Streptokinase for Injection BP 15,00,000 IU Taj Pharma

Streptokinase for Injection BP 15,00,000 IU

Name of the medicinal product

Streptokinase for Injection BP 15,00,000 IU Taj Pharma

Qualitative and quantitative composition

Each vial contains:
Streptokinase 15,00,000 IU
Excipients q.s.

For a full list of excipients, see section 6.1.

Pharmaceutical form

Powder for solution for infusion.

Clinical particulars

4.1 Therapeutic indications

Streptokinase is indicated in adults.

Acute myocardial infarction: within 12 hours of onset with persistent ST-segment elevation or recent left bundle-branch block. Note: No statement on therapy outcome can be made for administration beyond the time window indicated above.

4.2 Posology and method of administration

Posology

Paediatric population

The safety and efficacy of Streptokinase have not been sufficiently established in children. Due to low levels of plasminogen in newborns and in children with acquired plasminogen deficiency and due to the potential of streptokinase for allergic/anaphylactic reactions, it is not recommended in neonates, infants and children.

Adults

Systemic administration: A single dose of 1.5 million IU streptokinase should be infused intravenously over one hour.

Local intracoronary administration: A bolus of 20,000 IU streptokinase should be followed by a maintenance infusion of 2,000 IU to 4,000 IU per minute over 30 to 90 minutes depending on the achievement of coronary artery patency.

Method of Administration

The administration of streptokinase may be intravenous or intracoronary.

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

Upon reconstitution with physiological saline a clear solution, colourless to yellowish, is obtained.

Note: When thrombolytic therapy is necessary and a high antibody concentration against streptokinase is present or when recent streptokinase therapy has been given (more than 5 days and less than one year previously), homologous fibrinolytics should be used (see sections 4.4 and 4.8).

Adjuvant treatment

Treatment with aspirin (150 mg daily) for at least 4 weeks is recommended for prophylaxis after streptokinase therapy for acute myocardial infarction. The first dose should be given as soon as possible after the myocardial infarction.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Contraindications to treatment with Streptokinase, because of the increased risk of haemorrhage under thrombolytic therapy, include:

– existing or recent internal haemorrhage

– all forms of reduced blood coagulability, in particular spontaneous fibrinolysis and extensive clotting disorders

– recent cerebrovascular accident, intracranial or intraspinal surgery

– intracranial neoplasm

– recent head trauma

– arteriovenous malformation or aneurysm

– known neoplasm with risk of haemorrhage

– acute pancreatitis

– uncontrollable hypertension with systolic values over 200 mm Hg and/or diastolic values over 100 mm Hg or hypertensive retinal changes Grades III/IV

– recent implantation of a vessel prosthesis

– simultaneous or recent treatment with oral anticoagulants (INR >1.3)

– severe liver or kidney damage

– endocarditis or pericarditis. Isolated cases of pericarditis, misdiagnosed as acute myocardial infarction and treated with streptokinase, have resulted in pericardial effusions including tamponade

– known haemorrhagic diathesis

– recent major operations (6^thto 10^th post-operative day, depending on the extent of the procedure)

– invasive operations, e.g. recent organ biopsy, long-term (traumatic) closed chest cardiac massage

4.4 Special warnings and precautions for use

The following conditions would normally be considered contraindications to streptokinase therapy, but in certain situations the benefits could outweigh the potential risks:

– recent severe gastrointestinal bleeding, e.g. active peptic ulcer

– risk of severe local haemorrhage, e.g. in case of translumbar aortography

– recent trauma and cardiopulmonary resuscitation

– invasive operations, e.g. recent intubation

– puncture of non-compressible vessels, intramuscular injections, large arteries

– recent abortion or delivery

– pregnancy (see section 4.6)

– diseases of the urogenital tract with existing or potential sources of bleeding (implanted bladder catheter)

– known septic thrombotic disease

– severe arteriosclerotic vessel degeneration, cerebrovascular diseases

– cavernous pulmonary diseases, e.g. open tuberculosis or severe bronchitis

– mitral valve defects or atrial fibrilation

– aortic dissection

– diabetic retinopathy increase risk of local bleeding

Antistreptokinase

Repeat treatment with streptokinase administered more than 5 days and less than 12 months after initial treatment may not be effective. This is because of the increased likelihood of resistance due to antistreptokinase antibodies.

