1. NAME OF THE MEDICINAL PRODUCT

Protamine Sulfate Injection USP 50mg/5ml Taj Pharma
Protamine Sulfate Injection USP 250mg/25ml Taj Pharma

  1. QUALITATIVE AND QUANTITATIVE COMPOSITION

a) Protamine Sulfate Injection USP 50mg/5ml
Each ml contains:
Protamine sulfate   10mg
Sodium chloride      9mg
water for Injection  q.s

b) Protamine Sulfate Injection USP 250mg/25ml
Each ml contains:
Protamine sulfate   10mg
Sodium chloride      9mg
water for Injection  q.s

  1. PHARMACEUTICAL FORM

Solution for injection

A clear, colourless solution.

  1. CLINICAL PARTICULARS

4.1 Therapeutic indications

Protamine sulfate 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 sulfate 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 sulfate will usually neutralise at least 100 international units of mucous heparin or 80 units of lung heparin. The dose of protamine sulfate 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 sulfate 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 sulfate given by slow intravenous injection.

If heparin was administered subcutaneously, 1mg protamine sulfate 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.

Patients should be carefully monitored using either the activated partial thromboplastin time or the activated clotting time, carried out 5-15 minutes after protamine sulfate 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 sulfate 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 sulfate required in relation to the time which has elapsed since the last heparin dose.

Theoretically, the dose of protamine sulfate should be halved when one half-life has elapsed since the last LMW heparin dose. Intermittent injections or continuous infusion of protamine sulfate 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 sulfate may cause severe hypotension and anaphylactoid reactions. Facilities for resuscitation and treatment of shock should be available.

Protamine sulfate is not suitable for reversing the effects of oral anticoagulants. Caution should be observed when administering protamine sulfate 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.

4.5 Interaction with other medicinal products and other forms of interaction

None known.

4.6 Fertility, 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 use machines

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.

Gastrointestinal disorders: nausea and vomiting

Musculoskeletal and connective tissue disorders: back pain

General disorders and administration site conditions: lassitude

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important.

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.

  1. 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 sulfate 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.

  1. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium Chloride

Hydrochloric Acid

Sodium Hydroxide

Water for Injections

6.2 Incompatibilities

Protamine sulfate 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 and other handling

Not applicable.

7.Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Protamine Sulfate Injection USP 50mg/5ml Taj Pharma
Protamine Sulfate Injection USP 250mg/25ml Taj Pharma

Package leaflet: Information for the user

(PROTAMINE SULFATE)

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or nurse.
  • This medicine has been prescribed for you only.

Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

  • 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. See section 4.

The name of your medicine is Protamine Sulfate Injection 10mg/ml Solution for Injection. In the rest of this leaflet, it is called Protamine Sulfate Injection .

What is in this leaflet

1.What Protamine Sulfate Injection is and what it is used for
2.What you need to know before you use Protamine Sulfate Injection
3.How to use Protamine Sulfate Injection
4.Possible side effects
5.How to store Protamine Sulfate Injection
6.Contents of the pack and other information

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

The name of your medicine is Protamine Sulfate Injection . The active ingredient in Protamine Sulfate Injection is protamine sulfate.

Protamine Sulfate Injection contains protamine sulfate 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.WHAT YOU NEED TO KNOW BEFORE YOU USE PROTAMINE SULFATE INJECTION

Protamine Sulfate 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.

Do not use Protamine Sulfate Injection :

  • if you are allergic to protamine sulfate or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or pharmacist or nurse before using Protamine Sulfate Injection if you:

  • are allergic to fish, because you may also be allergic to Protamine Sulfate Injection as protamine sulfate comes from fish.
  • have ever had heart surgery
  • are an insulin dependent diabetic because Protamine Sulfate 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 Sulfate 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 Sulfate Injection .

If any of the above apply to you, speak to your doctor or nurse before Protamine Sulfate Injection is given to you.

Other medicines and Protamine Sulfate Injection

Tell your doctor or pharmacist if you are taking, have recently taken or might take 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 breast-feeding before Protamine Sulfate Injection is administered.

Driving and using machines

Protamine Sulfate Injection has not been reported to affect ability to drive or operate machines.

Protamine Sulfate Injection contains sodium

This medicine contains less than 1 mmol sodium (23mg) per 10mg/ml, that is to say essentially ‘sodium- free’.

  1. HOW TO USE PROTAMINE SULFATE INJECTION

Do not use in children aged 12 years or younger.

  • Blood clotting tests should be carried out to check on the effects of Protamine Sulfate Injection to see if you need further doses.
  • Protamine Sulfate Injection should be given slowly by infusing into a vein over a period of about ten minutes.
  • The dose of Protamine Sulfate Injection 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 sulfate 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.

  1. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side- effects particularly when it is first given, although not everybody gets them.

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, 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:

  1. HOW TO STORE PROTAMINE SULFATE INJECTION

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label. The expiry

date refers to the last day of that month.

Do not use this medicine 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.

Do not throw away any medicines via wastewater or household waste. Ask your

pharmacist how to throw away medicines you no longer use. These measures will help protect the environment

  1. CONTENTS OF THE PACK AND OTHER INFORMATION

What Protamine Sulfate Injection contains

a) Protamine Sulfate Injection USP 50mg/5ml
Each ml contains:
Protamine sulfate   10mg
Sodium chloride      9mg
water for Injection  q.s

b) Protamine Sulfate Injection USP 250mg/25ml
Each ml contains:
Protamine sulfate   10mg
Sodium chloride      9mg
water for Injection  q.s

What Protamine Sulfate Injection looks like and contents of the pack Protamine Sulfate Injection is a clear and colourless solution for injection. It is available in packs of 10 glass ampoules. Each ampoule contains 5ml of solution.

7.Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com