Patient Information Leaflet

AGRASTAT 0.25 mg/ml Concentrate for Solution for Infusion

(tirofiban)

Read this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What is AGRASTAT and what it is used for

2. What you need to know before you start using AGRASTAT

3. How to use AGRASTAT

4. Possible side effects

5. Storage of AGRASTAT

6. Contents of the pack and additional information

AGRASTAT is used to help facilitate blood flow to the heart, and to prevent chest pain and heart attacks. It works by preventing the aggregation of platelets, cells found in the blood, and that form blood clots.

This medication may also be used in patients whose veins are dilated with a balloon (percutaneous coronary intervention or PCI). This is a procedure that is achieved with the implantation of a small tube (stent) to improve blood flow to the heart.

AGRASTAT is intended to be used with aspirin and unfractionated heparin.

No use AGRASTAT:

• If you are allergic (hypersensitive) to tirofiban or any of the other components of AGRASTAT (listed in section 6).
• If you have an internal bleeding or a history of internal bleeding in the last 30 days.
• If you have a history of intracranial bleeding, a brain tumor, or abnormal blood vessels in the brain.
• If you have uncontrolled severe high blood pressure (malignant hypertension).
• If you have a low platelet count (thrombocytopenia) or blood coagulation disorders.
• If you developed thrombocytopenia while being treated with AGRASTAT or another medication in the same therapeutic group.
• If you have a history of stroke in the last 30 days or any history of hemorrhagic stroke.
• If you have had a major trauma or major surgery in the last six weeks.
• If you have severe liver failure.

Your doctor will review your medical history to see if you have a higher risk of experiencing side effects associated with the use of this medication.

Warnings and precautions

Consult your doctor before starting to use AGRASTAT, if you have or have had:

• Any medical condition.
• Any allergy
• CARDIOPULMONARY RESUSCITATION, BIOPSY, OR LITHOTRIPSY in the last two weeks.
• Severe trauma or major surgery in the last three months.
• Ulcer in the stomach or intestine (duodenum) in the last three months.
• Recent hemorrhagic disorder (in the last year) such as bleeding in the stomach or intestine, or blood in the urine or stool.
• Recent spinal intervention.
• History or symptoms of aortic dissection.
• Uncontrolled high blood pressure.
• Pericarditis (inflammation of the membrane that covers the heart).
• Active vasculitis (inflammation of the veins).
• Problems with blood vessels in the back of the eye (retina).
• Problems with medications that help prevent or dissolve blood clots.
• Kidney problems.
• Insertion of a special intravenous catheter below the clavicle in the last 24 hours.
• Heart failure.
• Cardiogenic shock (low blood pressure due to heart failure)
• Liver disorder
• Low blood count or anemia

Use of AGRASTAT with other medications:

AGRASTAT can generally be used with other medications. Please inform your doctor if you are taking, have taken recently, or may take any other medication, including over-the-counter medications, as it may affect their action. It is also important to inform your doctor if you are taking medications that prevent blood clot formation such as warfarin.

Use of AGRASTAT with food, drinks, and alcohol

Foods and drinks have no effect on this medication.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medication.

Driving and operating machinery

Due to your condition, you will not be able to drive or operate machinery while using AGRASTAT.

AGRASTAT contains sodium

This medication contains approximately 189 mg of sodium per 50 ml vial, which should be taken into account in the treatment of patients with low-sodium diets.

AGRASTAT should be prescribed by qualified doctors with experience in managing acute coronary syndromes.

AGRASTAT is administered intravenously. Your doctor will decide on the appropriate dose, depending on your condition and weight.

Use in children

The use in children is not recommended.

If you use more AGRASTAT than you should

Your AGRASTAT dose will be closely monitored and watched by your doctor and pharmacist.

The most reported adverse effect of overdose was bleeding. If you notice bleeding, you should inform your doctor immediately.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forgot to use AGRASTAT

Your doctor will decide when to administer AGRASTAT.

If you interrupt treatment with AGRASTAT

Your doctor will decide when treatment should be interrupted. However, if you wish to interrupt treatment early, you should discuss other options with your doctor.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

The most common side effect in treatment with AGRASTAT is bleeding that can occur anywhere in your body. This side effect can be severe and, rarely, can be fatal.

If you experience side effects, you may need medical attention. While using AGRASTAT, if you develop any of the following symptoms, you must contact your doctor immediately:

• Signs of intracranial bleeding such as headache, sensory deficiencies (visual or auditory), speech difficulties, numbness, or problems with movement or balance.
• Signs of internal hemorrhage such as coughing up blood or presence of blood in urine or stool.
• Signs of severe allergic reactions such as difficulty breathing or dizziness.

