamine (used to treat migraine and low blood pressure)

•    If you are taking cisapride (used to treat stomach disorders)

•    If you are taking pimozide (used to treat mental illness)

•    If you are taking terfenadine or astemizole (used to treat hay fever or allergy)

•    If you are taking lovastatin or simvastatin (HMG-CoA reductase inhibitors, commonly known as statins, used to lower levels of cholesterol (a type of fat) in the blood)

•    If you are taking colchicine (used to treat gout)

•    If you have abnormally low levels of potassium in your blood (a condition known as hypokalaemia)

•    If you have severe liver disease and kidney disease

•    If you have an irregular heart rhythm or if you are taking medicines which are known to cause serious disturbances in heart rhythm

•    If you or someone in your family has a history of heart rhythm disorders (ventricular cardiac arrhythmia, including torsade de pointes) or abnormality of electrocardiogram (ECG, electrical recording of the heart) called “long QT syndrome”.

If any of the above applies to you, consult your

doctor for advice on alternative medicines.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before

using clarithromycin:

•    If you have any liver or kidney problems

•    If you are pregnant or breast feeding

•    If you have, or are prone to, fungal infections (e.g. thrush)

•    If you have heart disease or (bradycardia) slow heart beat

•    If you have abnormally low magnesium levels in your blood (hypomagnesaemia)

•    If you have myasthenia gravis (weakness of muscles)

•    If you have any disturbance in heart rhythm.

If any of these apply to you, consult your doctor before being given Clarithromycin. If you develop severe or prolonged diarrhoea during or after receiving this medicine, consult your doctor immediately (see section ‘Possible side effects’). Children

Children under 12 years should not be given Clarithromycin IV. Your doctor will prescribe another suitable medicine for your child.

Other medicines and Clarithromycin:

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without prescription.

Especially if you are taking any of the medicines listed below:

•    Digoxin, quinidine or disopyramide (used to treat heart conditions)

•    Warfarin or other drugs (used to thin the blood)

•    Carbamazepine, valproate or phenytoin (used to treat epilepsy)

•    Theophylline (used to treat breathing difficulties such as asthma)

•    Triazolam (used to induce sleep)

•    Alprazolam (used to treat moderate to severe anxiety)

•    Midazolam (used in anaesthesia)

•    Cilostazol (used to treat poor circulation)

•    Simvastatin or lovastatin (used to treat high cholesterol)

•    Methylprednisolone (used to treat inflammation)

•    Vinblastine (used for the treatment of cancer)

•    Sildenafil (used to treat impotence)

•    Cyclosporin or Tacrolimus (used to reduce the activity of the patient's immune system)

•    Zidovudine (used to treat viral infections)

•    Rifabutin (used in treatment of some infections)

•    Ritonavir, Efavirenz, Nevirapine, Atazanavir, Saquinavir (used to treat HIV infection)

•    Colchicine (used to treat gout)

•    Pimozide (to treat mental problems)

•    Rifampicin (used to treat tuberculosis (TB))

The following information is intended for medical or healthcare professionals only:

Recommended Administration:

Clarithromycin 500 mg, powder for concentrate for solution for infusion should be administered into one of the larger proximal veins as an IV infusion over 60 minutes, using a solution concentration of about 2mg/ml.

Clarithromycin should not be given as a bolus or bv intramuscular injection.

Step A. Preparation of the vial solution

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Inject 10 ml of water for injections into a vial containing the product. Shake until the vial contents have dissolved. Use only water for injections for the dissolution. Other solvents may result in the formation of a precipitate.

Do not use solutions of inorganic salts or solutions containing preservatives. Store the solution at a temperature between 2 and 8°C and use within 48 hours. Step B. Preparation of infusion solution Make up 10ml of the vial solution prepared in step A (containing 500 mg clarithromycin lactobionate) to 250 ml using one of the following solutions:

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0.9% Sodium Chloride 5% Dextrose

5% Dextrose in 0.3% sodium chloride 5% Dextrose in 0.45% sodium chloride 5% Dextrose in Ringer's lactate solution and Ringer's lactate solution.

Compatibility with other IV additives has not been established.

Infusion solution prepared in this way contains 2mg / ml of clarithromycin lactobionate. Store the solution at a temperature between 2 and 8°C and use within 48 hours.

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•    Fluconazole, Itraconazole (used to treat fungal Infections)

•    Verapamil (used to treat hypertension)

•    Tolterodine (used for treatment of urge Incontinence and/or increased urinary frequency)

•    Cisapride (for stomach disorders)

•    Astemizole, terfenadine (used to treat allergies)

•    Ergotamine or dihydroergotamine (for migraine)

•    St. John's Wort (a herbal product used to treat depression)

•    Quetiapine or other atypical antipsychotic drugs (used to treat psychotic disorders).

