Daunorubicin and cytarabine liposomal
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: DO NOT INTERCHANGE WITH OTHER DAUNORUBICIN AND/OR CYTARABINE-CONTAINING PRODUCTS • VYXEOS has different dosage recommendations than daunorubicin hydrochloride injection, cytarabine injection, daunorubicin citrate liposome injection, and cytarabine liposome injection. Verify drug name and dose prior to preparation and administration to avoid dosing errors [see Warnings and Precautions ( 5.1 )] . WARNING: DO NOT INTERCHANGE WITH OTHER DAUNORUBICIN AND/OR CYTARABINE-CONTAINING PRODUCTS See full prescribing information for complete boxed warning.
• VYXEOS has different dosage recommendations than daunorubicin hydrochloride injection, cytarabine injection, daunorubicin citrate liposome injection, and cytarabine liposome injection. Verify drug name and dose prior to preparation and administration to avoid dosing errors ( 5.1 ).
Anthracycline Topoisomerase Inhibitor, Nucleoside Metabolic Inhibitor
Dosing in kidney impairment
Renal Impairment Dosage adjustment is not required for patients with mild (creatinine clearance [CL CR ] 60 mL/min to 89 mL/min by Cockcroft Gault equation [C-G]), moderate (CL CR 30 mL/min to 59 mL/min) or severe (CL CR 15 mL/min to 29 mL/min) renal impairment. VYXEOS has not been studied in patients with end-stage renal disease on hemodialysis [see Clinical Pharmacology] .
Dosing in liver impairment
Hepatic Impairment Dosage adjustment is not required for patients with a bilirubin level less than or equal to 3 mg/dL. VYXEOS has not been studied in patients with bilirubin level greater than 3 mg/dL [see Clinical Pharmacology].
Preparation and administration
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Preparation and Handling Instructions VYXEOS is a hazardous drug. Follow applicable special handling and disposal procedures. 1 VYXEOS is supplied as a single-dose vial and does not contain any preservatives. Do not save any unused portions for later administration. Reconstitute and further dilute VYXEOS prior to intravenous infusion.
Reconstitution:
Calculate the VYXEOS dose based on daunorubicin and individual patient's body surface area (BSA).
Calculate the number of vials of VYXEOS based on the daunorubicin dose.
Remove the appropriate number of vials of VYXEOS from the refrigerator and equilibrate to the room temperature for 30 minutes.
Then, reconstitute each vial with 19 mL of Sterile Water for Injection using a sterile syringe and immediately thereafter start a 5-minute timer.
Carefully swirl the contents of the vial for 5 minutes while gently inverting the vial every 30 seconds.
Do not heat, vortex, or shake vigorously.
After reconstitution, let rest for 15 minutes.
The reconstituted product should be an opaque, purple, homogeneous dispersion, essentially free from visible particulates. After reconstitution (but before final dilution), each mL will contain 2.2 mg of daunorubicin and 5 mg of cytarabine.
Use the reconstituted solution immediately. If needed, store the reconstituted solution in the vial refrigerated at 2ºC to 8ºC (36°F to 46°F) for up to 4 hours. Note that the reconstituted product in the vial and the reconstituted product which has been diluted into an infusion solution are stable for a total of 4 hours (not 4 hours each) when stored at 2°C to 8°C.
Dilution:
Calculate the volume of reconstituted VYXEOS required using the following formula: [volume required (mL) = dose of daunorubicin (mg/m 2 ) X patient's BSA (m 2 ) ÷ 2.2 (mg/mL)]
Gently invert each vial 5 times prior to withdrawing the reconstituted product for further dilution.
Aseptically withdraw the calculated volume of the reconstituted product from the vial(s) with a sterile syringe and transfer it to an infusion bag containing 500 mL of 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. There may be residual product remaining in the vial. Discard unused portion.
Gently invert the bag to mix the solution. The dilution of the reconstituted product results in a deep purple, translucent, homogeneous dispersion, free from visible particulates.
