Kengreal
(cangrelor)Dosage & Administration
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Kengreal Prescribing Information
KENGREAL is indicated as an adjunct to percutaneous coronary intervention (PCI) to reduce the risk of periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis (ST) in patients who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor [see Clinical Studies ( 14.1)].
2.3 Preparation and Administration
KENGREAL is intended for IV administration, after reconstitution and dilution.
Preparation
Reconstitute the vial prior to dilution in a bag. For each 50 mg/vial, reconstitute by adding 5 mL of Sterile Water for Injection. Swirl gently until all material is dissolved. Avoid vigorous mixing. Allow any foam to settle. Ensure that the contents of the vial are fully dissolved and the reconstituted material is a clear, colorless to pale yellow solution. Parenteral drug products should be inspected visually for particulate matter after reconstitution.
Before administration, each reconstituted vial must be diluted further with Normal Saline (Sodium Chloride Injection 0.9% USP) or 5% Dextrose Injection USP.
Withdraw the contents from one reconstituted vial and add to one 250 mL saline bag. Mix the bag thoroughly. This dilution will result in a concentration of 200 mcg/mL and should be sufficient for at least 2 hours of dosing. Patients 100 kg and over will require a minimum of 2 bags.
Reconstituted KENGREAL should be diluted immediately. Diluted KENGREAL is stable for up to 12 hours in 5% Dextrose Injection and 24 hours in Normal Saline at Room Temperature. Discard any unused portion of reconstituted solution remaining in the vial.
Administration
Administer KENGREAL via a dedicated IV line.
Administer the bolus volume rapidly (<1 minute), from the diluted bag via manual IV push or pump. Ensure the bolus is completely administered before the start of PCI. Start the infusion immediately after administration of the bolus [see Dosage and Administration ( 2.1)].
For Injection: 50 mg of KENGREAL lyophilized powder in a single-use 10 mL glass vial for reconstitution.
8.1 Pregnancy
Risk Summary
There are no available data on cangrelor use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Untreated myocardial infarction can be fatal to the pregnant women and fetus (see Clinical Considerations).
In animal reproduction studies, continuous infusion of cangrelor in pregnant rats and rabbits throughout organogenesis at dose approximately 2-times the maximum recommended human dose (MRHD) did not result in fetal malformations (see Data).
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Clinical Considerations
Disease-associated maternal and/or embryo/fetal risk
Myocardial infarction is a medical emergency in pregnancy which can be fatal to the pregnant woman and fetus if left untreated. Life-sustaining therapy for the pregnant woman should not be withheld due to potential concerns regarding the effects of cangrelor on the fetus.
Labor or delivery
Cangrelor use during labor and delivery may increase the risk for maternal bleeding and hemorrhage. Performance of neuraxial blockade procedures is not advised during cangrelor use due to potential risk of spinal hematoma. When possible, discontinue cangrelor 1 hour prior to labor, delivery, or neuraxial blockade [see Clinical Pharmacology ].
Data
Animal Data
A prenatal and postnatal development study in female rats demonstrated a slight increase in the incidence of maternal mortality in dams treated at doses up to 30 mcg/kg/min (approximately 7.5 times the MRHD) cangrelor continuous infusion from Day 6 of gestation up to Day 23 post-partum. Pregnancy rates, gestation index, length of gestation, numbers of live, dead and malformed pups, sex ratio, live birth index, and lactation of the maternal animals were unaffected.
Cangrelor administered at dose levels of ≥ 3 mcg/kg/min in pregnant rats from Day 6 to 17 post-coitum resulted in dose-related fetal growth retardation characterized by increased incidences of incomplete ossification and unossified hind limb metatarsals.
An embryo-fetal development study in rabbits administered 4, 12, or 36 mcg/kg/min cangrelor continuous IV infusion from Day 6 to Day 19 post-coitum resulted in increased incidences of abortion and intrauterine losses at ≥12 mcg/kg/min (3 times the MRHD). Fetal growth retardation occurred at 36 mcg/kg/min (9 times the MRHD) and was characterized by decreased fetal weights, slight reduction in ossification, and a slight increase in skeletal variants.
Cangrelor did not produce malformations in either the rat or rabbit embryo-fetal development studies and is not considered to be a teratogen.
8.2 Lactation
Risk Summary
There are no data on the presence of cangrelor in human milk or animal milk, the effects on the breastfed infant, or the effects on milk production. However, due to its short-half life, cangrelor exposure is expected to be very low in the breastfed infant.
8.4 Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
8.5 Geriatric Use
In CHAMPION PHOENIX, 18% of patients were ≥75 years. No overall differences in safety or effectiveness were observed between these patients and those patients <75 years [see Clinical Studies ( 14.1)].
8.6 Renal Impairment
No dosage adjustment is required for patients with mild, moderate, or severe renal impairment [see Clinical Pharmacology ( 12.3)].
8.7 Hepatic Impairment
KENGREAL has not been studied in patients with hepatic impairment. However, the metabolism of KENGREAL is not dependent of hepatic function, so dosage adjustment is not required for patients with hepatic impairment [see Clinical Pharmacology ( 12.3)].
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)].
5.1 Bleeding
Drugs that inhibit platelet P2Y12 function, including KENGREAL, increase the risk of bleeding.
In CHAMPION PHOENIX bleeding events of all severities were more common with KENGREAL than with clopidogrel [see Adverse Reactions ( 6.1)]. Bleeding complications with KENGREAL were consistent across a variety of clinically important subgroups (see Figure 1).
Once KENGREAL is discontinued, there is no antiplatelet effect after an hour [see Clinical Pharmacology ( 12.3)].