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Data Sheet

Fraxiparine® INJECTION

Nadroparin Calcium 9,500 IU anti-Xa (AXa)

per 1.0 mL solution for injection.

Bioavailability is almost complete (around 98%).

Anti-Xa (AXa) denotes anti factor Xa activity. The ratio of anti-Xa to anti-IIa activity is 2.5 to 4.0.

Indications

Prophylaxis against thromboembolic disorders, especially those associated with general or orthopaedic surgery.Treatment of thromboembolic disorders. Prevention of clotting during haemodialysis.

Dosage and Administration

Administration

The sponsor (pharmaceutical company) of thisproduct has advised Medsafe that this product haseither been discontinued or is no longer marketed inNew Zealand.Therefore this Data Sheet may not be up to date.Medsafe has elected to leave it on this web sitebecause supplies of this product may still beavailable, and health professionals should continue tohave access to this product information in the interim.You may be able to find a more current Data Sheetcontaining the same medicine by returning to the mainData Sheet page and searching by ingredient name.

Presentation

Fraxiparine is a sterile, clear preservative-free solution usually for subcutaneous injection containing NadroparinCalcium 9,500 IU AXa per 1.0 mL dissolved in water for injections.

Fraxiparine is a low molecular weight heparin made by depolymerisation of standard heparin. It is aglycosaminoglycan with a mean molecular weight around 4,500 daltons. It possesses a high ratio of anti-Xa activityto anti-IIa activity. Fraxiparine has both immediate and prolonged antithrombotic action.

Uses

Actions

Low molecular weight heparin.

Pharmacokinetics

Pharmacokinetics have been determined by measurement of plasma anti-Xa activity. The plasma peak occurs about3 hours after subcutaneous injection. The elimination half-life is about 3.5 hours. Anti-Xa activity persists for at least18 hours after injection.

Usually by subcutaneous injection into the lateral abdominal wall. When Fraxiparine is given by subcutaneousinjection, the usual site for injection is the lateral abdominal wall, although the thigh may be used as an alternative.The needle should be inserted perpendicularly into a pinched-up fold of skin which should be held gently but firmlyuntil the injection has been completed. Do not rub the injection site. Fraxiparine is not intended for IM administration.

Removal of packaging prior to injection

To divide the syringes, carefully fold, several times, the twin pack so that the syringes are back to back, then slowlyusing an even pressure divide the two syringes starting from the plunger end of the pack.

To remove the syringe from its plastic packaging, gently tear the top backing paper completely from the plastic tray(starting from the plunger end), then allow the syringe to roll onto the palm of your other hand.

The rubber cap over the needle may appear to be asymmetrical on the syringe, however, this occurs duringpackaging and does not mean that the needle is bent.

2.

3.

4.

Dosage

Prophylaxis of thromboembolic disorders:

General prophylaxis

Fraxiparine should be given as a single daily dose of 0.3 mL (2,850 IU AXa) for at least 7 days and in all casesthroughout the risk period until the patient is ambulant. For surgical patients the first dose should be given 2 to 4hours pre-operatively.

Orthopaedic surgery

Initial doses should be given 12 hours before surgery and 12 hours after the end of surgery. These and subsequentonce daily doses should be adjusted to body weight based on Table 1. Treatment should be for at least 10 days and

Preparation of syringe for subcutaneous injection

To remove the cap from the syringe needle:

Hold the syringe vertically (grey cap uppermost)

Hold the grey cap by its collar, and the syringe barrel in your other hand, then slowly rotate the syringe barrel gentlypulling downwards at the same time, until the needle is fully withdrawn from the cap.

Do not pull the cap upwards from the syringe - this may bend the needle.

Fraxiparine 0.2 mL, 0.3 mL and 0.4 mL prefilled syringes are intended for administration of unit dosages only. Theentire contents of the syringe should be injected. There may be a small air bubble in the syringe but this does nothave to be removed.

Fraxiparine 0.6 mL, 0.8 mL and 1.0 mL prefilled graduated syringes may be used to administer adjusted dosages.Hold the syringe vertically with the needle uppermost and ensure the air bubble is at the top of the syringe. Advancethe plunger to the volume/dosage required, expelling air and any excess.

Method for subcutaneous administration

A suitable site for injection is the subcutaneous tissue of the lateral abdominal wall, away from any wound orweight bearing site. Alternatively injection may be made into the thigh.

1.

Pinch a skin fold. Note: the use of alcohol may toughen the skin, making subsequent injection difficult.

Maintain the fold and insert the needle vertically to its full depth then inject Fraxiparine over 10 to 15 seconds.There may be a small air bubble in the barrel of the syringe but this does not have to be removed.

