Refludan 50 mg powder for solution for injection or infusion

Refludan is an antithrombotic medicine.

Antithrombotics are medicines to prevent formation of blood clots (thrombosis).

Refludan is used for anticoagulation in adult patients with heparin-induced thrombocytopenia (HIT) type II and thromboembolic disease requiring injected antithrombotic medicines. HIT type II is an illness which can occur after you have received heparin containing medicines. It constitutes a certain kind of allergy towards heparin. It may result in a too low number of blood platelets and/or clots in your blood vessels (thrombosis).

This may additionally lead to deposition of clots in organs.

Do not use Refludan

• if you are allergic (hypersensitive ) to lepirudin, to hirudins or any of the other ingredients of Refludan.
• if you are pregnant or breast-feeding.

Take special care with Refludan If you have a bleeding tendency, your doctor will weigh the risk of Refludan administration against its benefit. Thus, please tell your doctor if you have or have had Recent puncture of large vessels or organs Anomaly of vessels or organs Recent stroke, accident or surgery involving the brain High blood pressure Inflammation of the inner membrane of the heart Advanced kidney disease Advanced bleeding tendency

Recent major surgery Recent bleeding e.g. in brain, stomachintestine, eye, lung Obvious signs of bleeding Recent active peptic ulcer Age 65 years

Please inform your doctor if you suffer from reduced kidney function or liver cirrhosis (advanced disease of the liver) for he will then reduce the dosage.

You should also inform your doctor if you have ever received Refludan, hirudin or a hirudin analogue.

Taking other medicines
Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines, even those not prescribed.

Medicines given to break up clots or tablets to prevent clot formation (coumarins) may increase the risk of bleeding when given at the same time.

Pregnancy and breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine.

Refludan should not be administered to pregnant women or nursing mothers.

Your doctor will determine and control the dosage and duration of your treatment with Refludan according to your clinical condition, your body weight, and certain laboratory values.

If you have the impression that the effect of Refludan is too strong or too weak, talk to your doctor or pharmacist.

Refludan, once reconstituted with an appropriate solvent, will be administered into a vein, by injection and then by infusion.

Like all medicines, Refludan can have side effects although not everybody gets them.

Very common (at least 1 in 10 people)
? Bleeding

Reported bleeding events include: anaemia or drop in the haemoglobin value without obvious source of bleeding, bruising, bleeding from puncture sites, nose bleeding,blood in urine , gastrointestinal bleeding, vaginal bleeding, rectal bleeding, pulmonary haemorrhage, bleeding into chest space and around the heart following surgery , bleeding into the brain.

Severe bleeding and, in particular, intracranial bleeding may be fatal. In intensified post-marketing surveillance in HIT type II, fatal bleeding was reported in 1 % and intracranial bleeding in 0.2 % of patients. Severe bleeding may lead to decreased volume of circulating blood , low blood pressure , shock, and their clinical sequelae.

Rare (less than 1 in 1,000 people affected)
? Allergic skin reactions (including rash), itching , hot flushes, fever, chills.

Anaphylacticoid reactions including urticaria, difficulty in breathing e.g. consisting of spasms, cough, sharp sound when breathing, build-up of water in the body and in the inner wall of a vessel including face oedema, tongue oedema, throat oedema. In severe cases these may lead to shock and death. Injection site reactions, including pain.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use Refludan after the expiry date which is stated on the carton and the vial after EXP.

Do not store above 25°C. Do not freeze.

Keep the vial in the outer carton.

Do not use Refludan if the reconstituted solution is cloudy or contains particles.

Once reconstituted Refludan is to be used immediately.

Any unused solution must be discarded appropriately.

What Refludan contains

The active substance is lepirudin, a recombinant DNA product derived from yeast cells.

The other ingredients are mannitol (E421) and sodium hydroxide for pH adjustment.

What Refludan looks like and contents of the pack

Refludan is a white powder for solution for injection or infusion supplied in a vial containing 50 mg lepirudin. Refludan is available in packs of 1 or 10 vials. Not all pack sizes may be marketed.

Marketing Authorisation Holder

Celgene Europe Ltd., Riverside House, Riverside Walk, Windsor, SL4 1NA, United Kingdom.

Manufacturer

CSL Behring GmbH, Emil-von-Behring-Straße 76, 35041 Marburg, Germany.

This leaflet was last approved on {date}

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

Instructions for use and handling:

General recommendations Reconstitution and further dilution must be carried out under sterile conditions. For reconstitution water for injections or sodium chloride 9 mgml 0.9 solution are to be used. For further dilution sodium chloride 9 mgml 0.9 or glucose 5 solutions are suitable. For rapid, complete reconstitution, inject 1 ml of diluent into the vacuum vial and shake it gently. On reconstitution a clear, colourless solution is usually obtained within less than 3 minutes. Do not use solutions which are cloudy or contain particles. The reconstituted solution is to be used immediately. The preparation should be warmed to room temperature before administration. Any unused solution must be discarded appropriately. For injection only polypropylene syringes may be used.

Preparation of a Refludan solution with a concentration of5mg/ml
For intravenous. bolus injection a solution with a concentration of 5 mg/ml is needed: ? Reconstitute one vial (50 mg of lepirudin) with 1 ml of either water for injections or sodium chloride 9 mg/ml (0.9 %) solution.
? The final concentration of 5 mg/ml is obtained by transfer into a sterile, single-use syringe (of at least 10 ml capacity) and further dilution to a total volume of 10 ml using sodium chloride 9 mg/ml (0.9 %) or glucose 5 % solution.
? The final solution is to be administered in a body weight-dependent fashion.

Preparation of a Refludan solution with a concentration of2mg/ml
For continuous intravenous infusion, a solution with a concentration of 2 mg/ml is needed: ? Reconstitute two vials (each containing 50 mg of lepirudin) with 1 ml each using either water for injections or sodium chloride 9 mg/ml (0.9 %) solution.
? The final concentration of 2 mg/ml is obtained by transfer of both solutions into one sterile, single-use perfusor syringe (50 ml capacity) and further dilution to a total volume of 50 ml using sodium chloride 9 mg/ml (0.9 %) or glucose 5 % solution.
? The infusion speed of the perfusor automate is to be set in a body weight-dependent fashion. ? The perfusor syringe must be changed at least every 12 hours after the start of the infusion.