Consumer medicine information

Rapilysin Powder for injection

Reteplase

BRAND INFORMATION

Brand name

Rapilysin Powder for injection

Active ingredient

Reteplase

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Rapilysin Powder for injection.

What is in this leaflet

This leaflet answers some common questions about RAPILYSIN injection.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking RAPILYSIN against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What RAPILYSIN is used for

RAPILYSIN contains the active ingredient reteplase.

RAPILYSIN is used to treat acute myocardial infarctions (also called “heart attacks”). This condition occurs when the blood flow to part of the heart is blocked.

This blockage causes that part of the heart muscle (called the myocardium) to start to die.

RAPILYSIN works by dissolving the blood clot that is blocking your heart blood vessel. It is best given within six hours of the start of any heart symptoms.

If a myocardial infarction is not treated quickly, then it may lead to minor to severe heart damage and sometimes, death.

There are many different types of medicines used to treat myocardial infarctions.

RAPILYSIN belongs to a group of medicines called thrombolytics.

RAPILYSIN is related to a normal substance found in the blood. RAPILYSIN only acts for a short period of time to dissolve clots.

Your doctor, however, may have prescribed RAPILYSIN for another purpose.

Ask your doctor if you have any questions about why RAPILYSIN has been prescribed for you.

This medicine is available only with a doctor’s prescription.

Before you are given RAPILYSIN

When you must not have RAPILYSIN

Do not use RAPILYSIN if:

  1. you have had an allergic reaction to RAPILYSIN or any ingredients listed at the end of this leaflet
  2. you have had prolonged heart massage (also called CPR) in the last 10 days
  3. you have a tendency for bleeding, either easily caused or slow in stopping
  4. you are being treated with anticoagulant medicines (used to thin the blood and prevent clots) such as warfarin (Marevan®, Coumadin®) or phenindione (Dindevan®)
  5. you have a growth, cancer or blood vessel problems within your head
  6. you have previously had a stroke
  7. you currently have very high blood pressure
  8. you have an active ulcer in your stomach or intestine
  9. you have poor blood flow through the liver (called portal hypertension)
  10. you have severe liver or kidney problems
  11. you have inflammation of your pancreas or the area around your heart, or an infection affecting your heart
  12. you have bleeding behind or in the eye
  13. you have recently (in the last 3 months) had:
    - severe bleeding
    - a major physical injury
    - major surgery
    - given birth
    - had a part of a body organ tested (biopsied)
    - had a needle in a major blood vessel.
  14. the package is torn or shows signs of tampering.

If you are not sure if you should be having RAPILYSIN, talk to your doctor.

Do not give RAPILYSIN to children.

Safety and effectiveness in children have not been established.

Before you are given it

Tell your doctor if:

  1. you are pregnant.
    RAPILYSIN is not generally recommended for use in pregnant women unless the benefits of treatment outweigh the risk to the unborn baby.
  2. you have any other health problems, especially the following:
    - a stroke, shock or apoplexy (apoplexy: sudden loss of consciousness followed by paralysis)
    - dizziness or blacking-out spells
    - high blood pressure
    - recent bleeding from your stomach, bowel or genitals, or blood in your urine.
  3. you are allergic to any other medicines, foods, dyes or preservatives.
  4. you are older than 75 years of age.
  5. you are breast-feeding or intend to breast-feed.
    It is not known whether RAPILYSIN passes into breast milk. You should discard any breast milk for 24 hours after the injections.

If you have not told your doctor about any of the above, tell them before you start taking RAPILYSIN.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you have bought from a pharmacy, supermarket or health food shop.

Some medicines may interfere with RAPILYSIN. These medicines include:

  • heparin, enoxaparin (Lovenox®, Clexane®), nadroparin (Fraxiparine®), danaparoid (Orgaran®), abciximab (ReoPro®) or tirofiban (Aggrastat®) injections
  • warfarin or phenindione tablets (Marevan®, Coumadin®, Dindevan®)
  • aspirin tablets or capsules
  • dipyridamole tablets (Persantin®)
  • ticlopidine tablets (Ticlid®)
  • clopidogrel tablets (Isocover®, Plavix®)
  • any other medicines you may be taking to prevent clotting

These medicines may be affected by RAPILYSIN, or may affect how well it works. You may need to use different amounts of your medicine, or you may need to take different medicines. Your doctor will advise you.

