AGRASTAT 0.05 mg/ml SOLUTION FOR INFUSION

2. What you need to know before you use AGRASTAT

Do not use AGRASTAT:

• If you are allergic (hypersensitive) to tirofiban or any of the other ingredients of AGRASTAT (listed in section 6)
• If you have 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 severe uncontrolled 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 medicine in the same therapeutic group
• If you have had a stroke in the last 30 days or any history of hemorrhagic stroke
• If you have had 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 side effects associated with the use of this medicine

Warnings and precautions

Talk to your doctor before starting AGRASTAT if you have or have had:

• Any medical problem
• Any allergy
• Cardiopulmonary resuscitation, biopsy, or lithotripsy in the last 2 weeks
• Major trauma or major surgery in the last 3 months
• Stomach or intestinal ulcer (duodenum) in the last 3 months
• Recent bleeding disorder (in the last year) such as bleeding in the stomach or intestine, or blood in the urine or feces
• Recent spinal intervention
• History or symptoms of aortic rupture (aortic dissection)
• Uncontrolled high blood pressure
• Inflammation of the membrane that surrounds the heart (pericarditis)
• Inflammation of the veins (active vasculitis)
• Hemorrhagic retinopathy
• Thrombolytic treatment
• Liver problem
• Insertion of a special intravenous catheter under the collarbone in the last 24 hours
• Heart failure
• Low blood pressure due to heart failure (cardiogenic shock)

• Liver disorder
• Low blood count or anemia

Using AGRASTAT with other medicines:

Generally, AGRASTAT can be used with other medicines. Please tell your doctor if you are taking, have recently taken, or might take any other medicines, including those without a prescription, as they may affect the action of these. It is very important that you inform your doctor if you are taking medicines that prevent clot formation, such as warfarin

Using AGRASTAT with food, drinks, and alcohol

Food and drinks do not affect this medicine

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine

Driving and using machines

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

AGRASTAT contains sodium

This medicine contains approximately 917 mg of sodium per 250 ml bag. This should be taken into consideration in patients on a controlled sodium diet

3. How to use AGRASTAT

AGRASTAT should only be prescribed by doctors with experience in the management of acute coronary syndromes

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

Use in children

Use in children is not recommended

If you use more AGRASTAT than you should

Your dose of AGRASTAT will be carefully monitored and supervised by your doctor and pharmacist

The most commonly reported side 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 Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount taken

If you forget to use AGRASTAT

Your doctor will decide when to administer AGRASTAT

If you stop using AGRASTAT

Your doctor will decide when treatment should be stopped. However, if you wish to stop treatment beforehand, you should discuss other options with your doctor

If you have any further questions on the use of this product, ask your doctor or pharmacist

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them

The most common side effect of treatment with AGRASTAT is bleeding, which 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 you are using AGRASTAT, if you develop any of the following symptoms, you should contact your doctor immediately:

• Signs of intracranial bleeding such as headache, sensory disturbances (visual or auditory), speech difficulties, numbness, or problems with movement or balance
• Signs of internal bleeding such as coughing up blood or blood in the urine or feces
• Signs of serious allergic reactions such as difficulty breathing or dizziness

The following side effects have been reported in patients treated with AGRASTAT. These side effects are listed 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

Invisible blood in the urine or feces

Feeling dizzy

Headache

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

Blood in the urine

Coughing up blood

Nosebleeds

Bleeding in the gums and mouth

Bleeding at the puncture site

Decreased blood count (decreased hematocrit and hemoglobin)

Decreased platelet count below 90,000/mm3

Fever

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

Bleeding in the stomach or intestine

Vomiting blood

Decreased platelet count below 50,000/mm3

Side effects of unknown frequency (cannot be estimated from the available data):

Intracranial bleeding

Hematoma in the spinal region

Retroperitoneal bleeding

Blood accumulation around the heart

Pulmonary hemorrhage

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

Severe allergic reactions with chest tightness, hives, including reactions that can cause difficulty breathing and dizziness

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Monitoring System: www.notificaRAM.com

By reporting side effects, you can help provide more information on the safety of this medicine

5. Storage of AGRASTAT

Your doctor or pharmacist knows how to store and dispose of this medicine

Keep out of the sight and reach of children

Do not use this medicine after the expiry date which is stated on the bag after EXP. The expiry date is the last day of the month stated

Do not freeze

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

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

Medicines should not be disposed of via wastewater or household waste. Place the containers and medicines you no longer need in the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of containers and medicines no longer needed. This will help protect the environment

6. Container Content and Additional Information

AGRASTAT Content

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, water for injection, hydrochloric acid and/or sodium hydroxide (for pH adjustment).

