MULTIPARIN 25 000 I.U./ML SOLUTION FOR INJECTION OR CONCENTRATE FOR SOLUTION FOR INFUSION

Active substance: HEPARIN

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• suffer from allergies or have previously had an allergic
reaction to low molecular weight (LMW) heparin. A small test
dose of heparin sodium injection may be given first.
HEPARIN SODIUM 5,000 I.U./ml solution for
injection or concentrate for solution for infusion Your doctor will check your blood if you receive treatment for
longer than five days and may do other blood tests if you have
HEPARIN SODIUM 25,000 I.U./ml solution for
major surgery.
injection or concentrate for solution for infusion
Your doctor will take particular care if:
Contains Preservative
• the patient is an infant or child under three years old
• you have an epidural or an anaesthetic given into the spine.
Read all of this leaflet carefully before you start taking
Taking other medicines
this medicine.
It is very important that you inform your doctor if you are taking,
- Keep this leaflet. You may need to read it again.
or have recently taken, any other medicines, including those
- If you have any further questions, please ask your doctor
medicines obtained without a prescription, as some medicines
or nurse.
- This medicine has been prescribed for you. Do not pass it on may affect the way heparin injection works. Taking some
to others. It may harm them, even if their symptoms are the medicines at the same time as heparin may mean you may be
likely to bleed more.
same as yours.
In particular, tell your doctor if you are taking any of the following:
The name of your medicine is either heparin sodium 5,000
• aspirin or other non-steroidal anti-inflammatory drugs (e.g
I.U./ml or heparin sodium 25,000 I.U./ml solution for injection or
diclofenac or ibuprofen)
concentrate for solution for infusion. In the rest of this leaflet it is • dextran solutions (used to treat shock)
called heparin injection.
• medicines which may interfere with the proper clotting of the
blood (e.g. dipyridamole, epoprostenol, clopidogrel or
In this leaflet:
streptokinase)
1. What heparin injection is and what it is used for
• cephalosporins, used to treat infections
2. Before you are given heparin injection
• medicines called ACE inhibitors used for high blood pressure
3. How heparin injection is given
and heart failure (e.g. captopril enalapril, lisinopril or ramapril)
4. Possible side effects
• medicines that may increase the potassium level in your
5. How to store heparin injection
blood (e.g. amiloride, triamterene, eplerenone or
6. Further information
spironolactone
1. WHAT HEPARIN INJECTION IS AND WHAT IT IS USED FOR • glyceryl trinitrate given into a vein (for coronary heart disease)
• aminoglycoside antibiotics (e.g. gentamicin, amikacin,
Heparin belongs to a group of drugs that are called anticoaguneomycin or tobramycin)
lants. These help to stop blood clotting. Heparin injection 5,000 • probenecid, used in the treatment of gout
I.U./ml or 25,000 I.U./ml is used in conditions where blood
vessels may become blocked by blood clots. It is therefore used If you need one of the above medicines your doctor may decide
to alter the dose of heparin injection or the other medication. If
to treat and prevent:
you have any doubts about whether this medicine should be
• blood clots in leg veins (deep vein thrombosis)
administered then discuss things more fully with your doctor or
• blood clots in the lung (pulmonary embolism)
nurse before it is given.
as well as for:
• the treatment of chest pains resulting from disease of the
Tobacco smoke can also interfere with the working of heparin
heart arteries (unstable angina pectoris)
injection. You should inform your doctor if you smoke.
• the treatment of severe blockages affecting arteries in the
The presence of heparin in the blood can affect the results of
legs (acute peripheral arterial occlusion)
some blood tests such as thyroid tests and the levels of calcium
• the prevention of blood clots in the heart following a heart
or some antibiotics (e.g. gentamicin) in the blood.
attack (mural thrombosis).
Important information about the ingredients benzyl alcohol
It is also used during heart and lung operations and during
and methyl parahydroxybenzoate
kidney dialysis.
The benzyl alcohol in heparin injection may cause toxic reactions
and allergic reactions in infants and children up to three years old.
