Posology : מינונים

4.2 Posology and method of administration
Ixifi® 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. Ixifi® should be administered intravenously. Ixifi® infusions should be administered by qualified healthcare professionals trained to detect any infusion-related issues. Patients treated with Ixifi® should be given the package leaflet and the patient reminder card.

During Ixifi® treatment, other concomitant therapies, e.g. corticosteroids and immunosuppressants should be optimised.

Posology

Adults (≥ 18 years)
Rheumatoid arthritis
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.

Ixifi® 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.

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 infliximab should be given.
Available data do not support further infliximab 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).

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.

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 infliximab 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).

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.

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.

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 infliximab should be given.

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.

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 infliximab should be given.

Re-administration for Crohn’s disease and rheumatoid arthritis
If the signs and symptoms of disease recur, Ixifi® 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). The safety and efficacy of re- administration after an infliximab-free interval of more than 16 weeks has not been established. This applies to both Crohn’s disease patients and rheumatoid arthritis patients.

Re-administration for ulcerative colitis
The safety and efficacy of re-administration, other than every 8 weeks, has not been established (see sections 4.4 and 4.8).

Re-administration for ankylosing spondylitis
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).

Re-administration for psoriatic arthritis
The safety and efficacy of re-administration, other than every 8 weeks, has not been established (see sections 4.4 and 4.8).

Re-administration for psoriasis
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).
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 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). In this situation, Ixifi® should be re-initiated as a single dose followed by the maintenance dose recommendations described above.

Special populations

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). For more information about the safety of infliximab in elderly patients see sections 4.4 and 4.8.

Renal and/or hepatic impairment
Infliximab has not been studied in these patient populations. No dose recommendations can be made (see section 5.2).

Method of administration

Ixifi® should be administered intravenously over a 2 hour period. All patients administered Ixifi® are to be observed for at least 1-2 hours post-infusion for acute infusion-related reactions. Emergency equipment, such as adrenaline, antihistamines, corticosteroids and an artificial airway must be available. Patients may be pre-treated with e.g., an antihistamine, hydrocortisone and/or paracetamol and infusion rate may be slowed in order to decrease the risk of infusion-related reactions especially if infusion-related reactions have occurred previously (see section 4.4).

Shortened infusions across adult indications
In carefully selected adult patients who have tolerated at least 3 initial 2-hour infusions of Ixifi® (induction phase) and are receiving maintenance therapy, consideration may be given to administering subsequent infusions over a period of not less than 1 hour. If an infusion reaction occurs in association with a shortened infusion, a slower infusion rate may be considered for future infusions if treatment is to be continued.
Shortened infusions at doses > 6 mg/kg have not been studied (see section 4.8).

For preparation and administration instructions, see section 6.6.