Appearance of AGRASTAT and Container Content

AGRASTAT is a clear and colorless solution available as:

Freeflex® container of 250 ml (non-PVC plastic), colorless, with a multilayer polyolefin film and polyolefin injection-molded tubes, packaged in a pre-printed external laminated bag.

Container size: 1 or 3 containers with 250 ml of solution for infusion. Only some container sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Advanz Pharma Limited

Unit 17, Northwood House,

Northwood Crescent,

Dublin 9,

D09 V504,

Ireland

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 floor

28046 Madrid (Spain)

Phone: +34 900 834 889

[email protected]

Date of Last Revision of this Prospectus: August 2024

Other Sources of Information

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

This information is intended only for healthcare professionals:

This product is intended only for hospital use, to be used by specialist physicians with experience in the treatment of acute coronary syndromes.

Agrastat must be administered with unfractionated heparin and oral antiplatelet treatment, including acetylsalicylic acid (ASA).

Posology and Method of Administration

In patients who are treated with an early invasive strategy for Acute Coronary Syndrome without ST elevation (ACS-STE) and do not plan 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 must be administered with unfractionated heparin (generally 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 the activated partial thromboplastin time (APTT), which should be approximately twice the normal value) and oral antiplatelet treatment, including but not limited to ASA, unless contraindicated.

In patients with ACS-STE who undergo a scheduled percutaneous coronary intervention (PCI) within the first 4 hours after diagnosis or in patients with acute myocardial infarction with scheduled primary PCI, 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, and up to 48 hours. AGRASTAT must be administered with unfractionated heparin (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 ml min), the dose of agrastat should be reduced by 50%.< p>

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 who are treated with an early invasive strategy for Acute Coronary Syndrome without ST elevation (ACS-STE) and do not plan to undergo angiography for at least 4 hours and up to 48 hours after diagnosis, the AGRASTAT dosing regimen should be initiated after diagnosis at a rate of 0.4 micrograms/kg/min. The recommended duration of 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 no 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 the patient with a diagnosis of ACS-STE is treated with an invasive strategy and undergoes angiography within 4 hours after diagnosis, the AGRASTAT bolus regimen of 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 scheduled primary PCI, the bolus infusion regimen should be initiated as soon as possible after diagnosis.

Concomitant Treatment (Unfractionated Heparin, Oral Antiplatelet Treatment, including ASA)

Treatment with unfractionated heparin 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 agents, including but not limited to ASA, before the start of treatment with AGRASTAT. This medication should be continued for at least the duration of the infusion with AGRASTAT.

Most 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 controlled trials.

If angioplasty (PCI) is required, heparin should be discontinued after PCI, and the cannulas should be removed once coagulation has returned to normal, for example, when the activated clotting time (ACT) is less than 180 seconds (generally 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 line.

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 injectable famotidine.

Instructions for Use:

Check the expiration date

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

To open: tear the foil along the notch and remove the inner container (250 ml solution for infusion). Check for micro-leaks by firmly compressing the inner bag. If leaks are detected, discard the solution, as sterility may be compromised.

Do not use unless the solution is clear and the seal is intact.

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

CAUTION: Do not use plastic containers in series connections, as an air embolism may occur due to the extraction of residual air from the primary container before the liquid from the secondary container is completely administered. Preparation for administration

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

• Whenever the solution and container allow, parenteral drugs should be inspected for visible particles or coloration before use.
• AGRASTAT should only be administered intravenously and can be administered with unfractionated heparin through the same infusion tube.
• It is recommended to administer AGRASTAT with a calibrated infusion device using sterile material.
• Care should be taken not to prolong the initial infusion and to avoid calculation errors of 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 stated on the bag. The expiration date is the last day of the month indicated.

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

Product Appearance and Container Content

AGRASTAT is a clear and colorless solution available as:

Freeflex® container of 250 ml (non-PVC plastic), colorless, with multiple layers of polyolefin and polyolefin injection-molded tubes. It is packaged in a pre-printed external laminated bag.

Container size: 1 or 3 containers with 250 ml of solution for infusion. Only some container sizes may be marketed.

Special Precautions for Disposal and Other Handling

The disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.

"Detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS):http://www.aemps.gob.es/"