PACKAGE LEAFLET:    P0000/PMPLT000

Information for the user

Exembol

Exembol Multidose 100 mg/ml concentrate for solution for infusion Argatroban Monohydrate

Important information about some of the ingredients of Exembol Multidose

This product contains 400 mg/ml or 50% by volume of alcohol (ethanol) before dilution, which corresponds to 0.5% by volume after dilution in accordance with the instructions. The daily dose may therefore contain up to 5 ml (4 g) of alcohol, corresponding to 100 ml beer or 40 ml wine. This may be harmful for persons suffering from liver disease, alcoholism or epilepsy as well as for pregnant and nursing women and their children. This may also influence the effect of other medicines.

This medicine contains sorbitol. If you are intolerant to certain sugars, you must tell your doctor.

3. how to use exembol multidose

Exembol Multidose will always be given to you by medical personnel. Exembol Multidose will be given to you intravenously (into a vein) by continuous infusion. The doctor will decide the dose and how long you will be treated.

In this leaflet:

1.    What Exembol Multidose is and what it is used for

2.    Before you use Exembol Multidose

3.    How to use Exembol Multidose

4.    Possible side effects

5.    How to store Exembol Multidose

6.    Further information

1. WHAT exembol MuLTIDosE Is AND WHAT IT Is used for

Exembol Multidose is an anticoagulant (a drug that helps to prevent blood clots from forming in your blood circulation). It works by blocking the action of thrombin, a substance in your blood that is important in blood clotting.

Exembol Multidose is used if you are suffering from a disorder known as heparin-induced thrombocytopenia type II (HIT type II). If you have HIT type II, you are at risk of developing blood clots in your blood circulation that can cause heart attacks, stroke, breathing problems and problems with the blood supply to your limbs. Exembol Multidose can prevent these problems or prevent them from becoming worse.

2. before you use exembol multidose

Do not use Exembol Multidose

Exembol Multidose will not be given to you:

•    If you have uncontrolled bleeding

•    If you are allergic (hypersensitive) to argatroban or to any of the other ingredients of Exembol Multidose

•    If you have severely impaired liver function

Take special care with Exembol Multidose

Exembol Multidose will be given to you with special care:

•    If there is an increased risk of bleeding

•    If you have recently had injections or infusions of other anticoagulants such as heparin

•    If you have liver disease

using other medicines

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

Combined use with other blood thinning or blood clot dissolving medicines can increase the risk of bleeding.

Because Exembol Multidose contains ethanol, this can influence the effect of other medicines containing metronidazol (for infections) or disulfiram (for alcoholism).

Pregnancy and breast-feeding

If you are pregnant, your doctor will only give you Exembol Multidose if it is absolutely necessary. Avoid breast-feeding while you are being given Exembol Multidose.

Driving and using machines

Since Exembol Multidose contains alcohol you should not drive a car or use machines in connection with the treatment. (see also “Important information about some of the ingredients of Exembol Multidose).

4.    possible side effects

Like all medicines, Exembol Multidose can cause side effects, although not everybody gets them.

The most common side-effects are bleeding. Major bleeding can occur in about 5% of patients and minor bleeding in about 39% of patients. You must tell your doctor immediately if you experience any of the following symptoms:

•    Bleeding or bruising • blood in urine or stools • vomiting or coughing up blood • black stools • difficulty in breathing • cold sweaty skin • dry mouth • dilated pupils and/or weak rapid pulse.

These symptoms could indicate that you are experiencing bleeding problems.

Common side effects (affects more than 1 user in 100):

•    Anaemia^ blood clotting • bleeding, including numerous small bleedings in skin and mucus membranes (purpura) • nausea

uncommon side effects (affects more than 1 user in 1,000):

•    Infections such as urinary tract infection • changes in blood values • blood clotting • lack of appetite • low blood sugar levels

•    low sodium levels in the blood • confusion • dizziness • fainting

•    headache • stroke • muscle disorders • speech disorder • vision problems • deafness • heart attack • fluid in the heart sac • abnormal heart rhythm • fast heartbeat • low blood pressure • high blood pressure • inflammation of veins • shock • reduced oxygen supply to the tissues • breathing difficulties • fluid around the lungs • hiccup

•    blood in cough, vomit or stools • constipation • diarrhoea • stomach inflammation • difficulty in swallowing • tongue disorder • abnormal liver function • jaundice (yellowing of the skin and eyes) • changes in blood tests for liver function • rash including including nettle rash

•    itching,* increased sweating • hair loss • muscle weakness

•    muscle pain • kidney failure • fever • pain • tiredness • injection site reactions • swelling of the legs • increased wound drainage

•    abnormal laboratory results.

