vyxeos

Important safety information

Hemorrhage: Serious or fatal hemorrhagic events with associated prolonged thrombocytopenia have occurred with VYXEOS. Monitor blood counts regularly until recovery. ( 5.2 ) • Cardiotoxicity: VYXEOS treatment is not recommended in patients with cardiac function that is less than normal. Discontinue VYXEOS in patients with impaired cardiac function unless the benefit of continuing treatment outweighs the risk. ( 2.2 , 5.3 ) • Hypersensitivity: If severe or life-threatening hypersensitivity reaction occurs, discontinue VYXEOS, treat according to standard of care, and monitor until signs and symptoms resolve. ( 2.2 , 5.4 ) • Tissue Necrosis: Daunorubicin has been associated with local tissue necrosis at the site of drug extravasation. Confirm intravenous access before administration. ( 5.6 ) • Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.7 , 8.1 , 8.3 ) 5.1 Do Not Interchange With Other Daunorubicin And/Or Cytarabine-Containing Products Due to substantial differences in the pharmacokinetic parameters, the dose and schedule recommendations for VYXEOS are different from those for 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. Do not substitute other preparations of daunorubicin or cytarabine for VYXEOS. 5.2 Hemorrhage Serious or fatal hemorrhage events, including fatal central nervous system (CNS) hemorrhages, associated with prolonged severe thrombocytopenia, have occurred in patients treated with VYXEOS. In Study 1 (NCT01696084), the incidence of any grade hemorrhagic events during the entire treatment period was 74% of patients on the VYXEOS arm and 56% on the control arm. The most frequently reported hemorrhagic event was epistaxis (36% in VYXEOS arm and 18% in control arm). Grade 3 or greater events occurred in 12% of VYXEOS treated patients and 8% of patients treated with 7+3. Fatal treatment-emergent CNS hemorrhage not in the setting of progressive disease occurred in 2% of patients on the VYXEOS arm and in 0.7% of patients on the control arm. Monitor blood counts regularly until recovery and administer platelet transfusion support as required [see Adverse Reactions ( 6.1 )]. 5.3 Cardiotoxicity VYXEOS contains the anthracycline daunorubicin, which has a known risk of cardiotoxicity. Prior therapy with anthracyclines, pre-existing cardiac disease, previous radiotherapy to the mediastinum, or concomitant use of cardiotoxic drugs may increase the risk of daunorubicin-induced cardiac toxicity. Prior to administering VYXEOS, obtain an electrocardiogram (ECG) and assess cardiac function by multi-gated radionuclide angiography (MUGA) scan or echocardiography (ECHO). Repeat MUGA or ECHO determinations of left ventricular ejection fraction (LVEF) prior to consolidation with VYXEOS and as clinically required. Discontinue VYXEOS in patients with impaired cardiac function unless the benefit of initiating or continuing treatment outweighs the risk. VYXEOS treatment is not recommended in patients with LVEF that is less than normal. Total cumulative doses of non-liposomal daunorubicin greater than 550 mg/m 2 have been associated with an increased incidence of drug-induced congestive heart failure. The tolerable limit appears lower (400 mg/m 2 ) in patients who received radiation therapy to the mediastinum. Calculate the lifetime cumulative anthracycline exposure prior to each cycle of VYXEOS. VYXEOS treatment is not recommended in patients whose lifetime anthracycline exposure has reached the maximum cumulative limit. The exposure to daunorubicin following each cycle of VYXEOS is shown in Table 2. Table 2: Cumulative Exposure of Daunorubicin per Cycle of VYXEOS Therapy Daunorubicin per Dose Number of Doses per Cycle Daunorubicin per Cycle First Induction Cycle 44 mg/m 2 3 132 mg/m 2 Second Induction Cycle 44 mg/m 2 2 88 mg/m 2 Each Consolidation Cycle 29 mg/m 2 2 58 mg/m 2 5.4 Hypersensitivity Reactions Serious or fatal hypersensitivity reactions, including anaphylactic reactions, have been reported with daunorubicin and cytarabine. Monitor patients for hypersensitivity reactions. If a mild or moderate hypersensitivity reaction occurs, interrupt or slow the rate of infusion with VYXEOS and manage symptoms. If a severe or life-threatening hypersensitivity reaction occurs, discontinue VYXEOS permanently, treat symptoms according to the standard of care, and monitor until symptoms resolve [see Dosage and Administration ( 2.2 )] . 5.5 Copper Overload Reconstituted VYXEOS contains 5 mg/mL copper gluconate, of which 14% is elemental copper. There is no clinical experience with VYXEOS in patients with Wilson’s disease or other copper-related metabolic disorders. The maximum theoretical total exposure of copper under the recommended VYXEOS dosing regimen is 106 mg/m 2 [see Dosage and Administration ( 2.1 )] . Consult with a hepatologist and nephrologist with expertise in managing acute copper toxicity in patients with Wilson’s disease treated with VYXEOS. Monitor total serum copper, serum non-ceruloplasmin bound copper, 24-hour urine copper levels and serial neuropsychological examinations in these patients. Use VYXEOS in patients with Wilson’s disease only if the benefits outweigh the risks. Discontinue VYXEOS in patients with signs or symptoms of acute copper toxicity. 5.6 Tissue Necrosis Daunorubicin has been associated with severe local tissue necrosis at the site of drug extravasation. Administer VYXEOS by the intravenous route only. Confirm patency of the intravenous access before administration. Do not administer by the intramuscular or subcutaneous route. 5.7 Embryo-Fetal Toxicity Based on its mechanism of action and findings from animal studies with daunorubicin and cytarabine, 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. 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 risk to a fetus. Advise females and males of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of VYXEOS [see Use in Specific Populations ( 8.1 ) and ( 8.3 )] .