Danaparoid sodium

CLINICAL USE

Prophylaxis of DVT and PE

Thromboembolic disease requiring parenteral anticoagulation in patients with heparin induced thrombocytopenia (HIT)

Anticoagulation for haemodialysis

DOSE IN NORMAL RENAL FUNCTION

Prophylaxis, DVT and PE: 750 units twice daily for 7–10 days (SC

HIT: 2500 units IV bolus (Wt<55 kg: 1250 units; >90 kg: 3750 units) then an IV infusion of 400 units/hour for 2 hours, 300 units/hour for 2 hours, then 200 units/hour for 5 days

Haemodialysis

PHARMACOKINETICS

Molecular weight :Approx 6500

%Protein binding :No data

%Excreted unchanged in urine : 40–50

Volume of distribution (L/kg) :8–9

half-life – normal/ESRD (hrs) :25/>31

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function

10 to 20 : Use with caution

<10 : Use with caution. Reduce second and subsequent doses for thromboembolism prophylaxis

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Not dialysed. Dose as in GFR <10 mL/min

HD :Not dialysed. Dose as in GFR <10 mL/min

HDF/high flux :Unknown dialysability. Dose as in GFR <10 mL/min

CAV/VVHD :Not dialysed. Dose as in GFR=10–20 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugsEnhances effects of oral anticoagulants Interferes with laboratory monitoring of prothrombin time – monitor anticoagulation closely

ADMINISTRATION

Reconstition

Glucose 5% or sodium chloride 0.9%

Route

SC, IV

Rate of Administration

See dose

Comments

–

OTHER INFORMATION

Pharmacokinetic information is from Pharm Update. 1997, Nov/Dec; www.cc.nih.gov/phar/updates/97 novdec.html

Monitor anti-Xa activity in patients >90 kg and with renal impairmentCan also be used for haemodialysis anticoagulation: 2/3 times a week dialysis:

1st and 2nd dialysis: 3750 units IV bolus prior to dialysis. (If patient weighs <55 kg then give 2500 unit IV bolus.)

Subsequent dialysis: 3000 units by IV bolus prior to dialysis, provided there are no fibrin threads in the bubble chamber. (If patient weighs <55 kg then give 2000 unit IV bolus.)

Daily dialysis:

1st dialysis: 3750 units IV bolus prior to dialysis; if patient <55 kg give 2500 units

2nd dialysis: 2500 units IV bolus prior to dialysis; if patient <55 kg give 2000 units

Prior to the second and subsequent dialysis a specimen should be drawn for plasma anti-Xa levels (to be used for dosing a third and subsequent dialysis)

Expected pre-dialysis ranges of anti-Xa levels:If plasma anti-Xa levels are <0.3 U/ —mL, then 3rd or subsequent dialysis dose should be 3000 units. For patients weighing <55 kg use 2000 unitsIf plasma anti-Xa levels are 0.3–0.35 —U/mL, then 3rd or subsequent dialysis dose should be 2500 units. For patients weighing <55 kg use 1500 unitsIf plasma anti-Xa levels are 0.35–0.4 —U/mL, then 3rd or subsequent dialysis dose should be 2000 units. For patients weighing <55 kg use 1500 units.If plasma anti-Xa levels are >0.4 U/mL, —then do not give any danaparoid before dialysis. However, if fibrin threads form in the bubble chamber, then the patient may be given 1500 units IV bolus (irrespective of the patient’s weight)During dialysis the plasma anti-Xa level should be between 0.5–0.8 U/mLIf needed take a blood sample prior to every dialysis and during dialysis (at 30 minutes and at 4 hours)Alternative regime for

HD : (New Zealand data sheet): infusion of 600 units/hour for 4 hours then 200–600 units/hour to maintain anti-Xa levels of 0.5–1 U/mL. If patient <55 kg then use 400 units/hour for 4 hours then 150–400 units/hourProtamine is no use as an antidote for bleeding complications. If no anti-Xa monitoring is available then the first 4 dialysis sessions should have pre-dialysis IV bolus of 3750, 3750, 3000 and 2500 units respectively, then 2500 units thereafter. Take blood sample prior to 4th and 7th dialysis to ensure there is no accumulationOozing from puncture sites has been noted 24–36 hours post doseFor CVVH, an initial bolus of 750 units followed by an infusion of 0.7–2 units/kg/hr can be given. (Wester JPJ. Guidelines for anticoagulation with danaparoid sodium and lepirudin in continuous venovenous hemofiltration.

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

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