Tirofiban parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Infusions of tirofiban
Drugs List
Therapeutic Indications
Uses
Non ST elevation acute coronary syndrome: prevention of early MI
STEMI patients intended for PCI: reduction of major cardiovascular events
Prevention of early myocardial infarction in patients presenting with unstable angina or non-Q-wave myocardial infarction, with the last episode of chest pain occurring within 12 hours and with ECG changes and/or elevated cardiac enzymes.
Patients most likely to benefit from tirofiban treatment are those at high risk of developing myocardial infarction within the first 3 to 4 days after onset of acute angina symptoms including for instance those that are likely to undergo an early percutaneous coronary intervention (PCI).
Reduction of major cardiovascular events in patients with acute myocardial infarction (STEMI) intended for primary PCI.
Dosage
Tirofiban is intended for use with acetylsalicylic acid (aspirin) and unfractionated heparin.
Adults
In patients who are managed with an early invasive strategy for Non ST Elevation Acute Coronary Syndrome (NSTE-ACS) and 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 400 nanograms/kg/minute for 30 minutes. At the end of the initial infusion, tirofiban should be continued at a maintenance dose of 100 nanograms /kg/minute.
Tirofiban should be administered with unfractionated heparin ( the manufacturer of tirofiban suggests an intravenous bolus of 50 to 60 units/kg simultaneously with the start of tirofiban therapy, then approximately 1,000 units per hour, titrated on the basis of the activated thromboplastin time (APTT), which should be about twice the normal value) and antiplatelet therapy, unless contraindicated. Consult product literature to verify doses of heparin.
The following is provided as a guide to dosage adjustment by weight using a solution containing 50 microgram/ml:
Patient weighing 30 to 37 kg:
30 minute loading infusion rate = 16 ml/hour and maintenance infusion rate = 4 ml/hour
Patient weighing 38 to 45 kg:
30 minute loading infusion rate = 20 ml/hour and maintenance infusion rate = 5 ml/hour
Patient weighing 46 to 54 kg:
30 minute loading infusion rate = 24 ml/hour and maintenance infusion rate = 6 ml/hour
Patient weighing 55 to 62 kg:
30 minute loading infusion rate = 28 ml/hour and maintenance infusion rate = 7 ml/hour
Patient weighing 63 to 70 kg:
30 minute loading infusion rate = 32 ml/hour and maintenance infusion rate = 8 ml/hour
Patient weighing 71 to 79 kg:
30 minute loading infusion rate = 36 ml/hour and maintenance infusion rate = 9 ml/hour
Patient weighing 80 to 87 kg:
30 minute loading infusion rate = 40 ml/hour and maintenance infusion rate = 10 ml/hour
Patient weighing 88 to 95 kg:
30 minute loading infusion rate = 44 ml/hour and maintenance infusion rate = 11 ml/hour
Patient weighing 96 to 104 kg:
30 minute loading infusion rate = 48 ml/hour and maintenance infusion rate = 12 ml/hour
Patient weighing 105 to 112 kg:
30 minute loading infusion rate = 52 ml/hour and maintenance infusion rate = 13 ml/hour
Patient weighing 113 to 120 kg:
30 minute loading infusion rate = 56 ml/hour and maintenance infusion rate = 14 ml/hour
Patient weighing 121 to 128 kg:
30 minute loading infusion rate = 60 ml/hour and maintenance infusion rate = 15 ml/hour
Patient weighing 129 to 137 kg:
30 minute loading infusion rate = 64 ml/hour and maintenance infusion rate = 16 ml/hour
Patient weighing 138 to 145 kg:
30 minute loading infusion rate = 68 ml/hour and maintenance infusion rate = 17 ml/hour
Patient weighing 146 to 153 kg:
30 minute loading infusion rate = 72 ml/hour and maintenance infusion rate = 18 ml/hour
Patients undergoing PCI demonstrated clinical efficacy with treatment of tirofiban utilizing an initial bolus of 25 microgram/kg given over a 3 minute period, followed by a continuous infusion at a rate of 150 nanograms/kg/minute for 12 to 24, and up to 48 hours ( See table below). Tirofiban should be administered with unfractionated heparin and oral antiplatelet agents, unless contraindicated.
