FDA Advise-ERR: Vyxeos: Verify Drug Name and Dose to Avoid Errors!

This alert is to inform healthcare professionals that VYXEOS, the first fixed-combination liposomal formulation of DAUNOrubicin and cytarabine approved by the US Food and Drug Administration (FDA) this month, is different from other single entity DAUNOrubicin and cytarabine products that are often used together. Each Vyxeos vial contains 44 mg of DAUNOrubicin and 100 mg of cytarabine encapsulated together in liposomes. Vyxeos has unique dosing regimens and should never be interchanged with other DAUNOrubicin- and/or cytarabine-containing products. This is stated in a boxed warning in the prescribing information.

Vyxeos is indicated for the treatment of adults with newly diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AMLMRC). Vyxeos has substantially different pharmacokinetic parameters compared to other DAUNOrubicin- and/or cytarabine-containing products. The dose of Vyxeos is based on DAUNOrubicin and the patient’s body surface area (BSA). A full Vyxeos course consists of 1-2 cycles of induction therapy and up to 2 cycles of consolidation therapy at the doses and schedule listed in Table 1.

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 initiating each cycle of Vyxeos, calculate the prior cumulative anthracycline exposure for the patient. Vyxeos treatment is not recommended in patients whose lifetime anthracycline exposure has reached the maximum cumulative lifetime limit.

Vyxeos is supplied as a lyophilized cake in a single-dose vial. The prescribing information provides important preparation and administration instructions for Vyxeos.

Consider the recommendations below to help prevent errors with Vyxeos.

• Verify the drug name and dose prior to preparation and administration of Vyxeos to avoid dosing errors.
• Do not interchange other DAUNOrubicin and/or cytarabine products for Vyxeos.
• Work with information technology staff to create an order set for dosing Vyxeos based on the DAUNOrubicin component. Since Vyxeos is a fixed dose combination and dosing is based on the DAUNOrubicin component, the corresponding dose of cytarabine is included and does not need to be calculated.
• For patients requiring more than one cycle of Vyxeos: prior to initiating each cycle, calculate the lifetime cumulative anthracycline exposure for the patient. Vyxeos treatment is not recommended in patients whose lifetime anthracycline exposure has reached the maximum cumulative limit.
• The volume of reconstituted Vyxeos required for each dose is calculated based on the patient’s BSA (m2) and the dose of DAUNOrubicin (mg/m2).
• Review the prescribing information for important information on preparing and administering Vyxeos.

ISMP note: The warning against interchanging Vyxeos applies to single entity DAUNOrubicin and cytarabine products, whether liposomal or not.

ISMP thanks Nicole Garrison, PharmD, BCPS, and Hina Mehta, PharmD, at the US Food and Drug Administration (FDA) Division of Medication Error Prevention and Analysis, for providing this article.