Inaqovi

Treatment must be initiated and supervised by a physician experienced in the use of anticancer therapies. Posology The recommended dose of Inaqovi is 1 tablet once daily on Days 1 through 5 of each 28-day cycle. Cycles are to be repeated every 28 days.

Treatment is to be continued for a minimum of 4 cycles until disease progression or unacceptable toxicity. A complete or partial response may take longer than 4 cycles. • Substitution with an intravenous decitabine product within a cycle is not recommended.

4). • A delay or reduction in the dose per cycle is to be considered for patients who experience haematologic and non-haematologic toxicities (see “Dose adjustments”). 3 Missed or vomited dose • If the patient misses a dose within 12 hours of the time it is usually taken, the patient must take the missed dose as soon as possible and resume the normal daily dosing schedule.

• If the patient misses a dose by 12 or more hours, the patient must wait and take the missed dose the following day at the usual time and then extend the dosing period by one day for every missed dose to complete 5 daily doses for each cycle.

• If the patient vomits following dosing, no additional dose is to be taken that day. The next dose must be taken at the usual time and resume the normal daily dosing, with no extension of the dosing period. 0 × 109/L and platelets are less than 50 × 109/L in the absence of active disease.

0 × 109/L or greater and platelets are 50 × 109/L or greater. 0 × 109/L and platelets at least 50 × 109/L) within 2 weeks of the last treatment cycle, treatment is to be continued at the same dose. 0 × 109/L and platelets at least 50 × 109/L) within 2 weeks of the last treatment cycle: o Treatment must be delayed for up to 2 additional weeks AND o The patient must resume treatment at a reduced dose on Days 1 through 4.

Further dose reductions have to be considered in the order listed in Table 1 if myelosuppression persists after a dose reduction. o Dose has to be maintained or increased in subsequent cycles as clinically indicated. Patients are to be treated with a minimum of 4 cycles of treatments with active disease.

4). Non-haematologic adverse reactions Subsequent treatment cycles must be delayed for the following non-haematologic adverse reactions and resumed at the same or reduced dose upon resolution: • Serum creatinine 2 mg/dL or greater • Serum bilirubin 2 times the upper limit of normal (ULN) or greater • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2 times the ULN or greater 4 • Active or uncontrolled infection Dose adjustments for all other Grade 3 or higher adverse reactions should follow institutional guidelines.

Summary of safety profile The safety of Inaqovi was evaluated in one Phase 3 study (ASTX727-02-EU) where 80 AML patients received the medicinal product. The overall safety profile for Inaqovi is described below and also reflects the known safety profile of intravenous decitabine.

Among the 80 patients who received treatment, the most common adverse drug reaction (≥ 20%) including Grade ≥ 3 was thrombocytopaenia. The most common serious adverse reactions (≥ 20%) were febrile neutropaenia and pneumonia. Deaths while on treatment occurred in 24% of patients.

The most frequent adverse reactions resulting in death included pneumonia (8%), sepsis (3%) and central nervous system haemorrhage in the setting of thrombocytopaenia (3%). Permanent discontinuation occurred in 14% of patients while on treatment.

The most frequent adverse reaction resulting in permanent discontinuation was pneumonia (5%). 8 Treatment interruption and dose reductions occurred in 48% of patients. The most frequent adverse reaction resulting in treatment interruption and dose reduction was myelosuppression occurring in 19% of patients (n=15) (neutropaenia [13%, n=10], febrile neutropaenia [5%, n=4], and thrombocytopaenia [3%, n=2]).

The adverse reaction pneumonia led to treatment interruption and dose reduction in 5% of patients. Tabulated list of adverse reactions The safety evaluation of adverse reactions is largely based on experience with Dacogen in patients with AML.

The safety of Inaqovi in adult patients was evaluated in a safety population that included AML patients from one Phase 3 study (ASTX727-02-EU, N=80). Among the 80 patients who received Inaqovi, 38% were exposed for 6 months or longer and 6% were exposed for greater than 1 year.

Table 2 lists adverse drug reactions associated with Inaqovi (N=80), or that have been associated with intravenous decitabine, according to system organ class (SOC) in MedDRA. Within each SOC, the adverse drug reactions are ranked by frequency and then presented in order of decreasing seriousness.

8). Complete blood cell counts must be obtained prior to the initiation of treatment, prior to each cycle, and as clinically indicated to monitor response and toxicity. Growth factors and anti-infective therapies must be administered for treatment or prophylaxis as appropriate.

8). Patients must be monitored for signs and symptoms of infection and treated promptly. , G-CSF) for neutropaenia according to institutional guidelines. 2. Respiratory, thoracic and mediastinal disorders Cases of interstitial lung disease (ILD) (including pulmonary infiltrates, organising pneumonia and pulmonary fibrosis) without signs of infectious aetiology have been reported in patients receiving intravenous decitabine.

Patients with an acute onset or unexplained worsening of pulmonary symptoms must be carefully assessed to exclude ILD. 8). Hepatic impairment Use in patients with hepatic impairment has not been established. Caution must be exercised in the administration of medicinal product to patients with hepatic impairment and in patients who develop signs or symptoms of hepatic impairment.

2). Renal impairment Use in patients with severe renal impairment has not been studied. Caution must be exercised in the administration of the medicinal product to patients with severe renal impairment (CrCl < 30 mL/min). 2). Cardiac disease Patients with a history of severe congestive heart failure or clinically unstable cardiac disease were excluded from clinical studies and therefore, the safety and efficacy of the medicinal product in these patients has not been established.

8). Patients, especially those with a history of cardiac disease, must be monitored for signs and symptoms of heart failure. 8). 8). Treatment with high-dose intravenous corticosteroids and haemodynamic monitoring must be considered at first onset of symptoms or signs suggestive of differentiation syndrome.

Treatment must be temporarily discontinued until symptoms resolve, and if resumed, caution is advised. Administration of antiemetics Nausea and vomiting may occur during treatment. Administration of standard antiemetic therapy prior to each dose should be considered to minimise nausea and vomiting.

1. 6).