skeletal growth, immune function and sexual maturation Immunogenicity Observed with TCZ; clinical relevance needs further evaluation Malignancies Based on increased risk in RA and with other biological DMARDs; no imbalance noted for TCZ CYP450 enzyme Hypothetical risk of greater relevance – normalisation to agents with a narrow therapeutic index which are subject to regular monitoring or effect or concentration, & dosage adjustment, as standard clinical practice. Risk applies at initiation and withdrawal of TCZ treatment Important Elderly No clinical evidence of increased risk; missing no difference in PK information Paediatric patients Paediatric program ongoing (PIP approved) Effects during Use in pregnancy not recommended pregnancy Hepatic Caution to be exercised in this impairment subgroup; TCZ not subject to hepatic metabolism Renal impairment No dose adjustment required; TCZ not subject to renal elimination. No effect of mild renal impairment noted with TCZ. No formal study in patients with mild to moderate renal impairment. Combination of Study ongoing: rituximab + TCZ biologics Vaccinations Efficacy of proteinaceous and polysaccharide vaccines to be studied in comcomitant use with TCZ. Increased mortality Observation likely to reflect population in the Japanese being exposed. Patients are elderly PMS compared to with significant concurrent medical clinical study disease and multiple concomitant population medications.
skeletal growth, immune function and sexual maturation Immunogenicity Observed with TCZ; clinical relevance needs further evaluation Malignancies Based on increased risk in RA and with other biological DMARDs; no imbalance noted for TCZ CYP450 enzyme normalisation Hypothetical risk – of greater relevance to agents with a narrow therapeutic index which are subject to regular monitoring or effect or concentration, & dosage adjustment, as standard clinical practice. Risk applies at initiation and withdrawal of TCZ treatment Important missing information Elderly No clinical evidence of increased risk; no difference in PK Paediatric patients Paediatric program ongoing (PIP approved) Effects during pregnancy Use in pregnancy not recommended Hepatic impairment Caution to be exercised in this subgroup; TCZ not subject to hepatic metabolism Renal impairment No dose adjustment required; TCZ not subject to renal elimination. No effect of mild renal impairment noted with TCZ. No formal study in patients with mild to moderate renal impairment. Combination of biologics Study ongoing: rituximab + TCZ Vaccinations Efficacy of proteinaceous and polysaccharide vaccines to be studied in comcomitant use with TCZ. Increased mortality in the Japanese PMS compared to clinical study population Observation likely to reflect population being exposed. Patients are elderly with significant concurrent medical disease and multiple concomitant medications.
auspar-tocilizumab-140206.docx