The following are side effects that have occurred in patients after treatment with AGRASTAT. These side effects are classified in order of decreasing frequency.

Very common side effects (may affect more than 1 in 10 people):

Bleeding after surgery

Bleeding under the skin at the injection site, or in the muscle causing inflammation

Small red spots on the skin

Undetectable blood in urine or stool

Dizziness

Headache

Common side effects (may affect up to 1 in 10 people):

Blood in urine

Coughing up blood

Nasal bleeding

Bleeding in gums and mouth

Bleeding at the puncture site

Reduction in blood count (reduction in hematocrit and hemoglobin)

Decrease in platelet count below 90,000/mm3

Fever

Uncommon side effects (may affect up to 1 in 100 people):

Bleeding in stomach or intestine

Vomiting blood

Decrease in platelet count below 50,000/mm3

Side effects of unknown frequency (cannot be estimated based on available data):

Intracranial bleeding

Spinal hematoma

Retroperitoneal bleeding

Accumulation of blood around the heart

Pulmonary hemorrhage

Acute and severe decrease in platelet count below 20,000/mm3

Severe allergic reactions with chest tightness, urticaria, including reactions that may cause difficulty breathing and dizziness.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: www.notificaRAM.com. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Your doctor or pharmacist will know how to store and dispose of this medication.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears in the bag after CAD. The expiration date is the last day of the month indicated.

Do not freeze.

Do not use AGRASTAT if there are visible particles or if the solution is discolored before use.

Medicines should not be thrown down the drain or in the trash. Dispose of the containers and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medications you no longer need. By doing so, you will help protect the environment.

Composition of AGRASTAT

The active ingredient is tirofiban hydrochloride monohydrate.

1 ml contains 281 micrograms of tirofiban hydrochloride monohydrate equivalent to 250 micrograms of tirofiban.

The other components are: Sodium chloride, sodium citrate dihydrate, anhydrous citric acid, injection water, hydrochloric acid and/or sodium hydroxide (for pH adjustment).

Appearance of AGRASTAT and contents of the container

AGRASTAT is a clear and colourless concentrated solution that is presented in type I glass vials of 50 ml.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Advanz Pharma Limited

Unit 17, Northwood House,

Northwood Crescent,

Dublín 9,

D09 V504,

Ireland

Responsible for manufacturing

Orion Corporation, Orion Pharma Espoo site

Orionintie 1, FI 00220, Espoo, Finlandia

ARVATO DISTRIBUTION GMBH
Gottlieb-Daimler-Strasse, 1Harsewinkel,Germany 33428Germany

Local representative:

Advanz Pharma Spain S.L.U.

Paseo de la Castellana 135,

7ª28046 Madrid (Spain)

Tf: +34 900 834 889

[email protected]

Last review date of this leaflet: October 2013

Other sources of information

Detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu/.

This information is intended solely for healthcare professionals:

This product is intended solely for hospital use, to be used by experienced medical specialists in the treatment of acute coronary syndromes.

AGRASTAT concentrate must be diluted before use.

AGRASTAT must be administered with heparin non-fractured and oral antiplatelet treatment, including acetylsalicylic acid (ASA).

Dosage and administration

In patients treated with an early invasive strategy for acute coronary syndrome without ST elevation (SCA-SEST) and not planning to undergo angiography at least 4 hours and up to 48 hours after diagnosis, AGRASTAT is administered intravenously at an initial infusion rate of 0.4 micrograms/kg/min for 30 minutes. At the end of the initial infusion, AGRASTAT must be continued at a maintenance infusion rate of 0.1 micrograms/kg/min. AGRASTAT must be administered with heparin non-fractured (usually an intravenous bolus of 50-60 units (U)/kg simultaneously with the start of AGRASTAT therapy, after approximately 1000 (U) per hour, adjusted according to activated partial thromboplastin time (aPTT), which must be approximately double the normal value) and oral antiplatelet treatment, including but not limited to ASA, unless contraindicated.

In SCA-SEST patients undergoing planned percutaneous coronary intervention (PCI) within the first 4 hours after diagnosis or in patients with acute myocardial infarction with primary PCI planned, AGRASTAT must be administered using an initial bolus of 25 micrograms/kg administered over a period of 3 minutes, followed by a continuous infusion at a rate of 0.15 micrograms/kg/min for 12-24 hours and up to 48 hours. AGRASTAT must be administered with heparin non-fractured (dose indicated above) and oral antiplatelet treatment, including but not limited to acetylsalicylic acid (ASA), unless contraindicated.

