Heparin sodium (Baxter)

Yüklə 84,45 Kb.
Pdf görüntüsü
ölçüsü84,45 Kb.

Heparin Sodium (Baxter) 


New Zealand Data Sheet 





Heparin Sodium Data Sheet 22 April 2015 


Page 1 of 12 



Heparin Sodium 2U/mL (in 0.9% Sodium Chloride) IV Infusion solution 

Chemical structure 


HEPARIN SODIUM intravenous infusion is a sterile, non-pyrogenic solution of heparin 

sodium (BP) standardised for use as an anticoagulant in 0.9% Sodium Chloride 

Intravenous Infusion buffered with 0.4mg citric acid monohydrate and 5.8mg sodium 

phosphate-dibasic dodecahydrate (Na




 12 H


O) per mL to pH range of 5.5 - 8.0.  

It is supplied in single dose VIAFLEX plastic bag containers for intravenous 


Heparin is a heterogenous mixture of variably sulphated polysaccharide chains 

composed of repeating units of disaccharides, D-glucosamine and L-iduronic acid or D- 

glucosamine and D-glucuronic acids. It is extracted from porcine intestinal mucosa. 

Upon complete hydrolysis, it yields a mixture of D-glucosamine, D-glucuronic acid, L- 

iduronic acid, acetic acid and sulphuric acid. Heparin is strongly acidic because of its 

content of covalently linked sulphate and carboxylic acid groups. In heparin sodium, the 

acidic protons of the sulphate units are partially replaced by sodium ions. 

Although others may be present, the main sugars occurring in heparin are: (1) α-L- 

iduronic acid 2-sulfate, (2) 2-deoxy-2-sulfamino-α-D-glucose 6-sulfate, (3) β-D- 

glucuronic acid, (4) 2-acetamido-2-deoxy-α-D-glucose, and (5) α-L-iduronic acid. These 

sugars are present in decreasing amounts, usually in the order (2) > (1) > (4) > (3) > (5), 

and are joined by glycosidic linkages, forming polymers of varying sizes. 


Mechanism of action 

Heparin inhibits reactions that lead to the clotting of blood and the formation of fibrin 

clots both 

in vitro


in vivo

.  Heparin acts at multiple sites in the normal coagulation 

system. Small amounts of heparin in combination with Antithrombin III (heparin cofactor) 

can inhibit thrombosis by inactivating activated Factor X and inhibiting the conversion of 

prothrombin to thrombin. Once active thrombosis has developed, larger amounts of 

heparin can inhibit further coagulation by inactivating thrombin and preventing 

Heparin Sodium (Baxter) 


New Zealand Data Sheet 





Heparin Sodium Data Sheet 22 April 2015 


Page 2 of 12 


conversion of fibrinogen to fibrin. Heparin also prevents the formation of a stable fibrin 

clot by inhibiting the activation of the fibrin stabilising factor. 

Bleeding time is usually unaffected by heparin. Clotting time is prolonged by full 

therapeutic doses of heparin; in most cases it is not measurably affected by low doses 

of heparin. 

Heparin does not have fibrinolytic activity; therefore it will not lyse existing clots. Clinical 

trials have not demonstrated the superiority of heparin in the maintenance of catheter 

patency over fluid not containing anticoagulant medication (eg. normal saline). 


HEPARIN SODIUM Intravenous Infusion is indicated as an anticoagulant in 

extracorporeal circulation, dialysis procedures, and as an aid in the maintenance of 

catheter patency. 


HEPARIN SODIUM should not be used in the following patients:  

With severe thrombocytopaenia; 

In whom suitable blood coagulation tests - e.g. the whole-blood clotting time, partial 

thromboplastin time etc. - cannot be performed at appropriate intervals (this 

contraindication refers to full-dose heparin; there is usually no need to monitor 

coagulation parameters in patients receiving low dose heparin); 

With an uncontrollable active bleeding state (see 



except when this is due to disseminated intravascular coagulation. 



