ine aminotransferase, Increased aspartate aminotransferase, Increased international normalized ratio
* MedDRA version 14.1
** Rare occurrence cannot be estimated from the NAPOLI-1study due to the small sample size
Description of selected adverse reactions
The following adverse reactions were observed in the NAPOLI-1 clinical study:
Myelosuppression
Myelosuppression (neutropenia/leukopenia, thrombocytopenia and, anaemia) was more common in the ONIVYDE+5-FU/LV arm compared to the 5-FU/LV control arm.
Neutropenia/leukopenia
Neutropenia/leukopenia was the most notable important haematological toxicity. Grade 3 or higher neutropenia occurred more frequently in patients treated with ONIVYDE+5-FU/LV (27.4%) compared to patients treated with 5-FU/LV (1.5%). Neutropenic fever/sepsis appeared more frequently in the ONIVYDE+5-FU/LV combination arm [in 4 patients (3.4%)] compared to 5-FU/LV control arm [in 1 patient (0.7%)].
Thrombocytopenia
Grade 3 or higher thrombocytopenia occurred in 2.6% of patients treated with ONIVYDE+5-FU/LV and 0% in patients treated with 5-FU/LV.
Anaemia
Grade 3 or higher anaemia occurred in 10.3% of patients treated with ONIVYDE+5-FU/LV and in 6.7% of patients treated with 5-FU/LV.
Acute renal failure
Renal impairment and acute renal failure have been identified, usually in patients who become volume depleted from nausea/vomiting and/or diarrhoea. Acute renal failure was reported in 6 of 117 patients (5.1%) in the ONIVYDE+5-FU/LV arm, 10 of 147 (6.8%) in the ONIVYDE monotherapy arm and 6 of 134 patients (4.5%) in the 5-FU/LV arm.
Diarrhoea and related adverse reactions
Diarrhoea is a very common adverse reaction leading to colitis, ileus, gastroenteritis, fatigue, dehydration, weight loss, renal toxicities, hyponatraemia, and hypokalaemia. Renal impairment and acute renal failure have been identified, usually in patients who became volume depleted from severe vomiting and/or diarrhoea. In the clinical study Grade 3 or Grade 4 diarrhoea occurred in 15 out of 117 patients (12.8%) receiving ONIVYDE+5-FU/LV. For patients experiencing late diarrhoea, the median time to late diarrhoea onset was 8 days from the previous dose of ONIVYDE. Early onset diarrhoea, typically appearing ≤24 hours after dose administration, can occur and is usually transient. Early onset diarrhoea may also be accompanied by cholinergic symptoms that can include rhinitis, increased salivation, flushing, diaphoresis, bradycardia, miosis and hyperperistalsis that can induce abdominal cramping. In the clinical study, early diarrhoea onset occurred in 35 patients (29.9%) and cholinergic events occurred in 4 patients (3.4%) receiving ONIVYDE+5-FU/LV.
Withhold ONIVYDE for Grade 2-4 diarrhoea and initiate treatment for diarrhoea. Following recovery to Grade 1 diarrhoea, resume ONIVYDE at a reduced dose (see section 4.2).
Infusion reaction
Acute infusion reactions were reported in 8 of 117 patients (6.8%) in the ONIVYDE+5-FU/LV arm, 3 of 147 patients (2.0%) in the ONIVYDE monotherapy arm, and 8 of 134 patients (6.0%) in the 5-FU/LV arm.
Other special populations
Elderly
Overall, no major clinical differences in safety or efficacy were reported between patients ≥ 65 years and patients < 65 years, although a higher frequency of discontinuation (14.8% vs 7.9%) was noted in the former group treated with ONIVYDE+5-FU/LV in the NAPOLI-1 study and in some cases the adverse reactions did not resolve. Grade 3 |
