Microsoft word - 58-gp2ban _tirofiban hcl injection_.doc

For the use of a Registered Medical Practitioner or a Hospital or a Laboratory Only (Tirofiban Hydrochloride I.V. Injection) Composition:
Each 10 ml contains:
Tirofiban Hydrochloride
equivalent to Tirofiban …5 mg
Sodium Chloride I.P. … 0.9% w/v
Water for Injection … q.s.
Description:
Tirofiban hydrochloride is non-peptide antagonist of the platelet glycoprotein (GP)
llb/llla receptor which inhibits platelet aggregation. It is chemically described as
N -(butylsulfonyl)-0-[4-(4-piperidinyl) butyl]-L-tyrosine monohydrochloride
monohydrate. Its molecular formula is C22H36N2O5S●HCl● H2O with a molecular
weight of 495.08.
Mechanism of Action:
Tirofiban hydrochloride is a reversible antagonist of fibrinogen binding to the GP llb/llla
receptor, the major platelet surface receptor involved in platelet aggregation. When
administered intravenously tirofiban hydrochloride inhibits ex vivo platelet aggregation
in a dose, and concentration-dependent manner. When given according to the
recommended regimen, >90% inhibition is attained by the end of the 30-minute infusion.
Platelet aggregation inhibition is reversible following cessation of the infusion of
Tirofiban hydrochloride.

Pharmacokinetics:
Tirofiban has a half-life of approximately 2 hours. It is cleared from the plasma largely
by renal excretion, with about 65% of an administered dose appearing in urine and about
25% in feces, both largely as unchanged tirofiban. Metabolism appears to be limited.
Tirofiban is not highly bound to plasma proteins and protein binding is concentration
independent over the range of 0.01 to 25 mcg/ml. Unbound fraction in human plasma is
35%. The steady state volume of distribution of tirofiban ranges from 22 to 42 liters.
The recommended regimen of a loading infusion followed by a maintenance infusion
produces a peak tirofiban plasma concentration that is similar to the steady state
concentration during the infusion.
Indications:
Tirofiban hydrochloride, in combination with heparin (and ASA, unless contraindicated),
is indicated for the treatment of acute coronary syndrome (UA and NSTEMI), including
patients who are to be managed medically and those undergoing PTCA or atherectomy.
Contraindications:
Tirofiban hydrochloride is contraindicated in patients with the following: • known hypersensitivity to any component of the product. • active internal bleeding or a history of bleeding diathesis with the previous 30 • a history of intracranial haemorrhage intracranial neoplasm, arteriovenous • a history of thrombocytopenia following prior exposure to Tirofiban • history of stroke within 30 days prior to hospitalisation or any history of • major surgical procedure or severe physical trauma within the previous month. • history, symptoms, or findings suggestive of aortic dissection. • severe hypertension (systolic blood pressure > 180mmHg and/or diastolic blood • concomitant use of another parenteral GP llb/llla inhibitor.
Precautions and Warnings:
Keep out of reach of children.

