or higher and serious treatment emergent adverse reactions were more frequent in patients < 65 years (84.1% and 50.8%) compared to patients ≥ 65 years (68.5 % and 44.4%). Conversely, patients > 75 years (n=12) experienced more frequent serious adverse reactions, dose delay, dose reduction and discontinuation compared to patients ≤ 75 years (n=105) when treated with ONIVYDE+5-FU/LV in the pancreatic adenocarcinoma study.
Asian population
Compared to Caucasians, Asian patients were observed with a lower incidence of diarrhoea [14 (19.2%) out of 73 Caucasians had a ≥ Grade 3 diarrhoea, and 1 out of 33 (3.3%) Asians had a ≥ Grade 3 diarrhoea], but a higher incidence and higher severity of neutropenia. In patients receiving ONIVYDE+5-FU/LV, the incidence of ≥ Grade 3 neutropenia was higher among Asian patients [18 of 33 (55%)] compared to White patients [13 of 73 (18%)]. Neutropenic fever/neutropenic sepsis was reported in 6% of Asian patients compared to 1% of White patients. This is consistent with the population pharmacokinetic analysis that showed a lower exposure to irinotecan and a higher exposure to its active metabolite SN-38 in Asians than in Caucasians.
Patients with hepatic impairment
In clinical studies of non-liposomal irinotecan administered on a weekly dosage schedule, patients with modestly elevated baseline serum total bilirubin levels (1.0 to 2.0 mg/dl) had a significantly greater likelihood of experiencing first cycle Grade 3 or Grade 4 neutropenia than those with bilirubin levels that were less than 1.0 mg/dl.
Patients with prior Whipple procedure
In the clinical study eva luating ONIVYDE+5-FU/LV, patients with a prior Whipple procedure had a higher risk of serious infections following treatment with ONIVYDE+5-FU/LV [9 of 29 (30%)] compared to 11 of 88 (12.5%) patients with no prior Whipple procedure.
Patients with UGT1A1 allele
Individuals who are 7/7 homozygous for the UGT1A1*28 allele are at increased risk for neutropenia from non-liposomal irinotecan. In the clinical study eva luating ONIVYDE+5-FU/LV, the frequency of ≥ Grade 3 neutropenia in these patients [2 of 7 (28.6%)] was similar to the frequency in patients not homozygous for the UGT1A1*28 allele who received a starting dose of ONIVYDE of 80 mg/m2 [30 of 110 (27.3%)] (see section 5.1).
Underweight patients (body mass index < 18.5 kg/m2)
In the clinical study eva luating ONIVYDE+5-FU/LV, 5 of 8 underweight patients experienced a grade 3 or 4 adverse reaction, mostly myelosuppression, while 7 of the 8 patients required dose modification such as dose delay, dose reduction or dose discontinuation (see section 4.4).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
In clinical trials, ONIVYDE was administered at doses up to 240 mg/m2 to patients with various cancers. The adverse reactions in these patients were similar to those reported with the recommended dosage and regimen.
There have been reports of overdosage with non-liposomal irinotecan at doses up to approximately twice the recommended therapeutic dose of irinotecan, which may be fatal. The mos |
