TIROFIBAN Solution for infusion Ref.[8520] Active ingredients: Tirofiban

This product is for hospital use only, by specialist physicians experienced in the management of acute coronary syndromes.

Tirofiban should be administered with unfractionated heparin and oral antiplatelet therapy, including ASA.

Posology

In patients who are managed with an early invasive strategy for NSTE-ACS but not planned to undergo angiography for at least 4 hours and up to 48 hours after diagnosis, Tirofiban is given intravenously at an initial infusion rate of 0.4 microgram/kg/min for 30 minutes. At the end of the initial infusion, Tirofiban should be continued at a maintenance infusion rate of 0.1 microgram/kg/min. Tirofiban should be given with unfractionated heparin (usually an intravenous bolus of 50-60 units[U]/ kg simultaneously with the start of Tirofiban therapy, then approximately 1,000 U per hour, titrated on the basis of the activated thromboplastin time [APTT], which should be about twice the normal value) and oral antiplatelet therapy, including but not limited to ASA (see section 5.1), unless contra-indicated.

In NSTE-ACS patients planning to undergo PCI, within the first 4 hours of diagnosis or in patients with acute myocardial infarction intending for primary PCI, Tirofiban should be administered utilizing an initial bolus of 25 microgram/kg given over a 3 minute period, followed by a continuous infusion at a rate of 0.15 microgram/kg/min for 12-24, and up to 48 hours. Tirofiban should be administered with unfractionated heparin (dosage as above) and oral antiplatelet therapy, including but not limited to ASA (see section 5.1), unless contra-indicated.

Elderly

No dosage adjustment is necessary for the elderly (see section 4.4).

Patients with severe kidney failure

In severe kidney failure (creatinine clearance <30 ml/min) the dosage of Tirofiban should be reduced by 50% (see sections 4.4 and 5.2).

Paediatric population

The safety and efficacy of Tirofiban in children aged < 18 years have not been established. No data are available.

Table 1 is provided as a guide to dosage adjustment by weight.

Table 1. Dosing Table:

Start and duration of therapy with Tirofiban

In patients who are managed with an early invasive strategy for NSTE-ACS but not planned to undergo angiography for at least 4 hours and up to 48 hours after diagnosis, Tirofiban 0.4 microgram/kg/min loading dose regimen should be initiated upon diagnosis. The recommended duration of the maintenance infusion should be at least 48 hours. Infusion of Tirofiban and unfractionated heparin may be continued during coronary angiography and should be maintained for at least 12 hours and not more than 24 hours after angioplasty/atherectomy. Once a patient is clinically stable and no coronary intervention procedure is planned by the treating physician, the infusion should be discontinued. The entire duration of treatment should not exceed 108 hours.

If the patient diagnosed with NSTE-ACS and managed with an invasive strategy undergoes angiography within 4 hours after the diagnosis, Tirofiban 25 microgram/kg dose bolus regimen should be initiated at the start of PCI with the infusion continued for 12-24 hours and up to 48 hours

In patients with acute myocardial infarction intended for primary PCI, the 25 microgram/ kg dose bolus regimen should be initiated as soon as possible after diagnosis.

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

Treatment with unfractionated heparin is initiated with an i.v. bolus of 50-60 U/kg and then continued with a maintenance infusion of 1,000 U per hour. The heparin dosage is titrated to maintain an APTT of approximately twice the normal value.

Unless contra-indicated, all patients should receive oral antiplatelet agents, including but not limited to ASA, before the start of Tirofiban (see section 5.1). This medication should be continued at least for the duration of the infusion of Tirofiban.

Most studies investigating the administration of Tirofiban as an adjunct to PCI have used ASA in combination with clopidogrel as oral antiplatelet therapy. The efficacy of the combination of Tirofiban with either prasugrel or ticagrelor has not been established in randomised controlled trials.

If angioplasty (PCI) is required, heparin should be stopped after PCI, and the sheaths should be withdrawn once coagulation has returned to normal, e.g. when the activated clotting time (ACT) is less than 180 seconds (usually 2-6 hours after discontinuation of heparin).

Method of administration

Tirofiban SOLUTION

Instructions for use

Do not withdraw solution directly from the infusion bag with a syringe.

To open: Tear or cut foil overpouch and remove infusion bag. Some opacity of the plastic due to moisture absorption during the sterilisation process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. Check for minute leaks by squeezing inner bag firmly. If leaks are found, discard solution as sterility may be impaired.

Do not use unless solution is clear and seal is intact.

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

CAUTION: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is completed.

Preparation for administration:

1. Suspend container from eyelet support.
2. Remove plastic protector from outlet port at bottom of container.
3. Attach administration set. Refer to complete directions accompanying set.

Use according to the dosage table above. Where the solution and container permit, parenteral drugs should be inspected for visible particles or discoloration before use.

Tirofiban should only be given intravenously and may be administered with unfractionated heparin through the same infusion tube.

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

Care should be taken to ensure that no prolongation of the infusion of the initial dose occurs and that miscalculation of the infusion rates for the maintenance dose on the basis of the patient’s weight is avoided.

Inadvertent overdose with tirofiban hydrochloride occurred in the clinical studies, up to 50 microgram/kg as a three minute bolus or 1.2 microgram/kg/min as an initial infusion. Overdose with up to 1.47 microgram/kg/min as a maintenance infusion rate has also occurred.

Symptoms of overdose

The symptom of overdose most commonly reported was bleeding, usually mucosal bleeding and localised bleeding at the arterial puncture site for cardiac catheterisation but also single cases of intracranial haemorrhages and retroperitoneal bleedings (see section 4.4 and section 5.1).

Measures

Overdose with tirofiban hydrochloride should be treated in accordance with the patient’s condition and the attending physician’s assessment. If treatment of haemorrhage is necessary, the Tirofiban infusion should be discontinued.

Transfusions of blood and/or thrombocytes should also be considered. Tirofiban can be removed by haemodialysis.

Shelf life: 36 months.

Do not freeze. Keep infusion bag in foil overpouch to protect from light.

250 ml flexible plastic IV bag with Twist-off port stopper, colourless, 3-layer polypropylene film. It is packed in a pre-printed foil overpouch.

Some opacity of the plastic due to moisture absorption during the sterilisation process may be observed. This is normal and does not affect the solution quality or safety.

The opacity will diminish gradually. Check for minute leaks by squeezing inner bag firmly. If leaks are found, discard solution as sterility may be impaired.

Any unused solution should be discarded.