White Clot syndrome


It has been reported that patients on heparin may develop new thrombus formation in 

association with thrombocytopaenia resulting from irreversible aggregation of platelets 

induced by heparin, the so-called "white clot syndrome". The process may lead to 

severe thromboembolic complications like skin necrosis, gangrene of the extremities 

that may lead to amputation, myocardial infarction, pulmonary embolism, stroke and 

possible death. Therefore, heparin administration should be promptly discontinued if a 

patient develops new thrombosis in association with thrombocytopaenia. 

Heparin Sodium (Baxter) 


New Zealand Data Sheet 





Heparin Sodium Data Sheet 22 April 2015 


Page 3 of 12 


Spinal/Epidural haematomas


When neuraxial anaesthesia (epidural/spinal anaesthesia) or spinal puncture is 

employed, patients anticoagulated or scheduled to be anticoagulated with 

unfractionated heparin or low molecular weight heparins/heparinoids for prevention of 

thromboembolic complications are at risk of developing an epidural or spinal 

haematoma which can result in long-term or permanent paralysis. 

The risk of these events is increased by the use of indwelling epidural catheters for 

administration of analgesia or by the concomitant use of medicines affecting 

haemostasis such as non-steroidal anti-inflammatory drugs (NSAIDS), platelet inhibitors, 

or other anticoagulants. The risk also appears to be increased by traumatic or repeated 

epidural or spinal puncture. 

Patients should be frequently monitored for signs and symptoms of neurological 

impairment. If neurological compromise is noted, urgent treatment is necessary.  The 

physician should consider the potential benefit versus risk before neuraxial intervention 

in patient's anticoagulated or to be anticoagulated for thromboprophylaxis. 

Heparin resistance


Increased resistance to heparin is frequently encountered in fever, thrombosis, 

thrombophlebitis, infections with thrombosing tendencies, myocardial infarction, cancer 

and in post-surgical patients. 


Haemorrhage can occur at virtually any site in patients receiving heparin. An 

unexplained fall in haematocrit, fall in blood pressure, or any other unexplained 

symptom should lead to serious consideration of haemorrhagic event. 

HEPARIN SODIUM should be used with extreme caution in disease states in which 

there is increased danger of haemorrhage. Some of the conditions in which increased 

danger of haemorrhage exists are: 


  Subacute bacterial endocarditis. Severe hypertension. 


  During and immediately following (a) spinal tap or spinal anaesthesia or  

(b) major surgery, especially involving the brain, spinal cord or eye. 


Conditions associated with increased bleeding tendencies, such as 

haemophilia, thrombocytopaenia, and some vascular purpuras. 


 Ulcerative lesions and continuous tube drainage of the stomach 

or small intestine. 


 Menstruation, liver disease with impaired hemostasis. 

Heparin Sodium (Baxter) 


New Zealand Data Sheet 





Heparin Sodium Data Sheet 22 April 2015 


Page 4 of 12 


Coagulation testing


When HEPARIN SODIUM is administered in therapeutic amounts, its dosage should be 

regulated by frequent blood coagulation tests. If the coagulation test is unduly prolonged 

or if haemorrhage occurs, HEPARIN SODIUM should be discontinued promptly (see 





Thrombocytopaenia has been reported to occur in patients receiving heparin with a 

reported incidence of 0 to 30%.  Platelet counts should be obtained at baseline and 

periodically during heparin administration.  Mild thrombocytopaenia (count greater than 



) may remain stable or reverse even if heparin is continued. However, 

thrombocytopaenia of any degree should be monitored closely. If the count falls below 



 or if recurrent thrombosis develops (see 


 below), the heparin 

product should be discontinued. If continued heparin therapy is essential, administration 

of heparin from a different organ source can be reinstituted with caution. 

Solutions containing sodium ions should be used with great care in patients with 

congestive heart failure, severe renal insufficiency, and in clinical states in which there 

exists oedema with sodium retention.  These solutions should also be used with caution 

in patients receiving corticosteroids or corticotropin. 