2. BEFORE YOU ARE GIVEN HEPARIN INJECTION
The methyl parahydroxybenzoate in heparin injection may cause
Heparin injection should not be given if you:
allergic reactions (possibly delayed) and exceptionally
• are allergic to heparin or any of the other ingredients in your bronchospasm
medicine, (see ‘What heparin injection contains’ section 6 and
Pregnancy and breast-feeding
‘Important information about some of the ingredients of
You should let your doctor or nurse know before you are given
heparin injection’ below)
heparin injection if you are pregnant or wish to become pregnant.
• drink large amounts of alcohol
• are currently bleeding from anywhere in the body, (apart from
If you are being given heparin injection bleeding may be a
your normal period which does not stop you being given
problem during pregnancy or after delivery. Your bones may get
heparin injection)
• have haemophilia (a genetic disorder which may cause you thinner if you receive heparin for a long time during pregnancy.
to bleed excessively) or any other bleeding problem
Ask your doctor or nurse for advice if you wish to breast-feed
• have or have ever had thrombocytopenia (a serious blood
disorder which prevents blood from clotting properly)
Driving and using machines
• bruise easily (fragile capillaries) or have lots of purple spots
Heparin injection has not been reported to affect ability to drive or
that look like bruises (purpura)
operate machines.
• have very high blood pressure
• are suffering from tuberculosis (TB)
3. HOW HEPARIN INJECTION SHOULD BE GIVEN
• have had severe skin problems resulting from previous
Your doctor or nurse will inject your dose of heparin into a vein
heparin treatment
• are about to have surgery of the brain, spine or eye, a lumbar either all at once or over a longer period of time (usually via a drip).
Alternatively they may inject your heparin underneath your skin.
puncture or local anaesthetic nerve block, or some other
procedure where bleeding could be a problem
The amount injected all at once into a vein should not be greater
• have recently had an operation
• suffer from severe liver problems which can lead to bleeding than 15ml.
into the oesophagus (gullet)
You may need to have blood tests if you are receiving higher
• have bleeding into the brain.
doses of heparin or if you are pregnant to check on the effects of
Heparin injection must not be given to premature or
your heparin treatment.
newborn babies.
Heparin injection must not be given to premature or
Speak to your doctor before heparin injection is given if you: newborn babies.
• are over 60 years of age
• have any condition which makes you likely to bleed more
You may require a lower dose if you have kidney or liver disease.
easily (for example a stomach ulcer, hiatus hernia,
inflammation of the heart, problems in the back of your eye, To PREVENT blood clots in leg veins (deep vein thrombosis)
and blood clots in the lung (pulmonary embolism)
haemorrhoids (piles), a stroke, cancer or threatened
Adults
miscarriage), If you are unsure, ask your doctor or nurse.
The usual dose of heparin injection in adults is 5,000 units
• suffer from diabetes
injected under the skin 2 hours before your operation, followed
• suffer from excess acid or high levels of potassium in your
by 5,000 units injected under the skin every 8-12 hours, for 7-10
blood or are taking a medicine that may increase the
days or until you are fully able to move about.
potassium level in your blood (e.g. amiloride, triamterene,
eplerenone or spironolactone). If any of these apply you may Pregnancy
During pregnancy the dosage is 5,000-10,000 units injected
need to have a blood test before the start of your heparin
under the skin every 12 hours. The dose may be adjusted
treatment. If you are unsure, ask your doctor or nurse
according to your blood tests.