Your doctor or pharmacist has more information on medicines to be careful with or avoid during your treatment with RAPILYSIN.

Ask your doctor or pharmacist if you are not sure about this list of medicines.

No other medicines should be added to the RAPILYSIN injection solution.

How RAPILYSIN is given

How much is given

The dosage of RAPILYSIN is expressed in units (U). These units only have meaning for RAPILYSIN and cannot be compared to units (U) that are used for other medicines.

One vial of RAPILYSIN contains 10 units (10 U) of reteplase. 10 U of reteplase corresponds to 17.4 mg of the drug.

During the normal course of treatment, you will be given 2 vials worth of RAPILYSIN (20 U or 34.8 mg of reteplase).

How it is given

RAPILYSIN is given as an injection into a vein over approximately 2 minutes, when your doctor believes that you have had a myocardial infarction (heart attack).

Because RAPILYSIN is short acting, you will receive a second injection approximately 30 minutes later.

RAPILYSIN is not normally given again, unless you have another myocardial infarction.

You may receive other medicines for your condition as well, such as aspirin and heparin. Heparin must not be combined with RAPILYSIN in the same injection.

Side effects

Tell your doctor or nurse immediately if you do not feel well while you are receiving RAPILYSIN.

RAPILYSIN generally causes few side effects and helps most people with myocardial infarctions. However, it may have unwanted side effects in a few people, or you may have a problem caused by your recent myocardial infarction (heart attack). Side effects or further problems may require additional treatment.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor, pharmacist or nurse if you notice any of the following:

  • bruising at the site of injection
  • bleeding from the site of injection, or the gums, bowel or urine, or the eyes
  • low blood pressure causing fainting or dizziness
  • black-outs or loss of consciousness, numbness, inability to move parts of your body or difficulty speaking, confusion, abnormal thoughts, agitation, convulsions or fits.
    Bleeding into the brain is an uncommon serious side effect.
  • irregular or racing heart beats
  • nausea or vomiting
  • fevers
  • swelling, itching, shortness of breath, wheezing or cough. These can be signs of an allergic reaction.

These are some of the side effects of RAPILYSIN, though some of them may be caused by the myocardial infarction (heart attack) itself.

You may need urgent medical attention if some of these occur.

This is not a complete list of all possible side effects. Others may occur in some people and there may be some side effects not yet known.

Tell your doctor, pharmacist or nurse if you notice anything else that is making you feel unwell, even if it is not on this list.

Ask your doctor, pharmacist or nurse if you don’t understand anything on this list.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After receiving RAPILYSIN

Storage

RAPILYSIN will be stored in the pharmacy or on the hospital ward, in refrigerator, on a shelf or in a cupboard at a temperature below 25°C. Do not freeze the entire pack.

Product description

Availability

RAPILYSIN comes in one strength, being 10 units (17.4 mg) per vial.

RAPILYSIN comes in a pack of 2 vials, with 2 reconstitution spikes, 2 syringes with solvent (liquid) in each syringe and 2 needles.

What RAPILYSIN looks like

RAPILYSIN is a white powder, which is dissolved in sterile water to make a clear, colourless solution.

Ingredients

Active ingredient - reteplase

  • Each vial of RAPILYSIN powder contains 10 units (17.4 mg) reteplase

Inactive ingredients

  • Each vial of RAPILYSIN powder also contains:
    - tranexamic acid
    - phosphoric acid
    - polysorbate 80
    - potassium phosphate, dibasic
    - sucrose
  • Each syringe of solvent also contains:
    - water for injections

BRAND INFORMATION

Brand name

Rapilysin Powder for injection

Active ingredient

Reteplase

Schedule

S4

 

Name of the medicine

Reteplase (recombinant plasminogen activator, r-PA).

Excipients

Dibasic potassium phosphate, phosphoric acid, tranexamic acid, sucrose and polysorbate 80.
Solvent: sterile water for injections.
Rapilysin contains no preservative.

Description

Rapilysin is a sterile, purified, stable recombinant plasminogen activator (r-PA), (reteplase) concentrate produced from genetically engineered E. coli cells containing a cloned human gene for part of the plasminogen activator protein structure.
Rapilysin is a highly purified single chain protein with a molecular weight of 39 kD. Reteplase is obtained by genetic engineering technology, and is a variant of plasminogen activator comprising only the kringle 2 and protease domains. Rapilysin is a lyophilised powder for reconstitution prior to injection. Rapilysin is reconstituted with sterile water for injections.
Potency is expressed in units (U) using a reference standard which is specific for reteplase, and is not comparable for units used for other thrombolytic agents. 10 units of reteplase correspond to 17.4 mg of reteplase protein mass.

