KENGREXAL 50 mg POWDER FOR CONCENTRATE FOR INJECTION AND INFUSION SOLUTION

2. What you need to know before you use Kengrexal

Do not use Kengrexal

• if you are allergic to cangrelor or any of the other ingredients of this medicine (listed in section 6).
  • if you have a disease that is currently causing bleeding, such as bleeding in the stomach or intestines, or have a disease that increases the risk of uncontrolled bleeding (haemostasis disorder or irreversible coagulation disorders).
  • if you have recently undergone major surgery or have suffered any kind of severe physical trauma, such as a bone fracture or a traffic accident.
  • if you have very high and uncontrolled blood pressure.
  • if you have ever had a stroke or a mini-stroke (also known as a transient ischaemic attack, TIA) caused by a temporary interruption of blood flow to the brain.

Warnings and precautions

Talk to your doctor before you start using Kengrexal if:

• you have or think you may have a higher risk of bleeding. For example, if you have a disease that affects blood clotting or another disease that could increase the risk of bleeding, such as a recent severe injury, recent surgery, history of stroke or transient ischaemic attack, or recent bleeding from the stomach or intestines;
• you have kidney failure or require dialysis;
• you have ever had an allergic reaction to Kengrexal or any of its ingredients;
• you have respiratory problems, such as asthma;
• your doctor has told you that you have an intolerance to some sugars.

Children and adolescents

Kengrexal is not recommended for use in children and adolescents under 18 years of age.

Other medicines and Kengrexal

You may receive acetylsalicylic acid (ASA) while being treated with Kengrexal or another type of antiplatelet medicine (e.g. clopidogrel) before and after being treated with Kengrexal.

Tell your doctor if you are taking any medicine that may increase the risk of side effects such as bleeding, including blood thinners (anticoagulants, e.g. warfarin).

Tell your doctor if you are taking, have recently taken or might take any other medicine.

Pregnancy and breastfeeding

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before using this medicine. Kengrexal is not recommended during pregnancy.

Driving and using machines

The effect of Kengrexal disappears quickly and it is unlikely to affect your ability to drive or use machines.

Kengrexal contains sodium and sorbitol

Sorbitol is a source of fructose. If you have hereditary fructose intolerance (HFI), a rare genetic disorder, you should not receive this medicine. Patients with HFI cannot break down fructose, which can cause serious side effects.

Talk to your doctor before receiving this medicine if you have HFI.

This medicine contains less than 1 mmol of sodium (23 mg) per vial; this is essentially "sodium-free".

3. How to use Kengrexal

Your treatment with Kengrexal will be supervised by a doctor with experience in treating patients with heart disease. The doctor will decide how much Kengrexal you will receive and will prepare the medicine.

Kengrexal is given by injection, followed by an infusion (drip), into a vein. The dose given depends on your weight. The recommended dose is:

• 30 micrograms per kilogram of body weight by injection, followed immediately by
• 4 micrograms per kilogram of body weight per minute by infusion (drip), for at least 2 hours. The doctor will decide if you need treatment for a longer period.

If you use more Kengrexal than you should

A healthcare professional will give you this medicine. Your doctor will decide how to treat you, including stopping the medicine and monitoring for signs of side effects.

If you are unsure, talk to your doctor again.

4. Possible side effects

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

If you experience side effects, you may need medical attention.

Tell your doctor immediatelyif you notice any of the following:

• Bleeding anywhere in the body. Bleeding is a common side effect of treatment with Kengrexal (it can affect up to 1 in 10 people). Bleeding can be serious and has been reported to be fatal.
• Allergic reaction (skin rash, itching, narrowing/swelling of the throat, swelling of the tongue or lips, difficulty breathing). An allergic reaction is a rare side effect of treatment with Kengrexal (it can affect up to 1 in 1,000 people) but can be potentially serious.

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

• You may get minor bruising anywhere in the body (including small red bruises on the skin or at the injection site under the skin that cause swelling),
• shortness of breath,
• bleeding that causes a reduction in blood volume or red blood cell count,
• oozing from the injection site or catheter.

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

• Bleeding that causes fluid around the heart, blood in the chest cavity, or bleeding from the nose, digestive tract, abdomen, or urine, or from the injection site or catheter,

• increased creatinine levels in the blood (identified in blood tests), indicating reduced kidney function,
• changes in blood pressure,
• skin rash, itching, hives,
• bruising at the puncture site.