• have kidney or liver disease. Your doctor may decide that a
lower dose is necessary
PACKAGE LEAFLET: INFORMATION FOR THE USER

1. NAME OF THE MEDICINAL PRODUCT
Heparin sodium 5,000 I.U./ml solution for injection or concentrate for
solution for infusion
Heparin sodium 25,000 I.U./ml solution for injection or concentrate for
solution for infusion
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Heparin sodium 5,000 I.U./ml - Heparin sodium 5,000 I.U./ml
(25,000 I.U. in 5ml)
Heparin sodium 25,000 I.U./ml - Heparin sodium 25,000 I.U./ml
(125,000 I.U. in 5ml)
For a full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Solution for injection or concentrate for solution for infusion
A colourless or straw-coloured liquid, free from turbidity and from matter
that deposits on standing.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Prophylaxis of deep vein thrombosis and pulmonary embolism
Treatment of deep vein thrombosis, pulmonary embolism, unstable
angina pectoris and acute peripheral arterial occlusion.
Prophylaxis of mural thrombosis following myocardial infarction.
In extracorporeal circulation and haemodialysis.
4.2 Posology and method of administration
Route of administration
By continuous intravenous infusion in 5% glucose or 0.9% sodium chloride
or by intermittent intravenous injection, or by subcutaneous injection.
The intravenous injection volume of heparin injection should not exceed
15ml.
As the effects of heparin are short-lived, administration by intravenous
infusion or subcutaneous injection is preferable to intermittent intravenous
injections.
Recommended dosage
Prophylaxis of deep vein thrombosis and pulmonary embolism:
Adults:
2 hours pre-operatively:
5,000 units subcutaneously

x midpoint of normal range or control value.
Prophylaxis of mural thrombosis following myocardial infarction
Adults:
12,500 units 12 hourly subcutaneously
for at least 10 days.
Elderly:
Dosage reduction may be advisable

In extracorporeal circulation and haemodialysis
Adults:
Cardiopulmonary bypass:
Initially 300 units/kg intravenously,
adjusted thereafter to maintain the
activated clotting time (ACT) in the range
400-500 seconds.
Haemodialysis and
haemofiltration:
Initially 1,000-5,000 units,
Maintenance:
1,000-2,000 units/hour, adjusted to
maintain clotting time >40 minutes.
Heparin resistance
Patients with altered heparin responsiveness or heparin resistance may
require disproportionately higher doses of heparin to achieve the desired
effect. Also refer to section 4.4, Special warnings and precautions for use.
4.3 Contraindications
Known hypersensitivity to heparin or any of the other ingredients.
Must not be given to premature babies or neonates (contains benzyl
alcohol).
Patients who consume large amounts of alcohol, who are sensitive to the
drug, who are actively bleeding or who have haemophilia or other bleeding
disorders, severe liver disease (including oesophageal varices), purpura,
severe hypertension, active tuberculosis or increased capillary permeability.
Patients with present or previous thrombocytopenia. The rare occurrence
of skin necrosis in patients receiving heparin contra-indicates the further
use of heparin either by subcutaneous or intravenous routes because of
the risk of thrombocytopenia. Because of the special hazard of
post-operative haemorrhage heparin is contra-indicated during surgery of
the brain, spinal cord and eye, in procedures at sites where there is a risk
of bleeding, in patients that have had recent surgery, and in patients
undergoing lumbar puncture or regional anaesthetic block.
The relative risks and benefits of heparin should be carefully assessed in
Followed by:
5,000 units subcutaneously every 8-12
patients with a bleeding tendency or those patients with an actual or
hours, for 7-10 days or until the patient
potential bleeding site eg. hiatus hernia, peptic ulcer, neoplasm, bacterial
is fully ambulant.
endocarditis, retinopathy, bleeding haemorrhoids, suspected intracranial
haemorrhage, cerebral thrombosis or threatened abortion.
No laboratory monitoring should be necessary during low dose heparin
prophylaxis. If monitoring is considered desirable, anti-Xa assays should Menstruation is not a contra-indication.
be used as the activated partial thromboplastin time (APTT) is not
4.4 Special warnings and precautions for use
significantly prolonged.
Platelet counts should be measured in patients receiving heparin
During pregnancy:
5,000 - 10,000 units every 12 hours,
treatment for longer than 5 days and the treatment should be stopped
subcutaneously, adjusted according
immediately in those who develop thrombocytopenia.
to APTT or anti-Xa assay.
