Daunorubicin with cytarabine

Source: UK SPC (eMC) 4.2 for Vyxeos liposomal 44 mg/100 mg (https://www.medicines.org.uk/emc/product/9442/smpc). CRITICAL: 'Vyxeos liposomal has a different posology than daunorubicin injection and cytarabine injection and it must not be interchanged with other daunorubicin and/or cytarabine containing products.' Dosing is based on body surface area. FULL SCHEDULE (Table 1): first induction - daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 on days 1, 3 and 5; second induction - daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 on days 1 and 3; consolidation - daunorubicin 29 mg/m2 and cytarabine 65 mg/m2 on days 1 and 3. A subsequent induction course may be given in patients who do not show disease progression or unacceptable toxicity; attainment of a normal-appearing bone marrow may require more than one induction course, and bone marrow evaluation after recovery from the previous course determines whether a further induction course is required. CONSOLIDATION ELIGIBILITY: recommended for patients achieving remission who have recovered to an absolute neutrophil count above 500/microlitre and a platelet count above 50,000/microlitre, in the absence of unacceptable toxicity; a subsequent consolidation course may be given within 5 to 8 weeks after the start of the first consolidation. PRE-TREATMENT: patients may be pre-medicated for nausea and vomiting; anti-hyperuricaemic therapy (e.g. allopurinol) should be considered prior to initiating treatment. HYPERSENSITIVITY MANAGEMENT: mild symptoms (mild flushing, rash, pruritus) - stop treatment, supervise the patient including vital signs, then restart slowly once symptoms have resolved by halving the infusion rate, with intravenous diphenhydramine 20-25 mg and intravenous dexamethasone 10 mg. Moderate symptoms (moderate rash, flushing, mild dyspnoea, chest discomfort) - stop treatment, give intravenous diphenhydramine 20-25 mg (or equivalent) and intravenous dexamethasone 10 mg, do not restart the infusion; on retreatment give at the same dose and rate with premedication. Severe/life-threatening symptoms (hypotension requiring vasopressors, angioedema, respiratory distress requiring bronchodilators, generalised urticaria) - stop treatment, give intravenous diphenhydramine 20-25 mg and dexamethasone 10 mg, add adrenaline (epinephrine) or bronchodilators if indicated, do not reinitiate the infusion and do not retreat; permanently discontinue and monitor until symptoms resolve. CARDIOTOXICITY: assessment of cardiac function prior to starting treatment is recommended, especially in patients at high risk of cardiac toxicity; discontinue in patients who develop signs or symptoms of cardiomyopathy unless the benefits outweigh the risks. MISSED DOSE: administer as soon as possible and adjust the dosing schedule accordingly, maintaining the treatment interval. HEPATIC IMPAIRMENT: no dose adjustment required for bilirubin of 50 micromol/L or less; no experience above 50 micromol/L - use in severe hepatic impairment only if benefits outweigh risks. ELDERLY: no dose adjustment required in patients aged 65 years or over. PAEDIATRIC: outside its authorised indications the product has been studied in paediatric and young adult patients aged 1-21 years with relapsed AML, but due to the limited size of these studies no recommendation on a posology can be made. TREATMENT SETTING: should be initiated and monitored under the supervision of a physician experienced in the use of chemotherapeutic medicinal products. NOTE: the eMC 4.5 interactions section was not retrieved in this bundle, and the openFDA label in this bundle is for daunorubicin hydrochloride alone (not the liposomal fixed combination) so it has deliberately NOT been used - source the UK SPC 4.5 separately.