Also, the therapeutic effect may be reduced in patients with recent streptococcal infections such as streptococcal pharyngitis, acute rheumatic fever and acute glomerulonephritis.

Infusion rate and corticosteroid prophylaxis

At the beginning of therapy, a fall in blood pressure, tachycardia or bradycardia (in individual cases going as far a shock) are commonly observed. Therefore, at the beginning of therapy the infusion should be performed slowly.

Corticosteroids can be administered prophylactically to reduce the likelihood of infusion-related allergic reactions.

Pre-treatment with heparin or coumarin derivatives

If the patient is under active heparinization, it should be neutralised by administering protamine sulphate before the start of the thrombolytic therapy. The thrombin time should not be more than twice the normal control value before thrombolytic therapy is started. In patients previously treated with coumarin derivatives, the INR (International Normalized Ratio) must be less than 1.3 before starting the streptokinase infusion.

Simultaneous treatment with acetylsalicylic acid

Recent evidence indicates that controlled-dose adjuvant acetylsalicyclic therapy in combination with streptokinase is capable of improving the response in the management of acute myocardial infarction. See also section 4.2.

Streptokinase is not indicated for restoration of patency of intravenous catheters.

4.5 Interaction with other medicinal products and other forms of interaction

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants, e.g. heparin or drugs which inhibit platelet formation or function, e.g. platelet aggregation inhibitors, dextrans.

4.6 Fertility, pregnancy and lactation

Streptokinase is contraindicated in pregnancy. There is no evidence of the drug’s safety in pregnancy, nor is there evidence from animal work that it is free from hazard. Bleeding and anaphylactic reactions might cause abortion and foetal death, especially when streptokinase is given within the first 18 weeks of pregnancy. Use only when there is no safer alternative.

It is unknown whether streptokinase is excreted in human milk. Breast milk should be discarded during the first 24 hours following thrombolytic therapy.

4.7 Effects on ability to drive and use machines

Not relevant.

4.8 Undesirable effects

The following adverse reactions are based on clinical trial and post-marketing experience. The following standard categories are used:

Very common	more than1/10
Common	more than 1/100; less than 1/10
Uncommon	more than 1/1000; less than 1/100
Rare	more than 1/10,000; less than 1/1000
Very Rare	less than 1/10,000 (including isolated cases)

Blood and lymphatic system disorders

Common: haemorrhage at the injection site, ecchymoses, gastrointestinal bleeding, genitourinary bleeding, epistaxis

Uncommon: cerebral haemorrhages with their complications and possible fatal outcome, retinal haemorrhages, severe haemorrhages (also with fatal outcome), liver haemorrhages, retroperitoneal bleeding, bleeding into joints, splenic rupture. Blood transfusions are rarely required.

Very rare: haemorrhage into the pericardium including myocardial rupture during thrombolytic treatment of acute myocardial infarction

In serious haemorrhagic complications, streptokinase therapy should be discontinued and a proteinase inhibitor, e.g., aprotinin, should be given as follows. Initially 500 000 KIU (Kallikrein Inactivator Unit) up to one million KIU by slow intravenous injection or infusion. If necessary this should be followed by 200,000 KIU every four hours by intravenous drip until the bleeding stops. In addition, combination with synthetic antifibrinolytics is recommended. If necessary, clotting factors can be substituted. Additional administration of synthetic antifibrinolytics has been reported to be efficient in single cases of bleeding episodes.

Immune system disorders

Very Common: development of antistreptokinase antibodies (see also 4.4)

Common: allergic anaphylactic reactions, e.g. rash, flushing, itching, urticaria, angioneurotic oedema, dyspnoea, bronchospasm, hypotension

Very Rare: delayed allergic reactions, e.g. serum sickness, arthritis, vasculitis, nephritis, neuroallergic symptoms (polyneuropathy, e.g. Guillain Barré syndrome), severe allergic reactions up to shock including respiratory arrest.