Clarithromycin does not interact with oral contraceptives. Pregnancy, breast-feeding and fertility:

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Driving and using machines Do not drive or use machines, if you suffer from one of the following side effects: dizziness, confusion or disorientation. No studies on the effects on the ability to drive and use machines have been performed.

3. HOW TO USE CLARITHROMYCIN Dosage:

Clarithromycin may be given for 2 to 5 days by intravenous infusion. The total duration of treatment should not exceed more than 14 days.

Adults and adolescents:

The recommended dose is 1.0 gram daily of Clarithromycin powder for solution for infusion (appropriately diluted), administered as two separate 500mg doses at 12 hourly intervals. Method and Route of administration: Clarithromycin will be given to you by a doctor or nurse. Clarithromycin is prepared by dissolving the powder in the vial in sterile water. The solution obtained is added to a larger volume of sterile liquid, and this is then infused (like being given a blood transfusion) into one of your veins for at least an hour.

If you receive more Clarithromycin than you should Your doctor or nurse will know how much infusion to give you. If you think you have been given too much Clarithromycin you should talk to your nurse or doctor. An overdose with Clarithromycin is likely to cause vomiting and stomach pains.

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

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IMPORTANT: BOTH DILUENT STEPS (A and B) SHOULD BE COMPLETED BEFORE USE.

Dosage:

Clarithromycin may be given for 2 to 5 days by intravenous infusion. The total duration of treatment should not exceed more than 14 days.

Adults and adolescents: The recommended dose is 1.0 gram daily of Clarithromycin powder for solution for infusion (appropriately diluted), administered as two separate 500 mg doses at 12 hourly intervals. Children under 12 years should not be given

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4. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them. If any of the side effects listed below gets serious, or if you notice any side effects not listed in this leaflet, please contact your doctor immediately.

The chance of having side effects may also depend on whether you take Clarithromycin alone, or with any other medicines.

Some of the side effects of Clarithromycin can be serious. If you suffer from any of the following symptoms you should contact your doctor straight away:

•    Sudden wheeziness or chest tightness, breathing difficulties, swelling of eyelids, face or lips or collapse (fainting) as these may be symptoms of an acute allergic reaction to your medicine

•    Severe diarrhoea (this could indicate that you are suffering from a condition called “Pseudomembranous colitis”)

•    Blistering of the skin, mouth, eyes and genital organs which could indicate a severe adverse reaction.

The following side effects have been reported: Common (may affect up to 1 in 10 people)

•    Feeling sick or being sick, indigestion

•    Inflammation, tenderness or pain at the site of injection

•    Pain in your stomach

•    Your teeth or tongue may become discoloured or you may notice a bitter or metallic taste in your mouth

•    Oral thrush

•    Headaches

•    Smell alteration

•    Flushing

•    Loose stools

•    Abnormal liver function tests

•    Rash

•    Increased sweating

•    Increased blood urea nitrogen

•    Difficulty in sleeping.

Uncommon (may affect up to 1 in 100 people)

•    Reduction in the number of white cells

•    Decreased appetite

•    Nervousness

•    Problems with your liver such as inflammation or raised liver enzymes

•    Increase in time for your blood to clot

•    Pain in your joints or muscles, loss of muscle tissue

•    Jaundice

•    Allergic reactions ranging from urticaria to mild skin eruptions and angioedema to anaphylaxis

Clarithromycin IV. Your doctor will prescribe another suitable medicine for your child.

Renal Impairment:

Patients with severe renal impairment, with creatinine clearance less than 30ml/min, the dosage of clarithromycin should be reduced to one half of the normal recommended dose.

Shelf life

Unopened vials: 4 years

After reconstitution in 10 ml water for injections:

Chemical and physical in-use stability has been

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•    Skin infection characterized by pain, redness, swelling

•    Fungal infection (signs of which include redness, itching and discomfort)

•    Gastritis (feeling or being sick, loose stools)

•    Vaginal thrush (a fungal infection)

•    Loss of consciousness

•    Diminished voluntary movements and the presence of involuntary movements

•    Drowsiness

•    Involuntary muscle contractions

•    ‘Spinning’ sensation, difficulty hearing

•    The heart suddenly stops beating, palpitations, irregular heart beats

•    Bleeding from the nose

•    Blockage of the main artery of the lung (symptoms include chest pain, shortness of breath or coughing up blood)

•    Inflammation of the lining of the oesophagus (gullet), heartburn, the lining of the stomach becomes inflamed or swollen, abdominal distension, pain in the rectum, dry mouth, passing gas, constipation

•    Muscle stiffness

•    Pain, fever, weakness, fatigue

•    Abnormal kidney function tests

•    Feeling anxious.

