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
Dechra Veterinary Products Limited (A business unit of Dechra Pharmaceuticals PLC) Sansaw Business Park Hadnall, Shrewsbury Shropshire SY4 4AS Tel: 01939 211200 VOMEND ® 5 MG/ML SOLUTION FOR INJECTION diately and show the package leaflet or the label to FOR DOGS AND CATS Qualitative and quantitative composition pyramidal effects (agitation, ataxia, abnormal posi-Metoclopramide (as
Drugs of Abuse Assays Cross-Reactivity Manual by Trade Name, June 2005 COMPOUND (Trade Name) COMPOUND (Generic Name) Acetaminophen (See also Paracetamol) Acetaminophen (See also Paracetamol) Hydrocortisone Nifedipine Methylenedioxymethamphetamine (MDMA) Positive for Methamphetamine (mAMP) and Ecstasy (MDMA) Dexamphetamine Sulphate Positive for Amphetamine (AMP) De