In patients with advanced renal or hepatic disease, a reduction in dosage
Elderly:
may be necessary. The risk of bleeding is increased with severe renal
Dosage reduction and monitoring of APTT may be advisable.
impairment and in the elderly (particularly elderly women).
Children:
No dosage recommendations.
Although heparin hypersensitivity is rare, it is advisable to give a trial dose of
1,000 I.U. in patients with a history of allergy. Caution should be exercised
Treatment of deep vein thrombosis and pulmonary embolism:
in patients with known hypersensitivity to low molecular weight heparins.
Adults:
Heparin injection contains benzyl alcohol (10mg/ml) and methyl
Loading dose:
5,000 units intravenously (10,000 units
parahydroxybenzoate as preservatives. Caution should be used if
may be required in severe pulmonary
prescribing Heparin injection to susceptible patients. Benzyl alcohol may
embolism)
cause toxic reactions and anaphylactoid reactions in infants and children
Maintenance:
1,000-2,000 units/hour by intravenous
up to three years old. Methyl parahydroxybenzoate may cause allergic
infusion, or 10,000-20,000 units 12
reactions (possibly delayed) and, exceptionally, bronchospasm.
hourly subcutaneously, or
In most patients, the recommended low-dose regimen produces no
5,000-10,000 units 4-hourly by
alteration in clotting time. However, patients show an individual response to
intravenous injection.
heparin, and it is therefore essential that the effect of therapy on coagulation
Elderly:
time should be monitored in patients undergoing major surgery.
Dosage reduction may be advisable.
Caution is recommended in spinal or epidural anaesthesia (risk of spinal
Children and small adults:
haematoma).
Loading dose:
50 units/kg intravenously
Heparin can suppress adrenal secretion of aldosterone leading to
Maintenance:
15-25 units/kg/hour by intravenous
hyperkalemia, particularly in patients such as those with diabetes mellitus,
infusion,
chronic renal failure, pre-existing metabolic acidosis, a raised plasma
or 250 units/kg 12 hourly
potassium, or taking potassium sparing drugs. The risk of hyperkalemia
subcutaneouslyor 100 units/kg 4-hourly
appears to increase with duration of therapy but is usually reversible.
by intravenous injection
Plasma potassium should be measured in patients at risk before starting
heparin therapy and in all patients treated for more than 7 days.
Treatment of unstable angina pectoris and acute peripheral arterial
occlusion:
Heparin resistance
Adults:
There is considerable variation in individual anticoagulant responses to
Loading dose:
5,000 units intravenously
heparin.
Maintenance:
1,000-2,000 units/hour by intravenous
infusion, or 5,000-10,000 units 4-hourly
Heparin resistance, defined as an inadequate response to heparin at a
by intravenous injection.
standard dose for achieving a therapeutic goal occurs in approximately
Elderly:
5 to 30% of patients.
Dosage reduction may be advisable.
Factors predisposing to the development of heparin resistance, include:
Children and small adults:
· Antithrombin III activity less than 60% of normal (antithrombin IIILoading dose:
50 units/kg intravenously
dependent heparin resistance):
Maintenance:
15-25 units/kg/hour by intravenous
Reduced antithrombin III activity may be hereditary or more commonly,
infusion, or 100 units/kg 4-hourly by
acquired (secondary to preoperative heparin therapy in the main, chronic
intravenous injection
liver disease, nephrotic syndrome, cardiopulmonary bypass, low grade
Daily laboratory monitoring (ideally at the same time each day, starting
4-6 hours after initiation of treatment) is essential during full-dose heparin disseminated intravascular coagulation or drug induced, e.g. by
treatment, with adjustment of dosage to maintain an APTT value 1.5-2.5 aprotinin, oestrogen or possibly nitroglycerin)

Elderly
Lower doses may be used in the elderly. You may need to have
blood tests if you are elderly, to check on the effects of your
heparin treatment.
Children
No specific doses are recommended.
