Tirofiban (Concentrate) Instructions for Use

ATC Code

B01AC17 (Tirofiban)

Active Substance

Tirofiban (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antithrombotic agent. Platelet aggregation inhibitor

Pharmacotherapeutic Group

Antithrombotic agents; antiplatelet agents, other than heparin

Pharmacological Action

Platelet aggregation inhibitor, a non-peptide antagonist of glycoprotein IIb/IIIa receptors. Tirofiban reversibly inhibits platelet aggregation, preventing the binding of fibrinogen to glycoprotein IIb/IIIa receptors, thereby blocking platelet coagulation.

Tirofiban suppresses platelet functions, as evidenced by its ability to inhibit ex vivo ADP-induced aggregation and prolong bleeding time. Platelet function returns to baseline within 8 hours after discontinuation of tirofiban infusion.

Pharmacokinetics

Tirofiban does not bind strongly to plasma proteins; no concentration-dependent binding of tirofiban to plasma proteins is observed in the range of 0.01-25 µg/ml. The concentration of the unbound form of the drug in human plasma is 35%.

The V_d of tirofiban at steady state is 22-42 L. Tirofiban is metabolized to a limited extent in the body. Administration of ¹⁴C-labeled tirofiban showed that Tirofiban is excreted mainly unchanged in urine and feces. Radioactivity in circulating plasma originates primarily from unchanged tirofiban (for up to 10 hours after administration).

After IV administration of ¹⁴C-labeled tirofiban to healthy subjects, 66% of the radioisotopes were excreted in urine, 23% in feces. The total amount of drug excreted was 91%. Excretion in urine and bile is the main route of elimination for tirofiban.

In healthy individuals, the plasma clearance of tirofiban is about 250 ml/min. Renal clearance accounts for 39-69% of plasma clearance. T_1/2 is about 1.5 hours.

Indications

Prevention of early myocardial infarction in adult patients with signs of acute coronary syndrome without ST-segment elevation no later than 12 hours from the last angina attack, with ECG changes and/or elevated cardiac enzyme levels.

Preferably used in patients at high risk of developing myocardial infarction within the first 3-4 days after the onset of acute angina symptoms, including, for example, those who are highly likely to undergo primary percutaneous coronary intervention (PCI) early, and also to reduce major cardiovascular events in patients with acute myocardial infarction for whom primary PCI is indicated.

Used in combination with unfractionated heparin or acetylsalicylic acid (in the absence of contraindications).

ICD codes

Dosage Regimen

Administer intravenously using a calibrated infusion pump and sterile equipment. The concentrate requires dilution prior to administration.

For patients with acute coronary syndrome, initiate with an intravenous loading infusion of 0.4 mcg/kg/min for 30 minutes. Follow immediately with a continuous maintenance infusion of 0.1 mcg/kg/min.

In patients undergoing percutaneous coronary intervention (PCI), continue the infusion for at least 12 hours post-procedure. The total duration of infusion should not exceed 108 hours.

Adjust the dosage in patients with severe renal impairment (creatinine clearance < 30 mL/min). Reduce both the loading and maintenance infusion rates by 50%.

Concomitantly administer unfractionated heparin (target aPTT approximately two times control) and acetylsalicylic acid, unless contraindicated.

Monitor platelet count, hemoglobin, and hematocrit prior to initiation, within 2-6 hours after starting, and at least daily thereafter.

Discontinue the infusion prior to coronary artery bypass graft surgery. If bleeding occurs, evaluate the need to stop the infusion.

Adverse Reactions

From the hematopoietic system unknown – acute and/or severe (< 20,000/mm³) decrease in platelet count.

From the immune system unknown – severe allergic reactions, including anaphylactic reactions.

From the nervous system very common – headache; unknown – intracranial bleeding, spinal epidural hematoma.

From the cardiovascular system very common – hematoma; unknown – hemopericardium.

From the respiratory system common – hemoptysis, nosebleed; unknown – retroperitoneal bleeding.

From the digestive system very common – nausea; common – oral cavity bleeding, gum bleeding; uncommon – gastrointestinal bleeding, vomiting blood.

From the skin and subcutaneous tissues very common – ecchymosis.

From the urinary system common – hematuria.

General reactions common – fever.

Injuries and procedural complications very common – postoperative bleeding; common – bleeding at the vascular puncture site.

Laboratory data very common – occult blood in stool or urine; common – decreased hematocrit and hemoglobin, platelet count <90,000/mm³; uncommon – platelet count <50,000/mm³.

Contraindications

Hypersensitivity to tirofiban; prior development of thrombocytopenia in the patient in response to the administration of other glycoprotein IIb/IIIa receptor inhibitors; acute cerebrovascular accident (within 30 days prior to drug use) or history of hemorrhagic stroke; history of intracranial disease (neoplasm, arteriovenous malformation, aneurysm); currently active or occurring within the previous 30 days clinically significant bleeding (e.g., gastrointestinal bleeding); malignant hypertension; severe trauma or major surgery within the preceding 6 weeks; thrombocytopenia (platelet count <100,000/mm³), platelet function disorders; blood clotting disorders (e.g., prothrombin time more than 1.3 times the upper limit of normal or INR value >1.5); severe hepatic insufficiency; children under 18 years of age.

With caution

Recently experienced clinically significant bleeding (less than 1 year ago); puncture of a non-compressible vessel within 24 hours prior to tirofiban administration; recently performed epidural procedure (including lumbar puncture and spinal anesthesia); severe acute or chronic heart failure; cardiogenic shock; uncontrolled severe hypertension (systolic pressure above 180 mm Hg, diastolic above 110 mm Hg); mild or moderate degree of hepatic insufficiency; platelet count <150,000/mm³, known coagulopathy or platelet function disorder, or history of thrombocytopenia; hemoglobin concentration less than 11 g/ml or hematocrit <34%; hemorrhagic retinopathy.