The intravenous administration of solutions can cause fluid and/or solute overloading 

resulting in dilution of serum electrolyte concentrations, over hydration, congested 

states or pulmonary oedema. The risk of dilutional states is inversely proportional to the 

electrolyte concentrations and volume of the infusion. The risk of solute overload 

causing congested states with peripheral and pulmonary oedema is directly proportional 

to the electrolyte concentrations and volume of the infusion. 

Excessive administration of potassium free solutions may result insignificant 


In patients with diminished renal function, administration may result in sodium retention. 

Heparin-induced Thrombocytopaenia (HIT) and Heparin-induced 

Thrombocytopaenia and Thrombosis (HITT) 

Heparin-induced Thrombocytopaenia (HIT) is a serious antibody-mediated reaction 

resulting from irreversible aggregation of platelets. HIT may progress to the 

development of venous and arterial thromboses, a condition referred to as Heparin-

induced Thrombocytopaenia and Thrombosis (HITT). Thrombotic events may also be 

the initial presentation of HITT. These serious thromboembolic events include deep vein 

thrombosis, pulmonary embolism, cerebral vein thrombosis, limb ischemia, stroke, 

myocardial infarction, mesenteric thrombosis, renal arterial thrombosis, skin necrosis, 

gangrene of the extremities that may lead to amputation, and possibly death. 

Heparin Sodium (Baxter) 


New Zealand Data Sheet 





Heparin Sodium Data Sheet 22 April 2015 


Page 5 of 12 


Once HIT or HITT is diagnosed or strongly suspected, all heparin sodium sources 

(including heparin flushes) should be discontinued and an alternative anticoagulant 

used.  Future use of heparin sodium, especially within 3 to 6 months following the 

diagnosis of HIT or HITTS, and while patients test positive for HIT antibodies, should be 


Immune-mediated HIT is diagnosed based on clinical findings supplemented by 

laboratory test confirming the presence of antibodies to heparin sodium, or platelet 

activation induced by heparin sodium.  A drop in platelet count greater than 50% from 

baseline is considered indicative of HIT.  Platelet counts begin to fall 5 to 10 days after 

exposure to heparin sodium in heparin-naïve individuals, and reach a threshold by days 

7 to 14.  In contrast, ‘rapid onset’ HIT can occur very quickly (within 24 hours following 

heparin sodium initiation), especially in patients with a recent exposure to heparin 

sodium (ie. previous 3 months).  Thrombosis development shortly after documenting 

thrombocytopaenia is a characteristic finding in almost half of the patients. 

Thrombocytopaenia of any degree should be monitored closely.  If the platelet counts 

fall below 100,000/mm


 or if recurrent thrombosis develops, the heparin product should 

be promptly discontinued and alternative anticoagulant considered if patients require 

continued anticoagulation. 

Delayed onset of HIT and HITT 

Heparin-induced Thrombocytopenia (HIT) and Heparin-induced Thrombocytopenia and 

Thrombosis (HITT) can occur up to several weeks after the discontinuation of heparin 

therapy. Patients presenting with thrombocytopaenia or thrombosis after discontinuation 

of heparin should be evaluated for HIT and HITT. 

Laboratory tests 

Periodic platelet counts; hematocrits, and tests for occult blood in stool are 

recommended during the entire course of heparin therapy, regardless of the route of 

administration (see 



Carcinogenesis, mutagenesis, impairment of fertility 

No long-term studies in animals have been performed to evaluate carcinogenic potential 

of heparin. Also, no reproduction studies in animals have been performed concerning 

mutagenesis or impairment of fertility. 

Use in pregnancy (Category C) 

Heparin does not cross the placental barrier. Animal reproduction studies have not been 

conducted with HEPARIN SODIUM. It is not known whether HEPARIN SODIUM can 

cause foetal harm when administered to a pregnant woman or can affect reproduction 

capacity. HEPARIN SODIUM should be given to pregnant women only if clearly needed. 