To TREAT blood clots in leg veins (deep vein thrombosis)
and blood clots in the lung (pulmonary embolism).
Adults
The usual dose in adults is 5,000 units injected into a vein. This is
followed by:
• 1,000-2,000 units/hour injected slowly into a vein
or
• 10,000-20,000 units 12 hourly injected under the skin
or
• 5,000-10,000 units 4 hourly injected all at once into a vein
Elderly
Lower doses may be used in the elderly
Small adults and children
Small adults and children will be given 50 units/kg body weight
injected into a vein followed by:
• 15-25 units/kg body weight/hour injected slowly into a vein
or
• 250 units/kg body weight 12 hourly injected under the skin
or
• 100 units/kg body weight 4 hourly injected all at once into
a vein
To TREAT chest pains (unstable angina pectoris) and severe
blood clots in the arteries (acute peripheral arterial occlusion)
Adults
The usual dose in adults is 5,000 units injected into a vein. This is
followed by:
• 1,000-2,000 units/hour injected slowly into a vein
or
• 5,000-10,000 units 4 hourly injected all at once into a vein
Elderly
Lower doses may be used in the elderly
Small adults and children
Small adults and children will be given 50 units/kg body weight
injected into a vein followed by:
• 15-25 units/kg body weight/hour injected slowly into a vein
or
• 100 units/kg body weight 4 hourly injected all at once into a vein
You will have blood tests every day to check the effects of
your heparin
To prevent a blood clot in the heart following a heart attack.
Adults
The usual dose for adults is 12,500 units 12 hourly injected
under the skin for at least 10 days.
Elderly
A lower dose may be needed.
During Heart and Lung Surgery (Adults)
Initially you will be given 300 units/kg body weight. This will be
changed according to the results of your blood tests.
During kidney dialysis (Adults)
Initially you will be given 1,000-5,000 units. This will be changed
according to the results of your blood tests.
If you think you have been given too much heparin injection
Your doctor will decide which dose is best for you. Too much
heparin can cause bleeding. Slight bleeding can be stopped by
stopping your heparin treatment. However if you have more
severe bleeding you may need blood tests and an injection of a
medicine called protamine sulphate. If you think too much
medicine has been given to you contact your doctor or nurse.
4. POSSIBLE SIDE EFFECTS
Like all medicines, heparin injection may cause side effects in
some patients, although not everybody gets them. These are
most likely to occur when treatment is first started. You should
inform your doctor or nurse immediately if you feel unwell.
Important side effects to look out for:
• Severe allergic reactions
Heparin can cause a severe allergic reaction with wheezing,
difficulty breathing, a blue tinge to the lips, fever, chills, swelling of
the eyes and lips and shock.
Allergic reactions may be due to the ingredients in your heparin
rather than the heparin itself. This occurs particularly in infants or
children up to three years old.
If you think you are having a severe allergic reaction (see
symptoms above) you must tell your doctor or nurse
immediately.
• Bleeding and Bruising
Heparin injection can reduce the number of cells that help your
blood clot (thrombocytopenia) and so can cause bleeding and
bruising. This is most likely to occur within the first few days of
treatment but may occur later too. The risk of bleeding is
increased in the elderly (particlarly elderly women).
Signs that you are bleeding more easily include:
• unusual bruising or purple spots on your skin
• unusual bleeding from your gums
• unusual nose bleeds
• blood in your urine (which may cause this to go dark)

• black, tarry-looking stools
• bleeding that will not stop from any operation site or other injury
If you are concerned about unusual bleeding you must tell
your doctor or nurse immediately as you may need to stop
your heparin.
Other side effects include:
Common side effects (affects 1 to 10 users in 100):
• red lumps or red, itchy patches like eczema often develop
3-21 days after the start of heparin treatment, where
injections have been given under the skin
Rare side effects (affects 1 to 10 users in 10.000):
• raised levels of potassium in the blood, particularly in patients
with kidney failure or diabetes. If affected you may feel tired
and weak.