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

•    ‘Ringing’ in the ears (tinnitus)

•    Uncontrolled shaking of your body (fits or seizures).

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

•    Reduction of platelets in your blood which may cause bruising or your nose or gums to bleed

•    Changes in heart rhythm

•    Loss of hearing (which returns after stopping treatment)

•    Inflammation of the eye (mainly occurring in patients who take rifabutin (an antibiotic) at the same time)

•    Inflammation of the pancreas or infection of the intestine (caused by bacteria)

•    Liver failure

•    Numbness, tingling or prickling of the skin

•    Dizziness or loss of balance

•    Inflammation of the kidneys

•    Sudden onset of a severe rash or blistering or peeling skin. This may be associated with a high fever and joint pains (Stevens Johnson syndrome/Toxic epidermal Necrolysis).

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demonstrated for 24 hours at 25°C and for 48 hours at 5°C. From a microbiological point of view, the product should be diluted immediately. If not diluted 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 reconstitution has taken place in controlled and validated aseptic conditions.

After dilution to 250 ml in an appropriate diluent: Chemical and physical in-use stability has been demonstrated for 6 hours at 25°C and for 48 hours at 5°C.

Continued

Not known (frequency cannot be estimated from the available data)

•    Inflammation causing abdominal pain or diarrhoea due to a bacterial infection (Clostridium difficile colitis)

•    Skin infection characterized by pain, redness, swelling

•    Bacterial infection characterized by brown, scaly skin patches

•    Severe reduction in number of white blood cells which makes infections more likely

•    Serious allergic reaction which causes difficulty in breathing or dizziness

•    Low blood sugar (especially in patients taking medicines to treat diabetes)

•    Loss of sense of smell, taste and/or hearing

•    Life-threatening irregular heartbeat

•    Bleeding (when taken with warfarin)

•    Liver failure

•    Yellowing of the skin or whites of the eyes caused by liver or blood problems

•    Acne

•    Muscle weakness, breakdown of muscle

•    Kidney failure

•    Feeling elated or over-excited, which causes unusual behavior

•    Abnormal urine colour

•    Haemorrhage

•    Seeing things or hearing things, feeling confused or disorientated

•    Bad dreams

•    Depression.

Reporting of side effects

If you get any of the 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 (see details below).

By reporting side effects you can help provide more information on the safety of this medicine.

United Kingdom

Medicines and Healthcare Products Regulatory Agency

151 Buckingham Palace Road Victoria,

London, SW1W9SZ-

UKTel: + 0808 100 3352 (available from 10 a.m. to 2 p.m. Mondays to Fridays)

Website: www.mhra.gov.uk/yellowcard

From a microbiological point of view, the solution for infusion 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.

Storage

Do not store above 30°C.

Store in the original container in order to protect from light. See carton and vial for expiry date. The

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5.    HOW TO STORE CLARITHROMYCIN

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 of the product. The expiry date refers to the last day of that month.

Do not store above 30°C. Store in the original container in order to protect from light. For in use storage times of the reconstituted solution, please see the section on shelf life in the information intended for medical and healthcare professionals only.

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 Clarithromycin contains

The active substance is clarithromycin. Each vial contains 500mg clarithromycin (as lactobionate). Each millilitre of final reconstituted/diluted solution for infusion contains 2mg clarithromycin (as lactobionate).

The other ingredient is lactobionic acid.

What Clarithromycin looks like and contents of the pack

Type II clear glass vial with a Ph.Eur. Type I bromobutyl stopper with aluminium flipoff cap. Vials are packed in Units of 1,4 and 6. Not all pack sizes may be marketed. Pack size: 500mg Marketing Authorization Holder:

Mercury Pharmaceuticals Ltd,

Capital House, 85 King William Street,

London EC4N 7BL, UK

Manufacturer:

LABORATORIOS ALCALA FARMA,

S.L., Carretera M300 Km 29,920, Apartado de correos 3728802 Alcaic de Henares (Madrid), Spain. This medicinal product is authorised in the Member States of the EEA under the following Names:

Ireland :    Clarithromycin 500 mg, powder

for Concentrate for solution for infusion.

United Kingdom : Clarithromycin 500 mg, powder for Concentrate for solution for infusion.

This leaflet was last revised in October 2016.

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products should not be used after this date.

Product Licence number:    UK PL 12762/0404

101853/LF/048/03 551090/B

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REGULATORY AUTHORITY APPROVAL CONFIRMATION

Confirmation that this artwork has been approved by the appropriate market authority (if applicable, e.g. MHRA, HPRA, etc) and that Mercury Pharma have license approval to distribute this component for sale in the relevant market.

Accept Artwork / Reject Artwork

(Please strike off whichever NOT applicable)

Signature

Name

Date