No dose adjustment is required for elderly patients.

Patients with severe renal impairment

In severe renal impairment (creatinine clearance <30

Paediatric population

The safety and efficacy of AGRASTAT in children have not been established.

No data are available.

Initiation and duration of AGRASTAT

In patients treated with an early invasive strategy for acute coronary syndrome without ST elevation (SCA-SEST) and not planning to undergo angiography at least 4 hours and up to 48 hours after diagnosis, the dosing regimen of AGRASTAT that should be initiated after diagnosis will be 0.4 micrograms/kg/min loading dose. The recommended duration of the maintenance infusion should be at least 48 hours. The infusion of AGRASTAT and heparin non-fractured should be maintained during coronary angiography, and should be maintained for at least 12 hours and not more than 24 hours after angioplasty/atherectomy. Once the patient is clinically stable and no coronary intervention is planned by the doctor, the infusion should be discontinued. The entire duration of treatment should not exceed 108 hours.

If the patient with a diagnosis of SCA-SEST is treated with an invasive strategy and undergoes angiography within 4 hours after diagnosis, the loading dose regimen of AGRASTAT 25 micrograms/kg should be initiated at the start of PCI with a continuous infusion of 12 to 24 hours and up to 48 hours.

In patients with acute myocardial infarction with primary PCI planned, the bolus infusion regimen should be initiated as soon as possible after diagnosis.

Concomitant treatment (heparin non-fractured, oral antiplatelet treatment including ASA)

The treatment with heparin non-fractured is initiated with an intravenous bolus of 50-60 U/kg, and continued with a maintenance infusion of 1000 units per hour. The dose of heparin should be titrated to maintain an activated partial thromboplastin time (aPTT) of approximately double the normal value.

Unless contraindicated, all patients should receive oral antiplatelet treatment, including but not limited to ASA, before starting AGRASTAT treatment. This medication should be continued for at least the duration of the AGRASTAT infusion.

The majority of studies investigating the administration of AGRASTAT as an adjunct to PCI have used ASA in combination with clopidogrel as oral antiplatelet treatment. The efficacy of the combination of AGRASTAT with prasugrel or ticagrelor has not been established in randomized and controlled trials.

If angioplasty (PCI) is required, heparin should be discontinued after PCI, and cannulas should be removed once coagulation has returned to normal, for example, when activated clotting time (ACT) is less than 180 seconds (usually 2-6 hours after discontinuing heparin).

Incompatibilities

Cases of incompatibility with diazepam have been reported. Therefore, AGRASTAT and diazepam should not be administered through the same intravenous route.

No incompatibilities have been found between AGRASTAT and the following intravenous formulations: Atropine sulfate, dobutamine, dopamine, epinephrine hydrochloride, furosemide, heparin, lidocaine, midazolam hydrochloride, morphine sulfate, nitroglycerin, potassium chloride, propranolol hydrochloride, and famotidine injectable.

Instructions for use:

AGRASTAT Concentrate must be diluted before use:

1. Extract 50 ml from a 250 ml container of sterile 0.9% saline solution or 5% glucose solution in water and replace it with 50 ml of AGRASTAT (from a 50 ml puncture vial) to obtain a concentration of 50 micrograms/ml. Mix well before use.

2. Use it according to the dosage table.

A dosage table is provided as a guide for adjusting the dose based on patient weight.

AGRASTAT Concentrate must be diluted first as indicated inInstructions for use

• Whenever the solution and the container permit, parenteral drugs should be inspected for the presence of visible particles or coloration before use.
• AGRASTAT should only be administered intravenously and may be administered with heparin non-fractured through the same infusion tube.
• It is recommended to administer AGRASTAT with a calibrated infusion device using sterile materials.
• Care should be taken not to prolong the infusion of the initial dose and to avoid errors in calculating the infusion rates for the maintenance dose based on the patient's weight.

Special precautions for storage

Do not use AGRASTAT after the expiration date appearing on the labeling and on the outer carton. The expiration date is the last day of the month indicated.

Do not freeze. Keep the container in the box to protect it from light.

After dilution, the product should be used immediately. If not used immediately, the storage conditions should not exceed 24 hours at 2-8°C.

Appearance of the product and contents of the container

AGRASTAT is a clear and colourless concentrated solution that is presented in type I glass vials of 50 ml.

Special precautions for disposal and other manipulations

The disposal of unused medication and all materials that have been in contact with it will be carried out in accordance with local regulations.

“Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/”