tinzaparin sodium

CLINICAL USE

Peri- and postoperative surgical thromboprophylaxis Treatment of DVT and pulmonary embolism Prevention of thrombus formation in extracorporeal circulation during

HD :

DOSE IN NORMAL RENAL FUNCTION

General surgery: (low-moderate risk) 3500 IU daily Orthopaedic surgery: (high risk) 50 IU/kg or 4500 IU daily DVT and PE: 175 IU/kg bodyweight once daily for at least 6 days and until adequate oral anticoagulation is established

PHARMACOKINETICS

Molecular weight : 5500–7500 (average 6500)

%Protein binding : 14

%Excreted unchanged in urine : 80–90

Volume of distribution (L/kg) : 3.1–5 litres

half-life – normal/ESRD (hrs) : 1.5/5.2 (detectable anti-Factor Xa activity persists for 24 hours)

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function.

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD : Not dialysed. Dose as in GFR<20 mL/min

HD : Not dialysed. Dose as in GFR<20 mL/min

HDF/high flux : Dialysed. Dose as in GFR<20 mL/min

CAV/VVHD : Not dialysed. Dose as in GFR=

20 to 50

mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Analgesics: increased risk of bleeding with NSAIDs – avoid concomitant use with IV diclofenac; increased risk of haemorrhage with ketorolac – avoid concomitant use

Nitrates: anticoagulant effect reduced by infusions of glyceryl trinitrate Drotrecogin alfa: manufacturer advises to avoid use of high doses of heparin with drotrecogin alfa Use with care in patients receiving oral anticoagulants, platelet aggregation inhibitors, aspirin or dextran

Reconstition

–

Route

SC injection IV bolus/infusion

Rate of Administration

Comments

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OTHER INFORMATION

Tinzaparin is also indicated for prevention of clotting in the extracorporeal circulation during haemodialysis Dose for >4 hr session: IV bolus — (into arterial side of the dialyser or intravenously) of 3500–4500 IU Dose for <4 hr session: IV bolus of — 2500 IU Additional tinzaparin (500–1000 IU) may be given if concentrated RBCs or blood transfusions are given during dialysis, or additional treatment beyond the normal dialysis duration is employed Determination of plasma antifactor-Xa may be used to monitor the tinzaparin dose during haemodialysis; plasma antifactor-Xa, one hour after dosing should be within the range 0.4–0.5 IU/mL. Heparin can suppress adrenal secretion of aldosterone leading to hyperkalaemia particularly in patients with chronic renal impairment and diabetes mellitus Low molecular weight heparins are renally excreted and hence accumulate in severe renal impairment. While the doses recommended for prophylaxis against DVT and prevention of thrombus formation in extracorporeal circuits are well tolerated in patients with CKD 5, the doses recommended for treatment of DVT and PE have not yet been verified as safe. LMWHs have been associated with severe, sometimes fatal, bleeding episodes in such patients. Hence the use of unfractionated heparin would be preferable in these instances Information from Leo Pharma states that tinzaparin can safely be used in elderly patients with a GFR>20 mL/min for 10 days without any accumulation (Nagge J. Is impaired renal function a contraindication to the use of low-molecular weight heparin? Arch Intern Med. 2002; 162: 2605–09.) (Siguret V. Elderly patients treated with tinzaparin (Innohep) administered once daily (175 anti-Xa IU/kg): anti-Xa and anti-IIa activities over 10 days. Thromb Haemostat. 2000; 84: 800–04.) Additional doses may be required if using LMWHs for anticoagulation in HDF Use 1 mg of protamine for every 100 anti-Xa IU to neutralise the effects of tinzaparin. If prothrombin time is still raised 2–4 hours later, give 0.5 mg/kg infusion of protamine . TioGUAninE 729 Tioguanine

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

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