Heparin Sodium (Baxter) 


New Zealand Data Sheet 





Heparin Sodium Data Sheet 22 April 2015 


Page 6 of 12 


Use in lactation 

Heparin is not excreted in human milk. 

Paediatric use 

Safety and effectiveness in paediatric patients has not been established. 

Use in the elderly 

A higher incidence of bleeding has been reported in patients, particularly women, over 

60 years of age (see 


 above).  Clinical studies indicate 

that lower doses of heparin may be indicated in these patients. 


Oral anticoagulants 

HEPARIN SODIUM may prolong the one-stage prothrombin time. Therefore when 

HEPARIN SODIUM is given with dicumarol or warfarin sodium, a period of at least 5 

hours after the last intravenous dose, or 24 hours after the last subcutaneous dose 

should elapse before blood is drawn if a valid prothrombin time is to be obtained. 

Platelet inhibitors 

Medicines such as acetylsalicylic acid, dextran, phenylbutazone, ibuprofen, 

indomethacin, dipyridamole, hydroxychloroquine and others that interfere with platelet 

aggregation reactions (the main haemostatic defence of heparinised patients) may 

induce bleeding and should be used with caution in patients receiving HEPARIN 


Other interactions 

Digitalis, tetracyclines, nicotine or antihistamines may partially counteract the 

anticoagulant action of HEPARIN SODIUM. 

Drug/Laboratory tests interactions 


Significant elevations of aminotransferase (SGOT [S-

AST] and SGPT [S-ALT]) levels have occurred in a high percentage of patients (and 

healthy subjects) who have received heparin.  Since aminotransferase determinations 

are important in the differential diagnosis of myocardial infarction, liver disease, and 

pulmonary emboli, rises that might be caused by medicines (like heparin) should be 

interpreted with caution. 

Heparin Sodium (Baxter) 


New Zealand Data Sheet 





Heparin Sodium Data Sheet 22 April 2015 


Page 7 of 12 



1.  Haemorrhage 

Haemorrhage is the chief complication that may result from heparin therapy (see 


).  An overly prolonged clotting time or minor 

bleeding during therapy can usually be controlled by withdrawing the drug (see 



It should be appreciated that gastrointestinal or urinary tract 

bleeding during anticoagulant therapy may indicate the presence of an 

underlying occult lesion.

  Bleeding can occur at any site but certain specific 

haemorrhage complications may be difficult to detect: 

a.  Adrenal haemorrhage, with resultant acute adrenal insufficiency, has occurred 

during anticoagulant therapy. Therefore, such treatment should be discontinued 

in patients who develop signs and symptoms of acute adrenal haemorrhage and 

insufficiency. Initiation of corrective therapy should not depend on laboratory 

confirmation of the diagnosis, since any delay in an acute situation may result in 

a patient's death. 

b.  Ovarian (corpus luteum) haemorrhage developed in a number of women of 

reproductive age receiving short or long-term anticoagulant therapy. This 

complication, if unrecognised, may be fatal. 

c. Retroperitoneal haemorrhage. 

2.  Local Irritation 

Local irritation, erythema, mild pain, haematoma or ulceration may follow deep 

subcutaneous (intrafat) injection of HEPARIN SODIUM. These complications are much 

more common after intramuscular use, and such use is not recommended. 

3.  Hypersensitivity 

General hypersensitivity reactions have been reported, with chills, fever and urticaria as 

the most usual manifestations, and asthma, rhinitis, lacrimation, headache, nausea and 

vomiting, and anaphylactoid reactions, including shock, occurring more rarely. Itching 

and burning, especially on the plantar site of the feet, may occur. 

