ZIBOR 25.000 IU Solution for injection Ref.[8450] Active ingredients: Bemiparin

WARNING: The different low molecular weight heparins are different and are not necessarily equivalent. Therefore it is important to comply with the dosage regimen and the specific method of use specified for each of these medicinal products.

Posology

Adults

Treatment of deep vein thrombosis

Zibor 25,000 IU should be administered by the subcutaneous route at a dose of 115 IU anti-Xa/kg weight, once daily. The recommended duration of treatment is 7±2 days. The daily dose generally corresponds – depending on the body weight range- to the following doses and volumes of the product in prefilled syringes: < 50 kg, 0.2 ml (5,000 IU antiXa); 50-70 kg, 0.3 ml (7,500 IU anti-Xa), > 70 kg, 0.4 ml (10,000 IU anti-Xa). In patients weighing more than 100 kg body-weight, the dose should be calculated on the basis of 115 IU anti-Xa/kg/day, where the concentration of anti-Xa is 25,000 IU/ml.

In the absence of any contra-indication, oral anticoagulation should be commenced 3-5 days after beginning Zibor 25,000 IU first administration, and the dose adjusted so as to keep the International Normalized Ratio (INR) value between 2-3 times the control value. Bemiparin administration can be stopped as soon as the said INR value is achieved. Oral anticoagulation should be continued for at least 3 months.

Paediatric population

The safety and efficacy of Zibor in children has not been established due to a lack of data.

Older people

No dose adjustment required. If renal function is impaired please see section: 4.2 Posology and method of administration, renal impairment; 4.4 Special warnings and precautions for use; 5.2 Pharmacokinetic properties.

Renal impairment

(See section: 4.4 Special warnings and precautions for use; 5.2 Pharmacokinetic properties)

• In mild or moderate renal insufficiency (creatinine clearance 30-80 ml/min): no dose adjustment is necessary. However, a close monitoring is recommended.
• Severe renal insufficiency (creatinine clearance <30 mL/min) could influence the pharmacokinetics of bemiparin.

After a careful assessment of the individual bleeding and thrombotic risks of these patients (especially if pulmonary embolism is present), the dose may be necessary to be adjusted. In the latter case, based on pharmacokinetic data, up to a 75% (approximately 85 IU anti-Xa/kg once a day) of the dose could be recommended in patients with severe renal insufficiency for the treatment of established deep vein thrombosis, during the acute phase. A close monitoring is recommended. Measurement of peak anti-Xa levels at about 4 hours post-dose should be considered.

Hepatic impairment

There are insufficient data to recommend dose adjustment of bemiparin in this group of patients.

Method of administration

Subcutaneous injection technique

The pre-filled syringes are ready for immediate use and must not be purged before the subcutaneous injection. When Zibor is administered subcutaneously, the injection should be given in the subcutaneous cell tissue of the anterolateral or posterolateral abdominal waist, alternately on the left and right sides. The needle should be fully inserted, perpendicularly and not tangentially, into the thick part of a skin fold held between the thumb and the forefinger, the skin fold should be held throughout the whole injection. Do not rub the injection site.

Bleeding is the main symptom of overdosage. If bleeding occurs bemiparin should be discontinued depending on the severity of the haemorrhage and the risk of thrombosis.

Minor haemorrhages rarely need specific treatment. In case of major haemorrhages, administration of protamine sulphate may be needed.

The neutralisation of bemiparin with protamine sulphate has been studied in-vitro and in-vivo systems, with the aim of observing the reduction of anti-Xa activity and the effect on the Activated Partial Thromboplastin Time (APTT). Protamine sulphate exerts a partial decrease on anti-Xa activity for 2 hours after its intravenous administration, at a dose of 1.4 mg of protamine sulphate each 100 IU anti-Xa administered.

2 years.

After first opening, Zibor should be used immediately.

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

0.2 ml, 0.3 ml and 0.4 ml of solution in pre-filled syringe (Type I glass) with a plunger rod (polypropylene), rubber plunger stopper (chlorobutyl) and injection needle (stainless steel). Packs of 2, 10, 30 and 100 syringes.

Not all pack sizes may be marketed.

Single-dose container. Discard any unused content. Do not use if the protective package is opened or damaged. Only clear colourless or slightly yellowish solutions, free of visible particles, should be used.

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