Pharmacology

Pharmacodynamics.

Reteplase is recombinant plasminogen activator which catalyses the cleavage of endogenous plasminogen to generate plasmin. Plasmin in turn degrades fibrinogen and fibrin, which is a component of the matrix of the thrombi, thereby exerting its thrombolytic effect.
Reteplase (10 + 10 U) dose dependently reduces plasma fibrinogen levels by about 75 to 90%. The fibrinogen level normalises within 2 days. As with other plasminogen activators a rebound phenomenon then occurs during which fibrinogen levels reach a maximum within 9 days and remain elevated for up to 18 days.

Pharmacokinetics.

Intravenous administration.

Following intravenous bolus injection (10 + 10 U) in AMI patients, reteplase antigen is distributed in plasma with a dominant half-life (t½α) of 18 ± 5 minutes and eliminated with a terminal half-life (t½β) of 5.5 hours ± 12.5 minutes at a clearance rate of 121 ± 25 mL/minute. Reteplase activity is cleared from the plasma at a rate of 283 ± 101 mL/minute resulting in a dominant half-life (t½α) of 14.6 ± 6.7 minutes and a terminal half-life (t½β) of 1.6 hours ± 39 minutes. Only minor amounts of reteplase were immunologically detected in urine. Exact details of the main elimination route in humans are not available and the consequences of hepatic or renal insufficiency are not known. Animal experiments (rats) indicate the liver and kidney to be the main organs of active uptake and lysosomal degradation.
Additional studies in human plasma samples in vitro suggest that complexation with C1-inactivator, α2-antiplasmin and α1-antitrypsin contribute to the inactivation of reteplase in plasma. The relative contribution of the inhibitors to inactivation of reteplase decreases as follows: C1-inactivator > α2-antiplasmin > α1-antitrypsin.
The half-life of reteplase was increased in patients with AMI as compared to healthy volunteers. An additional increase of half-life activity in patients with myocardial infarction and severely impaired liver and kidney function cannot be excluded, but no clinical data relating to the pharmacokinetics of reteplase in these patients is available. Animal data show that in cases of severe impairment of renal function with pronounced concomitant elevation of serum creatine and serum urea, an increase in half-life of reteplase has to be expected.

Clinical Trials

Reductions of plasma levels of plasminogen and α2-antiplasmin normalise within one to three days. Coagulation factor V, α2-macroglobulin and C1-esterase inhibitor are only slightly reduced and normalised within 1 to 2 days. Prothrombin degradation product (F1 + 2) levels and thrombin-antithrombin III complexes increase during thrombolysis indicating thrombin production of which the clinical relevance is unknown.
A large comparative mortality trial (INJECT) in approximately 6000 patients showed that reteplase reduced the incidence of heart failure (secondary efficacy criterion) in a significant manner and was at least equally effective in terms of reducing mortality (primary efficacy criterion) when compared to streptokinase. Patients received 5000 IU intravenous heparin bolus injection prior to administration of the first reteplase bolus.

Indications

Thrombolytic therapy of acute myocardial infarction (AMI) (within 6 hours after the onset of AMI symptoms).

Contraindications

Hypersensitivity to reteplase, polysorbate 80 or any of the other ingredients.
Because thrombolytic therapy increases the risk of bleeding, reteplase is contraindicated in the following situations: recent (< 10 days) prolonged and vigorous external heart massage;
known haemorrhagic diathesis;
patients with current concomitant therapy with oral anticoagulants (e.g. warfarin sodium);
intracranial neoplasm, arteriovenous malformation or aneurysm;
neoplasm with increased bleeding risk;
history of cerebrovascular accident;
severe uncontrolled hypertension;
active peptic ulceration;
portal hypertension (oesophageal varices);
severe liver or renal dysfunction;
acute pancreatitis, pericarditis, bacterial endocarditis;
diabetic haemorrhagic retinopathy or other haemorrhagic ophthalmic conditions;
within 3 months of severe bleeding, major trauma or major surgery (e.g. coronary artery bypass graft, intracranial or intraspinal surgery or trauma), obstetrical delivery, organ biopsy, previous puncture of noncompressible vessels.

