Properties
Tinzaparin sodium is a low molecular weight heparin
produced by enzymatic depolymerization of
conventional heparin.
The molecular mass is between 1,000 and 14,000 dalton,
with a peak maximum molecular mass of approx. 4,500
dalton. Tinzaparin sodium is an anti-thrombotic agent.
innohep® has a bioavailability of about 90% following
subcutaneous injection. The absorption half-life is 200
minutes, peak plasma activity being observed after
4–6 hours.
The elimination half-life is about 80 minutes. Tinzaparin
sodium is eliminated, primarily with the urine, as
unchanged drug.
The pharmacokinetics/pharmacodynamics of innohep®
are monitored by anti-Xa activity. There is a linear doseresponse
relationship between plasma activity and the
dose administered.
The biological activity of innohep® is expressed in
international units anti-Xa.
Indications
Treatment of deep-vein thrombosis and pulmonary
embolism.
Prevention of postoperative deep-vein thrombosis in
patients undergoing general and orthopaedic surgery.
Prevention of clotting in in-dwelling intravenous lines
for extracorporeal circulation and haemodialysis.

Special precautions
innohep® should be given with caution to patients with
hepatic insufficiency. Precaution is recommended in
the treatment of patients with severe renal impairment
(creatinine clearance < 30 ml/min).
Precaution is recommended in the treatment of elderly
patients with renal impairment. Renal function should
be assessed and in patients with severe renal
impairment (creatinine clearance < 30 ml/min),
monitoring of anti-factor Xa activity should be
considered.
innohep® should not be administered by intramuscular
injection due to risk of local haematoma formation.
Patients receiving innohep® concurrently with spinal or
epidural anaesthesia should be closely monitored for
signs or symptoms of neurological injury.
Interactions
Concomitant administration of other drugs affecting
haemostasis, e.g. vitamin K antagonists and dextran,
may enhance the anticoagulant effect of innohep®.
Use during Pregnancy and Lactation
Data on a number (637) of exposed pregnancies
indicate no additional risk of tinzaparin on pregnancy or
on the health of the foetus / new-born child. No
transplacental passage was demonstrated in two (2)
clinical studies. Data from sequential pharmacokinetic
monitoring in 55 pregnancies suggest that
pharmacokinetic properties of tinzaparin do not differ
from the non-pregnant state.
Tinzaparin is not recommended for use in pregnant
women with prosthetic heart valves.
Caution should be exercised when prescribing tinzaparin to
pregnant women.
There are no data available concerning lactation.
For vials only:
Cases of "Gasping Syndrome" have occurred in
premature infants when large amounts of benzyl alcohol
have been administered (99-404 mg/Kg/day). Despite the
low content of benzyl alcohol in the vials (10 mg per ml),
as it may cross the placenta the use of innohep®
formulations containing benzyl alcohol is not
recommended during pregnancy.
Incompatibilities
innohep® is compatible with isotonic sodium chloride
(9 mg/ml) or isotonic glucose (50 mg/ml). It should not be
admixed with other infusion fluids.
 

Dosage
Treatment of DVT and PE:
The recommended dose is 175 IU anti-Xa/kg bodyweight
s.c. once daily.
Thromboprophylaxis in patients with moderate risk of
thrombosis (general surgery):
On the day of operation 3,500 IU anti-Xa s.c. 2 hours
before surgery and postoperatively once daily 3,500 IU
anti-Xa for 7–10 days.
Thromboprophylaxis in patients with high risk of
thrombosis (e.g. total hip replacement):
On the day of operation 4,500 IU anti-Xa s.c. 12 hours
before surgery or 50 IU anti-Xa/kg body-weight s.c.
2 hours before surgery and then once daily until the
patient has been mobilized.
For short-term haemodialysis (less than 4 hours):
A bolus dose of 2,000–2,500 IU anti-Xa into the arterial
side of the dialyser (or intravenously) at the beginning of
dialysis.
Long-term haemodialysis (more than 4 hours):
A bolus dose of 2,500 IU anti-Xa into the arterial side of
the dialyser (or intravenously) at the beginning of
dialysis, followed by an infusion of 750 IU anti-Xa /hour.
Dose adjustment: Increase or decrease of the bolus
dose, if required, can be made in steps of 250–500 IU
anti-Xa until a satisfactory response is obtained.
Elderly:
Renal function should be assessed with e.g. the
Cockcroft-Gault formula to estimate creatinine
clearance levels.
No dose reduction is needed in elderly patients with
normal renal function. (See Special precautions).
Renal impairment:
No dose reduction is needed in patients having
creatinine clearance levels down to 20 ml/min.
However, precaution is recommended when treating
patients with severe renal impairment (creatinine
clearance < 30 ml/min). (See Special precautions).

Overdose
An overdose of innohep® may be complicated by
haemorrhage. At recommended doses there should be
no need for an antidote, but in the event of accidental
administration of an overdose, the effect of innohep®
can be reversed by intravenous administration of 1%
protamine sulphate solution.
The dose of protamine sulphate required per
neutralization should be accurately determined by
titrating with the plasma of the patient. As a rule, 1 mg
of protamine sulphate neutralizes the effect of 100 IU
anti-Xa of tinzaparin.

Instructions for use of the innohep® syringes:
Wash your hands before you inject the medicine.
Wipe clean the skin around the injection site with spirit
and let it dry – do not rub.
Subcutaneous injection of innohep® should be carried
out according to the following steps:

1. Open the tube bending the
coloured lid all the way back
and remove the syringe.
Inspect the content of the
syringe before you use it. If
you observe cloudiness or
precipitate in the medicine, do
not use it but take another
syringe. The medicine may
turn yellow during storage but
can still be used if the solution
is clear.
2. Bend the safety device down
away from the cap on the
needle.
3. Remove the protective needle
cap without bending the
needle. Adjust the syringe to
the dose prescribed by your
doctor. Remove the remaining
solution by pressing the
plunger in vertical position.
Do not pull back the plunger
and do not press out the air
bubble. If the air bubble is not
placed right by the plunger,
then tap lightly on the syringe
until the air bubble is in place.
4. Hold a skin fold loosely
between thumb and index
finger of one hand and with
the other hand insert the
needle vertically at the skin
fold, at a right angle to the
skin.
5. Slowly inject the required
dose into the fatty tissue of
e.g. the abdominal skin, the
extensor sides of the thigh,
lower back or upper arm.
Wait a few seconds to give
the solution time to distribute
before you remove the needle
and release the skin fold.
6. Wipe off any blood with a tissue. Choose a different
injection site next time (for instance, move from the
left to the right of the abdomen).
7. Bend the safety device back
to its original position so it is
now underneath the needle.
Then with the safety device
flat against a hard surface,
push downwards until the
needle locks into the device.
8. You can either place the used
syringe in the tube with the
needle downwards or you can
put the used syringe into a
sharps container. The syringe
is now secured, and the tube
or sharps container can be
handed over for destruction at
the hospital or by the pharmacist.

Adverse effects
innohep® is safe with regard to bleeding risks, when
applied at the doses recommended, provided that
patients with increased bleeding potential (bleeding
disorders, severe thrombocytopenia) are excluded or
treated with special care.
Priapism and skin necrosis have been reported in only
a few cases.

Storage condition
Do not store above 30°C.