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PROTAMINE SULPHATE 10MG/ML SOLUTION FOR INJECTION

Active substance(s): PROTAMINE SULPHATE

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PACKAGE LEAFLET:
INFORMATION FOR THE USER

PROSULF® 10mg/ml Solution
for Injection
(PROTAMINE SULPHATE)

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 Prosulf® should not be shared
with other patients.
In this leaflet:
1. What Prosulf® is and what it is used for
2. Before you are given Prosulf®
3. How Prosulf® should be given
4. Possible side effects
5. How to store Prosulf®
6. Further information
1. WHAT PROSULF® IS AND WHAT IT IS USED FOR
The name of your medicine is Prosulf®. The active
ingredient in Prosulf® is protamine sulphate.
How does your medicine work?
Prosulf® 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 openheart surgery, if you bleed during heparin treatment or if
too much heparin has been given to you by accident.
2. BEFORE YOU ARE GIVEN PROSULF®
Prosulf® 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.
Prosulf® should not be used if you have ever had a
reaction or been told that you are allergic to protamine
sulphate or any of the other ingredients in the injection
(see list under ‘What Prosulf® contains’ in section 6 of
this leaflet).
Special care is needed if you:
• are allergic to fish, because you may also be allergic to
Prosulf® as protamine sulphate comes from fish
SUMMARY OF PRODUCT CHARACTERISTICS

• have ever had heart surgery
• are an insulin dependent diabetic because Prosulf®
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 Prosulf® are necessary, you may
occasionally experience bleeding up to 18 hours after
your operation, which will stop when you are given
further doses of Prosulf®.
If any of the above apply to you, speak to your doctor or
nurse before Prosulf® is given to you.
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.
Pregnancy and breast-feeding
You should let your doctor know if you are pregnant
or are breast-feeding before Prosulf® is administered.
Driving and using machines
Prosulf® has not been reported to affect ability to drive
or operate machines.
Important information about the sodium content
of Prosulf®
Prosulf® contains less than 1mmol sodium (23mg) per
10mg/ml dose, it is essentially ‘sodium- free’.
3. HOW PROSULF® SHOULD BE GIVEN
Prosulf® 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 Prosulf® to see if you need further doses.
• Prosulf® should be given slowly by infusing into a vein
over a period of about ten minutes.
• The dose of Prosulf® you will be given depends on the
amount and type of heparin to be neutralised, the way
the heparin was given to you, 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.
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.

1 NAME OF THE MEDICINAL PRODUCT
Prosulf® 10mg/ml Solution for Injection
Protamine Sulphate 10mg/ml Solution for Injection
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Protamine Sulphate 10mg/ml.

Neutralisation of low molecular weight (LMW) heparins:

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

A dose of 1mg per 100 units is usually recommended but
the manufacturer’s own guidelines should be consulted.

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:
Prosulf 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.
Neutralisation of unfractionated (UF) heparins:
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.
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.
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.

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.
Elderly:
There is no current evidence for alteration of the
recommended dose.
Children:
Safety and efficacy in children have not been established.
Not recommended.
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 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.

Measure bar should be 150mm at 100% scale

artwork.leicester@multipkg.com

Clearly mark any amendments on one proof and return to MPS

Warning! We cannot accept responsibility for any errors
in this proof after approval. Whilst we take extreme care
at all times to ensure accuracy to our clientʼs brief,
the final responsibility must be taken by our client.
IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING
FULL APPROVAL OF DESIGN AND TEXT.

Customer

Wockhardt UK Limited

Colours Used

Description

Prosulf 10mg/ml solution for injection leaflet

Process Black

Item Code

105005/4

Profile

n-a

Size

148 x 380mm

Min. Point Size

8.5pt (main body) / 8pt (variables)

Market

UK

Language

English

Proof By

elkie.bramall

Proof No.

1

Date

28/08/2015

Artwork No.

591983

Pharma
Code

Keylines (Does not print)

n-a

If you think you have been given too much Prosulf®
If you think you have been given too much Prosulf®,
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, Prosulf® 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.
Reporting of side effects
If you get any side effects, talk to your doctor,
or pharmacist or nurse. This includes any possible side
effects not listed in this leaflet. You can also report side
effects directly via the national reporting systems listed
below:
United Kingdom:
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard

Prosulf® 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 Prosulf® contains
The active ingredient in Prosulf® is protamine sulphate.
The injection comes in one strength of 10mg/ml.
Other ingredients in Prosulf® injection are sodium
chloride, water for injections and trace amounts of
hydrochloric acid and sodium hydroxide.
What Prosulf® looks like and contents of the pack
Prosulf® 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

Prosulf® 10mg/ml
Solution for Injection

PL 29831/0180


This is a service provided by the Royal National Institute
of Blind People.

Malta:
ADR Reporting
Website: www.medicinesauthority.gov.mt/adrportal

This leaflet was last revised in 08/2015

By reporting side effects you can help provide more
information on the safety of this medicine.
5. HOW TO STORE PROSULF®
Keep out of the reach and sight of children.
Prosulf® should not be used if the expiry date on the label
has passed. The expiry date refers to the last day of that
month.

4.5 Interaction with other medicinal products and
other forms of interaction
None known.

105005/4

5 PHARMACOLOGICAL PROPERTIES

4.6 Pregnancy and lactation
As with most drugs, to be used only if clearly indicated in
pregnancy and with caution during lactation.
4.7 Effects on ability to drive and to use machinery
None.
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).
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.

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.
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.
5.3 Preclinical safety data
No data are available.
6 PHARMACEUTICAL PARTICULARS
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.

Gastrointestinal disorders: nausea and vomiting
Musculoskeletal and connective tissue disorders:
back pain

6.3 Shelf life
48 months

General disorders and administration site conditions:
lassitude
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after
authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance
of the medicinal product. Healthcare professionals are
asked to report any suspected adverse reactions via:
UK - Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard.

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

Malta - ADR Reporting,
Website: www.medicinesauthority.gov.mt/adrportal.
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.

8 MARKETING AUTHORISATION NUMBER(S)
PL 29831/0180
MA154/02501

Hypotension, bradycardia, dyspnoea nausea, vomiting,
lassitude, transitory flushing and/ or a sensation of
warmth may also occur.

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

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.

10 DATE OF REVISION OF THE TEXT
08/2015

105005/4

Measure bar should be 150mm at 100% scale

artwork.leicester@multipkg.com

Clearly mark any amendments on one proof and return to MPS

Warning! We cannot accept responsibility for any errors
in this proof after approval. Whilst we take extreme care
at all times to ensure accuracy to our clientʼs brief,
the final responsibility must be taken by our client.
IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING
FULL APPROVAL OF DESIGN AND TEXT.

Customer

Wockhardt UK Limited

Colours Used

Description

Prosulf 10mg/ml solution for injection leaflet

Process Black

Item Code

105005/4

Profile

n-a

Size

148 x 380mm

Min. Point Size

8.5pt (main body) / 8pt (variables)

Market

UK

Language

English

Proof By

elkie.bramall

Proof No.

1

Date

28/08/2015

Artwork No.

591983

Pharma
Code

Keylines (Does not print)

n-a

Expand view ⇕

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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