New Zealand - English - Medsafe (Medicines Safety Authority)
Page 1 of 11
NEW ZEALAND DATA SHEET
DBL™ Heparin Sodium Injection BP
Solution for Injection, 1,000 IU/mL, 5,000 IU/mL and 25,000 IU/mL.
QUALITATIVE AND QUANTITATIVE COMPOSITION
Heparin Sodium Injection 1,000 IU/mL, 5,000 IU/mL and 25,000 IU/mL is prepared from
porcine intestinal mucosa and is free from pyrogenic substances.
Excipient(s) with known effect
Benzyl alcohol (vials only)
For the full list of excipients, see section 6.1.
DBL Heparin Sodium Injection is a colourless or straw coloured sterile solution for injection:
available as ampoules (1,000 IU/mL, 5,000 IU/mL and 25,000 IU/mL) or vials (1,000 IU/mL
only). The pH of the injection ranges between 5.0 and 8.0.
4.1 Therapeutic indications
Heparin is indicated for the prophylaxis and treatment of thromboembolic disorders such as
thrombophlebitis, pulmonary embolism and occlusive vascular disease. It is also used to
prevent thromboembolic complications arising from cardiac and vascular surgery, frostbite,
dialysis and other perfusion procedures. Heparin is also used as an anticoagulant in blood
4.2 Dose and method of administration
Heparin may be given by intermittent intravenous injection, intravenous infusion or deep
subcutaneous injection. It should not be given intramuscularly because of the danger of
Low dose prophylaxis against postoperative venous thromboembolism: The usual dose is
5,000 units by deep subcutaneous injection 2 hours before surgery and repeated every 8 to 12
hours for 7 days or longer until the patient is fully ambulatory.
Page 2 of 11
Treatment of established venous thrombosis or pulmonary embolism. Treatment may be
given by the following routes:
Continuous intravenous infusion: a bolus dose of 5,000 units may be given initially
followed by an infusion of 20,000 to 40,000 units over 24 hours.
Intermittent intravenous injection: an initial dose of 10,000 units followed by 5,000 to
10,000 units every 4 to 6 hours may be given.
Deep subcutaneous injection: the usual dose is 5,000 units injected intravenously
followed by subcutaneous injection of 10,000 units 8 hourly or 15,000 units 12
A suggested dosage is 50 units/kg bodyweight initially by I.V. infusion followed by 100
units/kg bodyweight every 4 hours according to the clotting time.
For single patient use. Use once only and discard any residue.
Heparin therapy is contraindicated in patients who are hypersensitive to the drug.
It should not be used in the following cases:
in the presence of actual or potential haemorrhagic states, eg. haemophilia, ascorbic
acid deficiency, increased capillary fragility, hiatus hernia, neoplasms, retinopathy,
bleeding haemorrhoids or other organic lesions likely to bleed;
haemorrhagic vascular accident;
immediate postpartum period;
subacute bacterial endocarditis or acute infectious endocarditis;
gastric or duodenal ulcers or other ulcerative conditions which may have a tendency
to haemorrhage, eg. ulcerative colitis;
advanced renal or hepatic disease;
during and immediately after spinal or major surgery, especially those involving the
brain, eye or spinal cord;
severe thrombocytopenia or a history of thrombocytopenia with any kind of heparin
or with pentosan polysulfate;
patients in whom suitable blood coagulation tests, eg 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).
Page 3 of 11
administered to premature or low birth-weight neonates. Benzyl alcohol has been associated
with deaths in these patients. Heparin Injection ampoules do not contain benzyl alcohol.
4.4 Special warnings and precautions for use
Heparin should not be given by intramuscular injection, due to the risk of haematoma
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
The risk of these
events is increased by the
use of indwelling epidural catheters
administration of analgesia or by concomitant use of drugs 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 patients anticoagulated or to be anticoagulated for thromboprophylaxis.
As heparin is derived from animal tissue, it should be used with caution in patients with a
history of allergy or asthma. Before a therapeutic dose is given to such a patient, a trial dose
of 1,000 units may be advisable.
Heparin should be used with extreme caution in patients with continuous tube drainage of the
stomach or small intestine.