Allergic reactions can largely be avoided by giving the infusion slowly. Moderate or mild allergic reactions can be managed with concomitant antihistamine and/or corticosteroid therapy. If a severe allergic reaction occurs the infusion of streptokinase should be discontinued immediately and the patient given the appropriate treatment. The current medical standards for shock treatment should be observed. Lysis therapy should be continued with homologous fibrinolytics, such as Urokinase or tPA.

Nervous system disorders

Rare: neurologic symptoms (e.g. dizziness, confusion, paralysis, hemiparesis, agitation, convulsion) in the context of cerebral haemorrhages or cardiovascular disorders with hypoperfusion of the brain

Eye disorders

Very rare: iritis/uveitis/iridocyclitis

Cardiac and vascular disorders

Common: at the start of therapy, hypotension, tachycardia, bradycardia

Very rare: crystal cholesterol embolism

During fibrinolytic therapy with streptokinase in patients with myocardial infarction, the following events have been reported as complications of myocardial infarction and/or symptoms of reperfusion:

Very common: hypotension, heart rate and rhythm disorders, angina pectoris

Common: recurrent ischaemia, heart failure, reinfarction, cardiogenic shock, pericarditis, pulmonary oedema

Uncommon: cardiac arrest (leading to respiratory arrest), mitral insufficiency, pericardial effusion, cardiac tamponade, myocardial rupture, pulmonary or peripheral embolism

These cardiovascular complications can be life-threatening and may lead to death.

During local lysis of peripheral arteries, distal embolization cannot be excluded.

Respiratory Disorders

Very rare: non-cardiogenic pulmonary oedema after intracoronary thrombolytic therapy in patients with extensive myocardial infarction

Gastrointestinal disorders

Common: nausea, diarrhoea, epigastric pain, vomiting

General disorders and administration site conditions

Common: headache, back pain, musculoskeletal pain, chills, fever, asthenia, malaise

Testing

Common: Transient elevations of serum transaminases and bilirubin

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.

4.9 Overdose

Long-term overdosage of streptokinase may induce the risk of rethrombosis by prolonged decrease of plasminogen. See also section 4.8 and 5.1.

Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Streptokinase (antithrombotic agents, enzymes)

Streptokinase is a highly purified streptokinase derived from β haemolytic streptococci of Lancefield group C. The activation of the endogenous fibrinolytic system is initiated by the formation of a streptokinase-plasminogen complex.

This complex possesses activator properties and converts plasminogen into the proteolytic and fibrinolytic active plasmin. The more plasminogen that is bound within this activator complex, the less plasminogen is left to be converted into its enzymatically active form. Therefore, high doses of streptokinase are associated with a lower bleeding risk and vice versa.

After intravenous administration and neutralisation of the individual antistreptokinase-antibody titre, streptokinase is immediately available systemically for activation of the fibrinolytic system.

Streptokinase has a very short half-life. The first rapid clearance from the plasma is due to the formation of the complex between streptokinase and streptokinase antibody. This complex is biochemically inert and is cleared rapidly from the circulation. Once the antibody has been neutralised, the streptokinase activates the plasminogen as described above.

5.2 Pharmacokinetic properties

The elimination kinetics of streptokinase follows a biphasic course. A small proportion of the dose is bound to anti-streptokinase antibodies and metabolised with a half-life of 18 minutes while most of it forms a streptokinase-plasminogen activator complex and is biotransformed with a half-life of about 80 minutes.

Peak fibrinolytic activity is found in the blood about 20 minutes after dosing.

Like other proteins, streptokinase is metabolised proteolytically in the liver and eliminated via the kidneys. Animal data suggest that streptokinase may also be excreted unchanged in the bile.

5.3 Preclinical safety data

In an Ames Test on Streptokinase, no evidence of mutagenic potential was found. No other preclinical safety studies have been performed on Streptokinase.

Pharmaceutical particulars

6.1 List of excipients

Human albumin, Aminoacetic acid (glycine), Mannitol.

6.2 Incompatibilities

No incompatibilities have been reported when Streptokinase is used as recommended. This medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

The shelf-life of unopened vials of Streptokinase 1 500 000 is 3 years.

