FDA

Tirofiban Hydrochloride

Approved 8 Apr 2021IntravenousSolution

The FDA lists this product in 5 strengths and forms.

Indications

Tirofiban hydrochloride injection is 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) . Tirofiban hydrochloride injection is a platelet aggregation inhibitor 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).

Contraindications

Tirofiban hydrochloride injection is contraindicated in patients with: Severe hypersensitivity reaction to tirofiban hydrochloride injection (i.e.,anaphylactic reactions) [see Adverse Reactions (6.2)]. A history of thrombocytopenia following prior exposure to tirofiban hydrochloride injection [see Adverse Reactions (6.1)]. Active internal bleeding or a history of bleeding diathesis, major surgical procedure or severe physical trauma within the previous month [see Adverse Reactions (6.1)].

Known hypersensitivity to any component of tirofiban hydrochloride injection. (4) History of thrombocytopenia with prior exposure to tirofiban hydrochloride injection. (4) Active internal bleeding, or history of bleeding diathesis, major surgical procedure or severe physical trauma within the previous month. (4)

Warnings and precautions

Tirofiban hydrochloride injection can cause serious bleeding. If bleeding cannot be controlled discontinue tirofiban hydrochloride injection. (5.1) Thrombocytopenia: Discontinue tirofiban hydrochloride injection and heparin. (5.2)

5.1General Risk of Bleeding

Bleeding is the most common complication encountered during therapy with tirofiban hydrochloride injection. Most bleeding associated with tirofiban hydrochloride injection occurs at the arterial access site for cardiac catheterization. Minimize the use of traumatic or potentially traumatic procedures such as arterial and venous punctures, intramuscular injections, nasotracheal intubation, etc. Concomitant use of fibrinolytics, anticoagulants and antiplatelet drugs increases the risk of bleeding.

5.2Thrombocytopenia

At a glance

Brand name: Tirofiban Hydrochloride
Route: Intravenous
Dosage form: Solution
Applicant: Gland
Status: Prescription
FDA approval: 8 Apr 2021
Application: ANDA206888-001

Indications

Contraindications

Warnings and precautions

5.1General Risk of Bleeding

5.2Thrombocytopenia

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

While published data cannot definitively establish the absence of risk, available published case reports have not established an association with tirofiban use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes. Untreated myocardial infarction can be fatal to the pregnant women and fetus (see Clinical Considerations). Studies with tirofiban HCl at intravenous doses up to 5 mg/kg/day (about 5 and 13 times the maximum recommended daily human dose for rat and rabbit, respectively, when compared on a body surface area basis) have revealed no harm to the fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Myocardial infarction is a medical emergency in pregnancy which can be fatal to the pregnant woman and fetus if left untreated.

Data Animal Data There was no evidence of maternal or developmental toxicity in any of the studies in Table 5. Table 5 Developmental Toxicity Studies Type of Study Species Dose/Exposure* Duration/Timing Exposure 1) Range-finding Rat (N=30) 1, 2, 5 mg/kg/day IV (N=10 per group) Once daily from GD 6 through LD 20 2) Developmental Toxicity Rat (N=66) 1, 2, 5 mg/kg/day IV (N=22 per group) Once daily from GD 6 through GD 20 3) Developmental Toxicity with Postweaning Evaluation Rat (N=66) 1, 2, 5 mg/kg/day IV (N=22 per group) Once daily from GD 6 through LD 20 4) Range-finding (non-pregnant) Rabbit (N=21) 1, 2, 5 mg/kg/day IV (N=7 per group) Once daily for 14 days 5) Range-finding (pregnant) Rabbit (N=30) 1, 2, 5 mg/kg/day IV (N=10 per group) Once daily from GD 7 through GD 20 6) Developmental Toxicity Rabbit (N=60) 1, 2, 5 mg/kg/day (N=20 per group) IV Once daily from GD 7 through GD 20 *5 mg/kg/day is ~5 and 13 times the maximum recommended daily human dose for rat and rabbit, respectively, when compared on a body surface area basis.

Adverse reactions

Bleeding is the most commonly reported adverse reaction. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Gland Pharma at 864-879-9994 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In the PRISM (Platelet Receptor Inhibition for Ischemic Syndrome Management), PRISM-PLUS (Platelet Receptor Inhibition for Ischemic Syndrome Management — Patients Limited by Unstable Signs and Symptoms) and RESTORE (Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis) trials, 1946 patients received tirofiban hydrochloride injection in combination with heparin and 2002 patients received tirofiban hydrochloride injection alone for about 3 days.

Forty-three percent of the population was > 65 years of age and approximately 30% of patients were female. In clinical studies with the recommended regimen (25 mcg/kg bolus followed by a 0.15 mcg/kg/min maintenance infusion), tirofiban hydrochloride injection was administered in combination with aspirin, clopidogrel and heparin or bivalirudin to over 8000 patients for typically ≤ 24 hours. Approximately 30% of the population was > 65 years of age and approximately 25% were female.