The following is provided as a guide to dosage adjustment by weight using a solution containing 50 microgram/ml:
Patient weighing 30 to 37 kg:
Bolus dose over 3 minutes = 17 ml and maintenance infusion rate = 6 ml/hour
Patient weighing 38 to 45 kg:
Bolus dose over 3 minutes = 21 ml and maintenance infusion rate = 7 ml/hour
Patient weighing 46 to 54 kg:
Bolus dose over 3 minutes = 25 ml and maintenance infusion rate = 9 ml/hour
Patient weighing 55 to 62 kg:
Bolus dose over 3 minutes = 29 ml and maintenance infusion rate =11 ml/hour
Patient weighing 63 to 70 kg:
Bolus dose over 3 minutes = 33 ml and maintenance infusion rate = 12 ml/hour
Patient weighing 71 to 79 kg:
Bolus dose over 3 minutes = 38 ml and maintenance infusion rate = 14 ml/hour
Patient weighing 80 to 87 kg:
Bolus dose over 3 minutes = 42 ml and maintenance infusion rate = 15 ml/hour
Patient weighing 88 to 95 kg:
Bolus dose over 3 minutes = 46 ml and maintenance infusion rate = 16 ml/hour
Patient weighing 96 to 104 kg:
Bolus dose over 3 minutes = 50 ml and maintenance infusion rate = 18 ml/hour
Patient weighing 105 to 112 kg:
Bolus dose over 3 minutes = 54 ml and maintenance infusion rate = 20 ml/hour
Patient weighing 113 to 120 kg:
Bolus dose over 3 minutes = 58 ml and maintenance infusion rate = 21 ml/hour
Patient weighing 121 to 128 kg:
Bolus dose over 3 minutes = 62 ml and maintenance infusion rate = 22 ml/hour
Patient weighing 129 to 137 kg:
Bolus dose over 3 minutes = 67 ml and maintenance infusion rate = 24 ml/hour
Patient weighing 138 to 145 kg:
Bolus dose over 3 minutes = 71 ml and maintenance infusion rate = 25 ml/hour
Patient weighing 146 to 153 kg:
Bolus dose over 3 minutes = 75 ml and maintenance infusion rate = 27 ml/hour
Start and duration of therapy:
In patients who are managed with an early invasive strategy for NSTE-ACS and not planning to undergo angiography for at least 4 hours and up to 48 hours after diagnosis, the tirofiban 400 nanograms/kg/minute loading dose regimen should be initiated upon diagnosis. The recommended duration 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, the tirofiban 25 microgram/kg dose bolus regimen should be initiated at the start of PCI with the infusion continued for 12 to 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.
Elderly
(See Dosage; Adult)
Patients with Renal Impairment
There is evidence from clinical studies that the risk of bleeding increases with decreasing creatinine clearance and hence also reduced plasma clearance of tirofiban. Patients with decreased renal function (creatinine clearance less than 60 ml/minute) should therefore be carefully monitored.
Patients with severe renal failure whose creatinine clearance is less than 30 ml/minute should have a reduction of dose of 50%. See the table below for a guide to dosage in patients with severe renal impairment.
The following is provided as a guide to dosage adjustment by weight using a solution containing 50 microgram/ml:
In place of the of the 400 nanogram/kg/minute use the following:
Patient weighing 30 to 37 kg:
30 minute loading infusion rate = 8 ml/hour and maintenance infusion rate = 2 ml/hour
Patient weighing 38 to 45 kg:
30 minute loading infusion rate = 10 ml/hour and maintenance infusion rate = 3 ml/hour
Patient weighing 46 to 54 kg:
30 minute loading infusion rate = 12ml/hour and maintenance infusion rate = 3 ml/hour
Patient weighing 55 to 62 kg:
30 minute loading infusion rate = 14 ml/hour and maintenance infusion rate = 4 ml/hour
Patient weighing 63 to 70 kg:
30 minute loading infusion rate = 16 ml/hour and maintenance infusion rate = 4 ml/hour
Patient weighing 71 to 79 kg:
30 minute loading infusion rate = 18 ml/hour and maintenance infusion rate = 5 ml/hour