6.4 Special precautions for storage

Do not store above +25°C and do not freeze.

Do not store the reconstituted solution for more than 24 hours in a refrigerator at +2°C to +8°C.

6.5 Nature and contents of container

Streptokinase 1 500 000 is supplied in glass vials with rubber closures and aluminium seal with plastic flip-top caps.

Streptokinase 1 500 000 is available in packages containing one vial.

6.6 Special precautions for disposal and other handling

The contents should be dissolved in 4-5 ml of physiological saline or water for injection. The solution should be swirled gently to facilitate quick reconstitution, but care should be taken to avoid foaming.

Streptokinase may be given by intravenous infusion in 50-200 ml of physiological saline, 5% glucose solution, 5% fructose solution, or Ringer-lactate solution.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

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

Streptokinase for Injection For Injection BP 15,00,000 IU Taj Pharma
(Streptokinase for Injection)

Patient information leaflet

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

Keep this leaflet. You may need to read it
If you have any further questions, ask your doctor or
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section

What is in this leaflet?

What Streptokinase for Injection is and what it is used
What you need to know before you are given Streptokinase for Injection.
How is given to you.
Possible side
How Streptokinase for Injection is
Contents of the pack and further

What Streptokinase for Injection is and what it is used for

Streptokinase for Injection contains a number of ingredients. The active substance is a protein called Streptokinase for Injection, an antithrombotic agent which dissolves blood clots.

You are being treated with Streptokinase for Injection because you have suffered a recent heart attack, which was caused by a blood clot blocking the blood supply to your heart. Streptokinase for Injection for Injection BP 15,00,000 IU is being given to you to break down the blood clot.

What you need to know before you are given Streptokinase for Injection.

You should not be treated with Streptokinase for Injection for Injection BP 15,00,000 IU if you:

are allergic to Streptokinase for Injection or any of the other ingredients in this medicine (listed in section 6)
are pregnant
are suffering from or have recently had internal bleeding
have recently suffered a stroke or a serious head injury
have recently had surgery, especially on your head (intracranial) or spine (intraspinal)
have a brain tumour or a tumour with a risk of bleeding
have uncontrollable high blood pressure
have problems with your blood vessels (e.g. weakness in an artery)
have a clotting disorder or are taking drugs to prevent blood clotting (anticoagulants)
have an unusual susceptibility to bleeding
have inflammation of the pancreas (acute pancreatitis) or inflammation in or around your heart (endocarditis or pericarditis)
have severe liver or kidney

Warnings and precautions

Talk to your doctor or nurse before you are given Streptokinase for Injection if you:

have recently had severe bleeding in your stomach (e.g. an ulcer) or another stomach or intestinal disorder that causes bleeding
have recently had a severe injury and have been resuscitated
are at risk of severe local bleeding for example if you have recently had an invasive operation (e.g. where you have had a tube or drip inserted into your body)
have recently given birth or had a miscarriage or an abortion
have any problems in the genital area or urinary tract, especially those with
have had blood poisoning that could cause clotting (septic thrombotic disease)
have a disease of the affecting the blood vessels of your brain (cerebrovascular disease)
have tuberculosis or similar lung diseases or severe bronchitis
have any heart or circulation problems or high blood pressure
have received any drug containing Streptokinase for Injection or have had an infection caused by streptococcal bacteria such as rheumatic fever or a throat infection
have damage to the eye caused by

Children

It is not recommended to use Streptokinase for Injection for Injection BP 15,00,000 IU in children, infants and neonates.

Other medicines and Streptokinase for Injection

Tell your doctor or nurse if you are taking or have recently taken any other medicines, including those obtained without a prescription.

In particular tell the doctor or nurse if you have been treated with any drugs that prevent blood clotting (anticoagulants). Examples of such drugs are heparins, coumarin derivatives, dipyridamole and dextrans.

Pregnancy and breast-feeding

You should not be given Streptokinase for Injection if you are pregnant.

You should not breastfeed your child while you are being treated with Streptokinase for Injection. Breast milk should be thrown away if you have been given Streptokinase for Injection within the last 24 hours.

