Actemra (tocilizumab) Product Information (PI) - Roche Australia
Actemra (tocilizumab) Product Information (PI) - Roche Australia
Actemra (tocilizumab) Product Information (PI) - Roche Australia
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<strong>tocilizumab</strong> decreasing the IL-6 driven effects on hepcidin production to increase iron<br />
availability.<br />
In healthy subjects administered <strong>tocilizumab</strong> in doses from 2 to 28 mg/kg, absolute<br />
neutrophil counts (ANC) decreased to their lowest levels 3 to 5 days following<br />
administration. Thereafter, neutrophils recovered towards baseline in a dose dependent<br />
manner. Patients with RA demonstrated a similar pattern of absolute neutrophil counts<br />
following <strong>tocilizumab</strong> administration (see PRECAUTIONS - Haematological<br />
Abnormalities).<br />
PHARMACOKINETICS<br />
Rheumatoid Arthritis<br />
The pharmacokinetics of <strong>tocilizumab</strong> were determined using a population<br />
pharmacokinetic analysis on a database composed of 1793 RA patients treated with a one<br />
hour infusion of 4 and 8 mg/kg every 4 weeks for 24 weeks.<br />
The pharmacokinetic parameters of <strong>tocilizumab</strong> did not change with time. A more than<br />
dose-proportional increase in area under the curve (AUC) and trough concentration (C min )<br />
was observed for doses of 4 and 8 mg/kg every 4 weeks. Maximum concentration (C max )<br />
increased dose-proportionally. At steady-state, predicted AUC and C min were 2.7 and 6.5<br />
fold higher at 8 mg/kg as compared to 4 mg/kg, respectively.<br />
The following parameters are valid for a dose of 8 mg/kg <strong>tocilizumab</strong> given every<br />
4 weeks. Predicted mean (– SD) steady-state AUC, C min and C max of <strong>tocilizumab</strong> were<br />
35000 – 15500 h·µg/mL, 9.74 – 10.5 mg/mL, and 183 – 85.6 µg/mL, respectively. The<br />
accumulation ratios for AUC and C max were small; 1.22 and 1.06, respectively. The<br />
accumulation ratio was higher for C min (2.35), which was expected based on the nonlinear<br />
clearance contribution at lower concentrations. Steady-state was reached following the<br />
first administration and after 8 and 20 weeks for C max , AUC, and C min , respectively.<br />
Tocilizumab AUC, C min and C max increased with increase of body weight. At body weight<br />
≥ 100 kg, the predicted mean (± SD) steady-state AUC, C min and C max of <strong>tocilizumab</strong><br />
were 55500 ± 14100 h·µg/mL, 19.0 ± 12.0 mg/mL, and 269 ± 57 mg/mL, respectively,<br />
which are higher than mean exposure values for the patient population. Therefore,<br />
<strong>tocilizumab</strong> doses exceeding 800 mg per infusion are not recommended in patients ≥ 100<br />
kg (see DOSAGE AND ADMINISTRATION).<br />
The following parameters are valid for a dose of 4 mg/kg <strong>tocilizumab</strong> given every 4<br />
weeks. Predicted mean (± SD) steady-state AUC, C min and C max of <strong>tocilizumab</strong> were<br />
13000 ± 5800•µg•h/mL, 1.49 ± 2.13 mg/mL, and 88.3 ± 41.4 µg/mL, respectively. The<br />
accumulation ratios for AUC and C max were small; 1.11 and 1.02, respectively. The<br />
accumulation ratio was higher for C min (1.96). Steady-state was reached following the<br />
first administration for both C max and AUC and from 16 weeks for C min .<br />
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