Patient weighing 80 to 87 kg:
30 minute loading infusion rate = 20 ml/hour and maintenance infusion rate = 5 ml/hour
Patient weighing 88 to 95 kg:
30 minute loading infusion rate = 22 ml/hour and maintenance infusion rate = 6 ml/hour
Patient weighing 96 to 104 kg:
30 minute loading infusion rate = 24 ml/hour and maintenance infusion rate = 6 ml/hour
Patient weighing 105 to 112 kg:
30 minute loading infusion rate = 26 ml/hour and maintenance infusion rate = 7 ml/hour
Patient weighing 113 to 120 kg:
30 minute loading infusion rate = 28 ml/hour and maintenance infusion rate = 7 ml/hour
Patient weighing 121 to 128 kg:
30 minute loading infusion rate = 30 ml/hour and maintenance infusion rate = 8 ml/hour
Patient weighing 129 to 137 kg:
30 minute loading infusion rate = 32 ml/hour and maintenance infusion rate = 8 ml/hour
Patient weighing 138 to 145 kg:
30 minute loading infusion rate = 34 ml/hour and maintenance infusion rate = 9 ml/hour
Patient weighing 146 to 153 kg:
30 minute loading infusion rate = 36 ml/hour and maintenance infusion rate = 9 ml/hour
In place of the 25 microgram/kg use the following doses:
Patient weighing 30 to 37 kg:
8 ml bolus injection and maintenance infusion rate = 3 ml/hour
Patient weighing 38 to 45 kg:
10 ml bolus injection and maintenance infusion rate = 4 ml/hour
Patient weighing 46 to 54 kg:
13 ml bolus injection and maintenance infusion rate = 5 ml/hour
Patient weighing 55 to 62 kg:
15 ml bolus injection and maintenance infusion rate = 5 ml/hour
Patient weighing 63 to 70 kg:
17 ml bolus injection and maintenance infusion rate = 6 ml/hour
Patient weighing 71 to 79 kg:
19 ml bolus injection and maintenance infusion rate = 7 ml/hour
Patient weighing 80 to 87 kg:
21 ml bolus injection and maintenance infusion rate = 8 ml/hour
Patient weighing 88 to 95 kg:
23 ml bolus injection and maintenance infusion rate = 8 ml/hour
Patient weighing 96 to 104 kg:
25 ml bolus injection and maintenance infusion rate = 9 ml/hour
Patient weighing 105 to 112 kg:
27 ml bolus injection and maintenance infusion rate = 10 ml/hour
Patient weighing 113 to 120 kg:
29 ml bolus injection and maintenance infusion rate = 10 ml/hour
Patient weighing 121 to 128 kg:
31 ml bolus injection and maintenance infusion rate = 11 ml/hour
Patient weighing 129 to 137 kg:
33 ml bolus injection and maintenance infusion rate = 12 ml/hour
Patient weighing 138 to 145 kg:
35 ml bolus injection and maintenance infusion rate = 13 ml/hour
Patient weighing 146 to 153 kg:
37 ml bolus injection and maintenance infusion rate = 13 ml/hour
Start and duration of therapy:
(See Dosage; Adult)
Additional Dosage Information
Concurrent heparin and acetylsalicylic acid (aspirin) therapy:
Tirofiban should be given with unfractionated heparin. The manufacturer of tirofiban suggests an intravenous bolus of 50 to 60 units/kg of heparin simultaneously with the start of tirofiban therapy, then approximately 1000 units per hour, titrated on the basis of the activated thromboplastin time (APTT), which should be maintained at about twice the normal value. This may be given using the same infusion tube as for tirofiban, unless contraindicated. Consult product literature to verify dose of heparin.
All patients should be given oral antiplatelet agents prior to tirofiban therapy, unless contra-indicated. This should continue for at least the duration of the infusion of tirofiban.
If angioplasty (PCI) is required, heparin should be stopped after PCI, and the sheaths withdrawn once coagulation has returned to normal e.g. when the activated clotting time is less than 180 seconds (usually 2 to 6 hours after discontinuation of heparin).
Administration
For intravenous infusion.