Special precautions should be observed with the simultaneous concomitant use of drugs that affect the hemostatic system and increase the risk of bleeding, for example, ticlopidine, clopidogrel, adenosine, dipyridamole, sulfinpyrazone, and prostacyclin.

Use in Pregnancy and Lactation

Data on the use of tirofiban during pregnancy are absent or limited. Not recommended for use during pregnancy except in cases of extreme necessity.

During breastfeeding, a decision should be made to discontinue breastfeeding or discontinue therapy, taking into account the importance of treatment for the mother.

Use in Renal Impairment

Contraindicated in severe renal failure.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Elderly patients have a higher risk of bleeding complications, so use with caution in this category of patients.

Special Precautions

Tirofiban should be used in a hospital setting, by specialists experienced in the treatment of acute coronary syndromes.

Monotherapy with tirofiban without unfractionated heparin is not recommended.

Tirofiban should be administered together with unfractionated heparin and oral antiplatelet therapy, including acetylsalicylic acid.

It is not recommended to administer tirofiban hydrochloride separately without unfractionated heparin.

The efficacy of tirofiban in combination with enoxaparin has not been definitively established to date. The safety and efficacy of tirofiban when used with other low molecular weight heparins have not been sufficiently studied.

There is insufficient experience with the use of tirofiban hydrochloride in the following diseases and conditions, which are presumed to carry an increased risk of bleeding. Thus, due to the lack of adequate clinical data, the drug cannot be unequivocally recommended for: traumatic or prolonged cardiopulmonary resuscitation, organ biopsy or lithotripsy within the last 2 weeks; severe trauma or extensive surgery more than 6 weeks but less than 3 months prior to the intended administration of tirofiban, respectively; exacerbation of peptic ulcer within a period of 3 months prior to the intended administration of tirofiban; acute vasculitis or history of vasculitis; suspected aortic dissection, as well as history of aortic dissection; occult blood in stool or hematuria; acute pericarditis; concomitant use of other drugs that may significantly increase the risk of bleeding.

Due to the lack of adequate experience with the use of tirofiban in patients who require concomitant thrombolytic therapy, the use of tirofiban hydrochloride cannot be unequivocally recommended in combination with thrombolytic therapy.

Infusion of tirofiban hydrochloride should be stopped immediately if circumstances arise during its administration that require the initiation of thrombolytic therapy (including acute occlusion during PCI) or if the patient must undergo emergency coronary artery bypass graft surgery or requires the insertion of an intra-aortic balloon pump.

Elderly patients and/or women had a higher rate of bleeding complications than younger patients or men, respectively. In patients with low body weight, the frequency of bleeding was higher than in patients with higher body weight. For these reasons, Tirofiban should be used with caution in such patients, heparin exposure should be carefully monitored.

According to clinical studies, as creatinine clearance decreases, the risk of bleeding increases, as does the decrease in tirofiban plasma clearance. Therefore, patients with impaired renal function (CrCl <60 ml/min) require careful clinical monitoring during treatment.

During treatment with tirofiban, a significant increase in the frequency of bleeding is noted, especially in the area of the femoral artery into which the catheter guide is inserted.

Due to the increased risk of bleeding, the number of vascular punctures and intramuscular injections should be reduced during treatment with tirofiban. The use of urinary catheters, nasopharyngeal intubation, and nasogastric tubes should be critically considered (their number should be minimized).

Platelet count, hemoglobin, and hematocrit levels should be determined before starting treatment with tirofiban, as well as within 2-6 hours after the start of tirofiban therapy and at least once daily during therapy (or more often if there is evidence of a significant decrease).

In patients who have previously received glycoprotein IIb/IIIa receptor antagonists (cross-reactivity may occur), platelet count should be monitored immediately, for example, within the first hour of administration after re-exposure. In case of confirmed thrombocytopenia, treatment with tirofiban and heparin should be discontinued.

Patients require careful clinical monitoring during treatment. If treatment for bleeding is required, the possibility of discontinuing tirofiban therapy should be considered. In cases of profuse or uncontrolled bleeding, treatment with tirofiban should be stopped immediately.

Drug Interactions

The use of several platelet aggregation inhibitors increases the risk of bleeding, as does combination with heparin, warfarin, and thrombolytics. Clinical and biological parameters of hemostasis should be regularly monitored. Concomitant use of tirofiban and acetylsalicylic acid increases platelet inhibition to a greater extent than acetylsalicylic acid alone.

Concomitant use of tirofiban and unfractionated heparin increases bleeding time to a greater extent compared with monotherapy with unfractionated heparin.

With simultaneous use of tirofiban hydrochloride, unfractionated heparin, acetylsalicylic acid, and clopidogrel, a comparable frequency of bleeding was observed, compared with the combined use of only unfractionated heparin, acetylsalicylic acid, and clopidogrel.

Tirofiban prolonged bleeding time; however, the combined use of tirofiban and ticlopidine did not additionally affect bleeding time. Simultaneous use of tirofiban hydrochloride with warfarin and heparin is associated with an increased risk of bleeding.

When using levothyroxine and omeprazole concomitantly with tirofiban therapy, the clearance of tirofiban increased.

Concomitant use with enoxaparin (1 mg/kg subcutaneously every 12 hours) does not affect the clearance of tirofiban.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.