Patient Information Leaflet: Information for the Patient

AGRASTAT 0.05 mg/ml Infusion Solution

(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, consult 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 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 clotting 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).
• Bleeding retinopathy.
• Thrombolytic treatment.
• Liver problem.
• Insertion of a special intravenous catheter under 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 very important to inform your doctor if you are taking medications that prevent blood clotting such as warfarin.

Use of AGRASTAT with food, drinks, and alcohol

Foods and beverages have no effect on this medication.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, believe you may be pregnant, or intend 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 917 mg of sodium per 250 ml bag. This should be considered in patients who have a sodium-controlled diet.

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

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 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 serious 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 deficits (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

Rare 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 from 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 of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it ispossible side effects that do not appear in this prospectus. You can also report them directly through the Spanish System of 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 out of the sight and reach of children.

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

Do not freeze.

Keep the container in the laminated outer bag to protect it from light.

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

Medications should not be thrown away through drains or in the trash. Dispose of containers and medications you no longer need at the SIGRE drop-off point at the pharmacy. If in doubt, ask your pharmacist how to dispose of containers and medications you no longer need. This will help protect the environment.

Active Ingredient Content of AGRASTAT

The active ingredient is tirofiban hydrochloride monohydrate.

1 ml of AGRASTAT solution for infusion contains 56 micrograms of tirofiban hydrochloride monohydrate equivalent to 50 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 packaging contents

AGRASTAT is a transparent and colorless solution available as:

ContainerFreeflexof 250 ml (non-PVC plastic), colorless, multi-layered polyolefin film with injection-molded polyolefin tubes packaged in a pre-printed aluminum foil pouch.

Container size: 1 or 3 containers with 250 ml of infusion solution. Some container sizes may only be marketed.

Marketing Authorization Holder and Responsible Manufacturer:

Marketing Authorization Holder

Advanz Pharma Limited

Unit 17, Northwood House,

Northwood Crescent,

Dublin 9,

D09 V504,

Ireland

Responsible Manufacturer

ARVATO DISTRIBUTION GMBH

Gottlieb-Daimler-Strasse, 1

33428 Harsewinkel, Germany

Tjoapack Netherlands B.V.

Nieuwe Donk 9,

Etten-Leur, 4879 AC,

Netherlands

Local Representative:

Advanz Pharma Spain S.L.U.

Paseo de la Castellana 135, 7th

28046 Madrid (Spain)

Tf: +34 900 834 889

[email protected]

Last review date of this leaflet: August 2024

Other sources of information

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

This information is intended solely for healthcare professionals:

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

Agrastat should be administered with unfractionated heparin and oral antiplatelet therapy, 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 for 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 should be continued at a maintenance infusion rate of 0.1 micrograms/kg/min. AGRASTAT should be administered with unfractionated heparin (usually an intravenous bolus of 50-60 units (U)/kg simultaneously with the start of AGRASTAT therapy, after approx. 1000 (U) per hour, adjusted according to activated partial thromboplastin time (aPTT), which should be approximately twice the normal value) and oral antiplatelet therapy, including but not limited to ASA, unless contraindicated.

In patients with SCA-SEST undergoing planned percutaneous coronary intervention (PCI) within 4 hours of diagnosis or in patients with acute myocardial infarction with primary PCI planned, AGRASTAT should 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 should be administered with unfractionated heparin (dose indicated above) and oral antiplatelet therapy, 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

Pediatric 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 for at least 4 hours and up to 48 hours after diagnosis, the dose regimen of AGRASTAT to 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 unfractionated heparin 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 physician, the infusion should be discontinued. The total duration of treatment should not exceed 108 hours.

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

Concomitant treatment (unfractionated heparin, oral antiplatelet therapy, including ASA)

Unfractionated heparin treatment 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 is titrated to maintain an activated partial thromboplastin time (aPTT) of approximately twice the normal value.

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

Most studies investigating the administration of AGRASTAT as an adjunct to PCI have used ASA in combination with clopidogrel as oral antiplatelet therapy. 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 the 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 injection.

Instructions for use:

Check the expiration date

Do not extract the solution directly from the container with a syringe.

To open:tear along the perforation the covering sheet and remove the inner container (250 ml infusion solution).Check if there are microleaks by compressing the inner bag firmly. If leaks are detected, discard the solution, as the sterility may be compromised.

Do not use unless the solution is transparent and the closure is intact.

Do not add supplementary medication or extract the solution directly from the bag with a syringe.

WARNING: Do not use plastic containers in series connections, as it may cause air embolism due to the extraction of residual air from the primary container before the secondary container is completed. Preparation for administration

The following table is provided as a guide for adjusting the dose based on weight.

• Whenever the solution and container permit, parenteral drugs should be inspected for visible particles or coloration before use.
• AGRASTAT should only be administered intravenously and may be administered with unfractionated heparin through the same infusion tube.
• It is recommended to administer AGRASTAT with a calibrated infusion set using sterile material.
• 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 bag. The expiration date is the last day of the month indicated.

Do not freeze. Keep the container in the laminated outer bag (250 ml infusion solution) to protect it from light.

Appearance of the product and packaging contents

AGRASTAT is a transparent and colorless solution available as:

ContainerFreeflex?of 250 ml (non-PVC plastic), colorless, multi-layered polyolefin film with injection-molded polyolefin tubes packaged in a pre-printed aluminum foil pouch.

Container size: 1 or 3 containers with 250 ml of infusion solution. Some container sizes may only be marketed.

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/”