• Vyxeos is a combination chemotherapy medicine that contains two commonly used drugs for AML, daunorubicin, and cytarabine in a 1:5 molar ratio, that may be given to treat acute myeloid leukemia.
• Daunorubicin and cytarabine contained in Vyxeos work synergistically to kill leukemia cells. Daunorubicin forms complexes with DNA, which inhibits topoisomerase II activity and polymerase activity and affects the regulation of gene expression. This produces DNA-damaging free radicals. Cytarabine is cell cycle-specific which means it only affects cells during the S-phase of cell division. Cytarabine acts primarily through the inhibition of DNA polymerase.
• Vyxeos is encapsulated in liposomes, this is a fat-like coating or membrane which is easy for the body to absorb. Once injected, the liposomes in Vyxeos enter and are concentrated in the bone marrow, and are taken up intact by bone marrow cells. Animal studies have shown that liposomes are taken up by leukemia cells to a greater extent than by normal bone marrow cells. After they have been taken up by the cell, the liposomes break down, releasing cytarabine and daunorubicin directly inside the cell.
• Vyxeos belongs to the class of medicines known as antineoplastic combinations.

• Vyxeos may be used to treat adults with acute myeloid leukemia (AML) caused by previous chemotherapy treatment or AML with myelodysplasia-related changes (AML-MRC).
• May also be used in children aged one year and older to treat newly-diagnosed therapy-related t-AML or AML with myelodysplasia-related changes (AML-MRC).
• First-of-its-kind formulation.
• Vyxeos encapsulates daunorubicin and cytarabine in tiny bubble-like carriers called liposomes. This fat-like coating allows Vyxeos to safely get to the bone marrow where it is taken up preferentially by leukemic cells. This minimizes the side effects on healthy tissue.
• A dosage adjustment is not required for people with mild renal impairment. Has not been studied in those with severe renal impairment or end-stage renal disease.
• A dosage adjustment is not required for people with bilirubin levels less than or equal to 3 mg/dL.
• Vyxeos is given via an infusion into the vein over 90 minutes.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Most people experience side effects with Vyxeos. Mild hemorrhage (such as nose bleeds), febrile neutropenia, a rash, edema, nausea, diarrhea, mouth ulcers, constipation, musculoskeletal or abdominal pain, or cough are the most common side effects reported. A headache, shortness of breath, fatigue, arrhythmia, a decreased appetite, pneumonia, sleep disorders, and infections may also occur.
• Other side effects include anxiety, delirium, itch, sepsis, hemorrhoids, petechiae, transfusion reactions, kidney problems, visual or hearing impairment, or hallucinations.
• All patients develop severe neutropenia, thrombocytopenia, and anemia. Over 25% developed prolonged thrombocytopenia and over 10% developed prolonged neutropenia in the induction and consolidation phases of treatment. Low sodium, potassium, and albumin levels may also occur in addition to high bilirubin levels.
• May cause hypersensitivity (allergic) reactions, including anaphylaxis. Stop the Vyxeos infusion immediately if symptoms occur, and the rate of infusion reduced or treatment discontinued, depending on the severity. For mild symptoms, reinitiate the infusion once symptoms have resolved at half the prior rate. Consider premedication with antihistamines or corticosteroids before subsequent doses. For moderate symptoms, do not reinitiate the infusion. Ensure the patient is premedicated with antihistamines or corticosteroids prior to initiating the infusion at the same rate. For severe/life-threatening symptoms, permanently discontinue Vyxeos treatment and treat the reaction. Monitor the patient until symptoms resolve. Do not administer to people with a history of serious hypersensitivity reactions to cytarabine, daunorubicin, Vyxeous, or a component of the formulation.
• Do not interchange Vyxeos with any other daunorubicin or cytarabine-containing products.
• Serious, sometimes fatal, hemorrhages have occurred in people being treated with Vyxeos, including CNS hemorrhages (2%). The most frequently reported hemorrhagic event was bleeding noses (36%).
• Vyxeous contains 5mg/mL copper gluconate when reconstituted, which equates to 14% elemental copper. There is no data regarding the use of Vyxeos in people with Wilson's disease or other copper-related metabolic disorders. Following recommended Vxyeous dosing regimens, the maximum theoretical copper exposure is 106 mg/m². Use in people with Wilson's disease only if the benefit outweighs the risks. Discontinue if signs of copper toxicity occur and consult with a hematologist if needed.
• Daunorubicin, contained in Vyxeos, has a known risk of cardiotoxicity. Those at higher risk include people previously treated with anthracyclines, pre-existing cardiac disease, previous radiotherapy to the mediastinum, or concomitant use of cardiotoxic drugs. Do not continue with Vyxeos in those who show impairment in their heart's function, unless the benefits outweigh the risks. The lifetime cumulative anthracycline exposure should be calculated before each cycle of Vyxeos and treatment is not recommended in those that have received total cumulative doses of non-liposomal daunorubicin greater than 550 mg/m², or 400 mg/m² in people who have previously had radiation therapy to the mediastinum.
• Requires infusion by a healthcare provider. A full Vyxeos course usually consists of one or two initial cycles (called induction cycles) followed by up to 2 more cycles called consolidation cycles. The first induction cycle is usually given on days 1, 3, and 5. Induction cycles are typically a higher dosage than consolidation cycles. The full cycle of Vyxeos may be given for six to 14 weeks depending on the number of cycles given.
• Vyxeos needs to be diluted and infused soon after preparation. If not used straight away the diluted infusion should be stored at 2ºC to 8ºC (36°F to 46°F) for up to 4 hours. If not used within that time, discard the solution. An in-line filter may be used during the infusion as long as the minimum pore diameter of the filter is greater than or equal to 15µm. Store unreconstituted Vyxeos in a refrigerator at 2ºC to 8ºC (36°F to 46°F).
• For intravenous use only. Not for IM or subcutaneous use.
• Do not administer or mix with other drugs. Vyxeos has different dosage recommendations than other daunorubicin or cytarabine injections. Verify drug name and dose prior to preparation and administration to minimize dosing errors.
• Can cause embryo-fetal harm when administered to a pregnant woman. Advise women of childbearing potential not to become pregnant during Vyxeous treatment. If they inadvertently do become pregnant they should tell their doctor immediately. Males and females of reproductive potential should use effective contraception during treatment and for 6 months following the last dose of Vyxeos. Women should not breastfeed for at least 2 weeks after the last dose.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

