Kengreal

Contraindications

Significant active bleeding

Hypersensitivity

Cautions

Increased risk of bleeding; bleeding events of all severities were more common with cangrelor than with clopidogrel

GENERIC AVAILABLE: No

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• Other medications that inhibit platelet activation and aggregation, including clopidogrel (Plavix) and prasugrel (Effient)

This is not a complete list of Kengreal drug interactions. Ask your doctor or pharmacist for more information.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X - are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Kengreal falls into category C. There are no well-controlled studies that have been done in pregnant women. Kengreal should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

• Store Kengreal at room temperature.
• Keep this and all medicines out of the reach of children.

General

• Intended to be given to patients prior to PCI in conjunction with other standard-of-care therapy (e.g., aspirin, anticoagulants).1 5

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Reconstituted drug requires further dilution prior to administration.1

Administer by rapid IV (“bolus”) injection (over <1 minute) from the prepared IV infusion bag via manual IV push or infusion pump, followed by IV infusion.1 9

Reconstitute vial containing 50 mg of lyophilized cangrelor with 5 mL of sterile water for injection (swirl gently).1

Dilute reconstituted solution in 250 mL of 5% dextrose or 0.9% sodium chloride injection to a final concentration of 200 mcg/mL for rapid IV injection and infusion.1

Rapid IV (“bolus”) injection: Administer over <1 minute.1

Continuous IV infusion: Administer for at least 2 hours or for duration of PCI, whichever is longer.1 2

Dosage

Available as cangrelor tetrasodium; dosage expressed in terms of cangrelor.1

Adults

30 mcg/kg by rapid IV (“bolus”) injection prior to PCI, immediately followed by 4 mcg/kg per minute by continuous IV infusion for at least 2 hours or for the duration of the procedure, whichever is longer.1 2 13 14

After discontinuance of cangrelor infusion, administer an oral P2Y12-receptor antagonist (clopidogrel, prasugrel, or ticagrelor) to maintain platelet inhibition.1 16 17

If ticagrelor used, administer 180 mg any time during cangrelor infusion or immediately after discontinuance of the infusion.1

If clopidogrel used, administer 600 mg immediately after discontinuance of cangrelor infusion; do not administer concurrently with cangrelor.1 (See Specific Drugs under Interactions.)

If prasugrel used, administer 60 mg immediately after discontinuance of cangrelor infusion; do not administer concurrently with cangrelor.1 (See Specific Drugs under Interactions.)

Special Populations

Renal Impairment

Dosage adjustment not required.1

Hepatic Impairment

Dosage adjustment not required. 1 (See Hepatic Impairment under Cautions.)

• If you have an allergy to Kengreal (cangrelor) or any part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have active bleeding.

This is not a list of all drugs or health problems that interact with Kengreal.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

4.1       Significant Active Bleeding

Kengreal is contraindicated in patients with significant active bleeding [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].

4.2       Hypersensitivity

Kengreal is contraindicated in patients with known hypersensitivity (e.g., anaphylaxis) to Kengreal or any component of the product [see Adverse Reactions (6.1)].

There is no specific treatment to reverse the antiplatelet effect of Kengreal but the effect is gone within one hour after the drug is discontinued.

In clinical trials, 36 patients received an overdose of Kengreal, ranging from 36 to 300 mcg/kg (bolus dose) or 4.8 to 13.7 mcg/kg/min (infusion dose). The maximum overdose received was 10 times the PCI bolus dose or 3.5 times the PCI infusion dose in 4 patients. No clinical sequela were noted as a result of overdose following completion of Kengreal therapy.

Kengreal is a direct-acting P2Y12 platelet receptor inhibitor that blocks adenosine diphosphate (ADP)-induced platelet activation and aggregation. The chemical structure is similar to adenosine triphosphate (ATP).

The chemical name of Kengreal is tetrasodium salt of N6-[2-(methylthio)ethyl]-2-[(3,3,3,-trifluoropropyl)-5’-adenylic acid, monanhydride with (dichloromethylene) bisphosphonic acid.

The empirical formula of Kengreal is C17H21N5Cl2F3Na4O12P3S2 and the molecular weight is 864.3 g/mol.

The chemical structure is represented below:

Cangrelor for Injection is a sterile white to off-white lyophilized powder for IV infusion. In addition to the active ingredient, cangrelor, each single use vial contains mannitol, sorbitol, and sodium hydroxide to adjust the pH.

13.1       Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

No carcinogenicity studies were conducted.

Mutagenesis

Cangrelor was non-mutagenic and non-clastogenic in genetic toxicology studies, including in vitro bacterial gene mutation assay, mouse lymphoma thymidine kinase assay, chromosome aberration assay in human peripheral lymphocytes, and in vivo bone marrow micronucleus assay in mice.

Impairment of Fertility

Cangrelor had no significant effect on male or female rats fertility treated for 28 days, or on early embryonic development at steady state plasma concentration (Css) of approximately the same as that achieved in the PCI setting at the MRHD.