Still holding the skin fold, withdraw the needle vertically. Do not rub the site of injection. Fraxiparine is notintended for IM or IV administration.

should continue in all cases throughout the risk period until the patient is ambulant.

TABLE 1

Orthopaedic Surgery Volume To Be Injected Subcutaneously Once Daily

Body Weight (kg) Pre-Operatively and until Day 3 From Day 4 Onwards

<50 0.2 mL 0.3 mL

50-69 0.3 mL 0.4 mL

≥70 0.4 mL 0.6 mL

Treatment of thromboembolic disorders

Fraxiparine should be given subcutaneously twice daily for 10 days with the dose adjusted to body weight as shown

An additional smaller dose may be given during dialysis for sessions lasting longer than 4 hours. The dose insubsequent dialysis sessions should be adjusted as necessary according to observed effect.

Contraindications

Fraxiparine is contraindicated in patients hypersensitive to nadroparin, or who have a history of thrombocytopeniawith nadroparin (see Warnings and Precautions). Fraxiparine is also contraindicated in patients with an increased riskof haemorrhage including those with bleeding disorders (except for disseminated intravascular coagulation notinduced by heparin), organic lesions likely to bleed (such as active peptic ulceration), haemorrhagic cerebrovascularaccident or infective endocarditis.

in Table 2.

TABLE 2

Treatment Of Thromboembolic Disorders

Body Weight (kg) Volume to be Injected Subcutaneously Twice Daily

<50 0.4 mL

50-59 0.5 mL

60-69 0.6 mL

70-79 0.7 mL

80-89 0.8 mL

≥90 0.9 mL

Platelet count must be monitored throughout Fraxiparine treatment (see Warnings and Precautions)

Prevention of Clotting During Haemodialysis

Optimisation of dosage is required for each individual patient. Fraxiparine is usually given as a single dose into thearterial line at the start of each session. For patients without increased risk of haemorrhage the following initialdoses are suggested in Table 3:

TABLE 3

Prevention of Clotting During Haemodialysis

Body Weight (kg) Volume to be Injected into Arterial Line at Start of Dialysis

<50 0.3 mL

50-69 0.4 mL

≥70 0.6 mL

Warnings and Precautions

Because of the possibility of heparin induced thrombocytopenia, regular monitoring of platelet count is recommendedthroughout the course of treatment with Fraxiparine.

Rare cases of thrombocytopenia, occasionally severe, have been reported. Treatment should be discontinuedimmediately. The thrombocytopenia may be associated with arterial or venous thrombosis, exacerbation of thepre-existing thrombosis or disseminated intravascular coagulation, the platelet count should be assessed if theseevents are suspected. These events are probably immunological in origin and in the case of a first course of heparintreatment usually occur between the 5th and 21st day of therapy but may occur much earlier if there is a history ofheparin-related thrombocytopenia.

Where there is a history of thrombocytopenia occurring with another heparin, careful clinical monitoring includingassessment of platelet count at least once daily should be undertaken and treatment should be discontinuedimmediately if thrombocytopenia occurs (since early recurrences have been reported).

Therefore, the concomitant prescription of central nervous blockade or spinal puncture and anti-coagulant therapyshould be decided only after careful individual benefit/risk assessment in the following situations:

in patients already treated with anticoagulant therapy, the benefits of central nervous blockade or spinalpuncture must be carefully balanced against the risks.in patients planned to undergo elective surgery with central nervous blockade or spinal puncture, the benefitsof anticoagulant therapy must be carefully balanced against the risks.

In the case of patients with lumbar puncture, spinal anaesthesia and epidural anaesthesia, a sufficient interval of timeshould be observed between the injection of Fraxiparine and the insertion or the removal of the spinal/epiduralcatheter or needle.

Where concomitant prescription of central nervous blockade or spinal puncture and LMWH is used, patients shouldbe frequently monitored for signs and symptoms of neurological impairment, with urgent treatment to be started if

Substitution with Fraxiparine may be considered where thrombocytopenia has occurred with another heparinpreparation but careful monitoring should be undertaken at least once a day. There have been reports of the initialthrombocytopenia continuing after substitution with Fraxiparine; in such cases treatment should be discontinued assoon as possible. In vitro aggregation tests are of limited value and expert advice should be obtained.

Reduced doses should be considered in patients with moderate to severe renal insufficiency. Administer with cautionin cases of hepatic insufficiency, severe arterial hypertension, history of peptic ulceration or other organic lesion likelyto bleed, vascular disorder of the chorio-retina and in the post-operative period following surgery of the brain, spinalcord or eye.

The concomitant use of aspirin, other salicylates, non steroidal anti-inflammatory drugs, ticlopidine or anti-plateletagents represents a relative contraindication for Fraxiparine administration.