Precautions

Current data generally do not support the use of thrombolytic therapy in patients when the ECG shows only ST depression (with the exception of those patients with a ‘true posterior’ infarct, as indicated by tall R waves and marked ST depression in leads V1 to V3).
One anaphylactoid/ anaphylactic reaction has been observed in the course of a clinical trial.
Reteplase should be used by physicians experienced in the use of thrombolytic treatment and with the facilities to monitor that use.
Each patient being considered for therapy with reteplase should be carefully evaluated.

Bleeding.

The most common complication encountered during reteplase therapy is bleeding. The concomitant use of heparin anticoagulation may contribute to bleeding. As fibrin is lysed during reteplase therapy, bleeding from recent puncture sites may occur. Therefore, thrombolytic therapy requires careful attention to all possible bleeding sites (including catheter insertion sites, arterial and venous puncture sites, cutdown sites and needle puncture sites). The use of rigid catheter as well as intramuscular injections and nonessential handling of the patient should be avoided during treatment with reteplase.
Caution should be employed when used with other medicinal products affecting haemostasis such as heparin, low molecular weight heparins, heparinoids, oral anticoagulants and antiplatelet agents other than acetylsalicylic acid, such as dipyridamole, ticlopidine, clopidogrel or glycoprotein IIb/IIIa receptor antagonists.
Should serious bleeding, in particular cerebral haemorrhage, occur, any concomitant heparin should be terminated immediately. In addition, the second bolus of reteplase should not be given if the serious bleeding occurs before it is administered. In general, however, it is not necessary to replace the coagulation factors because of the relatively short half-life of reteplase. Most patients who have bleeding can be managed by interruption of thrombolytic and anticoagulant therapy, volume replacement and manual pressure applied to an incompetent vessel. Protamine should be considered if heparin has been administered within 4 hours of the onset of bleeding. In patients who fail to respond to these conservative measures, judicious use of transfusion products may be indicated. Transfusions of cryoprecipitate, fibrinogen, fresh frozen plasma and platelets should be considered with clinical and laboratory reassessment after each administration. A target fibrinogen level of 1 g/L is desirable with cryoprecipitate or fibrinogen infusion.
In the following conditions the risks of reteplase therapy may be increased and should be weighed against the anticipated benefits: cerebrovascular disease; systolic blood pressure at entry > 160 mmHg; recent gastrointestinal or genitourinary bleeding (within 10 days); high likelihood of left heart thrombus, e.g. mitral stenosis with atrial fibrillation; septic thrombophlebitis or occluded arteriovenous cannula at seriously infected site; advanced age, i.e. over 75 years old; any other condition in which bleeding constitutes a significant hazard or would be particularly difficult because of its location.
At present, no sufficient data in patients with a diastolic blood pressure > 100 mmHg prior to thrombolytic therapy are available for reteplase.

Cholesterol embolisation.

Cholesterol embolisation has been reported rarely in patients treated with thrombolytic agents; the true incidence is unknown. This serious condition, which can be lethal, is also associated with invasive vascular procedures (e.g. cardiac catheterisation, angiography, vascular surgery) and/or anticoagulant therapy. Clinical features of cholesterol embolism may include livedo reticularis, ‘purple toe’ syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis, myocardial infarction, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction and rhabdomyolysis.

Arrhythmias.

Coronary thrombolysis may result in arrhythmias associated with reperfusion. It is strongly recommended that antiarrhythmic therapy for bradycardia and/or ventricular tachyarrhythmias (e.g. ventricular tachycardia or fibrillation) be available when reteplase is administered.

Seizure.

As with other thrombolytics, convulsions have been observed in isolated cases, and are most likely caused by transient cerebral ischaemia or embolisation (see Adverse Effects, Postmarketing).

Readministration.

Since at present there is no experience with readministration of reteplase, readministration is not recommended.
If an anaphylactoid reaction occurs, the injection should be discontinued immediately and appropriate therapy should be initiated.

Use in hepatic or renal insufficiency.

There is no clinical experience with use of reteplase in patients with severely impaired hepatic or renal function.

Use in children.

Safety and efficacy of reteplase in children has not been established.

Mutagenesis, carcinogenesis and impairment of fertility.