Contraindications
Children under 18 years
Haemorrhage
Patients requiring thrombolytic therapy
Platelet count below 100 x 10 to the power of 9/ L
Recent haemorrhage
Within 6 weeks of surgery
Within 6 weeks of trauma
Breastfeeding
Coagulopathy
History of glycoprotein IIb/IIIa antagonist induced thrombocytopenia
History of haemorrhagic cerebrovascular accident
History of intracranial disorder
Malignant hypertension
Severe hepatic impairment
Within 30 days of a cerebrovascular accident
Precautions and Warnings
Elderly
Haemoglobin concentration below 11g / dL
Haemorrhage within previous 12 months
Platelet count below 150 x 10 to the power of 9 / L
Recent organ biopsy
Restricted sodium intake
Spinal/epidural anaesthesia
Underweight patients
Within 2 weeks of prolonged or traumatic cardiopulmonary resuscitation
Within 24 hours of puncture of a non-compressible blood vessel
Within 3 months of major surgery
Within 3 months of trauma
Within 48 hours of thrombolytic therapy
Abnormal platelet function
Acute cardiac failure
Acute pericarditis
Aortic dissection
Blood in stool
Cardiogenic shock
Chronic cardiac failure
Haematuria
Haemorrhagic retinopathy
Hepatic impairment
History of coagulopathy
History of vasculitis
Peptic ulcer
Pregnancy
Recent lithotripsy
Renal impairment - creatinine clearance 30-60ml/minute
Uncontrolled hypertension
Vasculitis
Reduce dose in patients with creatinine clearance below 30ml/min
Sodium content of formulation may be significant
Treatment to be initiated and supervised by a specialist
Aspirin and heparin should be given concurrently
Caution when puncturing femoral artery: esp prone to increased bleed rates
Do not use if solution is discoloured or particulates are apparent
Ensure minimal intramuscular injections during treatment
Ensure minimal vascular punctures during treatment
Limited experience with re-administration
Only obtain intravenous access at compressible sites of the body
Use urinary catheter/nasotracheal/nasogastric tube cautiously
Monitor full blood count prior to and within 2-6 hrs of starting treatment
Document and monitor all vascular puncture sites
Monitor APTT throughout treatment and adjust dose accordingly
Monitor for bleeding during treatment
Monitor haematological parameters daily throughout therapy
Discontinue if thrombocytopenia occurs
Discontinue if circumstances arise that require thrombolytic therapy
Discontinue if emergency cardiac surgery necessary
Discontinue if intra-aortic balloon pump necessary
Discontinue if severe haemorrhage occurs
The efficacy and safety of tirofiban has not been investigated in combination with low molecular weight heparins.
Monitor patients for bleeding during treatment. If treatment of haemorrhage is necessary, discontinuation of tirofiban should be considered.
Use tirofiban with caution and monitor the heparin effect in the elderly, female and/or low body weight patients and carefully monitor. The elderly and/or female patients had a higher incidence of bleeding complications than younger or male patients, respectively. Patients with a low body weight had a higher incidence of bleeding than patients with a higher body weight.
During treatment with tirofiban in patients with a femoral artery line there is a significant increase in bleeding rates, especially in the femoral artery area, where the catheter sheath is introduced. Care should be taken to ensure that only the anterior wall of the femoral artery is punctured. Arterial sheaths may be removed when coagulation has returned to normal, e.g. when activated clotting time is less than 180 seconds, (usually 2 to 6 hours after discontinuation of heparin).
After removal of the introducer sheath, careful haemostasis should be ensured under close observation.
Pregnancy and Lactation
Pregnancy
Use tirofiban with caution in pregnancy.
There is limited information at the time of writing. The primary risk, however appears to be from maternal haemorrhage during drug administration. If this is adequately controlled, the benefits of the drug far outweigh the unknown risks to the foetus (Briggs, 2015).
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Tirofiban is contraindicated in breastfeeding.
At the time of writing no reports describing the use of tirofiban during human breastfeeding have been located. The molecular weight (about 441 for the non hydrated free base), limited metabolism, and moderate plasma protein binding (65%) suggest that the drug will be excreted into breast milk. The effect of this exposure on a nursing infant is unknown, as is its oral bioavailability. However, the safest course is to withhold breastfeeding during the infusion (Briggs, 2015).
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Side Effects
Anaphylactic reaction
Bleeding
Blood in stool
Bronchospasm
Cardiac tamponade
Chills
Decrease in haemoglobin and haematocrit
Ecchymosis
Epidural haematoma
Epistaxis
Fever
Gastrointestinal bleeding
Gingival bleeding
Haematemesis
Haematoma
Haematuria
Haemopericardium
Haemoptysis
Haemorrhage (injection site)
Haemorrhoidal bleeding
Headache
Hypersensitivity reactions
Intracranial bleeding
Nausea
Occult blood in urine
Post operative wound haemorrhage
Pulmonary haemorrhage
Reduced platelet count
Retroperitoneal bleeding
Thrombocytopenia
Urticaria
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: July 2016
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press Accessed on 13 July 2016.
Summary of Product Characteristics: Aggrastat 50 mcg/ml Solution for infusion. Correvio UK Ltd. Revised December 2014.
Summary of Product Characteristics: Aggrastat 250 mcg/ml Concentrate for solution for infusion. Correvio UK Ltd. Revised March 2015.
Summary of Product Characteristics: Tirofiban 50 mcg/ml solution for infusion. Aspire Pharma Ltd. Revised September 2015.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.