Kengrexal

Package leaflet: Information for the patient

Kengrexal 50 mg powder for concentrate for solution for injection/infusion

cangrelor
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• If you get any side effects, talk to your doctor. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

1. What Kengrexal is and what it is used for
2. What you need to know before you use Kengrexal
3. How to use Kengrexal
4. Possible side effects
5. How to store Kengrexal
6. Contents of the pack and other information

1. What Kengrexal is and what it is used for

Kengrexal is an antiplatelet medicine that contains the active substance cangrelor.
Platelets are very small cells in the blood that can clump together and help the blood to clot.
Sometimes clots can form inside a damaged blood vessel, such as in a coronary artery, and this can be very dangerous because the clot may block the blood supply (a thrombotic event), causing a heart attack (myocardial infarction).
Kengrexal reduces platelet aggregation and thereby decreases the likelihood of blood clot formation.
You have been prescribed Kengrexal because you have blocked blood vessels in your heart (coronary artery disease) and require a procedure (called percutaneous coronary intervention – PCI) to remove the blockage. During this procedure, a stent may be placed in your blood vessel to help keep it open. The use of Kengrexal reduces the risk of clot formation and new blockages in the blood vessels caused by this procedure.
Kengrexal is intended for use in adults only.

2. What you need to know before using Kengrexal

Do not use Kengrexal

• if you are allergic to cangrelor or to any of the other ingredients of this medicine (listed in section 6).
• if you have a condition currently causing bleeding, such as bleeding from the stomach or intestines, or have a condition that increases your risk of uncontrolled bleeding (impaired hemostasis or irreversible coagulation disorders).
• if you have recently undergone major surgery or have suffered any form of severe physical trauma, such as a bone fracture or a road traffic accident.
• if you have uncontrolled high blood pressure.
• if you have ever had a stroke or a 'mini-stroke' (also known as transient ischemic attack, TIA) caused by a temporary interruption of blood supply to the brain.

Warnings and precautions
Talk to your doctor before using Kengrexal:

• if you have or think you may have an increased risk of bleeding. For example, if you have a condition affecting blood clotting or due to another condition that may increase the risk of bleeding, such as recent severe trauma, any recent surgery, history of stroke or transient ischemic attack, or recent bleeding from the stomach or intestines.
• if you have impaired kidney function or require dialysis.
• if you have ever had an allergic reaction to Kengrexal or any of its ingredients.
• if you suffer from breathing difficulties such as asthma.
• if your doctor has told you that you have an intolerance to certain sugars.

Children and adolescents
Kengrexal is not recommended for children and adolescents under 18 years of age.
Other medicines and Kengrexal
You may receive acetylsalicylic acid (ASA) while being treated with Kengrexal or with another type of antiplatelet medicine (e.g. clopidogrel) before and after treatment with Kengrexal.
Inform your doctor if you are taking other medicines that may increase the risk of adverse effects such as bleeding, including blood thinners (anticoagulants, e.g. warfarin).
Inform your doctor if you are currently taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, or are planning to become pregnant, consult your doctor before taking this medicine. Kengrexal is not recommended for use during pregnancy.
Driving and using machines
The effect of Kengrexal disappears rapidly and it is unlikely to affect your ability to drive or use machinery.
Kengrexal contains sodium and sorbitol
Sorbitol is a source of fructose. If you have been diagnosed with hereditary fructose intolerance, a rare genetic disorder, you must not take this medicine. Patients with hereditary fructose intolerance are unable to metabolize fructose, which may cause severe side effects.
Before taking this medicine, inform your doctor if you suffer from hereditary fructose intolerance.
This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e. essentially 'sodium-free'.

3. How to use Kengrexal

Your treatment with Kengrexal will be supervised by a doctor experienced in treating patients
with heart disease. The doctor will decide how much Kengrexal you should receive and will prepare the
medicinal product.
Kengrexal is administered by injection, followed by an infusion (intravenous drip) into a vein. The dose administered depends on your body weight.
The recommended dose is:

• 30 micrograms per kilogram of body weight by injection, immediately followed by
• 4 micrograms per kilogram of body weight per minute by infusion (intravenous drip) for at least 2 hours. Your doctor will decide whether you should be treated for longer periods.