How Streptokinase for Injection is given to you

Streptokinase for Injection for Injection BP 15,00,000 IU will be given to you by a doctor or nurse. Your doctor will decide how much will be given and for how long. It will be infused slowly into one of your veins with a drip.

It may also be infused by a drip into an artery supplying blood to your heart.

After treatment with Streptokinase for Injection, your doctor may decide to give you aspirin for about four weeks to help thin your blood.

If you are given more Streptokinase for Injection for Injection BP 15,00,000 IU than you should have been

If this medicine is given for too long, bleeding problems may occur. You may be at risk of another blood clot (thrombosis). The symptoms are listed in section 4 under possible side effects. Tell your doctor or nurse if you think you have been given too much.

Possible side effects.

Like all medicines, Streptokinase for Injection for Injection BP 15,00,000 IU can cause side effects, although not everybody gets them.

Immediately report allergic reactions such as skin rash, flushing, itching, blistering, swelling (may also affect the tongue or throat), or shortness of breath, low blood pressure (may feel light headed) to your doctor or nurse.

If you receive a lot of Streptokinase for Injection, you may be at risk of a blood clot (thrombosis).

Symptoms of a blood clot include:

unusual pain or swelling in your legs
sudden sharp pain in your chest
sudden difficulty breathing
an unusual, severe, or long-lasting headache
dizziness or

If you experience any of these side effects tell your doctor or nurse immediately.

Very common side effects (may affect more than 1 in 10 people)

development of antibodies (proteins in the blood that help fight disease) against the active ingredient Streptokinase for Injection

Common side effects (may affect up to 1 in 10 people)

bleeding, especially at the injection site, bruising of the skin, bleeding into the stomach, reproductive and urinary systems, nosebleed
slow or fast heartbeat
feeling or being sick, diarrhoea, stomach pain
headache, muscle pain including back pain, fever, chills, weakness, generally feeling unwell

Uncommon side effects (may affect up to 1 in 100 people)

bleeding into eyes, liver abdomen or joints, tearing of the spleen
stroke (cerebrovascular haemorrhage)

Rare side effects (may affect up to 1 in 1,000 people)

dizziness, confusion, agitation
seizures
weakness or paralysis on one or both sides of the body

Very rare side effects (may affect up to 1 in 10,000 people)

bleeding into the space around the heart, including tearing of the heart muscle
delayed allergic reactions, e.g. serum sickness (pain and swelling in joints and lymph nodes, rash, fall in blood pressure and shock), arthritis, inflammation of blood vessels and kidneys, numbness or pins and needles feeling in arms or legs
blockage of blood vessels caused by cholesterol crystals
fluid in the lungs (not caused by heart failure)
inflammation in the

The following events have been reported in patients with heart attack being treated with Streptokinase for Injection, but they may not have been caused by the medicine: irregular heartbeat, chest pain, lack of oxygen to the heart, heart failure, heart attack, heart shock, inflammation around the heart, fluid around the heart, stopping of heartbeat, heart valve

insufficiency, blockage of a blood vessel.

Reporting of side effects

If you get any side effects, talk to your doctor or nurse immediately. This includes any possible side effects not listed in this leaflet.

How Streptokinase for Injection is stored

Your medicine will be given to you by your doctor. Normally, you will not need to store this medicine.

Keep this medicine out of the sight and reach of children. Do not store above +25°C. Do not freeze.

After the injection has been prepared it may be kept in a fridge at +2°C to +8°C for up to 24 hours.

Do not use this medicine after the expiry date which is stated on the carton and vial label.

6. What Streptokinase for Injection contains

Each vial contains:
Streptokinase for Injection 15,00,000 IU
Excipients q.s.

The other ingredients are human albumin, glycine and mannitol.

What Streptokinase for Injection looks like and contents of the pack.

Streptokinase for Injection 1 500 000 is supplied in glass vials with rubber closures and aluminium seal with plastic flip-top caps.

Streptokinase for Injection 1 500 000 is available in packages containing one vial.

Each pack contains one vial with

1 500 000 IU of Streptokinase for Injection.