Dosing Flixabi™1

3 mg/kg bw given as an intravenous infusion followed by additional 3 mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter.

Flixabi™ must be given concomitantly with methotrexate.

Available data suggest that the clinical response is usually achieved within 12 weeks of treatment. If a patient has an inadequate response or loses response after this period, consideration may be given to increase the dose step-wise by approximately 1.5 mg/kg bw, up to a maximum of 7.5 mg/kg bw every 8 weeks. Alternatively, administration of 3 mg/kg bw as often as every 4 weeks may be considered. If adequate response is achieved, patients should be continued on the selected dose or dose frequency. Continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit within the first 12 weeks of treatment or after dose adjustment.

Re-administration

If the signs and symptoms of disease recur, Flixabi™ can be re-administered within 16 weeks following the last infusion. In clinical studies, delayed hypersensitivity reactions have been uncommon and have occurred after Flixabi™-free intervals of less than 1 year (see sections 4.4 and 4.8 of the Summary of Product Characteristics). The safety and efficacy of re-administration after an Flixabi™-free interval of more than 16 weeks has not been established.

5 mg/kg bw given as an intravenous infusion followed by an additional 5 mg/kg bw infusion 2 weeks after the first infusion. If a patient does not respond after 2 doses, no additional treatment with Flixabi™ should be given. Available data do not support further Flixabi™ treatment, in patients not responding within 6 weeks of the initial infusion.

In responding patients, the alternative strategies for continued treatment are:

• Maintenance: Additional infusion of 5 mg/kg bw at 6 weeks after the initial dose, followed by infusions every 8 weeks or
• Re-administration: Infusion of 5 mg/kg bw if signs and symptoms of the disease recur (see ‘Re-administration’ below and section 4.4 of the Summary of Product Characteristics).

Although comparative data are lacking, limited data in patients who initially responded to 5 mg/kg bw but who lost response indicate that some patients may regain response with dose escalation (see section 5.1 of the Summary of Product Characteristics). Continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit after dose adjustment.

Fistulising, active Crohn’s disease

5 mg/kg bw given as an intravenous infusion followed by additional 5 mg/kg bw infusions at 2 and 6 weeks after the first infusion. If a patient does not respond after 3 doses, no additional treatment with Flixabi™ should be given.

In responding patients, the alternative strategies for continued treatment are:

• Maintenance: Additional infusions of 5 mg/kg bw every 8 weeks or
• Re-administration: Infusion of 5 mg/kg bw if signs and symptoms of the disease recur followed by infusions of 5 mg/kg bw every 8 weeks (see ‘Re-administration’ below and section 4.4 of the Summary of Product Characteristics).

Although comparative data are lacking, limited data in patients who initially responded to 5 mg/kg bw but who lost response indicate that some patients may regain response with dose escalation (see section 5.1 of the Summary of Product Characteristics). Continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit after dose adjustment.

In Crohn’s disease, experience with re-administration if signs and symptoms of disease recur is limited and comparative data on the benefit/risk of the alternative strategies for continued treatment are lacking.

Re-administration

If the signs and symptoms of disease recur, Flixabi™ can be re-administered within 16 weeks following the last infusion. In clinical studies, delayed hypersensitivity reactions have been uncommon and have occurred after Flixabi™-free intervals of less than 1 year (see sections 4.4 and 4.8 of the Summary of Product Characteristics). The safety and efficacy of re-administration after an Flixabi™-free interval of more than 16 weeks has not been established.

5 mg/kg bw given as an intravenous infusion followed by additional 5 mg/kg bw infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter.

Available data suggest that the clinical response is usually achieved within 14 weeks of treatment, i.e. three doses. Continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit within this time period.

Re-administration

The safety and efficacy of re-administration, other than every 8 weeks, has not been established (see sections 4.4 and 4.8 of the Summary of Product Characteristics).

5 mg/kg bw given as an intravenous infusion followed by additional 5 mg/kg bw infusion doses at 2 and 6 weeks after the first infusion, then every 6 to 8 weeks. If a patient does not respond by 6 weeks (i.e. after 2 doses), no additional treatment with Flixabi™ should be given.

Re-administration

The safety and efficacy of re-administration, other than every 6 to 8 weeks, has not been established (see sections 4.4 and 4.8 of the Summary of Product Characteristics).

5 mg/kg bw given as an intravenous infusion followed by additional 5 mg/kg bw infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter.

Re-administration

The safety and efficacy of re-administration, other than every 8 weeks, has not been established (see sections 4.4 and 4.8 of the Summary of Product Characteristics).

5 mg/kg bw given as an intravenous infusion followed by additional 5 mg/kg bw infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter. If a patient shows no response after 14 weeks (i.e. after 4 doses), no additional treatment with Flixabi™ should be given

Re-administration

Limited experience from re-treatment with one single Flixabi™ dose in psoriasis after an interval of 20 weeks suggests reduced efficacy and a higher incidence of mild to moderate infusion reactions when compared to the initial induction regimen (see section 5.1 of the Summary of Product Characteristics).

Limited experience from re-treatment following disease flare by a re-induction regimen suggests a higher incidence of infusion reactions, including serious ones, when compared to 8-weekly maintenance treatment (see section 4.8 of the Summary of Product Characteristics).

In case maintenance therapy is interrupted, and there is a need to restart treatment, use of a re-induction regimen is not recommended (see section 4.8 of the Summary of Product Characteristics). In this situation, Flixabi™ should be re-initiated as a single dose followed by the maintenance dose recommendations described for each indication.

5 mg/kg bw given as an intravenous infusion followed by additional 5 mg/kg bw infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter. Available data do not support further Flixabi™ treatment in children and adolescents not responding within the first 10 weeks of treatment (see section 5.1 of the Summary of Product Characteristics).

Some patients may require a shorter dosing interval to maintain clinical benefit, while for others a longer dosing interval may be sufficient. Patients who have had their dose interval shortened to less than 8 weeks may be at greater risk for adverse reactions. Continued therapy with a shortened interval should be carefully considered in those patients who show no evidence of additional therapeutic benefit after a change in dosing interval.

The safety and efficacy of Flixabi™ have not been studied in children with Crohn’s disease below the age of 6 years. Currently available pharmacokinetic data are described in section 5.2 of the Summary of Product Characteristics but no recommendation on a posology can be made in children younger than 6 years.

5 mg/kg bw given as an intravenous infusion followed by additional 5 mg/kg bw infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter. Available data do not support further Flixabi™ treatment in paediatric patients not responding within the first 8 weeks of treatment (see section 5.1 of the Summary of Product Characteristics).

The safety and efficacy of Flixabi™ have not been studied in children with ulcerative colitis below the age of 6 years. Currently available pharmacokinetic data are described in section 5.2 of the Summary of Product Characteristics, but no recommendation on a posology can be made in children younger than 6 years.

Specific studies of Flixabi™ in elderly patients have not been conducted. No major age-related differences in clearance or volume of distribution were observed in clinical studies. No dose adjustment is required (see section 5.2 of the Summary of Product Characteristics). For more information about the safety of Flixabi™ in elderly patients (see sections 4.4 and 4.8 of the Summary of Product Characteristics).

Flixabi™ has not been studied in these patient populations. No dose recommendations can be made (see section 5.2 of the Summary of Product Characteristics).