Rare side effects: may affect up to 1 in 1,000 people

• Bleeding that causes a low platelet count or anaemia,
• bleeding in the eyes, brain (including stroke), pelvis, and lungs,
• bleeding from wounds,

• swelling like a balloon in an artery or heart wall, affecting only some layers of the vessel wall,

• severe allergic reactions,

• reduced blood clotting,
• bruising,

• swelling of the face.

Very rare side effects: may affect up to 1 in 10,000 people

• Bleeding under the skin or around the eyes,
• infection at bleeding sites,
• heavy menstrual bleeding,
• bleeding from the penis, ear, or pre-existing skin tumours.

Reporting of side effects

If you experience any side effects, talk to your doctor, even if they are not listed in this leaflet.

You can also report side effects directly to the Spanish Medicines Monitoring System for Human Use https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Kengrexal

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

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

No special storage conditions are required.

Reconstituted solution: the powder should be reconstituted immediately before dilution and use. Do not refrigerate.

Diluted solution: from a microbiological point of view, the medicine should be used immediately, unless the method of reconstitution and dilution excludes the risk of microbial contamination. If not used immediately, the in-use storage times and conditions are the responsibility of the user.

6. Contents of the pack and further information

Composition of Kengrexal

• The active substance is cangrelor. Each vial contains 50 mg of cangrelor. After reconstitution, 1 ml of concentrate contains 10 mg of cangrelor and after dilution, 1 ml of solution contains 200 micrograms of cangrelor.
• The other ingredients are mannitol, sorbitol, and sodium hydroxide to adjust the pH.

Appearance and pack contents

Powder for concentrate for solution for injection and infusion in a glass vial.

Kengrexal is a white to off-white lyophilised powder.

Kengrexal is marketed in packs of 10 vials.

Marketing authorisation holder

Chiesi Farmaceutici S.p.A.Via Palermo, 26/A

43122 Parma

Italy

Manufacturer

Diapharm GmbH & CO. KG

Am Mittelhafen 56

48155 Münster

Germany

You can obtain further information on this medicine from the local representative of the marketing authorisation holder:

Date of last revision of this leaflet: January 2023

Other sources of information

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

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This information is intended only for healthcare professionals:

Kengrexal should be administered by a doctor with experience in acute coronary care or coronary intervention procedures and is intended for specialized use in a hospital setting.

Dosage

The recommended dose of Kengrexal for patients undergoing PCI is an intravenous bolus of 30 micrograms/kg followed immediately by an intravenous infusion of 4 micrograms/kg/min. The bolus and infusion should be started before the procedure and should continue for at least 2 hours or for the duration of the procedure, whichever is longer. At the doctor's discretion, the infusion may continue for a total of 4 hours, see section 5.1.

Patients should be transitioned to oral P2Y12 therapy for chronic treatment. For transition, a loading dose of oral P2Y12 therapy (clopidogrel, ticagrelor, or prasugrel) should be administered immediately after discontinuing the cangrelor infusion. Alternatively, a loading dose of ticagrelor or prasugrel, but not clopidogrel, may be administered up to 30 minutes before the end of the cangrelor infusion, see section 4.5.

Preparation instructions

Kengrexal should be prepared using aseptic techniques.

The vial should be reconstituted immediately before dilution and use. Reconstitute each 50 mg vial by adding 5 ml of sterile water for injection. Gently swirl the vial until all the contents have dissolved. Avoid vigorous mixing. Allow the foam to settle. Ensure that the contents of the vial have dissolved completely and that the reconstituted product is a clear, colourless to pale yellow solution.

Do not use undiluted. Before administration, it is necessary to withdraw 5 ml of reconstituted solution from each vial, which should be further diluted with 250 ml of sodium chloride 9 mg/ml (0.9%) injection solution or glucose (5%) injection solution. Mix the bag well.

After reconstitution, the medicine should be inspected visually for particulate matter.

Kengrexal is administered in a weight-based regimen consisting of an initial intravenous bolus followed by an intravenous infusion. The bolus and infusion should be administered from the infusion solution.

This dilution will produce a concentration of 200 micrograms/ml and should be sufficient for at least 2 hours of administration, as needed. Patients weighing 100 kg or more will require a minimum of two bags.