PROSULF 10MG/ML SOLUTION FOR INJECTION

Active substance: PROTAMINE SULPHATE

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PACKAGE LEAFLET:
INFORMATION FOR THE USER
®

Protamine Sulphate 10mg/ml
Solution for Injection
Read all of this leaflet carefully before you start
taking this medicine.
- Keep this leaflet. You may need to read it again while
you are receiving your treatment.
- If you have any further questions, please ask your
doctor or nurse.
- This medicine has been prescribed for you. The
contents of your vial of Protamine Sulphate 10mg/ml
Solution for Injection should not be shared with other
patients.
The name of your medicine is Protamine Sulphate
10mg/ml Solution for Injection. In the rest of this leaflet
it is called Protamine Sulphate Injection.

to protamine sulphate or any of the other ingredients in the
injection (see list under ‘What Protamine Sulphate
Injection contains’ in section 6 of this leaflet).
Special care is needed if you:
• are allergic to fish, because you may also be allergic
to Protamine Sulphate Injection as protamine sulphate
comes from fish
• have ever had heart surgery
• are an insulin dependent diabetic because Protamine
Sulphate Injection may cause problems if you have
previously used protamine insulin
• are a man and you have had a vasectomy or are infertile.
If you are undergoing a long operation, where
repeated doses of Protamine Sulphate Injection
are necessary, you may occasionally experience
bleeding up to 18 hours after your operation, which
will stop when you are given further doses
of Protamine Sulphate Injection.
If any of the above apply to you, speak to your doctor or
nurse before Protamine Sulphate Injection is given to you.

In this leaflet:
1. What Protamine Sulphate Injection is and what it is
used for
2. Before you are given Protamine Sulphate Injection
3. How Protamine Sulphate Injection should be given
4. Possible side effects
5. How to store Protamine Sulphate Injection
6. Further information

Taking other medicines
Please tell your doctor or pharmacist if you are taking,
or have recently taken, any other medicines, including
those medicines obtained without a prescription.

1. WHAT PROTAMINE SULPHATE INJECTION IS
AND WHAT IT IS USED FOR

Driving and using machines
Protamine Sulphate Injection has not been reported to
affect ability to drive or operate machines.

The name of your medicine is Protamine Sulphate
Injection. The active ingredient in Protamine Sulphate
Injection is protamine sulphate.
How does your medicine work?
Protamine Sulphate Injection contains protamine
sulphate which is a heparin antidote which neutralises
the anti blood-clotting effect of heparin and prevents it
from thinning the blood too much.
It is used before surgery, after kidney dialysis, after open
- heart surgery, if you bleed during heparin treatment or
if too much heparin has been given to you by accident.

2. BEFORE YOU ARE GIVEN PROTAMINE
SULPHATE INJECTION
Protamine Sulphate Injection should only be given as an
antidote to heparin. It is not suitable for use as an
antidote to other medicines that are used to thin the
blood that are taken by mouth.
Protamine Sulphate Injection should not be used if you
have ever had a reaction or been told that you are allergic

SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Protamine Sulphate 10mg/ml Solution for Injection

2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Protamine Sulphate 10mg/ml.

3 PHARMACEUTICAL FORM
Solution for injection
A clear, colourless solution.

4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Protamine sulphate is used to counteract the
anticoagulant effect of heparin: before surgery; after
renal dialysis; after open-heart surgery; if excessive
bleeding occurs and when an overdose has
inadvertently been given.
4.2 Posology and method of administration
Adults:
Protamine Sulphate Injection should be administered by
slow intravenous injection over a period of about
10 minutes. No more than 50mg of protamine sulphate
should be given in any one dose.
The dose is dependent on the amount and type of
heparin to be neutralised, its route of administration and
the time elapsed since it was last given, since heparin is
continuously being excreted. Ideally, the dose required
to neutralise the action of heparin should be guided by
blood coagulation studies or calculated from a
protamine neutralisation test.
In gross excess, protamine itself acts as an
anticoagulant.

Pregnancy and breast-feeding
You should let your doctor know if you are pregnant or
are breast-feeding before Protamine Sulphate Injection
is administered.

Important information about the sodium content
of Protamine Sulphate Injection
Protamine Sulphate Injection contains less than 1mmol
sodium (23mg) per 10mg/ml dose, it is essentially
‘sodium-free’.