• allergic reactions including an itchy skin rash, eye
irritation, runny nose, wheezing, rapid breathing, a blue
tinge to the lips, fever, chills, swelling of the eyes and lips,
and shock.
• irritation or sloughing of skin which may occur around the
injection site.
Side effects with unknown frequency:
• loss of hair (alopecia) if heparin sodium injection is given over
many months
• weakening of the bones (osteoporosis) if heparin sodium
injection is given over many months
• persistent erection of the penis (priapism)
• abnormal liver tests
• the amount of a hormone called aldosterone may be lower
than normal Your doctor can explain this more.
• high lipid levels on stopping heparin
If any of the side effects get serious or you notice any side effect
not listed in this leaflet, please tell your doctor or nurse.
5. HOW TO STORE HEPARIN INJECTION
Keep this medicine out of the reach and sight of children.
Your doctor or nurse will usually be responsible for storing and
preparing heparin injection before use and for checking that the
vials have not passed their expiry date stated on the carton and
the label. The medicine must not be used after the expiry date
which is stated on the carton and the label. The expiry date refers
to the last day of the month.
Heparin injection should not be given if it shows signs of
deterioration such as discolouration.
Do not store above 25°C. Store in the original packaging in order
to protect the product from light.
After opening, heparin vials may be kept for 28 days at 25°C,
after which they should be discarded.
Medicines should not be disposed of via wastewater or
household waste. Ask your pharmacist how to dispose of
medicines no longer required. These measures will help to
protect the environment.
6. FURTHER INFORMATION
What heparin injection contains
The active substance is heparin sodium.
1ml of solution of heparin sodium injection 5,000 I.U./ml contains
5,000 international units of the active ingredient. It is available in
5ml multidose vials containing 25,000 I.U. in 5ml of solution.
1ml of solution of heparin sodium injection 25,000 I.U./ml contains
25,000 international units of the active ingredient. It is available in
5ml multidose vials containing 125,000 I.U. in 5ml of solution.
Other ingredients include benzyl alcohol (10mg/ml), methyl
parahydroxybenzoate (E218), water for injections, hydrochloric
acid and sodium hydroxide.
What heparin injection looks like and contents of the pack
Heparin injection is a colourless or straw-coloured liquid.
Each carton contains 10 glass vials.
Other formats
To listen to or request a copy of this leaflet in Braille, large print or
audio please call, free of charge:
0800 198 5000 (UK Only)
Please be ready to give the following information:
Product Name
Reference Number
Heparin sodium 5,000 I.U./ml
29831/0110
solution for injection or
concentrate for solution for infusion
Heparin sodium 25,000 I.U./ml
29831/0108
solution for injection or concentrate
for solution for infusion
This is a service provided by the Royal National Institute of
Blind People.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder: Wockhardt UK Ltd,
Ash Road North, Wrexham, LL13 9UF, UK.
Manufacturer: CP Pharmaceuticals Ltd, Ash Road North,
Wrexham, LL13 9UF, UK.
This leaflet was revised in June 2010.
105013/3

· Patients with normal or supranormal antithrombin III levels (antithrombin III- 4.9 Overdose

A potential hazard of heparin therapy is haemorrhage, but this is usually
due to overdosage and the risk is minimised by strict laboratory control.
Slight haemorrhage can usually be treated by withdrawing the drug. If
bleeding is more severe, clotting time and platelet count should be
determined. Prolonged clotting time will indicate the presence of an
factor, fibrinogen, platelet factor 4 or histidine-rich glycoprotein
excessive anticoagulant effect requiring neutralisation by intravenous
· Active infection (sepsis or endocarditis)
protamine sulphate, at a dosage of 1 mg for every 100 I.U. of heparin to
· Preoperative intra-aortic balloon counterpulsation
be neutralised. The bolus dose of protamine sulphate should be given
· Thrombocytopenia
slowly over about 10 minutes and not exceed 50 mg. If more than 15
· Thrombocytosis
minutes have elapsed since the injection of heparin, lower doses of
· Advanced age
protamine will be necessary.
