Interactions with drugs modulating CYP3A4 and P-gp activities Gastrointestinal perforation Important potential risks Haemodynamic changes potentially leading to serious cardiovascular events (including effects on trial pressure and syncope) Off-label use Interference with opioid-mediated analgesia Efficacy/safety in methadone treated population Missing information Efficacy safety in cancer pain population Efficacy/safety in high risk cardiovascular patients Efficacy/safety beyond 1 year Efficacy/safety in patients >75 of age Efficacy/safety in patients with severe renal impairment (creatinine clearance <30mL/min) Efficacy/safety in patients with hepatic impairment Efficacy/safety in non-Caucasian and non-African-Americans/Black patients Efficacy/safety in Paediatric populations Efficacy/safety in Pregnancy/lactation RMP reviewer comment in short term opioid treatment’ should be added as an item of missing ‘Efficacy/safety information. in patients receiving opioids for opioid dependence’ should be as an ‘Efficacy/safety item of missing information. Appropriate pharmacovigilance and risk minimisation should be applied to the recommended additional items of missing information. Otherwise, subject to the evaluation of the nonclinical and clinical aspects of the Safety Specification, the summary of safety concerns is considered acceptable. Pharmacovigilance plan Routine pharmacovigilance is proposed for a number of safety concerns. Routine pharmacovigilance includes the use of a targeted follow-up questionnaire for adverse event reports relating to the important potential risk perforation’. ‘Gastrointestinal The following additional pharmacovigilance activities are also proposed in the EU RMP (note that no Australian subjects are to be included in these studies) (Table 15). Table 15: Ongoing safety concerns. Additional activity Assigned safety Actions/outcome Estimated concern proposed planned submission of final data Study D3820C00016 Missing An open label, Estimated information: sequential, multiple 4Q2016 Multiple Dose paediatric Safety in oral dose study to pharmacokinetic and paediatric assess the safety study. populations pharmacokinetics and safety of naloxegol in paediatric patients aged 6months to < ≥ 18 years with opioid-induced constipation
Interactions with drugs modulating CYP3A4 and P-gp activities Important potential risks Gastrointestinal perforation Haemodynamic changes potentially leading to serious cardiovascular events (including effects on pressure and syncope) Off-label use Interference with opioid-mediated analgesia Missing information Efficacy/safety in methadone treated population Efficacy safety in cancer pain population Efficacy/safety in high risk cardiovascular patients Efficacy/safety beyond 1 year Efficacy/safety in patients >75 of age Efficacy/safety in patients with severe renal impairment (creatinine clearance <30mL/min) Efficacy/safety in patients with hepatic impairment Efficacy/safety in non-Caucasian and non-African-Americans/Black patients Efficacy/safety in Paediatric populations Efficacy/safety in Pregnancy/lactation RMP reviewer comment ‘Efficacy/safety in short term opioid treatment’ should be added as an item of missing information. ‘Efficacy/safety in patients receiving opioids for opioid dependence’ should be as an item of missing information. Appropriate pharmacovigilance and risk minimisation should be applied to the recommended additional items of missing information. Otherwise, subject to the evaluation of the nonclinical and clinical aspects of the Safety Specification, the summary of safety concerns is considered acceptable. Pharmacovigilance plan Routine pharmacovigilance is proposed for a number of safety concerns. Routine pharmacovigilance includes the use of a targeted follow-up questionnaire for adverse event reports relating to the important potential risk ‘Gastrointestinal perforation’. The following additional pharmacovigilance activities are also proposed in the EU RMP (note that no Australian subjects are to be included in these studies) (Table 15). Table 15: Ongoing safety concerns. Additional activity Assigned safety concern Actions/outcome proposed Estimated planned submission of final data Study D3820C00016 Multiple Dose paediatric pharmacokinetic and safety study. Missing information: Safety in paediatric populations An open label, sequential, multiple oral dose study to assess the pharmacokinetics and safety of naloxegol in paediatric patients aged ≥ 6months to < 18 years with opioid-induced constipation Estimated 4Q2016 trial
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