The characteristics of Fraxiparine are different from those of other proprietary Low Molecular Weight Heparinstherefore switching to an alternative product is not recommended during a course of treatment.

Hyperkalaemia

Heparin can suppress adrenal secretion of aldosterone leading to hyperkalaemia, particularly in patients with araised plasma potassium or at risk of increased plasma potassium levels (such as patients with diabetes mellitus,chronic renal failure, pre-existing metabolic acidosis or taking drugs that may increase plasma potassium levels ie.ACE Inhibitors, NSAIDs).

The risk of hyperkalaemia appears to increase with duration of therapy but is usually reversible. Plasma potassiumshould be monitored in patients at risk.

Spinal/epidural haematomas

The risk of spinal/epidural haematomas is increased by indwelling epidural catheters or by concomitant use of otherdrugs which may affect haemostasis such as NSAIDs, platelet inhibitors or other anticoagulants. The risk alsoappears to be increased by traumatic or repeated epidural or spinal puncture.

neurological compromise is noted.

Use in Pregnancy

Category C.Studies in animals have not shown any teratogenic of foetotoxic effects. However, there is only limited informationand clinical data concerning transplacental passage. The use of Fraxiparine in pregnancy is not advised unless nosafer alternative can be found.

Use in Lactation

Due to limited information on excretion in breast milk and subsequent absorption in the neonate, use of Fraxiparineduring breast feeding is not advised.

Fraxiparine should be administered with caution in patients receiving other drugs which increase the risk of bleedingsuch as oral anticoagulants, aspirin, non steroidal anti-inflammatory drugs, other anti-platelet agents, corticosteroidsand dextrans. Where concomitant use is necessary (such as during transfer from Fraxiparine to oral anticoagulanttherapy), careful clinical and biological monitoring should be undertaken.

Overdosage

Haemorrhage is the major clinical sign of overdosage. The platelet count and other coagulation parameters shouldbe measured. Minor bleeding rarely requires specific therapy, and reducing or delaying subsequent doses ofFraxiparine is usually sufficient.

The use of protamine sulphate should be considered only in more serious cases. It largely neutralises theanticoagulant effect of Fraxiparine, but some anti-Xa activity will remain.

Adverse Effects

In common with other heparin preparations:

Haemorrhage manifestations at various sites, more frequent in patients with other risk factors (seeContraindications).

Some rare cases of thrombocytopenia, sometimes thrombogenic, have been reported (see Warnings andPrecautions).

Some rare cases of cutaneous necrosis, usually occurring at the injection site, have been reported. They arepreceded by purpura or infiltration or painful erythematous blotches, with or without systemic illness. Treatmentshould be discontinued immediately.

Occasional cases of small haematoma at the injection site, pain and bruising are minimised by careful injectiontechnique. In some cases, the emergence of firm nodules may be noted. These nodules usually disappear after afew days.

Rare cutaneous or generalised hypersensitivity reactions, including angioedema, sometimes requiring discontinuationof treatment.

Raised transaminases, usually transient.

Occasional cases of reversible hypoaldosteronism have been reported, either asymptomatic or associated withhyperkalemia and/or hyponatremia (see Warnings and Precautions).

Eosinophilia, which is reversible after treatment discontinuation.

Rare cases of priapism.

Interactions

6 mg of protamine sulphate neutralises about 0.1mL (950 IU AXa) Fraxiparine.

Pharmaceutical Precautions

Shelf life - 3 years. Store below 25°C but do not freeze. Do not refrigerate as cold injections may be painful. Discardany unused portion of each syringe. Do not mix with other preparations. Do not use after the expiry date shown onthe carton.

Medicine Classification

Prescription Medicine.

Date of Preparation

Date: 28 October 2004

Issue: 1

FRAXIPARINE® is a trade mark of the GlaxoSmithKline group of companies.

© This data sheet is copyrighted to GlaxoSmithKline and may be reproduced but not altered in any way.

Package Quantities

Disposable prefilled glass single use syringes containing nadroparin calcium 9,500 IU AXa per 1.0 mL in water forinjections with sufficient Calcium Hydroxide or dilute Hydrochloric acid to adjust the pH to between 5 and 7.5.

Volume Type of Syringe Nadroparin Calcium

(IU anti-Xa)

Pack size

0.2 mL Ungraduated 1,900 2 and 10

0.3 mL Ungraduated 2,850 2 and 10

0.4 mL Ungraduated 3,800 2 and 10

0.6 mL Graduated 5,700 2 and 10

0.8 mL Graduated 7,600 10

1.0 mL Graduated 9,500 10

Name and Address

GlaxoSmithKline NZ LtdQuay TowerCnr Albert & Customs StreetsPrivate Bag 106600DowntownAucklandNEW ZEALAND

Telephone (09) 367 2900Facsimile (09) 367 2506