Thrombocytopaenia has been reported to occur in patients receiving heparin with a 

reported incidence of 0 - 30%. While often mild and of no obvious clinical significance, 

such thrombocytopaenia can be accompanied by severe thromboembolic complications 

such as skin necrosis, gangrene of the extremities that may lead to amputation, 

myocardial infarction, pulmonary embolism, stroke and possible death (see 


for Thrombocytopaenia, Heparin-induced Thrombocytopaenia(HIT) and Heparin-

induced Thrombocytopaenia and Thrombosis (HITT)


Heparin Sodium (Baxter) 


New Zealand Data Sheet 





Heparin Sodium Data Sheet 22 April 2015 


Page 8 of 12 


Certain episodes of painful, ischaemic, and cyanosed limbs have in the past been 

attributed to allergic vasospastic reactions. Whether these are in fact identical to the 

thrombocytopenia-associated complications remains to be determined. 

4.  Miscellaneous 

Osteoporosis following long term administration of high doses of heparin, cutaneous 

necrosis after systemic administration, suppression of aldosterone synthesis, delayed 

transient alopecia, priapism, and rebound hyperlipaemia on discontinuation of heparin 

sodium have also been reported. Significant elevations of aminotransferase (SGOT [S- 

AST] and SGPT [S-ALT]) levels have occurred in a high percentage of patients (and 

healthy subjects) who have received heparin. 



HEPARIN SODIUM is not effective by oral administration and should not be given orally. 

Parenteral drug products should be inspected visually for particulate matter and 

discolouration prior to administration. Use of a final filter is recommended during 

administration of all parenteral solutions, where possible. 

Do not administer unless solution is clear and seal is intact. 

Use in extracorporeal therapy 

The concentration of 2units/mL will suffice to prevent clotting on initiation of 

extracorporeal therapy by priming the devices with this solution. NOTE: A proper and 

effective heparinisation schedule must be initiated in the patient before and maintained 

throughout the procedures to prevent subsequent clotting and blood path obstruction. 

The particular manufacturer's directions for use of the dialyser or other extracorporeal 

apparatus must be referred to. The direction sheets for the use of therapeutic dosage 

forms of heparin must equally be referred to and adjusted to a given patients condition 

and response to achieve sustained, effective anticoagulation within clinically safe 

parameters. Both intermittent and continuous infusion of 5000, 10000 or 20000 units are 

employed for this purpose and are unrelated to the low dose heparin in this preparation 

that is directed at preparing the apparatus for initial use. 

Maintenance of catheter patency 

Although the rate for infusion of the 2units/mL formulation is dependent upon age, 

weight, clinical condition of the patient and the procedure being employed, an infusion 

rate of 3mL/hour has been found to be satisfactory. 

Periodic platelet counts; hematocrits, and tests for occult blood in stool are 

recommended during the entire course of heparin therapy, regardless of the route of 


Heparin Sodium (Baxter) 


New Zealand Data Sheet 





Heparin Sodium Data Sheet 22 April 2015 


Page 9 of 12 


All injections in VIAFLEX plastic containers are intended for administration using sterile 

equipment. It is recommended that the intravenous administration apparatus be 

replaced at least every 24 hours. 

Because dosages of this drug are titrated to response, no additives should be made to 




Bleeding is the chief sign of heparin overdosage. Nosebleeds, blood in urine or tarry 

stools may be noted as the first sign of bleeding. Easy bruising or petechial formations 

may precede frank bleeding. 


Neutralization of heparin effect:  

When clinical circumstances (bleeding) require 

reversal of heparinisation, protamine sulphate (1% solution) by slow infusion will 

neutralise HEPARIN SODIUM. No more than 50mg should be administered, very slowly 

in any 10-minute period. Each mg of protamine sulphate neutralises approximately 100 

USP heparin units. The amount of protamine required decreases over time as heparin is 

metabolised. Although the metabolism of heparin is complex, it may, for the purpose of 

choosing a protamine dose, be assumed to have a half-life of about 30 minutes after 

intravenous injection. 