If the diluted infusion solution is not used immediately, store in a refrigerator at 2ºC to 8ºC (36°F to 46°F) for up to 4 hours. If the reconstituted solution in the vial was stored for 4 hours, the diluted infusion solution must be used immediately and cannot be stored for an additional 4 hours.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Only solutions without visible particles should be used.
Administration Instructions
For intravenous use only.
Do not mix VYXEOS with or administer as an infusion with other drugs.
Administer VYXEOS by constant intravenous infusion over 90 minutes via an infusion pump through a central venous catheter or a peripherally inserted central catheter. An in-line membrane filter may be used for the intravenous infusion of Vyxeos, provided the minimum pore diameter of the filter is greater than or equal to 15 microns.
Flush the line after administration with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP.
Drug interactions
Check daunorubicin and cytarabine liposomal against a medication listLabel text (3 paragraphs)
7 DRUG INTERACTIONS • Monitor cardiac function more frequently when coadministered with cardiotoxic agents. ( 7.1 ) • Monitor hepatic function more frequently when coadministered with hepatotoxic agents. ( 7.2 )
7.1 Cardiotoxic Agents Concomitant use of cardiotoxic agents may increase the risk of cardiotoxicity. Assess cardiac function more frequently when VYXEOS is coadministered with cardiotoxic agents [see Warnings and Precautions ( 5.3 )].
7.2 Hepatotoxic Agents Concomitant use with hepatotoxic agents may impair liver function and increase the toxicity of VYXEOS. Monitor hepatic function more frequently when VYXEOS is coadministered with hepatotoxic agents.
Contraindications
The use of VYXEOS is contraindicated in patients with the following: • History of serious hypersensitivity reaction to cytarabine, daunorubicin, or any component of the formulation [see Warnings and Precautions ( 5.4 )] . • History of serious hypersensitivity to daunorubicin, cytarabine or any component of the formulation. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on anecdotal data of cytarabine in pregnant women and results of studies of daunorubicin and cytarabine in animals, VYXEOS can cause embryo-fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of VYXEOS, daunorubicin, or cytarabine in pregnant women. Daunorubicin and cytarabine are reproductive and developmental toxicants in multiple species (mice, rats, and/or dogs), starting at a dose that was approximately 0.02 times the exposure in patients at the recommended human dose on a mg/m 2 basis [see Animal Data] . Patients should be advised to avoid becoming pregnant while taking VYXEOS.
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential harm to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively. Data Human Data Cytarabine can cause fetal harm if a pregnant woman is exposed to the drug.
Four anecdotal cases of major limb malformations have been reported in infants after their mothers received intravenous cytarabine, alone or in combination with other agents, during the first trimester. Animal Data A liposomal formulation of daunorubicin was administered to rats on gestation days 6 through 15 at 0.3, 1.0, or 2.0 mg/kg/day (about 0.04, 0.14, or 0.27 the recommended human dose on a mg/m 2 basis) and produced severe maternal toxicity and embryolethality at 2.0 mg/kg/day and was embryotoxic and caused fetal malformations (anophthalmia, microphthalmia, incomplete ossification) at 0.3 mg/kg/day.
Embryotoxicity was characterized by increased embryo-fetal deaths, reduced numbers of litters, and reduced litter sizes. Cytarabine was teratogenic in mice (cleft palate, phocomelia, deformed appendages, skeletal abnormalities) when doses ≥ 2 mg/kg/day were administered intraperitoneal (IP) during the period of organogenesis (about 0.06 times the recommended human dose on a mg/m 2 basis), and in rats (deformed appendages) when 20 mg/kg was administered as a single IP dose on day 12 of gestation (about 1.2 times the recommended human dose on a mg/m 2 basis). Single IP doses of 50 mg/kg in rats (about 3 times the recommended human dose on a mg/m 2 basis) on day 14 of…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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