Any action which may cause vascular injury, with the exception of necessary intravenous or
subcutaneous injections, should be avoided where possible.
Outpatients should be warned of the haemorrhagic risks in case of possible trauma.
Heparin should be administered with caution to patients with hepatic or renal disease,
hypertension, a history of ulcers, or with vascular diseases of the chorio-retina. Dosage
reduction may be necessary in patients with advanced renal or hepatic disease.
thrombophlebitis, infections with thrombosing tendencies, myocardial infarction, cancer and
in post-surgical patients.
Heparin therapy increases the risk of localised haemorrhage during and following oral
therefore be advisable prior to oral surgery.
Page 4 of 11
Heparin therapy should be monitored carefully. Adequate monitoring of therapy reduces the
risk of overdosage and consequent risk of haemorrhage and is an important guide to the
development of serious adverse reactions such as delayed onset thrombocytopenia.
Platelet counts should be monitored in patients receiving heparin for more than a few days,
since heparin may cause thrombocytopenia with severe thromboembolic complications.
Heparin should be discontinued if thrombocytopenia develops.
Patients on heparin may rarely develop Heparin-induced Thrombosis-Thrombocytopenia
Syndrome (HITTS or “white clot syndrome”): new thrombus formation in association with
thrombocytopenia, as a result of irreversible platelet aggregation. This may lead to severe
thromboembolic complications such as skin necrosis, gangrene of the extremities, myocardial
infarction, pulmonary embolism and stroke. Heparin administration should therefore be
discontinued if a patient develops new thrombosis in association with thrombocytopenia.
These effects are probably of immuno-allergic nature, and occur mostly between the 5th and
21st day of treatment in patients being treated with heparin for the first time.
Delayed Onset of HIT and HITT
Thrombosis can occur up to several weeks after the discontinuation of heparin therapy.
Patients presenting with thrombocytopenia or thrombosis after discontinuation of heparin
should be evaluated for HIT and HITT.
Use in geriatrics
Dosage should be reduced in elderly people. Patients aged 60 years or over, especially
women, may be more susceptible to haemorrhage during heparin therapy.
DBL Heparin Sodium Injection BP vials contain benzyl alcohol as a preservative, and should
not be administered to premature or low birth-weight neonates (see section 4.3). DBL
Heparin Sodium Injection ampoules do not contain benzyl alcohol.
Effects on laboratory tests
Significant elevations of AST and ALT levels have occurred in a high percentage of patients
(and healthy subjects) who have received heparin. Since AST determinations are important in
the differential diagnosis of myocardial infarction, liver disease and pulmonary embolism,
rises that might be caused by drugs (like heparin) should be interpreted with caution.
4.5 Interaction with other medicines and other forms of interaction
Heparin may prolong the one-stage prothrombin time. Therefore, when heparin is given with
oral anticoagulants such as warfarin, a period of at least 5 hours after the last intravenous
dose, or 24 hours after the last subcutaneous dose of heparin, should elapse before blood is
drawn for a valid prothrombin time to be obtained.
Drugs which affect platelet function, eg aspirin, other salicylates and other non-steroidal anti-
inflammatory agents, dextran, dipyridamole and systemic corticosteroids, may increase the
Page 5 of 11
risk of haemorrhage and should be used with caution in patients receiving heparin. Where
concomitant use cannot be avoided, careful clinical and biological monitoring should be
probenecid, vitamin K antagonists, cytostatic agents, cephamandole, valproic acid and. High
doses of penicillins, some contrast media, asparaginase and epoprostenol may also affect the
coagulation process and increase the risk of haemorrhage.
Concomitant use of thrombolytic agents such as alteplase, streptokinase or may also increase
the risk of haemorrhage.
Antihistamines, digitalis glycosides, tetracyclines, nicotine, ascorbic acid and quinine may
reduce the anticoagulant effect of heparin.
Glyceryl trinitrate has been reported to reduce the activity of heparin when both drugs are
administered simultaneously intravenously. This effect may be due to the presence of
interaction has been reported when the glyceryl trinitrate was administered immediately after
intravenous glyceryl trinitrate may be required.
Heavy alcohol drinkers are at greater risk of major heparin-associated bleeding than moderate
or non drinkers.
corticosteroids and insulin.