· Plasma albumin concentration ≤ 35g/dl
· Relative hypovolaemia
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Heparin resistance is also often encountered in acutely ill patients, in
Heparin is an anticoagulant and acts by inhibiting thrombin and by
patients with malignancy and during pregnancy or the post-partum
potentiating the naturally occurring inhibitors of activated Factor X (Xa).
period.
5.2 Pharmacokinetic properties
4.5Interaction with other medicinal products and other forms
As heparin is not absorbed from the gastrointestinal tract and sublingual
of interaction
sites it is administered by injection. After injection heparin extensively
Analgesics: Drugs that interfere with platelet aggregation eg. aspirin and
binds to plasma proteins.
other NSAIDs, should be used with care. Increased risk of haemorrhage
with ketorolac (avoid concomitant use even with low-dose heparin).
Heparin is metabolised in the liver and the inactive metabolic products are
Anticoagulants, platelet inhibitors, etc: Increased risk of bleeding with oral excreted in the urine.
The half life of heparin is dependent on the dose.
anticoagulants, epoprostenol, clopidogrel, ticlopidine, streptokinase,
dipyridamole, dextran solutions, or any other drug which may interfere
5.3 Preclinical Safety Data
with coagulation.
There are no pre-clinical data of relevance to the prescriber which are
additional to those already included in other sections.
Cephalosporins: Some cephalosporins, e.g. cefaclor, cefixime and
6. PHARMACEUTICAL PARTICULARS
ceftriaxone, can affect the coagulation process and may therefore
6.1 List of excipients
increase the risk of haemorrhage when used concurrently with heparin.
Benzyl alcohol
ACE inhibitors: Hyperkalaemia may occur with concomitant use.
Methyl parahydroxybenzoate (E218)
Nitrates: Reduced activity of heparin has been reported with
Water for injections
simultaneous intravenous glyceryl trinitrate infusion.
Sodium hydroxide solution
Probenecid: May increase the anticoagulant effects of heparin.
Hydrochloric acid
6.2 Incompatibilities
Tobacco smoke: Nicotine may partially counteract the anticoagulant
effect of heparin. Increased heparin dosage may be required in smokers. Heparin is incompatible with many injectable preparations e.g. some
antibiotics, opioid analgesics and antihistamines.
Interference with diagnostic tests may be associated with
pseudo-hypocalcaemia (in haemodialysis patients), artefactual increases The following drugs are incompatible with heparin;
in total thyroxine and triiodothyronine, simulated metabolic acidosis and
Alteplase, amikacin sulphate, amiodarone hydrochloride, ampicillin
inhibition of the chromogenic lysate assay for endotoxin. Heparin may
sodium, aprotinin, benzylpenicillin potassium or sodium, cefalotin sodium,
interfere with the determination of aminoglycosides by immunoassays.
chlorpromazine hydrochloride, ciprofloxacin lactate, cisatracurium
besilate, cytarabine, dacarbazine, daunorubicin hydrochloride, diazepam,
4.6 Pregnancy and lactation
doxorubicin hydrochloride, droperidol, erythromycin lactobionate,
Heparin is not contraindicated in pregnancy. Heparin does not cross the
gentamicin sulphate, haloperidol lactate, hyaluronidase, hydrocortisone
placenta or appear in breast milk. The decision to use heparin in
sodium succinate, kanamycin sulphate, labetolol hydrochloride, meticillin
pregnancy should be taken after evaluation of the risk/benefit in any
sodium, methotrimeprazine, netilmicin sulphate, nicardipine
particular circumstances. Reduced bone density has been reported with
hydrochloride, oxytetracycline hydrochloride, pethidine hydrochloride,
prolonged heparin treatment during pregnancy.
polymyxin B sulphate, promethazine hydrochloride, streptomycin
Haemorrhage may be a problem during pregnancy or after delivery.
sulphate, tobramycin sulphate, triflupromazine hydrochloride, vancomycin
4.7 Effects on ability to drive and use machines
hydrochloride and vinblastine sulphate.
