Refludan

Treatment with Refludan should be initiated under the guidance of a physician with experience in coagulation disorders. 15 mg / kg body weight / hour as a continuous intravenous infusion for 2 - 10 days or longer if clinically needed.

Normally, the dosage depends on the patient's body weight. This is valid up to a body weight of 110 kg. In patients with a body weight exceeding 110 kg the dosage should not be increased beyond the 110 kg body weight dose (see also tables 2 and 3, below).

Monitoring and modification of the Refludan dosage regimen Standard recommendations Monitoring: – In general, the dosage (infusion rate) should be adjusted to the activated partial thromboplastin time, aPTT. Medicinal product no longer authorised 3 – The aPTT should be monitored at least once daily.

More frequent determinations may be necessary, for example, in patients with renal impairment or with an increased risk of bleeding. 5 fold to 3 fold prolongation of the normal control value. 5 fold prolongation of the normal control value.

5 g/ml lepirudin (upper limit). Dose modifications: – Any aPTT value out of the target range is to be confirmed at once before drawing conclusions with respect to dose modifications, unless there is a clinical need to react immediately.

– If the confirmed aPTT value is above the target range, the infusion should be stopped for two hours. At restart, the infusion speed should be decreased by 50 % (no additional intravenous bolus should be administered). The aPTT should be determined again 4 hours later.

– If the confirmed aPTT value is below the target range, the infusion speed should be increased by 20 %. The aPTT should be determined again 4 hours later. 21 mg/kg/hour should not be exceeded without checking for coagulation abnormalities which might be preventing an appropriate aPTT response.

Recommendations for use in patients scheduled for a switch to oral anticoagulation If a patient is scheduled to receive coumarin derivatives (vitamin K antagonists) for oral anticoagulation after Refludan therapy, the following should apply: Coumarin derivatives should be initiated only when platelet counts are normalising.

The intended maintenance dose should be started with no loading dose. To avoid prothrombotic effects when initiating coumarin, continue parenteral anticoagulation for 4 to 5 days (see oral anticoagulant package insert for information).

The majority of undesirable effects experienced by patients treated with Refludan were generally related to bleeding (>1/10). Life-threatening bleeding events (including intracranial bleeding) were uncommonly reported (≥1/1,000 to <1/100) in patients with acute coronary syndrome included in clinical studies.

2 % of patients Adverse events reported on Refludan are shown in the table below:Medicinal product no longer authorised 7 Very common (>1/10); Common (>1/100, <1/10); Uncommon (>1/1,000 <1/100); Rare (>1/10,000 <1/1,000); Very Rare (<1/10,000) System Organ Class Very common Rare Immune System Disorders Anaphylactic/oid reactions Vascular Disorders Anemia or drop in the haemoglobin value without obvious source of bleeding Haematoma Bleeding from puncture sites Epistaxis Haematuria Gastrointestinal bleeding Vaginal bleeding Rectal bleeding Pulmonary haemorrhage Postoperative haemothorax Haemopericardium Intracranial bleeding Hot flushes Shock including fatal shock Respiratory, thoracic and mediastinal disorders Cough Stridor Dyspnea Skin and Subcutaneous Tissue Disorders Allergic Skin Reactions (including rash) Pruritus Urticaria Angio-oedema (including: face oedema, tongue oedema, larynx oedema) General Disorders and Administration Site Conditions Fever Chills Injection site reactions including pain.

4 Intravenous infusion: For continuous intravenous infusion, a solution with a concentration of 2 mg/ml is needed. The speed of the perfusor automate [ml per hour] is to be set in a body weight dependent fashion. 6) Where there is active bleeding or bleeding tendency it is generally not advisable to administer Refludan.

The physician should carefully weigh the risk of Refludan administration versus its anticipated benefit, taking into account possible measures to control bleeding. g. intracranial, gastrointestinal, intraocular, pulmonary) – Overt signs of bleeding – Recent active peptic ulcer – Age > 65 years.

8). Fatal anaphylactic reactions have been reported in patients re-exposed to Refludan in a second or subsequent treatment course. Therefore, alternative treatment options must be considered before the decision to re-expose a patient to Refludan.

As these reactions are immune-mediated, patients with recent exposure to hirudin or hirudin analog may be at an increased risk. Treatment initiation with Refludan should be undertaken only in a setting where medical assistance is readily available and where there is access to treatment for anaphylactic reactions.

– Patients should be informed that they have received Refludan. – In case of renal impairment relative overdose may occur even under a standard dosage regimen. Therefore, the treating physician should carefully weigh the risk of administration versus its anticipated benefit.

It may be necessary to exclude patients with renal impairment from treatment with lepirudin regimen. 2). – There is no experience with lepirudin in patients with significant liver impairment. Liver cirrhosis may also affect the renal excretion of lepirudin.

g. liver cirrhosis) may enhance the anticoagulant effect of lepirudin due to coagulation defects secondary to reduced generation of vitamin K-dependent coagulation factors. – Formation of anti-hirudin antibodies was observed in about 40 % of HIT type II patients and have been reported especially with a treatment period exceeding five days.

6) Where there is active bleeding or bleeding tendency it is generally not advisable to administer Refludan. The physician should carefully weigh the risk of Refludan administration versus its anticipated benefit, taking into account possible measures to control bleeding.

g. intracranial, gastrointestinal, intraocular, pulmonary) – Overt signs of bleeding – Recent active peptic ulcer – Age > 65 years.