Reteplase was not genotoxic in a battery of tests for gene mutations and chromosomal damage. Long-term studies in animals have not been done to evaluate the carcinogenic potential of reteplase. No adverse effects on fertility were seen in male and female rats when reteplase was administered at intravenous doses up to 4.3 U/kg/day.

Use in pregnancy.

(Category C)
No experience in pregnant women is available for reteplase. Animal studies showed no evidence of embryotoxicity, fetotoxicity or teratogenicity in pregnant rats when reteplase was administered intravenously during organogenesis at doses up to 4.3 U/kg/day. In a preliminary study in rabbits, however, IV dosing at 0.9 U/kg/day caused abortion associated with haemorrhage in the genital tract. Potential embryotoxicity and teratogenicity have not been adequately assessed in rabbits, and perinatal effects have not been investigated. A potential risk of haemorrhage and abortion can be expected in pregnant women, and the use of reteplase in pregnancy is contraindicated except in life saving situations.

Use in lactation.

It is not known whether reteplase is excreted into breast milk, and there are no animal data on effects on postnatal development. Breast milk should be discarded within the first 24 hours after thrombolytic therapy.

Interactions

Heparin, vitamin K antagonists and drugs that alter platelet function (such as acetylsalicylic acid, dipyridamole and abciximab) may increase the risk of bleeding if administered prior to, during or after reteplase therapy. Attention should be paid to this effect especially during periods of low plasma fibrinogen (up to about 2 days after fibrinolytic therapy of AMI).
The combination of full dose reteplase and abciximab should be avoided due to an increased risk of bleeding. If a patient who has recently received abciximab requires treatment with reteplase, the doses of reteplase and heparin should be reduced.

Adverse Effects

Haemorrhage.

Very common (> 10%): injection site; common (1% to 10%): gastrointestinal, gingival, genitourinary; uncommon (< 1%): haemopericardium, retroperitoneal bleeding, cerebral haemorrhage, epistaxis.
Reports of intracranial bleeding, many of which are fatal, are of particular concern.
Systolic blood pressure > 160 mmHg before thrombolysis with reteplase was associated with greater risk for cerebral bleeding. Blood transfusions were required rarely.
Death and permanent disability are not uncommonly reported in patients who have experienced stroke (including intracranial bleeding) and other serious bleeding episodes.
The risk of intracranial bleeding and fatal intracranial bleeding increase with increasing age.

Cardiovascular.

Very common (> 10%): hypotension; common (1 to 10%): arrhythmias (e.g. complete AV block, ventricular tachycardia and fibrillation).
These cardiovascular events can be life threatening and may lead to death.

Hypersensitivity.

Hypersensitivity reactions (e.g. allergic reactions) have rarely been reported. Serious anaphylaxis/ anaphylactoid reactions have been observed in isolated cases.
Regarding reteplase, available evidence does not indicate an antibody mediated origin of these hypersensitivity reactions.

Other adverse effects.

Patients administered reteplase as treatment for myocardial infarction have experienced many events which are frequent sequelae of myocardial infarction and may or may not be attributable to reteplase therapy. These events include cardiogenic shock, arrhythmias (e.g. sinus bradycardia, accelerated idioventricular rhythm, ventricular premature depolarisations, supraventricular tachycardia, atrial fibrillation/ flutter), A-V block, pulmonary oedema, heart failure, cardiac arrest, recurrent ischaemia/ angina, reinfarction, mitral regurgitation, pericardial effusion, pericarditis, venous thrombosis and embolism, pulmonary embolism, cerebral embolism, ventricular septal defect and electromechanical dissociation. These events can be life-threatening and may lead to death. Other adverse events have been reported including nausea and/or vomiting and fever.

Postmarketing.

Haemorrhage.

Uncommon: eye haemorrhage and ecchymosis (see also Precautions for more information regarding bleeding).
Haematoma, haematemesis, melaena and haemoptysis.

Nervous system.

Rare: events related to the nervous system (e.g. convulsion, aphasia, speech disorder, delirium, acute brain syndrome, agitation, confusion, depression, psychosis) have been reported. Ischaemic or haemorrhagic cerebrovascular events may be contributing or underlying conditions (see also Precautions for information regarding seizures).

Application site.

A local reaction at injection site for example a burning sensation, can occur.

