REVASC Powder and solvent for solution for injection Ref.[9397] Active ingredients: Desirudin

Warnings

Anaphylaxis

Revasc may cause allergic reactions including anaphylaxis and shock (see section 4.8). Fatal anaphylactic reactions have been reported in patients re-exposed to hirudin product therapy in a second or subsequent treatment course. Although fatal reactions have not been reported with desirudin, alternative treatment options must be considered before the decision to re-expose a patient to Revasc. As these reactions are immune-mediated, patients with previous exposure to hirudin or hirudin analogue may be at an increased risk. Treatment initiation with Revasc 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 Revasc.

Desirudin should not be administered by intramuscular injection owing to the risk of local haematoma.

Desirudin should be used with caution in conditions with increased risks of haemorrhage such as major surgery, biopsy or puncture of a non-compressible vessel within the last month; a history of haemorrhagic stroke, intracranial or intraocular bleeding including diabetic (haemorrhagic) retinopathy; a cerebral ischaemic attack within the last 6 months, a known haemostatic disorder (congenital or acquired, e.g. haemophilia, liver disease) or a history of gastrointestinal or pulmonary bleeding within the past 3 months.

Precautions

When desirudin is administered in patients with increased risk of bleeding complications, mild to moderate hepatic dysfunction and/or mild to moderate renal impairment, aPTT should be monitored and peak aPTT should not exceed twice the control value. If necessary, therapy with desirudin should be interrupted until aPTT returns to less than twice the control value at which time treatment with desirudin can be resumed at a reduced dose.

Desirudin should be used with care in patients receiving anticoagulants, and/or platelet inhibitors, and/or non-steroidal anti-inflammatory medicinal products. Monitoring for evidence of bleeding is advised (see section 4.5). The concomitant use of desirudin with thrombolytics and ticlopidine has not been investigated in this patient population.

The anticoagulant effect of desirudin is poorly reversible. aPTT levels can, however, be reduced by intravenous administration of DDAVP (desmopressin).

Laboratory Tests

Activated partial thromboplastin time (aPTT) should be monitored in patients with increased risk of bleeding and/or renal or hepatic impairment. Peak aPTT should not exceed twice the control value. If necessary, therapy with desirudin should be interrupted until aPTT falls to less than twice the control at which time treatment with desirudin can be resumed at a reduced dose (see also section 4.5).

Any agent which may enhance the risk of haemorrhage should be discontinued prior to initiation of desirudin therapy. If co-administration cannot be avoided, close clinical and laboratory monitoring should be conducted (see section 4.4).

During prophylaxis, concomitant use of medicinal products containing heparins (unfractionated and low-molecular weight heparins) and dextrans is not recommended. The effects of desirudin and unfractionated heparins on prolongation of aPTT have been shown to be additive (see section 4.4).

As with other anticoagulants desirudin should be used with caution in conjunction with medicinal products which affect platelet function these medicinal products include: acetylsalicylic acid and NSAIDs, ticlopidine and clopidogrel, glycoprotein IIb/IIIa antagonists (abciximab, eptifibatide, tirofiban) and iloprost.

If a patient is switched from oral anticoagulants to desirudin therapy or from desirudin to oral anticoagulants, the anticoagulant activity should continue to be closely monitored with appropriate methods. That activity should be taken into account in the evaluation of the overall coagulation status of the patient during the switch (see section 4.2).

There are no adequate data from the use of desirudin in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Revasc is contraindicated in pregnancy (see section 4.3).

It is not known whether desirudin is excreted in human milk. However, lactating mothers should be advised to avoid breast feeding or alternative medicinal products used.

Revasc has no or negligible influence on the ability to drive and use machines.

In controlled clinical trials investigating desirudin 15 mg twice daily and a standard dose of unfractionated heparin, the nature of the hip surgery operation and the mode of action of the two drugs studied account for most of the adverse experiences reported. As with other anticoagulants, bleeding is the most common adverse reaction.

The following related adverse reactions were listed below by system organ class and within each frequency grouping, adverse reactions are presented in order of decreasing seriousness: common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000).

Investigations

Uncommon: Increase in serum transaminases

Blood and the lymphatic system disorders

Common: Anaemia

Nervous system disorders

Uncommon: Dizziness, insomnia, confusion

Respiratory, thoracic and mediastinal disorders

Uncommon: Dyspnoea

Gastrointestinal disorders

Common: Nausea

Uncommon: Haematemesis, vomiting, constipation

Renal and urinary disorders

Uncommon: Haematuria, urinary retention

Skin and subcutaneous tissue disorders

Uncommon: Rash, urticaria

Metabolism and nutrition disorders

Uncommon: Hypokalaemia

Infections and infestations

Uncommon: Urinary tract infection, cystitis

Injury, poisoning and procedural complications

Common: Wound secretion

Uncommon: Impaired wound healing

Vascular disorders

Common: Hypotension, deep thrombophlebitis

Uncommon: Epistaxis, hypertension

General disorders and administration site conditions

Common: Fever, injection site mass, haematomas, oedema in legs

Uncommon: Pain in legs, pain, abdominal and chest pain

Immune system disorders

Common: Allergic reactions have been reported in the same proportion (1.6%) of patients treated with desirudin (N=2,367) or with unfractionated heparin (N=1,134) in clinical trials, regardless of causality.

Rare: Anti-hirudin antibodies have been detected upon re-exposure to desirudin in clinical trials.

Adverse reactions irrespective of trial drug relationship reported during clinical trials were bleeding episodes, oliguria, hyperpyrexia and joint dislocation.

In post-marketing surveillance, rare reports of major haemorrhages, some of which were fatal; and rare reports of non-fatal anaphylactic or anaphylactoid reactions leading to shock have been received.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.