3. HOW PROTAMINE SULPHATE INJECTION
SHOULD BE GIVEN
Protamine Sulphate Injection is not recommended for
use in children (persons aged 12 years or younger).
• Blood clotting tests should be carried out to check on
the effects of Protamine Sulphate Injection to see if
you need further doses.
• Protamine Sulphate Injection should be given slowly
by infusing into a vein over a period of about ten minutes.
• The dose of Protamine Sulphate Injection you will be
given depends on the amount and type of heparin to
be neutralised, the way the heparin was given to you,

In the reversal of UF heparin following cardiopulmonary
bypass, either a standard dose of protamine may be
given, as above, or the dose may be titrated according
to the activated clotting time.
Patients should be carefully monitored using either the
activated partial thromboplastin time or the activated
clotting time, carried out 5-15 minutes after protamine
sulphate administration. Further doses may be needed
because protamine is cleared from the blood more
rapidly than heparin.
Neutralisation of low molecular weight (LMW) heparins:
A dose of 1mg per 100 units is usually recommended
but the manufacturer's own guidelines should be
consulted.
The anti-Xa activity of LMW heparins may not be
completely reversible with protamine sulphate and may
persist for up to 24 hours after administration.
The longer half-life of LMW heparins (approximately
twice that of UF heparin) should also be borne in mind
when estimating the dose of protamine sulphate
required in relation to the time which has elapsed since
the last heparin dose.
Theoretically, the dose of protamine sulphate should be
halved when one half-life has elapsed since the last
LMW heparin dose. Intermittent injections or
continuous infusion of protamine sulphate have been
recommended for the neutralisation of LMW heparin
following subcutaneous administration, as there may be
continuing absorption from the subcutaneous depot.
Patients should be carefully monitored. Further doses
may be needed because protamine is cleared from the
blood more rapidly than heparin, especially low
molecular weight heparin.

Neutralisation of unfractionated (UF) heparins:

Elderly:
There is no current evidence for alteration of the
recommended dose.

1mg of protamine sulphate will usually neutralise at
least 100 international units of mucous heparin or 80
units of lung heparin. The dose of protamine sulphate
should be reduced if more than 15 minutes have
elapsed since intravenous injection.

Children:
Safety and efficacy in children have not been
established. Not recommended.

For example, if 30-60 minutes have elapsed since
heparin was injected intravenously, 0.5-0.75mg
protamine sulphate per 100 units of mucous heparin is
recommended. If two hours or more have elapsed,
0.25-0.375mg per 100 units of mucous heparin should
be administered.
If the patient is receiving an intravenous infusion of
heparin, the infusion should be stopped and 25-50mg of
protamine sulphate given by slow intravenous injection.
If heparin was administered subcutaneously, 1mg
protamine sulphate should be given per 100 units of
mucous heparin - 25-50mg by slow intravenous
injection and the balance by intravenous infusion over
8-16 hours.

4.3 Contraindications
None known.
4.4 Special warnings and precautions for use
Too rapid administration of protamine sulphate may
cause severe hypotension and anaphylactoid reactions.
Facilities for resuscitation and treatment of shock
should be available.
Protamine sulphate is not suitable for reversing the
effects of oral anticoagulants. Caution should be
observed when administering protamine sulphate to
patients who may be at increased risk of allergic
reaction to protamine. These patients include those
who have previously undergone procedures such as
coronary angioplasty or cardio-pulmonary by-pass
which may include use of protamine, diabetics who

and the amount of time that has passed since your
last heparin injection.
• No more than 50 milligrams protamine sulphate
should be given to you in one dose. Your doctor will
decide the dose that is best for you.
If you do not understand, or are in any doubt, ask your
doctor or nurse.
If you think you have missed a dose
If you think that an injection has been missed, speak to
your doctor or nurse.
If you think you have been given too much
Protamine Sulphate Injection
If you think you have been given too much Protamine
Sulphate Injection, speak to your doctor or nurse. Signs
of an overdose include hypotension (a lowering of blood
pressure), an abnormally slow heart rate, a shortness of
breath, excessive/unexplained bleeding and/or bruising,
feeling sick, being sick, a feeling of weakness or facial
flushing and/or a feeling of warmth.

4. POSSIBLE SIDE EFFECTS
Like many medicines, Protamine Sulphate Injection
may cause side-effects in some patients, particularly
when it is first given.
These include:
• slowing of the pulse
• low blood pressure (you may feel dizzy or faint or you
may black out)
• high blood pressure
• shortness of breath
• flushing and a feeling of warmth in the body
• back pain
• feeling sick
• being sick
• tiredness
Rarely, allergic reactions occur resulting in breathing
difficulties or a rash. This can sometimes be more
serious with fainting and collapse, swelling of the lips and
face, and a blue discoloration of the lips and tongue. The
doctor treating you will be ready to treat these effects if
they occur.
If you experience any other side-effects or feel that the
medicine is affecting you badly, tell your doctor or nurse
immediately.

