INAQOVI Film-coated tablet Ref.[51639] Active ingredients: Cedazuridine Decitabine Decitabine and Cedazuridine

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.
• Premedication with standard antiemetic therapy prior to each dose to minimise nausea and vomiting is to be considered (see section 4.4).
• 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”).

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.

Dose adjustments

Haematologic adverse reactions

The next cycle must be delayed if absolute neutrophil count (ANC) is less than 1.0 × 10⁹/L and platelets are less than 50 × 10⁹/L in the absence of active disease. Complete blood cell (CBC) counts must be monitored until ANC is 1.0 × 10⁹/L or greater and platelets are 50 × 10⁹/L or greater.

In the absence of active disease:

• If haematological recovery occurs (ANC at least 1.0 × 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.
• If haematological recovery does not occur (ANC at least 1.0 × 10⁹/L and platelets at least 50 × 10⁹/L) within 2 weeks of the last treatment cycle:
  • Treatment must be delayed for up to 2 additional weeks AND
  • 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.
  • 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.

Table 1. Recommended dose reductions for myelosuppression:

Persistent severe neutropaenia and febrile neutropaenia have to be managed with supportive treatment (see section 4.4).

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
• Active or uncontrolled infection

Dose adjustments for all other Grade 3 or higher adverse reactions should follow institutional guidelines.

Special populations

Hepatic impairment

Studies in patients with hepatic impairment have not been conducted. The need for dose adjustment in patients with hepatic impairment has not been evaluated. If worsening hepatic function occurs, patients should be carefully monitored (see sections 4.4 and 5.2).

Renal impairment

No adjustment of starting dose is recommended for patients with mild or moderate renal impairment (creatinine clearance [CrCl] ≥30 mL/min/1.73 m²). Due to the potential for increased adverse reactions, patients with moderate renal impairment (CrCl 30 to 59 mL/min/1.73 m²) must be monitored. Inaqovi has not been studied in patients with severe renal impairment (CrCl 15 to 29 mL/min/1.73 m²) or end stage renal disease (CrCl <15 mL/min/1.73 m²) (see sections 4.4 and 5.2).

Paediatric population

The safety and efficacy of Inaqovi in the paediatric population (aged less than 18 years) have not been established. No data are available.

Method of administration

Inaqovi is for oral use. The tablets must be swallowed whole with water at approximately the same time each day. Food is not to be consumed 2 hours before and 2 hours after taking treatment in order to avoid a risk for lack of efficacy (see section 4.5).

The tablets must not be chewed, crushed, or broken in order to avoid skin contact or release of active substance into the air.

Inaqovi is a cytotoxicmedicinal product. For proper handling and disposal procedures see section 6.6.

Signs and symptoms

Overdose could cause increased myelosuppression and neutropaenia-related infections such as pneumonia and sepsis.

Management

There is no known antidote for overdose with the medicinal product. In the event of an overdose, patients must be closely monitored for signs or symptoms of adverse reactions and appropriate symptomatic treatment instituted.

3 years.

Store in the original package in order to protect from moisture.

This medicinal product does not require any special temperature storage conditions.

5 film-coated tablets in PVC/Aluminum blisters with laminated desiccant (3-ply cold formable aluminumplastic).

Safe handling of Inaqovi film-coated tablets

The handling of Inaqovi film-coated tablets should follow guidelines for the handling of cytotoxic medicinal products according to prevailing local recommendation and/or regulations.

Provided the outer coating of the tablet is intact, there is no risk in handling Inaqovi film-coated tablets.

Inaqovi film-coated tablets must not be crushed or divided.

Disposal

Any unused medicinal product should be destroyed in accordance with relevant local requirements concerning the disposal of cytotoxic medicinal products.