None stated.
Dobutamine hydrochloride and heparin should not be mixed or infused
4.8 Undesirable effects
through the same intravenous line, as this causes precipitation.
Haemorrhage (see also Special Warnings and Precautions and
Heparin and reteplase are incompatible when combined in solution.
Overdosage Information).
If reteplase and heparin are to be given through the same line this,
Adrenal insufficiency secondary to adrenal haemorrhage has been
together with any Y-lines, must be thoroughly flushed with a 0.9% saline
associated with heparin (rarely).
or a 5% glucose solution prior to and following the reteplase injection.
Thrombocytopenia has been observed occasionally (see also Special
6.3 Shelf life
Precautions and Warnings). Two types of heparin-induced thrombocyto36 months
penia have been defined. Type I is frequent, mild (usually >50 x 109/L)
and transient, occurring within 1-5 days of heparin administration. Type II Chemical and physical in use stability has been demonstrated for 28 days
at 25°C.
is less frequent but often associated with severe thrombocytopenia
(usually <50 x 109/L). It is immune-mediated and occurs after a week or From a microbiological point of view, once opened, the product may be
stored for a maximum of 28 days at 25°C. Other in use storage times
more (earlier in patients previously exposed to heparin). It is associated
and conditions are the responsibility of the user.
with the production of a platelet-aggregating antibody and thromboembolic complications which may precede the onset of thrombocytopenia.
6.4 Special precautions for storage
Heparin should be discontinued immediately.
Do not store above 25°C.
Store in the original package
There is some evidence that prolonged dosing with heparin (ie. over
many months) may cause alopecia and osteoporosis. Significant bone
6.5 Nature and contents of container
demineralisation has been reported in women taking more than 10,000
5ml multidose neutral glass (Type 1, Ph Eur) vial. Carton containing 10 vials.
I.U. per day of heparin for at least 6 months.
6.6 Special precautions for disposal
Heparin products can cause hypoaldosteronism which may result in an
Each multidose vial should be restricted to use in a single patient.
increase in plasma potassium. Rarely, clinically significant hyperkalemia
7. MARKETING AUTHORISATION HOLDER
may occur particularly in patients with chronic renal failure and diabetes
Wockhardt UK Ltd, Ash Road North, Wrexham , LL13 9UF, UK.
mellitus (see Warnings and Precautions).
8. MARKETING AUTHORISATION NUMBER(S)
Hypersensitivity reactions to heparin are rare. They include urticaria,
conjunctivitis, rhinitis, asthma, cyanosis, tachypnoea, feeling of oppression, Heparin sodium injection 5,000 I.U./ml –
PL 29831/0110, PA 1339/9/7
fever, chills, angioneurotic oedema and anaphylactic shock. In some
Heparin sodium injection 25,000 I.U./ml –
instances the precipitating agent will prove to be the preservative rather
PL 29831/0108, PA 1339/9/8
than the heparin itself.
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE
Local irritation and skin necrosis may occur but are rare. Erythematous
AUTHORISATION
nodules, or infiltrated and sometimes eczema-like plaques, at the site of
Date of first authorisation:
subcutaneous injections are common, occurring 3-21 days after starting Heparin sodium injection 5,000 I.U./ml
- 20 September 2007 (UK)
heparin treatment.
-16 November 2007 (Ireland)
Priapism has been reported. Increased serum transaminase values may Heparin sodium injection 25,000 I.U./ml
- 15 October 2007 (UK)
occur but usually resolve on discontinuation of heparin. Heparin
-16 November 2007 (Ireland)
administration is associated with release of lipoprotein lipase into the
10. DATE OF REVISION OF THE TEXT
plasma; rebound hyperlipidaemia may follow heparin withdrawal.
June 2010.
independent heparin resistance)

· Thromboembolic disorders
· Increased heparin clearance
· Elevated levels of heparin binding proteins, factor VIII, von Willebrand

105013/3

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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