Posology : מינונים

4.2      Posology and method of administration

Remsima treatment is to be initiated and supervised by qualified physicians experienced in the diagnosis and treatment of conditions for which Remsima is indicated. Patients treated with Remsima should be given the package leaflet and the patient safety information card. Instruction for use is provided in the package leaflet.
For subsequent injections and after proper training in subcutaneous injection technique, patients may self-inject with Remsima if their physician determines that it is appropriate and with medical follow- up as necessary. Suitability of the patient for subcutaneous home use should be assessed and patients should be advised to inform their healthcare professional if they experience symptoms of an allergic reaction before administering the next dose. Patients should seek immediate medical attention if developing symptoms of serious allergic reactions (see section 4.4).

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

It is important to check the product labels to ensure that the correct formulation (intravenous or subcutaneous) is being administered to the patient, as prescribed. Remsima subcutaneous formulation is not intended for intravenous administration and should be administered via a subcutaneous injection only.

Posology

Adults (≥18 years)
Rheumatoid arthritis
Treatment with Remsima administered subcutaneously should be initiated as maintenance therapy 4 weeks after the last administration of two intravenous infusions of infliximab 3 mg/kg given 2 weeks apart. The recommended dose for Remsima subcutaneous formulation is 120 mg once every 2 weeks.

Remsima must be given concomitantly with methotrexate.

Available data suggest that the clinical response is usually achieved within 12 weeks of treatment.
Continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit within the first 12 weeks of treatment (see section 5.1).

Moderately to severely active Crohn’s disease
Treatment with Remsima administered subcutaneously should be initiated as maintenance therapy 4 weeks after the last administration of two intravenous infusions of infliximab 5 mg/kg given 2 weeks apart. The recommended dose for Remsima subcutaneous formulation is 120 mg once every 2 weeks.
If a patient does not respond after 2 doses of intravenous infusions, 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.

Fistulising, active Crohn’s disease
Remsima 120 mg given as a subcutaneous injection 4 weeks after the last administration of two intravenous infusions of infliximab 5 mg/kg given 2 weeks apart. The recommended dose for Remsima subcutaneous formulation is 120 mg once every 2 weeks. If a patient does not respond after 6 doses (i.e. 2 intravenous infusions and 4 subcutaneous injections), no additional treatment with infliximab should be given.

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
Treatment with Remsima administered subcutaneously should be initiated as maintenance therapy 4 weeks after the last administration of two intravenous infusions of infliximab 5 mg/kg given 2 weeks apart. The recommended dose for Remsima subcutaneous formulation is 120 mg once every 2 weeks.

Available data suggest that the clinical response is usually achieved within 14 weeks of treatment, i.e.
2 intravenous infusions and 4 subcutaneous injections (see section 5.1). Continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit within this time period.

Ankylosing spondylitis
Treatment with Remsima administered subcutaneously should be initiated as maintenance therapy 4 weeks after the last administration of two intravenous infusions of infliximab 5 mg/kg given 2 weeks apart. The recommended dose for Remsima subcutaneous formulation is 120 mg once every 2 weeks.
If a patient does not respond by 6 weeks (i.e. after 2 intravenous infusions), no additional treatment with infliximab should be given.

Psoriatic arthritis
Treatment with Remsima administered subcutaneously should be initiated as maintenance therapy 4 weeks after the last administration of two intravenous infusions of infliximab 5 mg/kg given 2 weeks apart. The recommended dose for Remsima subcutaneous formulation is 120 mg once every 2 weeks.

Psoriasis
Treatment with Remsima administered subcutaneously should be initiated as maintenance therapy 4 weeks after the last administration of two intravenous infusions of infliximab 5 mg/kg given 2 weeks apart. The recommended dose for Remsima subcutaneous formulation is 120 mg once every 2 weeks.
If a patient shows no response after 14 weeks (i.e. 2 intravenous infusions and 5 subcutaneous injections), no additional treatment with infliximab should be given.

Re-administration for Crohn’s disease and rheumatoid arthritis
From experience with intravenous infliximab, if the signs and symptoms of disease recur, infliximab can be re-administered within 16 weeks following the last administration. In clinical studies with intravenous infliximab, 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
From experience with intravenous infliximab, 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
From experience with intravenous infliximab, 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
From experience with intravenous infliximab, 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 intravenous 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 of intravenous infliximab 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 of intravenous infliximab (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 of intravenous infliximab is not recommended (see section 4.8). In this situation, infliximab should be re-initiated as a single dose of intravenous infliximab followed by the maintenance dose recommendations of subcutaneous infliximab described above given 4 weeks after the last administration of intravenous infliximab.

Switching to and from Remsima subcutaneous formulation across indications When switching from the maintenance therapy of infliximab intravenous formulation to the subcutaneous formulation of Remsima, the subcutaneous formulation may be administered 8 weeks after the last administration of infliximab 100 mg I.V.

There is insufficient information regarding the switching of patients who received Remsima 100 mg I.V. higher than 3 mg/kg for rheumatoid arthritis or 5 mg/kg for Crohn’s disease every 8 weeks to the subcutaneous formulation of Remsima.
Information regarding switching patients from the subcutaneous formulation to the intravenous formulation of Remsima is not available.

Missed dose

If patients miss an injection of Remsima subcutaneous formulation, they should be instructed to take the missed dose immediately in case this happens within 7 days from the missed dose, and then remain on their original dosing schedule. If the dose is delayed by 8 days or more, the patients should be instructed to skip the missed dose, wait until their next scheduled dose, and then remain on their original dosing schedule.

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 with infliximab intravenous formulations and the same is expected for subcutaneous formulation. 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).

Paediatric population
Remsima 120 mg/ml S.C. is not indicated for children and adolescents under 18 years old.
The safety and efficacy of Remsima subcutaneous therapy in children aged below 18 years of age have not yet been established. No data are available.


Method of administration

Remsima 120 mg/ml S.C. solution for injection in pre-filled syringe or in pre-filled pen are administered by subcutaneous injection only. Full instructions for use are provided in the package leaflet. For the two initial intravenous infusions, 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). The physician should ensure appropriate follow-up of patients for any systemic injection reaction and localised injection site reaction after the initial subcutaneous injection is administered.