The SmPC has been updated following an EU harmonisation work-sharing procedure.

Sections 4.1 and 4.2 have been updated, with consequential changes to sections 4.4 and 4.8. Information on use in patients with active cancer also included.

Changes detailed below:

4.1     Therapeutic indications – revised wording

Treatment of venous thrombosis and thromboembolic disease including deep vein thrombosis and pulmonary embolus in adults.

Extended treatment of venous thromboembolism and prevention of recurrences in adult patients with active cancer.

For some patients with pulmonary embolism (e.g. those with severe haemodynamic instability) alternative treatment, such as surgery or thrombolysis, may be indicated.

4.2     Posology and method of administration – revised wording

Posology

Treatment in adults

175 anti-Xa IU/kg body weight given subcutaneously once daily for at least 6 days and until adequate oral anticoagulation is established.

Extended treatment in adult patients with active cancer

175 anti-Xa IU/kg body weight given subcutaneously once daily for a recommended treatment period of 6 months. The benefit of continued anticoagulation treatment beyond 6 months should be evaluated.

Neuraxial anaesthesia

Treatment doses of innohep (175 IU/kg) are contraindicated in patients who receive neuraxial anaesthesia, see section 4.3. If neuraxial anaesthesia is planned, innohep should be discontinued at least 24 hours before the procedure is performed. innohep should not be resumed until at least 4-6 hours after the use of spinal anaesthesia or after the catheter has been removed.

Interchangeability

For interchangeability with other LMWHs, see section 4.4.

Renal impairment

If renal impairment is suspected, renal function should be assessed using a formula based on serum creatinine to estimate creatinine clearance level.

Use in patients with a creatinine clearance level <30 ml/minute is not recommended, as dosage in this population has not been established. Available evidence demonstrates no accumulation in patients with creatinine clearance levels down to 20 ml/min. When required in these patients, innohep treatment can be initiated with anti-Xa monitoring, if the benefit outweighs the risk (see section 4.4: Renal impairment). In this situation, the dose of innohep should be adjusted, if necessary, based on anti-factor Xa activity. If the anti-factor Xa level is below or above the desired range, the dose of innohep should be increased or reduced respectively, and the anti-factor Xa measurement should be repeated after 3-4 new doses. This dose adjustment should be repeated until the desired anti-factor Xa level is achieved. For guidance, mean levels between 4 and 6 hours after administration in healthy volunteers and patients without severe renal insufficiency have been between 0.5 and 1.5 IU/anti-factor Xa IU/ml. Anti-factor Xa activity determinations were by a chromogenic assay.

Elderly

innohep should be used in the elderly in standard doses. Precaution is recommended in the treatment of elderly patients with renal impairment. If renal impairment is suspected, see section 4.2: Renal impairment and section 4.4: Renal impairment.

Method of administration

Information on injection site included.

4.4     Special warnings and precautions for use

The following subsections have been updated in line with the revised statements in Section 4.2.

·       Heparin-induced thrombocytopenia

·       Renal impairment

Interchangeability with other LMWHs: Minor revision to wording.

4.8     Undesirable effects

Information added on patients with cancer on extended treatment.

10 Date of revision of SmPC

Updated to November 2016

‘bleeding’ changed to ‘haemorrhage’

Editorial updates throughout.

‘bleeding’ changed to ‘haemorrhage’

Updated information on heparin-induced thrombocytopenia and renal impairment.

Heparin-induced thrombocytopenia

Because of the risk of immune-mediated heparin-induced thrombocytopenia (Type II), platelet count should be measured before the start of treatment and periodically thereafter. innohep must be discontinued in patients who develop immune-mediated heparin-induced thrombocytopenia (type II) (see Ssections 4.3 and 4.8). Platelet counts will usually normalise within 2 to 4 weeks after withdrawal.

Renal Failure:

As tinzaparin sodium is excreted at least partially via the kidney, care should be taken when treating DVT and PE patients with severe renal failure.

Renal Impairment:

All available evidence demonstrates no accumulation in patients with creatinine clearance levels down to 20 ml/minute. Although anti-Xa monitoring is the most appropriate measure of the pharmacodynamic effects of innohep^®, it remains a poor predictor of bleeding risk, nonetheless monitoring of anti-factor Xa activity may be considered in patients with severe renal impairment (creatinine clearance < 30 ml/minute). Caution is recommended when treating patients with severe renal impairment (creatinine clearance < 30 ml/minute). There is limited data available in patients with an estimated creatinine clearance level below 20 ml/minute.

Renal impairment

Available evidence demonstrates no accumulation in patients with creatinine clearance levels down to 20 ml/minute. Although anti-Xa monitoring is the most appropriate measure of the pharmacodynamic effects of innohep, it remains a poor predictor of haemorrhage risk. Nonetheless, monitoring of anti-factor Xa activity may be considered in patients with severe renal impairment (creatinine clearance <30 ml/minute).

Caution is recommended when treating patients with severe renal impairment (creatinine clearance < 30 ml/minute).

There is limited data available in patients with an estimated creatinine clearance level below 20 ml/minute.

it remains a poor predictor of bleeding risk, nonetheless monitoring of anti-factor Xa activity may be considered in patients with severe renal impairment (creatinine clearance < 30 ml/minute). Caution is recommended when treating patients with severe renal impairment (creatinine clearance < 30 ml/minute). There is limited data available in patients with an estimated creatinine clearance level below 20 ml/minute.

Elderly are more likely to have reduced renal function, (see Section 4.4: Renal impairment); therefore caution should be exercised when prescribing innohep^® to the elderly.