Flixabi™ treatment is to be initiated and supervised by qualified physicians experienced in the diagnosis and treatment of rheumatoid arthritis, inflammatory bowel diseases, ankylosing spondylitis, psoriatic arthritis or psoriasis. Flixabi™ should be administered intravenously. Flixabi™ infusions should be administered by qualified healthcare professionals trained to detect any infusion-related issues. Patients treated with Flixabi™ should be given the package leaflet and the patient reminder card.

During Flixabi™ treatment, other concomitant therapies, e.g. corticosteroids and immunosuppressants should be optimised.

DOSlNG FLlXABl™ lN ADULTS1

RHEUMATOID ARTHRITIS (RA)

3 mg/kg 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, up to a maximum of 7.5 mg/kg every 8 weeks. Alternatively, administration of 3 mg/kg 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, FlixabiTM can be re‑administered within 16 weeks following the last infusion. In clinical studies, delayed hypersensitivity reactions have been uncommon and have occurred after infliximab-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 infliximab‑free interval of more than 16 weeks has not been established.

MODERATELY TO SEVERELY ACTIVE CROHN’S DISEASE

5 mg/kg given as an intravenous infusion followed by an additional 5 mg/kg 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 at 6 weeks after the initial dose, followed by infusions every 8 weeks or
  • Re‑administration: Infusion of 5 mg/kg 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 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 given as an intravenous infusion followed by additional 5 mg/kg 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 every 8 weeks or
  • Re‑administration: Infusion of 5 mg/kg if signs and symptoms of the disease recur followed by infusions of 5 mg/kg 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 but who lost response indicate that some patients may regain response with dose escalation (see section 5.1). 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 infliximab‑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 infliximab‑free interval of more than 16 weeks has not been established.

ULCERATIVE COLITIS

5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg 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).

ANKYLOSING SPONDYLITIS

5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg 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).

PSORIATIC ARTHRITIS

5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg 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).

PSORIASIS

5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg 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 FlixabiTM should be given.

Re-administration

Limited experience from re‑treatment with one single infliximab 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).

RE-ADMINISTRATION ACROSS ALL INDICATIONS

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, FlixabiTM should be re-initiated as a single dose followed by the maintenance dose recommendations described for each indication.

DOSlNG FLlXABl™ lN CHlLDREN AND ADOLESCENTS1

CROHN’S DISEASE (6 TO 17 YEARS)

5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter. Available data do not support further infliximab 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 infliximab 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.

ULCERATIVE COLITIS (6 TO 17 YEARS)

5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter. Available data do not support further infliximab 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 infliximab 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.

PSORIASIS

The safety and efficacy of infliximab in children and adolescents younger than 18 years for the indication of psoriasis have not been established. Currently available data are described in section 5.2 of the Summary of Product Characteristics but no recommendation on a posology can be made.

JUVENILE IDIOPATHIC ARTHRITIS, PSORIATIC ARTHRITIS AND ANKYLOSING SPONDYLITIS

The safety and efficacy of infliximab in children and adolescents younger than 18 years for the indications of juvenile idiopathic arthritis, psoriatic arthritis and ankylosing spondylitis have not been established. Currently available data are described in section 5.2 of the Summary of Product Characteristics but no recommendation on a posology can be made.

JUVENILE RHEUMATOID ARTHRITIS

The safety and efficacy of infliximab in children and adolescents younger than 18 years for the indication of juvenile rheumatoid arthritis have not been established. Currently available data are described in sections 4.8 and 5.2 of the Summary of Product Characteristics but no recommendation on a posology can be made.

DOSlNG FLlXABl™ lN OTHER SPEClAL POPULATlONS1

ELDERLY

Specific studies of infliximab 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 infliximab in elderly patients see sections 4 4 and 4.8 of the Summary of Product Characteristics.

RENAL AND/OR HEPATlC lMPAlRMENT

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

FLlXABlTM lNDlVlDUAL DOSlNG ACCORDlNG TO lNDlCATlON

Therapeutic indications, dosage and infusion intervals

Flixabi™ is dosed individually depending on indication and body weight.

Indication for adults

Dosage/infusion interval induction phase

Maintenance therapy

Crohn’s disease moderate to severe

5 mg/kg week 0, 2, 6 (only in responding patients)

5 mg/kg
every 8 weeks

Inadequate response/loss of response:

Treatment of moderately to severely active Crohn’s disease, in adult patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies.

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

Crohn’s disease with fistulation

5 mg/kg
week 0, 2, 6 (only in responding patients)

5 mg/kg
every 8 weeks

Inadequate response/loss of response:

Treatment of fistulising, active Crohn’s disease, in adult patients who have not responded despite a full and adequate course of therapy with conventional treatment (including antibiotics, drainage and immunosuppressive therapy).

Ulcerative colitis

5 mg/kg
week 0, 2, 6

5 mg/kg
every 8 weeks

Inadequate response /loss of response:

Continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit within 14 weeks of treatment.

Rheumatoid arthritis

Administration in combination with MTX

3 mg/kg
week 0, 2, 6

3 mg/kg
every 8 weeks

Inadequate response/loss of response:
If a patient has an inadequate response or loss of response after the first 12 weeks of therapy, consideration may be given to increase the dose step-wise by 1.5 mg/kg, up to a maximum of 7.5 mg/kg every 8 weeks.
Alternatively, administration of 3 mg/kg 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 after dose adjustment.

Ankylosing spondylitis

5 mg/kg
week 0, 2, 6

5 mg/kg
every 6 to 8 weeks

Inadequate response /loss of response:

If a patient does not respond by 6 weeks (i.e. after 2 doses), no additional treatment with Flixabi™ should be given.

Psoriatic arthritis

5 mg/kg
week 0, 2, 6

5 mg/kg
every 8 weeks

Psoriasis

5 mg/kg
week 0, 2, 6

5 mg/kg
every 8 weeks

Inadequate response /loss of response:

If a patient shows no response after 14 weeks (i.e. after 4 doses), no additional treatment with Flixabi™ should be given.

Indication for children and adolescents (6-17 years)

The safety and efficacy of infliximab have not been studied in children below the age of 6 years.

Dosage/infusion interval induction phase

Maintenance therapy

Crohn’s disease

5 mg/kg
week 0, 2, 6

5 mg/kg
every 8 weeks

Available data does not support further infliximab treatment in children and adolescents not responding within the first 10 weeks of treatment.

In some patients a shorter dosing interval may be required to maintain clinical benefit, for others a longer dosing interval may be sufficient.

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.

Ulcerative colitis

5 mg/kg
week 0, 2, 6

5 mg/kg
every 8 weeks

Available data do not support further infliximab treatment in paediatric patients not responding within the first 8 weeks of treatment.

Assessment of therapeutic response

  • CD moderate to severe in adults: after 2nd  dose no response ➞ treatment should be discontinued
  • CD with fistulation in adults: after 3rd  dose no response ➞ treatment should be discontinued
  • UC: after 3rd  dose no response ➞ treatment continuation should be carefully considered
  • RA: no therapeutic benefit within the first 12 weeks or after dose adjustment ➞ treatment continuation should be carefully considered
  • AS: after 2nd  dose no response ➞ treatment should be discontinued
  • Pso: after 4th  dose no response ➞ treatment should be discontinued
  • CD in children/adolescents: the current data situation does not support continuing treatment if no response within the first 10 weeks
  • UC in children/adolescents: the current data situation does not support continuing treatment if no response within the first 8 weeks.