Tirofiban (GPIIb/IIIa Inhibitor — ACS/PCI)

SCOPE: the regimen above is the UK SPC §4.2 bolus regimen, for 'NSTE-ACS patients planned to undergo PCI within the first 4 hours of diagnosis or in patients with acute myocardial infarction intended for primary PCI' — verbatim: 'Aggrastat 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.' || THE SECOND UK REGIMEN (same indication, different timing pathway), verbatim §4.2: '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, Aggrastat is given intravenously at an initial infusion rate of 0.4 microgram/kg/min for 30 minutes. At the end of the initial infusion, Aggrastat should be continued at a maintenance infusion rate of 0.1 microgram/kg/min.' For that regimen 'The recommended duration of the maintenance infusion should be at least 48 hours.' || NO ABSOLUTE DOSE CEILING EXISTS IN EITHER LABEL, so maxDose is deliberately empty — every ceiling in the sources is either a rate (0.15 microgram/kg/min) or a duration. The duration ceiling, verbatim §4.2: 'The entire duration of treatment should not exceed 108 hours.' Infusion of Aggrastat 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.' || MANDATORY CO-THERAPY, verbatim §4.2: '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 Aggrastat.' §4.4: 'The administration of Aggrastat alone without unfractionated heparin is not recommended.' 'The efficacy of the combination of Aggrastat with either prasugrel or ticagrelor has not been established in randomised controlled trials.' || SHEATH REMOVAL, verbatim §4.2: 'If angioplasty (PCI) is required, heparin should be stopped after PCI, and the sheaths should be withdrawn once coagulation has returned to normal, e.g. when the activated clotting time (ACT) is less than 180 seconds (usually 2-6 hours after discontinuation of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).' || US LABEL DIFFERENCES (§2.1): 'The recommended dosage is 25 mcg/kg administered intravenously within 5 minutes and then 0.15 mcg/kg/min for up to 18 hours' — bolus over 5 minutes rather than 3, and a maximum of 18 hours rather than 12-48. The US renal threshold is also different (see renalAdjustment). || PAEDIATRIC — none. §4.2: 'The safety and efficacy of Aggrastat in children aged < 18 years have not been established. No data are available.' §4.4: 'There is no therapeutic experience with Aggrastat in children, thus, the use of Aggrastat is not recommended in these patients.' US §8.4: 'Safety and effectiveness in pediatric patients have not been established.' For any under-18 patient, verify against a children's formulary and specialist advice. || STOP RULES, §4.4: 'Aggrastat infusion should be stopped immediately if circumstances arise that necessitate thrombolytic therapy (including acute occlusion during PCI) or if the patient must undergo an emergency coronary artery bypass graft (CABG) operation or requires an intra-aortic balloon pump.' 'In cases of major or uncontrollable bleeding, tirofiban hydrochloride should be discontinued immediately.' || ADMINISTRATION CARE, §4.2: '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.' A weight-banded ml/hr dosing table (30 kg to 153 kg, for both regimens and for severe kidney failure) is provided in §4.2 Table 1 of the SPC.