Tinzaparin sodium

  • 9005-49-6 (Heparin )
  • 9041-08-1 (sodium salt)

Nonspecific

6500 Dalton ( tinzaparin sodium ·, average)

B01AB10

IE/24h 550,000 ( = 7,930 IE/kg/24h ) ( LDLO, man, iv )

Tinzaparin is a blood coagulation inhibitor and belongs to the group of low molecular weight heparins. It is produced by the Danish company LEO Pharma and marketed worldwide as tinzaparin sodium, under the trade name Innohep. Tinzaparin is used for prevention and treatment of deep vein thrombosis and pulmonary embolism, and administered by subcutaneous injection. Tinzaparin is also used for hemodialysis in the extracorporeal circuit.

Tinzaparin sodium is the sodium salt of the active substance by enzymatic depolymerization ( = splitting ) is derived from unfractionated heparin chains by heparinase. Heparinase from Flavobacterium heparinum won. Tinzaparin is available on prescription.

Pharmacology

Tinzaparin has an inhibitory effect on various clotting factors in the coagulation cascade. Here are inhibited antithrombin clotting factor X as well as coagulation factor II. In addition, the tissue factor on the release of Tissue Factor Pathway Inhibitor (TFPI ) is inhibited. Consequently, less thrombin is produced and therefore the production of fibrin is inhibited. The result is a decreased clotting.

The potency of tinzaparin is determined using the anti-factor Xa - determination and expressed in anti-Xa international units ( IU).

The overall effect of a low molecular weight heparin can not be measured directly. Anti-Xa and anti- IIa measurements are used for low molecular weight heparins as primary Surrogatbiomarker helping out. A measurement of the anti - Xa level is usually not performed in clinical practice, since this measurement does not correlate directly with the effect in the body.

The average molar mass is 5500-7500 daltons ( median = 6,500 daltons).

The table below summarizes the basis of detected anti-Xa measurements pharmacokinetic properties (mean ( standard deviation) ) of tinzaparin together:

Indications

In Germany tinzaparin is approved for the following applications:

  • Postoperative thrombosis prophylaxis in surgical procedures in the medium and low risk area, including accompanying dispositional risk factors.
  • Therapy of thromboembolic events, including deep vein thrombosis and pulmonary embolism
  • Use in the extracorporeal circuit during hemodialysis

In other EU countries in addition approvals for the following application areas are:

  • Postoperative thromboprophylaxis in high-risk (eg, hip and knee replacement surgery )
  • Immobilization by severe internal diseases

Development

The clinical development of tinzaparin resulted in 1994 in the admission area prophylaxis after surgery. 1997 tinzaparin in Germany, as the first representative of low molecular weight heparins for the initial therapy of deep vein thrombosis, admitted for acute treatment of pulmonary embolism in hemodynamically stable patients (up to the beginning of stage III ) 1999.

The current clinical development of the compound on the one hand focuses on the longer-term (6 -month ) use of tinzaparin after acute deep vein thrombosis or pulmonary embolism (secondary prophylaxis) and partly on its use in patients with age-related renal dysfunction.

Convenience Features

In all application areas tinzaparin is only 1 x injected daily subcutaneously. This applies in particular for use in the therapeutic range.

Tinzaparin does not accumulate in elderly patients with impaired renal function and leads in patients 70 years and older compared with the aPTT -adjusted unfractionated heparin use no increased bleeding tendency. Dose adjustment is not necessary in these patients. Characterized a possible loss of efficacy of tinzaparin is prevented.

Contraindications (excerpt)

  • Tinzaparin may, like other low molecular weight heparins are also not used in cases of hypersensitivity to the active substance, with coagulation disorders, such as the presence of a reduced number of platelets ( thrombocytopenia) or a lack of clotting factors in bleeding about by ulcers or other organ changes and injuries, and in severe hepatic impairment.

Warnings (excerpt)

  • A dose reduction is necessary in patients with creatinine clearance of 20 ml / min or higher. However, caution should be exercised when treating patients with severe renal impairment (creatinine clearance <30 ml / min). Caution should be exercised when treating elderly patients with renal impairment. Renal function should be determined and (<30 ml / min creatinine clearance ) control of the anti - Xa activity should be considered in patients with severe renal impairment.
CAS registry number Anatomical Therapeutic Chemical Classification System Hemostasis
776313
de