Heparin is incompatible with certain substances in aqueous solution. Reference to specialised
literature should be made to verify in which solution the incompatibility was noted. The
antihistamines, narcotic analgesics, phenothiazines and antibiotics.
4.6 Fertility, pregnancy and lactation
No data available.
Category C. The use of heparin in pregnancy has the usual risks for the mother, in particular
osteoporosis and thrombocytopenia. Although heparin does not cause malformations, an
increased incidence of human foetal loss and prematurity associated with haemorrhage has
Heparin is not distributed into milk and heparin therapy is therefore not contraindicated in
women who are breast-feeding. However, administration to breast-feeding women has rarely
Page 6 of 11
been reported to cause rapid (within 2 to 4 weeks) development of severe osteoporosis and
4.7 Effects on ability to drive and use machines
No data available.
4.8 Undesirable effects
ecchymoses to major haemorrhagic complications. An overly prolonged clotting time or
minor bleeding can usually be controlled by discontinuing the heparin (see section 4.9). The
occurrence of significant gastrointestinal or urinary tract bleeding during heparin therapy may
indicate the presence of an underlying occult lesion.
Bleeding can occur at any site, but some specific haemorrhagic complications can be difficult
a) Adrenal haemorrhage with resultant acute adrenal insufficiency has occurred during
anticoagulant therapy. Anticoagulant treatment should be discontinued in patients who
develop signs and symptoms of acute adrenal haemorrhage and insufficiency. Plasma
initiated promptly, before laboratory confirmation of the diagnosis, as any delay in
treatment may result in the patient’s death.
b) Ovarian (corpus luteum) haemorrhage may be fatal if unrecognised.
c) Retroperitoneal haemorrhage.
Thrombocytopenia has been reported to occur in up to 30% of patients receiving heparin.
Although the thrombocytopenia is often mild and of no obvious clinical significance, it may
be accompanied by severe thromboembolic complications such as skin necrosis, gangrene of
the extremities, myocardial infarction, pulmonary embolism and stroke (see section 4.4).
Certain episodes of painful, ischaemic and cyanosed limbs have in the past been attributed to
allergic vasospastic reactions; however these reactions may instead be complications of
Delayed onset thrombocytopenia is also a possible complication of heparin therapy. If this
occurs, the drug should be withdrawn immediately.
Skin necrosis has infrequently been reported at injection sites. It is thought to be a localised
manifestation of heparin-induced platelet aggregation and thrombosis, and should be taken as
a warning sign in patients who develop it. Heparin should be discontinued immediately.
Local irritation, erythema, mild pain, haematoma or ulceration may follow deep subcutaneous
injection. The emergence of firm nodules may be noted in some cases; however, these
nodules usually disappear after a few days.
Allergic reactions to heparin occur rarely. Hypersensitivity may be manifested by pruritus,
vomiting and anaphylactoid reactions, including angioedema and shock. The most common
Page 7 of 11
manifestations are urticaria, chills and fever. Itching and burning, especially on the plantar
side of the feet, may occur.
Osteoporosis complicated by spontaneous bone fracture has been reported with prolonged use
of large doses of heparin.
Alopecia and priapism have occurred rarely in patients treated with heparin.
Suppression of aldosterone synthesis with hyperkalaemia and/or metabolic acidosis have
been noted in patients at risk (eg. diabetes, renal failure).
Suppression of renal functions has occurred following long-term, high dose administration of
Significant elevations of AST and ALT levels have occurred in a high percentage of subjects
who have received heparin (see section 4.4).
Hypereosinophilia, which is reversible on discontinuation of heparin treatment, has occurred.
Rebound hyperlipidaemia has been reported following discontinuation of heparin therapy has
also been reported.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It
haemorrhage. Examples of types of bleeding observed in patients receiving heparin sodium
ecchymoses, epistaxis, haematemesis, intracranial haemorrhages, pulmonary haemorrhage
and other haemorrhage.
Slight haemorrhage due to overdosage can usually be treated by withdrawing the drug.
