Tirofiban

Indications

Tirofiban is used for: Acute Coronary Syndrome

Adult Dose

Intravenous Acute coronary syndrome Adult: Non-ST Elevated Acute Coronary Syndrome Indicated to reduce the rate of thrombotic cardiovascular events (combined endpoint of death, myocardial infarction, or refractory ischemia/repeat cardiac procedure) in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) Loading dose: 25 mcg/kg IV infused within 5 min, THEN Post loading dose infusion: 0.15 mcg/kg/min IV for up to 18 hr Hepatic impairment: Severe: Contraindicated.

Child Dose

Renal Dose

Renal impairment: CrCl (ml/min) Dosage Recommendation <30 Reduce dose by 50%.

Administration

IV Preparation Available only as premixed 50 mcg/mL solution for injection (100 mL or 250 mL bags) IV Administration See adult dosing for infusion rate

Contra Indications

History of thrombocytopenia during earlier use of GP IIb/IIIa receptor antagonist; history of stroke w/in 30 days or history of haemorrhagic stroke; history of intracranial disease (e.g. neoplasm, aneurysm); active or recent (w/in 30 days) clinically relevant bleeding (e.g. GI bleeding); malignant HTN; relevant trauma or major surgery (w/in the past 6 wk); thrombocytopenia (platelet count <100,000/mm3), disorders of platelet function; clotting disturbances. Severe hepatic failure.

Precautions

Patient w/ anaemia, active peptic ulcer (w/in the past 3 mth), uncontrolled HTN, acute pericarditis, active or history of vasculitis, suspected aortic dissection, haemorrhagic retinopathy, occult blood in stool or haematuria, thrombocytopenia (platelet count <150,000/mm3) or known history of platelet function disturbance, recent bleeding (<1 yr), severe CHF, cardiogenic shock. Severe trauma or surgery (>6 wk but <3 mth previously); traumatic or protracted CPR, organ biopsy or lithotripsy (w/in the past 2 wk), puncture of a non-compressible vessel (w/in 24 hr), recent epidural procedure. Renal and mild to moderate hepatic impairment. Pregnancy and lactation. Monitoring Parameters Monitor signs of bleeding, platelet counts, activated thromboplastin time (aPTT), haematocrit and Hb before and periodically (e.g. w/in the first 6 hr of the loading infusion and daily thereafter).

Pregnancy-Lactation

Pregnancy While published data cannot definitively establish the absence of risk, available published case reports have not established an association with therapy during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes Untreated myocardial infarction can be fatal to the pregnant woman and fetus; myocardial infarction is a medical emergency in pregnancy which can be fatal to pregnant woman and fetus if left untreated Animal data Studies with intravenous doses up to 5 mg/kg/day (about 5 and 13 times maximum recommended daily human dose for rat and rabbit, respectively, compared on a body surface area basis) have revealed no harm to fetus Lactation There is no data on presence of drug in human milk, effects on breastfed infant, or on human milk production; however, the drug is present in rat milk; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal condition

Interactions

Increased risk of bleeding w/ drugs that affect haemostasis including anticoagulants, thrombolytics, other glycoprotein IIb/IIIa inhibitors, platelet aggregation inhibitors.

Adverse Effects

Side effects of Tirofiban : >10% Bleeding, minor (11%) 1-10% Pelvic pain (6%) Coronary artery dissection (5%) Bradycardia (4%) Dizziness (3%) Lower extremity pain (3%) Edema (2%) Sweating (2%) Bleeding, major (1-2%) Thrombocytopenia (1.5%)

Mechanism of Action

Tirofiban is a non-peptide tyrosine derivative that prevents fibrinogen binding to the glycoprotein (GP) IIb/IIIa receptor, leading to inhibition of platelet function, evidenced by its ability to inhibit ex vivo ADP-induced platelet aggregation and prolong bleeding time.