AGREDUR READY 50 mcg/ml I.V. solution for infusion

THE FOLLOWING INFORMATION IS INTENDED FOR HEALTHCARE PROFESSIONALS ADMINISTERING THIS MEDICINE.

This product should only be administered in hospitals, by specialist physicians experienced in the treatment of acute coronary syndromes. AGREDUR READY should be administered in combination with fractional heparin and oral antiplatelet therapy including acetylsalicylic acid (ASA).

Administration frequency and duration

In non-ST elevation unstable angina patients managed with an early invasive strategy in whom angiography is not planned for at least 4 hours and up to 48 hours after diagnosis, AGREDUR READY is administered intravenously at an initial infusion rate of 0.4 micrograms/kg/min for 30 minutes. At the end of the initial infusion, AGREDUR READY should be continued at a maintenance infusion rate of 0.1 micrograms/kg/min. AGREDUR READY is administered with unfractionated heparin (generally given as an intravenous bolus dose of 5000 U (units) at the start of AGREDUR READY treatment, then titrated to approximately 1000 U/hour based on activated partial thromboplastin time which should be maintained at approximately twice normal) and antiplatelet therapy including but not limited to ASA, unless contraindicated.

Patients undergoing Percutaneous Coronary Intervention

In patients with non-ST elevation acute coronary syndrome in whom percutaneous coronary intervention is planned within the first 4 hours after diagnosis, or in patients with acute myocardial infarction primarily intended for percutaneous coronary intervention, it should be administered following an initial bolus of 25 micrograms/kg tirofiban over 3 minutes, with a continuous infusion at 0.15 micrograms/kg/minute for 12-24 hours and up to 48 hours. Tirofiban is administered with unfractionated heparin (at the dose given above) and antiplatelet therapy including but not limited to ASA, unless contraindicated.

Initiation of AGREDUR READY treatment and treatment duration

In non-ST elevation acute coronary syndrome patients managed with an early invasive strategy in whom angiography is not planned for at least 4 hours and up to 48 hours after diagnosis, the 0.4 micrograms/kg/min loading dose regimen should be initiated upon diagnosis. The 0.4 micrograms/kg/min loading dose regimen should be initiated. The recommended duration of maintenance infusion should be at least 48 hours. AGREDUR READY and unfractionated heparin infusion may be continued during coronary angiography and should be maintained for at least 12 hours and up to 24 hours after angioplasty/atherectomy. Infusion should be discontinued when the patient is clinically stabilized and no coronary intervention procedure is planned by the treating physician. The total treatment duration should not exceed 108 hours.

In patients diagnosed with non-ST elevation acute coronary syndrome (NSTE-ACS) who are treated with an invasive strategy and undergo angiography within 4 hours after diagnosis, a 25 micrograms/kg tirofiban bolus dose should be initiated at the start of percutaneous coronary intervention (PCI), and continued with infusion for 18-24 hours and up to 48 hours.

In patients with acute myocardial infarction primarily directed to percutaneous intervention (PCI), the bolus dose regimen should be initiated as soon as possible after diagnosis.

Concurrent treatment (unfractionated heparin, oral antiplatelet therapy including ASA)

Treatment with unfractionated heparin is initiated with 5000 U, I.V. bolus and then continued with a maintenance infusion of 1000 U per hour. Heparin dose is titrated to maintain aPTT at approximately twice the normal value.

Unless contraindicated, all patients should receive oral antiplatelet agents including but not limited to ASA before starting AGREDUR READY (see Summary of Product Characteristics). This medicine should be continued at least during the duration of AGREDUR READY infusion.

In most studies investigating the use of tirofiban as an adjunct to percutaneous intervention, clopidogrel has been used as oral antiplatelet therapy together with ASA. The efficacy of the combination of tirofiban with prasugrel or ticagrelor has not been established in randomized controlled studies.

If angioplasty (PTCA) is required, heparin should be discontinued after PTCA, and sheaths should be removed as soon as coagulation returns to normal, i.e., when activated clotting time (ACT) falls below 180 seconds (usually 2-6 hours after heparin is discontinued).

• No dosage adjustment is required for the elderly.
• In severe renal impairment (creatinine clearance < 30 mL/min), the dose should be reduced by 50%.
• There is no experience with tirofiban treatment in the pediatric population; therefore, use is not recommended.

Incompatibilities

Incompatibility with diazepam has been identified. Therefore, tirofiban and diazepam should not be administered in the same intravenous line.

Method of administration

Using the container

To open: Tear the packaging from the top and remove the bag containing the solution. Some opacity may be seen on the plastic due to moisture absorption during sterilization. This is normal and does not affect the quality and safety of the solution. The opacity will disappear over time. Check the inner bag by squeezing for leakage. If leakage is found, discard the solution as sterility may be compromised. Do not use if the solution is not clear or if the packaging is damaged.

Do not add supplementary medication or withdraw solution directly from the bag with a syringe.

WARNING: Do not use plastic containers in series connections. This type of use can cause air embolism due to residual air being withdrawn from the first container before fluid delivery from the secondary container is complete.

Preparation for administration

1. Hang the medicine bag on an IV pole.
2. Twist the plastic twist-off at the outlet at the bottom of the container.
3. Attach the administration set. Refer to the accompanying set for instructions to complete.
4. Use according to the dosage table.

Parenteral products should be inspected visually for particulate matter and discoloration prior to use, as permitted.

AGREDUR READY should only be given by the intravenous route and can be administered through the same infusion line with unfractionated heparin.

It is recommended that AGREDUR READY be administered using a calibrated infusion set with sterile equipment.

Care should be taken to avoid errors when calculating the initial dose infusion duration and maintenance dose infusion rates based on patient body weight.

A guide for dose adjustment based on body weight is provided.