Bleeding is the most common complication encountered during therapy with Tirofiban
hydrochloride. Administration of Tirofiban hydrochloride is associated with an increase
in bleeding even classified as both major and minor bleeding events by criteria developed
by the Thrombolysis in Myocardial Infarction Study group (TIMI). Most major bleeding
associated with Tirofiban hydrochloride occurs at the arterial access site for cardiac
catheterization. Therapy with Tirofiban hydrochloride is associated with increase in
bleeding rates particularly at the site of arterial access for femoral sheath placement.
Care should be taken when attempting vascular access that only the anterior wall of the
femoral artery is punctured. Prior to pulling the sheath heparin should be discontinued
for 3-4 hours and activated clotting time (ACT) < 180 seconds or APTT < 45 seconds
should be documented. Care should be taken to obtain proper hemostasis after removal
of the sheaths using standard compressive techniques followed by close observation.
While the vascular sheath is in place, patients should be maintained on complete bed rest
with the head of the bed elevated 30o and the affected limb restrained in a straight
position. Sheath hemostasis should be achieved at least 4 hours before hospital
discharge. Other arterial and venous punctures, intramuscular injections, and the use of
urinary catheters, nasotracheal intubation and nasogastric tubes should be minimized.
When obtaining intravenous access, non-compressible sites (e.g. subclavian or jugular
veins) should be avoided.
Tirofiban hydrochloride should be used with caution in patients with platelet count <
150,000/mm3, recent bleeding, including a history of GI bleeding or genitor urinary
bleeding of clinical significance and in patients with hemorrhagic retinopathy. Platelet
counts, hemoglobin and hematocrit should be monitored prior to treatment, within 6
hours following the loading infusion, and at least daily thereafter during therapy with
tirofiban hydrochloride. If thrombocytopenia is confirmed, tirofiban hydrochloride and
heparin should be discontinued and the condition appropriately monitored and treated.
The use of Tirofiban hydrochloride, in combination with heparin and aspirin, has been
associated with an increase in bleeding compared to heparin and aspirin alone. Caution
should be employed when Tirofiban hydrochloride is used with other drugs that affect
hemostasis (e.g. warfarin). Safety of use of Tirofiban hydrochloride with thrombolytic
agents not established.
During therapy with Tirofiban hydrochloride, patients should be monitored for potential
bleeding. When bleeding cannot be controlled with pressure, infusion of Tirofiban
hydrochloride and heparin should be discontinued.
In clinical studies, patients with severe renal insufficiency (creatinine clearance
< 30 mL/min) showed decreased plasma clearance of Tirofiban hydrochloride. The
dosage of Tirofiban hydrochloride should be reduced in these patients.
Drug Interactions:
There were no clinically significant effects of co-administration of these drugs on the
plasma clearance of tirofiban : acebutolol, acetaminophen, alprazolam, amlodipine,
aspirin preparations, atenolol, bromazepam, captopril, diazepam, digoxin, diltiazem,
docusate sodium, enalapril, furosemide, glyburide, heparin, insulin, isosorbide,
lorazepam, lovastatin, metoclopramide, metoprolol, morphine, nifedipine, nitrate
preparations, oxazepam, potassium chloride, propranolol, ranitidine, simvastatin,
sucralfate and temazepam.
Use in pregnancy, lactation and children:
There are no adequate and well-controlled studies in pregnant women. Because animal
reproduction studies are not always predictive of human response, this drug should be
used during pregnancy only if clearly needed. It is not known whether tirofiban is
excreted in human milk. Because many drugs are excreted in human milk, and because
of the potential for adverse effects on the nursing infant, a decision should be made
whether to discontinue nursing or discontinue the drug, taking into account the
importance of the drug to the mother. Safety and effectiveness of Tirofiban
hydrochloride in pediatric patients (< 18 years old) have not been established.
Adverse Reactions:
The most common drug-related adverse event reported during therapy with Tirofiban
hydrochloride when used concomitantly, with heparin and aspirin, was bleeding (usually
reported by the investigators as oozing or mild). The other reported adverse events
include the following: edema/swelling, vasovagal reaction, bradycardia, dizziness and
sweating. Patients treated with tirofiban hydrochloride, along with heparin, were more
likely to experience decreases in platelet counts than the control group. These decreases
were reversible upon discontinuation of tirofiban hydrochloride.
Overdosage:
The most frequently reported manifestation of overdosage was bleeding; primarily minor
mucocutaneous bleeding events and minor bleeding at the sites of cardiac catheterization.
Overdosage of tirofiban hydrochloride should be treated by assessment of the patient’s
clinical condition and cessation or adjustment of the drug infusion as appropriate.
Tirofiban hydrochloride can be removed by hemodialysis.

Dosage and Administration:
In most patients, tirofiban hydrochloride should be administered intravenously, at an
initial rate of 0.4 mcg/kg/min for 30 minutes and then the continued at 0.1 mcg/kg/min.
Patients with severe renal insufficiency (creatinine clearance < 30mL/min) should receive
half the usual dosage. No dosage adjustment is recommended for elderly or female
patients. Tirofiban hydrochloride has been administered in combination with heparin for
48 to 108 hours. The infusion should be continued throughout angiography and for 12 to
24 hours after angioplasty and atherectomy.
Presentation:
Pack of 100 ml
Store in a cool place
Do not freeze
Protect from light during storage.
* Trade mark pending.
Manufactured by:
GLAND PHARMA LIMITED
Plot No.9, Anrich Industrial Estate, Bollaram Medak (Dt.), Hyderabad – 502 325, India

Source: http://glandpharma.in/images/products/58-GP2ban%20_Tirofiban%20HCl%20Injection_1.pdf