T) > 2.5 times upper limit of normal (ULN) or > 5 times ULN if liver metastasis is present (see section 4.4).
Renal impairment
No dedicated renal impairment study has been conducted with ONIVYDE. No dose adjustment is recommended in patients with mild to moderate renal impairment (see sections 4.4 and 5.2). ONIVYDE is not recommended for use in patients with severe renal impairment (CLcr < 30 ml/min).
Elderly
Forty-one percent (41%) of patients treated with ONIVYDE across the clinical program were ≥ 65 years. No dose adjustment is recommended.
Paediatric population
The safety and efficacy of ONIVYDE in children and adolescents aged ≤ 18 years have not yet been established. No data are available.
Method of administration
ONIVYDE is for intravenous use. The concentrate must be diluted prior to administration and given as single intravenous infusion over 90 minutes. For more details see section 6.6.
Precautions to be taken before handling or administering the medicinal product
ONIVYDE is a cytotoxic medicinal product. The use of gloves, goggles and protective clothing when handling or administering ONIVYDE is recommended. Pregnant staff should not handle ONIVYDE.
4.3 Contraindications
History of severe hypersensitivity to irinotecan or to any of the excipients listed in section 6.1.
Breast-feeding (see section 4.6).
4.4 Special warnings and precautions for use
General
ONIVYDE is a liposomal formulation of irinotecan with different pharmacokinetic properties compared to non-liposomal irinotecan. The dose concentration and strength are different in comparison to non-liposomal irinotecans.
ONIVYDE is not equivalent to other non-liposomal irinotecan formulations and should not be interchanged.
In the limited number of patients with prior exposure to non-liposomal irinotecan, no benefit of ONIVYDE has been demonstrated.
Myelosuppression/neutropenia
Complete blood cell count monitoring is recommended during ONIVYDE treatment. Patients should be aware of the risk of neutropenia and the significance of fever. The median time to nadir for ≥ Grade 3 neutropenia is 23 (range 8-104) days post first dose of treatment with ONIVYDE. Febrile neutropenia (body temperature > 38°C and neutrophil count≤ 1,000 cells/mm3) should be urgently treated in the hospital with broad-spectrum intravenous antibiotics. ONIVYDE should be withheld if neutropenic fever occurs or the absolute neutrophil count drops below 1500/mm3. Sepsis with neutropenic fever and consequent septic shock with fatal outcome has been observed in patients with metastatic pancreatic adenocarcinoma treated with ONIVYDE.
In patients who experienced severe haematological events, a dose reduction or treatment discontinuation is recommended (see section 4.2). Patients with severe bone marrow failure should not be treated with ONIVYDE.
History of prior abdominal radiation increases the risk of severe neutropenia and febrile neutropenia following ONIVYDE treatment. Close monitoring of blood counts is recommended, and the use of myeloid growth factors should be considered for patients with a history of abdominal radiation. Caution should be exercised in patients receiving concurrent administration of ONIVYDE with irradiation.
Patients with deficient glucuronidation of bilirubin, such as those with Gilbert's syndrome, may be at greater risk of myelosuppression when receiving therapy with ONIVYDE.
Compared to Caucasian pa |