Administration of protamine sulphate can cause severe hypotensive and anaphylactoid 

reactions. Because fatal reactions often resembling anaphylaxis have been reported, 

the drug should be given only when resuscitation techniques and treatment of 

anaphylactoid shock are readily available. 

For additional information the labelling of Protamine Sulphate Injection, USP products 

should be consulted. 

For information on the management of overdose, contact 0800 764 766 (0800 POISON) 

in New Zealand or the Poisons Information Centre on 12 11 26 in Australia. 


Instructions for use/handling 

Directions for use of Viaflex Plastic Container:  

WARNING Do not use plastic 

containers in series connections. Such use could result in air-embolism due to residual 

air being drawn from the primary container before administration of the fluid from the 

secondary container is completed. 

Heparin Sodium (Baxter) 


New Zealand Data Sheet 





Heparin Sodium Data Sheet 22 April 2015 


Page 10 of 12 


To Open:  

Tear over pouch down side at slit and remove solution container. Some 

opacity of the plastic due to moisture absorption during the sterilisation process may be 

observed. This is normal and does not affect the solution quality or safety. The opacity 

will diminish gradually. Check for minute leaks by squeezing inner bag firmly. If leaks 

are found discard solution as sterility may be impaired.  

Do not add supplementary medication. 

Preparation for Administration:  

Suspend container from eyelet support. 

Remove plastic protector from outlet port at bottom of container. 

Attach administration set. Refer to complete directions accompanying set. 


Inactive ingredients: sodium chloride, citric acid monohydrate, sodium phosphate-

dibasic dodecahydrate (Na






O), and water for injection.


Shelf life 

The shelf-life of the various presentations are as follows. 

Presentation Shelf 


HEPARIN SODIUM, 2 IU/mL in Viaflex IV 

Bag - 500 mL 

24 months from date of manufacture

HEPARIN SODIUM, 2 IU/mL in Viaflex IV 

Bag - 1000 mL 

24 months from date of manufacture

All product should be stored below 30°C. 

Not all pack sizes may be available. 

Heparin Sodium (Baxter) 


New Zealand Data Sheet 





Heparin Sodium Data Sheet 22 April 2015 


Page 11 of 12 


Package quantities 

HEPARIN SODIUM IV infusion is available in the following presentations:  

Code No. 

Name of the composition 

expressed in concentrations 

(g, mmol/Unit Vol) 








AHB0944 Active: 

heparin sodium (2000IU) 


sodium chloride (9, 154);  

citric acid 1.H


O (0.4, 1.9);  

sodium phosphate-dibasic 



O (5.8, 16.2) and  

water for injection to 1000mL 

378 (350)







AHB0953 Active: 

heparin sodium (1000IU) 


sodium chloride (4.5, 77); 

citric acid 1.H


O (0.2, 0.95); 

sodium phosphate-dibasic 



O (2.9, 8.1) and  

water for injection to 500mL 

378 (350) 





§Note: the osmolarity is a calculated figure, whilst the figures in brackets are approximate molality 



Prescription only medicine.  


Distributed in New Zealand by 

Baxter Healthcare Limited 

33 Vestey Drive 

Mt Wellington 


PO Box 14-062 



Heparin Sodium (Baxter) 


New Zealand Data Sheet 





Heparin Sodium Data Sheet 22 April 2015 


Page 12 of 12 


Distributed in Australia by 

Baxter Healthcare Pty Ltd 

1 Baxter Drive  

Old Toongabbie NSW 2146 



22 April 2015 




























Based on Australian PI approved on 20 December 2013 and RSI 2012 0821. 

Please refer to the Medsafe website (www.medsafe.govt.nz) for most recent data sheet. 

Baxter is trademark of Baxter International Inc. 

Yüklə 84,45 Kb.

Dostları ilə paylaş:

Verilənlər bazası müəlliflik hüququ ilə müdafiə olunur ©azkurs.org 2022
rəhbərliyinə müraciət

    Ana səhifə