If you experience side effects, talk with your doctor or pharmacist.

This includes any possible side effects not listed in this leaflet. You may also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. By reporting adverse events you can help to increase information on the safety of medicines.

5.    how to store exembol multidose

Keep out of the reach and sight of children.

Keep vial in the outer carton in order to protect from light.

Do not freeze.

Diluted solutions should not be exposed to direct sunlight.

Solutions should not be used if they are cloudy or contain any particles.

After opening, before dilution: Chemical and physical stability has been demonstrated in use following multiple needle entries and product withdrawal for 28 days at both 25°C and at 2 to 8°C.

Diluted solution: chemical and physical in-use stability has been demonstrated for up to 14 days at 25°C and 2 to 8°C in sodium chloride 9 mg/ml (0.9%) solution for infusion, glucose 50 mg/ml (5%) solution for infusion, or sodium lactate intravenous infusion compound.

From a microbiological point of view, the product 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 2-8°C, unless dilution has taken place in a controlled and validated aseptic conditions.

Do not use Exembol Multidose after the expiry date which is stated on the carton/vial after “EXP". The expiry date refers to the last day of that month.

6. FURTHER INFORMATION

What Exembol Multidose contains

The active substance is argatroban monohydrate 100 mg/ml.

1 ml concentrate for solution for infusion contains argatroban as 100 mg argatroban monohydrate.

1 Vial with 2.5 ml concentrate for solution for infusion contains argatroban as 250 mg argatroban monohydrate.

The other ingredients are anhydrous ethanol, sorbitol and water for injections

What Exembol Multidose looks like and contents of the pack

This medicinal product is a clear colourless to pale yellow concentrate for solution for infusion. Each vial contains 2.5 ml of solution and the vials are packed in cardboard boxes of 1 or 6 vials.

Not all pack sizes may be marketed.

Marketing authorisation holder

Mitsubishi Tanabe Pharma Europe Ltd, Dashwood House, 69 Old Broad Street, London, EC2M 1QS, United Kingdom.

Manufacturer

Penn Pharmaceutical Services Limited, Tredegar, Gwent NP22 3AA,

UK.

The constituted solution must be mixed by repeated inversion of the diluent bag or bottle for one minute. The diluted solution should be clear and practically free from visible particles. Upon preparation, the solution may show slight but brief haziness due to the formation of microprecipitates that rapidly dissolve upon mixing. The pH of the intravenous solution prepared as recommended is 3.2-7.5.

Multiple use of Exembol Multidose applies to the 100 mg/ml concentrate for solution for infusion in its original container. The diluted solution should be used immediately. Any unused solution should be discarded.

Light resistant measures such as foil protection for intravenous lines are not necessary. No significant potency losses have been noted following simulated delivery of the solution through intravenous tubing.

Any unused product or waste material should be disposed of in accordance with local requirements.

Information can be obtained from:

Mitsubishi Medical Information,

Mitsubishi Tanabe Pharma Europe Ltd, Dashwood House, 69 Old Broad Street, London, EC2M 1QS, United Kingdom.

Telephone number: 0207 382 9000

Email address: medinfo@mt-pharma-eu.com

This medicinal product is authorised in the Member states of the EEA under the following names:

Argatra Multidose Novastan Multidose Novastan Arganova Argatra Multidose Novastan Multidose Novastan Multidose Arganova Multidose Novastan

Novastan Multidose Exembol Multidose

This leaflet was last revised in: 06-2014

The following information is only for doctors and medical personnel.

Instructions for use, handling and disposal

Exembol Multidose should be diluted in sodium chloride 9 mg/ml (0.9%) solution for infusion, glucose 50 mg/ml (5%) solution for infusion, or Sodium Lactate Intravenous Infusion Compound to a final concentration of 1 mg/ml. If the solution is cloudy, or if an insoluble precipitate is noted, the vial should be discarded.

Following multiple needle entries and product withdrawals, the vials maintain microbial, chemical and physical stability for up to 28 days at 25°C and at 2 to 8°C. Other in-use storage times and conditions are the responsibility of the user.

The 100 mg/ml concentrate for solution for infusion should be diluted 100-fold by mixing with diluent. For a starting infusion rate of 0.5 microgram/kg/min, use 50 mg (0.5 ml) concentrate for solution for infusion per 50 ml of diluent.