• Vyxeos is administered by an infusion into the vein over 90 minutes.
• Vyxeos may be used to treat acute myeloid leukemia (AML). AML happens when young abnormal white blood cells called blasts, begin to fill up the bone marrow, preventing normal blood production. Doctors diagnose AML when 20 out of every 100 white blood cells in the bone marrow are blast cells.
• A full Vyxeos course usually consists of one or two initial cycles (called induction cycles) followed by up to 2 more cycles called consolidation cycles. The actual dosage given of Vyxeos is calculated according to a person’s body surface area, which is calculated based on their height and weight. Anti-nausea medications are usually administered about 30 minutes before Vyxeos is given. Vyxeos is colored purple.
• You are likely to develop some side effects as a result of Vyxeos infusion and you should be aware that there is a risk of fatal bleeding associated with Vyxeos infusions, although the most common bleeding side effects are nose bleeds. Keep your scheduled appointments for blood work and necessary transfusions. Contact a healthcare provider if you develop a fever, symptoms of infection, or if you notice unusual bleeding or bruising.
• Also tell your doctor if you develop any worrying side effects such as shortness of breath, extreme fatigue, facial swelling, heart problems, or if you are not tolerating the drug.
• Vyxeos is not recommending during pregnancy and while breastfeeding. Use effective contraception if you are a woman of childbearing potential or if you are a man with a female partner that could become pregnant during Vyxeos treatment and for 6 months after the last dose. Tell your doctor immediately if you or your partner inadvertently become pregnant. Do not breastfeed for at least 2 weeks after the last dose.
• Vyxeos may cause temporary or permanent infertility in males.

• Vyxeos was compared to a standard combination of cytarabine and daunorubicin (7+3) in patients 60 to 75 years with newly diagnosed t-AML or AML-MRC. The median survival was 9.6months in the Vyxeos group and 5.9 months in the 7+3 group. The Complete Remission rate was 38% in the Vyxeos group and 26% in the &+3 group.
• Vyxeos's liposomal membrane is made up of di-stearoyl phosphatidylcholine (DSPC), di-stearoyl phosphatidylglycerol (DSPG), and cholesterol in a 7:2:1 molar ratio. This allows more active drug to reach the bone marrow and helps to reduce the harmful effects of daunorubicin and cytarabine on healthy tissue.

Medicines that interact with Vyxeos may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with Vyxeos. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Vyxeos interacts with over 425 medications; the majority of these interactions are considered major or moderate. Common medications that may interact with Vyxeos include:

• antibiotics, such as azithromycin
• antidepressants such as citalopram, escitalopram, or doxepin
• antipsychotics, such as clozapine, haloperidol, risperidone, or ziprasidone
• antineoplastics, such as capecitabine, cyclophosphamide, cytarabine, or daunorubicin
• antivirals, such as efavirenz or ritonavir
• biologics, such as adalimumab, etanercept, golimumab, or infliximab
• busulfan
• chloroquine or hydroxychloroquine
• cladribine
• droperidol
• etanercept
• fingolimod
• heart medications such as amiodarone, sotalol,
• herbals, such as brewer's yeast
• hydroxyurea
• immunosuppressants such as azathioprine, cyclosporine, or tacrolimus
• infliximab
• interferon
• lithium
• live vaccines and some other vaccines, such as BCG, cholera, sars-cov-2 (covid-19) vaccines, measles, hepatitis b vaccines, yellow fever, or live influenza vaccines
• methadone
• methotrexate
• pimozide
• probiotics, such as lactobacillus
• quinidine
• salmeterol
• vardenafil.

Cardiotoxic agents, such as 5-fluorouracil, targeted treatments (such as tyrosine kinase inhibitors), and paclitaxel may cause additive cardiotoxic effects and should be avoided.

Concomitant use with hepatotoxic agents can impair liver function and increase the toxicity of Vyxeos.

Note that this list is not all-inclusive and includes only common medications that may interact with Vyxeos. You should refer to the prescribing information for Vyxeos for a complete list of interactions.