Dosage and Administration

Treatment with Rapilysin should be initiated as soon as possible after the onset of AMI symptoms.
Rapilysin is administered as a 10 + 10 U double bolus injection.
Each bolus should be administered as a slow intravenous injection over not more than 2 minutes. The second bolus is administered 30 minutes after administration of the first bolus injection.
The bolus injection is given via an intravenous line. Ensure that the injection is not mistakenly given paravenously.
Heparin and Rapilysin are incompatible when combined in solution. Other incompatibilities may also exist. No other medication should be added to the injection solution.
In those patients where the same line has to be used, this line (including Y-line) must be flushed thoroughly with 0.9% sodium chloride or 5% dextrose solution prior to and following the Rapilysin injection.
Heparin and acetylsalicylic acid should be administered before and following the administration of reteplase to reduce the risk of rethrombosis. The recommended heparin dose is 5000 IU given as a bolus injection prior to reteplase therapy followed by an infusion of 1000 IU/hour starting after the second reteplase bolus. Heparin should be administered for at least 24 hours, preferably for 48 (-72) hours, aiming to keep aPTT values 1.5 to 2 times normal.
The initial dose of acetylsalicylic acid prior to thrombolysis should be at least 250 mg (250 to 350 mg) followed by 75 to 150 mg/day at least until discharge.

Instructions for use/ handling.

1. Use aseptic technique throughout.
2. Remove the protective flip-cap from the vial of reteplase and clean the rubber closure with an alcohol wipe.
3. Open the package containing the reconstitution spike, remove the protective cap from the Luer-Lok port of the reconstitution spike.
4. Open the package containing the 10 mL syringe with Luer tip. Remove the tip cap from the syringe and connect the syringe to the reconstitution spike.
5. Remove the protective cap from the spike end of the reconstitution spike and insert the spike through the rubber closure into the vial of reteplase. Transfer the 10 mL of solvent into the vial of reteplase.
6. With the reconstitution spike and syringe still attached to the vial, swirl the vial gently to dissolve the reteplase powder. Do not shake. The reconstituted preparation results in a clear, colourless solution.
7. Withdraw 10 mL of reteplase solution back into the syringe. A small amount of solution may remain in the vial due to overfill.
8. Disconnect the syringe from the reconstitution spike and attach the sterile needle provided. The dose is now ready for intravenous administration.

Administration.

The injection is prepared by reconstituting the lyophilisate with the content of the accompanying syringe (sterile water for injections).
Do not mix with other drugs or use any solvents other than sterile water for injections.
Heparin and Rapilysin are incompatible when combined in solution. Other incompatibilities may also exist. No other medication should be added to the injection solution.
Only solutions which are clear, colourless and practically free of visible particles may be injected. Discard any unused solution.
The reconstituted solution may be held at 2 to 8°C for not more than 4 hours.

Overdosage

In the event of overdosage one may expect depletion of fibrinogen and other blood coagulation components (e.g. coagulation factor V) with a consequent risk of bleeding.
Should serious bleeding, in particular cerebral haemorrhage, occur, any concomitant heparin should be terminated immediately. In addition, the second bolus of reteplase should not be given if the serious bleeding occurs before it is administered. In general, however, it is not necessary to replace the coagulation factors because of the relatively short half-life of reteplase. Most patients who have bleeding can be managed by interruption of thrombolytic and anticoagulant therapy, volume replacement and manual pressure applied to an incompetent vessel. Protamine should be considered if heparin has been administered within 4 hours of the onset of bleeding. In patients who fail to respond to these conservative measures, judicious use of transfusion products may be indicated. Transfusions of cryoprecipitate, fibrinogen, fresh frozen plasma and platelets should be considered with clinical and laboratory reassessment after each administration. A target fibrinogen level of 1 g/L is desirable with cryoprecipitate or fibrinogen infusion.
Treatment of overdose should consist of general supportive measures.
Contact the Poisons Information Centre for advice on management of overdosage.

Presentation

Vials, 10 U (rDNA) nominal activity (lyophilised powder for reconstitution): 2's (plus single use prefilled syringes of water for injections 10 mL: 2's; reconstitution devices: 2's; and needles: 2's).

Storage

Rapilysin must not be used after the expiry date.
Store below 25°C. Do not freeze.
Protect from light.
To reduce microbiological hazard, use as soon as practicable after reconstitution/ preparation. If storage is necessary, hold at 2 to 8°C for not more than 4 hours.

Poison Schedule

S4.