Bleeding PRISM-PLUS Regimen The incidences of major and minor bleeding using the TIMI criteria in the PRISM-PLUS study are shown below. Table 2 TIMI Major and Minor Bleeding in PRISM-PLUS PRISM-PLUS (NSTE-ACS) Bleeding (TIMI Criteria)‡ § Tirofiban Hydrochloride Injection * + Heparin (N=773) Heparin alone (N=797) Major Bleeding 1.4% 0.8% Minor Bleeding 10.5% 8.0% Transfusions 4.0% 2.8% * 0.4 mcg/kg/min initial infusion; 0.10 mcg/kg/min maintenance infusion. ‡Major = Hemoglobin drop of >5.0 g/dL with or without an identified site, intracranial hemorrhage, or cardiac tamponade. §Minor = Hemoglobin drop of >3.0 g/dL with bleeding from a known site, spontaneous gross hematuria, hematemesis or hemoptysis.

The incidence rates of TIMI major bleeding in patients undergoing percutaneous procedures in PRISM-PLUS are shown below. Table 3 TIMI Major Bleeding Associated with Percutaneous Procedures in PRISM-PLUS Tirofiban Hydrochloride Injection + Heparin Heparin alone N % N % Prior to Procedures 773 0.3 797

0.1 Following Angiography 697 1.3 708

0.7 Following PTCA 239 2.5 236

2.2 The incidence rates of TIMI major bleeding in patients undergoing coronary artery bypass graft surgery (CABG) in PRISM-PLUS within one day of discontinuation of tirofiban hydrochloride injection were 17% on tirofiban hydrochloride injection plus heparin (N=29) and 35% on heparin alone (N=31). Recommended ("High-Dose Bolus") Regimen Rates of major bleeds (including any intracranial, intraocular or retroperitoneal hemorrhage, clinically overt signs of hemorrhage associated with a drop in hemoglobin of > 3 g/dL or any drop in hemoglobin by 4g/dL, bleeding requiring transfusion of ≥ 2U blood products, bleeding directly resulting in death within 7 days or hemodynamic compromise requiring intervention) were consistent with the rates observed in subjects administered the PRISM-PLUS regimen of tirofiban hydrochloride injection.

There was a trend toward greater bleeding in ST segment elevation myocardial infarction (STEMI) patients treated with fibrinolytics prior to administration of tirofiban hydrochloride injection using the recommended regimen during rescue PCI. Non-Bleeding The incidences of non-bleeding adverse events that occurred at an incidence of > 1% and numerically higher than control, regardless of drug relationship, are shown below: Table 4 Non-bleeding Adverse Reactions in PRISM-PLUS Tirofiban Hydrochloride Injection + Heparin (N=1953) % Heparin alone (N=1887) % Body as a Whole Edema/swelling 2 1 Pain, pelvic 6 5 Reaction, vasovagal 2 1 Cardiovascular System Bradycardia 4 3 Dissection, coronary artery 5 4 Musculoskeletal System Pain, leg 3 2 Nervous System/Psychiatric Dizziness 3 2 Skin and Skin Appendage Sweating 2 1 Thrombocytopenia Patients treated with tirofiban hydrochloride injection plus heparin, were more likely to experience decreases in platelet counts than were those on heparin alone.

These decreases were reversible upon discontinuation of tirofiban hydrochloride injection. The percentage of patients with a decrease of platelets to < 90,000/mm 3 was 1.5%, compared with 0.6% in the patients who received heparin alone. The percentage of patients with a decrease of platelets to < 50,000/mm 3 was 0.3%, compared with 0.1% of the patients who received heparin alone.

6.2Post-Marketing Experience

The following additional adverse reactions have been identified during post-approval use of tirofiban hydrochloride injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the drug exposure. Hypersensitivity: Severe allergic reactions including anaphylactic reactions have occurred during the first day of tirofiban hydrochloride injection infusion, during initial treatment, and during readministration of tirofiban hydrochloride injection.

Some cases have been associated with severe thrombocytopenia (platelet counts < 10,000/mm 3 ). No information is available on the formation of antibodies to tirofiban.

Tirofiban Hydrochloride

Indications

Contraindications

Warnings and precautions

5.1General Risk of Bleeding

5.2Thrombocytopenia

At a glance

Two medicines in one question?

Tirofiban Hydrochloride

Indications

Contraindications

Warnings and precautions

5.1General Risk of Bleeding

5.2Thrombocytopenia

At a glance

Two medicines in one question?

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trial Experience

6.2Post-Marketing Experience

Composition

Strengths and forms

Official product information