If you use more Kengrexal than you should
This medicine will be administered to you by a healthcare professional. The doctor will decide how to manage your treatment, including stopping the medicine and monitoring for signs of adverse effects.
If you have any doubts about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
If they occur, side effects may require medical attention.
Tell your doctor immediately if you notice any of the following:

• Bleeding from any part of the body. Bleeding is a common side effect of treatment with Kengrexal (may affect up to 1 in 10 people). Bleeding can be serious, and fatal outcomes have been reported.
• Allergic reaction (rash, itching, tightness/swelling of the throat, swelling of the tongue or lips, difficulty breathing). Allergic reaction is a rare side effect of treatment with Kengrexal (may affect up to 1 in 1,000 people) but can potentially be serious.

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

• Minor bruising may occur anywhere on the body (including small red bruises on the skin or at the site of a subcutaneous injection causing swelling),
• dyspnoea (shortness of breath),
• bleeding leading to reduced blood volume or red blood cell count,
• fluid leakage from injection or catheter sites.

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

• Bleeding resulting in fluid accumulation around the heart, blood in the chest cavity, or bleeding from the nose, gastrointestinal tract, abdomen, urine, or from injection or catheter sites,
• increased creatinine levels in the blood (detected by blood tests), indicating reduced kidney function,
• changes in blood pressure,
• skin rash, itching, urticaria,
• haematoma at the vascular puncture site.

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

• Bleeding leading to low platelet count or anaemia,
• bleeding into the eyes, brain (including stroke), pelvis, or lungs,
• bleeding from wound sites,
• balloon-like swelling in an artery or in the heart wall, involving only a few layers of the blood vessel walls,
• severe allergic reactions,
• reduced blood clotting,
• bruising,
• facial swelling.

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 from pre-existing skin tumours.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor.
You can also report side effects directly via the national reporting system listed in Annex V.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Kengrexal

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton after 'Exp.'. The expiry date refers to the last day of that month.
This medicine requires no special storage conditions.
Reconstituted solution: The powder must be reconstituted immediately before dilution and use. Do not refrigerate.
Diluted solution: From a microbiological standpoint, unless the method of reconstitution/dilution excludes the risk of microbiological contamination, the medicine should be used immediately. If not used immediately, the duration of storage during use and the conditions prior to use are under the responsibility of the user.

6. Package contents and other information

What Kengrexal contains
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 components are mannitol, sorbitol and sodium hydroxide for pH adjustment.

Description of the appearance of Kengrexal and contents of the pack
Lyophilised powder for concentrate for solution for injection/infusion in a glass vial.
Kengrexal is a white to off-white lyophilised powder.
Kengrexal is available in packs of ten 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
Amryt Pharmaceuticals Designated Activity Company
45 Mespil Road,
Dublin 4, D04 W2F1,
Ireland
Chiesi Farmaceutici S.p.A.
Via San Leonardo, 96
43122 Parma,
Italy

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Ferrer Benelux B.V. Chiesi Pharmaceuticals GmbH
Tél/Tel: +31 (0)88 – 2045 888 Tel: +43 1 4073919

България Luxembourg/Luxemburg
Chiesi Bulgaria EOOD Ferrer Benelux B.V.
Teл.: + 359 29201205 Tél/Tel: +31 (0)88 – 2045 888

Česká republika Magyarország
Chiesi CZ s.r.o. Chiesi Hungary Kft.
Tel: +420 261221745 Tel.: +36 - 1 - 429 1060

Danmark Malta
Chiesi Pharma AB Chiesi Farmaceutici S.p.A.
Tlf: +46 8 753 35 20 Tel: + 39 0521 2791

Deutschland Nederland
Ferrer Deutschland GmbH Ferrer Benelux B.V.
Tel: +49 (0) 2407 502311-0 Tél/Tel: +31 (0)88 – 2045 888