expiry date on the label has passed. The expiry date
refers to the last day of that month.
Protamine Sulphate Injection should not be used if it is
discoloured or has gone cloudy.
The injection should be stored between 15°C and 25°C
in the package or container in which it was dispensed.
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 Protamine Sulphate Injection contains
The active ingredient in Protamine Sulphate Injection is
protamine sulphate.The injection comes in one strength
of 10mg/ml.
Other ingredients in Protamine Sulphate Injection injection
are sodium chloride, water for injections and trace
amounts of hydrochloric acid and sodium hydroxide.
What Protamine Sulphate Injection looks like and
contents of the pack
Protamine Sulphate Injection is a clear and colourless
solution for injection. It is available in packs of 10 glass
ampoules. Each ampoule contains 5ml of solution.
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.
Other formats
To listen to or request a copy of this information 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

Protamine Sulphate 10mg/ml
Solution for Injection

29831/0180

This is a service provided by the Royal National Institute
of Blind People.
Leaflet prepared: August 2010.

5. HOW TO STORE PROTAMINE SULPHATE
INJECTION

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Keep out of the reach and sight of children.
Protamine Sulphate Injection should not be used if the

have been treated with protamine insulin, patients
allergic to fish and men who have had a vasectomy or
are infertile and may have antibodies to protamine.
Patients undergoing prolonged procedures involving
repeated doses of protamine should be subject to
careful monitoring of clotting parameters. A rebound
bleeding effect may occur up to 18 hours
post-operatively which responds to further doses of
protamine.
4.5 Interaction with other medicinal products and
other forms of interaction
None known.

5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Although protamine is a potent antidote for heparin, its
precise mechanism of action is unknown. However,
when the strongly basic protamine combines with the
strongly acid heparin, a stable salt is formed lacking in
anticoagulant activity. 1mg of protamine sulphate
neutralises between 80 and 120 units of heparin.
However, methods of standardisation and the use of
heparin from different sources (mucosal, lung) may
produce different responses to protamine.

4.6 Pregnancy and lactation
As with most drugs, to be used only if clearly indicated in
pregnancy and with caution during lactation.

5.2 Pharmacokinetic properties
The onset of action of protamine occurs within five
minutes following intravenous administration. The fate
of the protamine-heparin complex is unknown, but it
may be partially degraded, thus freeing heparin.

4.7 Effects on ability to drive and to use machinery
None.

5.3 Preclinical safety data
No data are available.

4.8 Undesirable effects
Blood and lymphatic system disorders: anticoagulant
effect (when used at doses in excess of that required to
neutralise the anticoagulant effect of heparin).

6 PHARMACEUTICAL PARTICULARS

Immune system disorders: Hypersensitivity reactions,
including angioedema anaphylactoid reactions and fatal
anaphylaxis, have been reported.
Cardiac disorders: bradycardia
Vascular disorders: sudden fall in blood pressure,
pulmonary and systemic hypertension, transitory
flushing and a feeling of warmth, severe, acute
pulmonary vasoconstriction with cardiovascular collapse
Respiratory, thoracic and mediastinal disorders:
Dyspnoea. There have been rare instances of
noncardiogenic pulmonary oedema with prolonged
hypotension, with significant morbidity and mortality.
Gastrointestinal disorders: nausea and vomiting
Musculoskeletal and connective tissue disorders:
back pain
General disorders and administration site conditions:
lassitude
4.9 Overdose
Symptoms:- Protamine has weak anticoagulating
properties and if given in the absence of heparin, or at
doses in excess of those required to neutralise the
anticoagulant effect of heparin, exerts its own
anticoagulant effect.
Hypotension, bradycardia, dyspnoea nausea, vomiting,
lassitude, transitory flushing and/ or a sensation of
warmth may also occur.
Treatment:- Includes monitoring of coagulation tests,
respiratory ventilation and symptomatic treatment.
If bleeding is a problem, fresh frozen plasma or fresh
whole blood should be given.

6.1 List of excipients
Sodium Chloride
Hydrochloric Acid 3M
Sodium Hydroxide 3M
Water for Injections
6.2 Incompatibilities
Protamine sulphate is incompatible with certain
antibiotics, including several cephalosporins and penicillin.
6.3 Shelf life
48 months
6.4 Special precautions for storage
Store between 15°C and 25°C.
6.5 Nature and contents of container
5ml and 10ml neutral type 1 hydrolytic glass ampoules
in pack sizes of 10 ampoules in cartons.
6.6 Special precautions for disposal
Not applicable.

7 MARKETING AUTHORISATION HOLDER
Wockhardt UK Ltd
Ash Road North
Wrexham
LL13 9UF
UK

8 MARKETING AUTHORISATION NUMBER(S)
PL 29831/0180

9 DATE OF FIRST AUTHORISATION/RENEWAL OF
THE AUTHORISATION
27 June 2007

10 DATE OF REVISION OF THE TEXT
August 2010.

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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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