Severe bleeding may be reduced by the administration of protamine sulphate. Protamine
sulphate should be administered intravenously. To avoid circulatory side effects, the injection
should be given slowly at a rate of 5 mL over a period of about 10 minutes. Not more than
50 mg should be given at any one time. The dose of protamine sulphate required is governed
by the amount of heparin that has to be neutralised; approximately 1mg of protamine sulphate
neutralises 110 units of heparin (mucous) that has been injected in the previous 15 minutes.
Since heparin is being continuously excreted, the dose should be reduced as more time
elapses after the heparin injection. Ideally, the dose of protamine sulphate required should be
Page 8 of 11
accurately determined by titration methods as the antagonist itself, in gross excess, acts as an
For advice on the management of overdose please contact the National Poisons Centre on
0800 POISON (0800 764766).
5.1 Pharmacodynamic properties
Mechanism of action
Heparin is a naturally occurring mucopolysaccharide which inhibits the clotting of blood in
vitro and in vivo. It enhances the rate at which antithrombin III neutralises thrombin and
activated factor X (X
). Antithrombin III also neutralises other activated coagulation factors,
e.g. factors IX, XI, XII and plasmin.
With low-dose heparin therapy, anticoagulation appears to result from neutralisation of X
which prevents the conversion of prothrombin to thrombin. With full dose heparin therapy,
anticoagulation appears to result primarily from neutralisation of thrombin which prevents
the conversion of fibrinogen to fibrin. Full-dose heparin therapy also prevents the formation
of a stable fibrin clot by inhibiting activation of fibrin stabilising factor.
5.2 Pharmacokinetic properties
Heparin is not absorbed from the gastrointestinal tract and must be administered parenterally.
Its onset of action is immediate following I.V. administration. There may be considerable
variation among patients in the extent of absorption following deep subcutaneous injection of
heparin; however, the onset of activity usually occurs within 20-60 minutes.
Heparin is extensively bound to plasma proteins. It does not cross the placenta and is not
distributed into milk.
The metabolic fate of heparin is not fully understood. No biotransformation in plasma or
liver, nor any renal excretory mechanism has been identified as primarily responsible for
reticuloendothelial system may play a role, or that heparin may be partially metabolised in
the liver. After administration of large doses intravenously, a small fraction of unchanged
drug is excreted in the urine.
5.3 Preclinical safety data
No data available.
No data available.
Page 9 of 11
Reproductive and developmental toxicity
No data available.
6.1 List of excipients
Water for injections
Water for injections
amiodarone, ampicillin sodium, benzylpenicillin sodium, cephalothin sodium, ciprofloxacin
hydrochloride, doxorubicin hydrochloride, droperidol, erythromycin lactobionate, gentamicin
sulphate, haloperidol lactate, hyaluronidase, hydrocortisone sodium succinate, kanamycin
hydrochloride, polymyxin B sulphate, promazine hydrochloride, promethazine hydrochloride,
tobramycin sulphate, vancomycin hydrochloride and vinblastine sulphate. Heparin sodium
hydrochloride and nicardipine hydrochloride. Admixture with glucose can have variable
effects. Incompatibility has been reported between heparin and fat emulsion.
6.3 Shelf life
Ampoules: 36 months
Vials: 24 months
6.4 Special precautions for storage
Store below 25°C.
Page 10 of 11
6.5 Nature and contents of container
Ampoules, glass (bacteriostat free)
DBL Heparin Sodium Injection BP
1,000 IU/1 mL
5's and 50's
5,000 IU/0.2 mL
5's and 50's
5,000 IU/1 mL
5's and 50's
5,000 IU/5 mL
5's and 50's
25,000 IU/5 mL
Not all pack sizes may be marketed
Vials, glass (with 1.0% v/v benzyl alcohol as bacteriostat)
DBL Heparin Sodium Injection BP
35,000 IU/35 mL
6.6 Special precautions for disposal
Any unused medicine or waste material should be disposed of in accordance with local
Pfizer New Zealand Limited
P O Box 3998
Auckland, New Zealand, 1140
Toll Free Number: 0800 736 363
DATE OF FIRST APPROVAL
06 March 1980
10. DATE OF REVISION OF THE TEXT
22 November 2019
Page 11 of 11
Summary table of changes
Summary of new information
Included statement regarding use in one patient on one occasion only
Addition of hypersentivity information
Included information about neuraxial intervention