Eesti Norge
Chiesi Pharmaceuticals GmbH Chiesi Pharma AB
Tel: +43 1 4073919 Tlf: +46 8 753 35 20

Ελλάδα Österreich
Chiesi Hellas AEBE Chiesi Pharmaceuticals GmbH
Τηλ: + 30 210 6179763 Tel: + 43 1 4073919

España Polska
Ferrer Farma, S.A. Ferrer Internacional, S.A.
Tel: +34 93 600 3700 Tel.: +48 518 630 955

France Portugal
Bioprojet Pharma Ferrer Portugal, S.A
+33 (0)1 47 03 66 33 Tel: +351 214449600

Hrvatska România
Chiesi Pharmaceuticals GmbH Chiesi Romania S.R.L.
Tel: + 43 1 4073919 Tel: + 40 212023642

Ireland Slovenija
Chiesi Farmaceutici S.p.A. Chiesi Slovenija d.o.o.
Tel: + 39 0521 2791 Tel: + 386 - 1 - 43 00 901

Ísland Slovenská republika
Chiesi Pharma AB Chiesi Slovakia s.r.o.
Tlf: +46 8 753 35 20 Tel: + 421 259300060

Italia Suomi/Finland
Chiesi Italia S.p.A. Chiesi Pharma AB
Tel: + 39 0521 2791 Tlf: +46 8 753 35 20

Κύπρος Sverige
Chiesi Farmaceutici S.p.A. Chiesi Pharma AB
Τηλ: + 39 0521 2791 Tlf: +46 8 753 35 20

Latvija
Chiesi Pharmaceuticals GmbH
Tel: + 43 1 4073919

Other sources of information
More detailed information on this medicine is available on the website of the European Medicines Agency: https://www.ema.europa.eu .

The following information is intended for healthcare professionals only:

Kengrexal must be administered by a physician experienced in acute coronary therapy or coronary procedures and is intended for specialized use in hospital settings during acute situations.
Dosage
The recommended dose of Kengrexal for patients undergoing PCI is an intravenous bolus of 30 micrograms/kg followed immediately by a continuous intravenous infusion of 4 micrograms/kg/min. The bolus and infusion must be initiated prior to the procedure and continued for at least two hours or for the duration of the procedure, whichever is longer. At the physician's discretion, the infusion may be continued for a total duration of four hours (see section 5.1).
For chronic treatment, patients should be transitioned to oral P2Y₁₂ receptor inhibitors. For transition, an oral loading dose of P2Y₁₂ receptor inhibitor therapy (clopidogrel, ticagrelor, or prasugrel) should be administered immediately after discontinuation of cangrelor infusion. Alternatively, a loading dose of prasugrel—but not clopidogrel—may be given up to 30 minutes before the end of the infusion. A standard loading dose of ticagrelor may be administered at any time during cangrelor infusion; see section 4.5.
Instructions for preparation
Aseptic techniques must be used when preparing Kengrexal.
The vial should be reconstituted immediately before dilution and use. Reconstitute each 50 mg vial by adding 5 mL of sterile water for injections. Gently swirl in a circular motion until all material is dissolved. Avoid vigorous mixing. Allow any foam formed to settle. Ensure that the vial contents are completely dissolved and that the reconstituted solution is a clear, colourless to pale yellow liquid.
Do not use without dilution. Prior to administration, withdraw 5 mL of the reconstituted solution from each vial and further dilute it with 250 mL of either 9 mg/mL (0.9%) sodium chloride injection solution or 5% glucose injection solution. Mix the bag thoroughly.
The medicinal product should be inspected visually for particulate matter after reconstitution.
Kengrexal is administered using a weight-based regimen consisting of an initial intravenous bolus followed by continuous intravenous infusion. Both the bolus and the infusion must be delivered from the infusion solution.
This dilution results in a concentration of 200 micrograms/mL and should be sufficient for at least two hours of administration as required. For patients weighing 100 kg or more, at least two bags are required.