REMSIMA Solution for injection Ref.[116266] Active ingredients: Infliximab

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 reminder 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 subcutaneous formulation should be initiated with loading doses of infliximab which may be intravenous or subcutaneous. When subcutaneous loading is used, Remsima 120 mg should be given as a subcutaneous injection followed by additional subcutaneous injections at 1, 2, 3 and 4 weeks after the first injection, then every 2 weeks thereafter. If intravenous loading doses of infliximab are given to initiate treatment, 2 intravenous infusions of infliximab 3 mg/kg should be given 2 weeks apart. The first treatment with Remsima administered subcutaneously should be initiated as maintenance therapy 4 weeks after the second intravenous administration. The recommended maintenance 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

The first treatment with Remsima administered subcutaneously should be initiated as maintenance therapy 4 weeks after the last administration of intravenous infusions. Before initiating treatment with Remsima subcutaneous formulation, 2 intravenous infusions of infliximab 5 mg/kg should be given at 2 weeks apart, and an additional intravenous infusion of infliximab 5 mg/kg may be given 4 weeks after the second infusion. The recommended maintenance dose for Remsima subcutaneous formulation is 120 mg once every 2 weeks. If a patient does not respond after loading doses of intravenous infliximab, 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.

Limited data in patients who initially responded to induction regimen with infliximab 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

The first treatment with Remsima administered subcutaneously should be initiated as maintenance therapy 4 weeks after the last administration of intravenous infusions. Before initiating treatment with Remsima subcutaneous formulation, 2 intravenous infusions of infliximab 5 mg/kg should be given at 2 weeks apart, and an additional intravenous infusion of infliximab 5 mg/kg may be given 4 weeks after the second infusion. The recommended maintenance dose for Remsima subcutaneous formulation is 120 mg once every 2 weeks. If a patient does not respond after loading doses of intravenous infliximab, no additional treatment with infliximab should be given. Available data do not support further infliximab treatment, in patients not responding within 14 weeks of the initial infusion.

Limited data in patients who initially responded to induction regimen with infliximab 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

The first treatment with Remsima administered subcutaneously should be initiated as maintenance therapy 4 weeks after the last administration of intravenous infusions. Before initiating treatment with Remsima subcutaneous formulation, 2 intravenous infusions of infliximab 5 mg/kg should be given at 2 weeks apart, and an additional intravenous infusion of infliximab 5 mg/kg may be given 4 weeks after the second infusion. The recommended maintenance 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 (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 at the time of next planned administration of the intravenous infusions of infliximab.

There is insufficient information regarding the switching of patients who received the intravenous infusions of infliximab 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

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. Therefore, subcutaneous use of Remsima is recommended for use only in adults.

Method of administration

Remsima 120 mg 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.

Single intravenous doses up to 20 mg/kg have been administered without toxic effects and repeated doses of Remsima subcutaneous formulation up to 240 mg have been administered without toxic effects. There is no specific treatment for Remsima overdose. In the event of an overdose, the patient should be treated symptomatically and supportive measures instituted as required.

4 years.

Store in a refrigerator (2°C - 8°C).

Do not freeze. Keep the pre-filled syringe/pre-filled pen in the outer carton in order to protect from light.

The medicinal product may be stored at temperatures up to a maximum of 25°C for a period of up to 28 days. The medicinal product must be discarded if not used within the 28-day period.

Remsima 120 mg solution for injection in pre-filled syringe:

Remsima 120 mg solution for injection in single-use pre-filled syringe (type I glass) with a plunger stopper (flurotec-coated elastomer) and needle with a rigid needle shield.

Packs of:

• 1 prefilled syringe (1 mL sterile solution) with 2 alcohol pads.
• 2 prefilled syringes (1 mL sterile solution) with 2 alcohol pads.
• 4 prefilled syringes (1 mL sterile solution) with 4 alcohol pads.
• 6 prefilled syringes (1 mL sterile solution) with 6 alcohol pads.

Remsima 120 mg solution for injection in pre-filled syringe with automatic needle guard:

Remsima 120 mg solution for injection in single-use pre-filled syringe with automatic needle guard. The syringe is made from type I glass with a plunger stopper (flurotec-coated elastomer) and needle with a rigid needle shield.

Packs of:

• 1 prefilled syringe with automatic needle guard (1 mL sterile solution) with 2 alcohol pads.
• 2 prefilled syringes with automatic needle guard (1 mL sterile solution) with 2 alcohol pads.
• 4 prefilled syringes with automatic needle guard (1 mL sterile solution) with 4 alcohol pads.
• 6 prefilled syringes with automatic needle guard (1 mL sterile solution) with 6 alcohol pads.

Remsima 120 mg solution for injection in pre-filled pen:

Remsima 120 mg solution for injection in single-use pre-filled pen. The syringe inside the pen is made from type 1 glass with a plunger stopper (flurotec-coated elastomer) and needle with a rigid needle shield.

Packs of:

• 1 prefilled pen (1 mL sterile solution) with 2 alcohol pads.
• 2 prefilled pens (1 mL sterile solution) with 2 alcohol pads.
• 4 prefilled pens (1 mL sterile solution) with 4 alcohol pads.
• 6 prefilled pens (1 mL sterile solution) with 6 alcohol pads.

Not all pack sizes may be marketed.

Remsima is a solution that is clear to opalescent, colourless to pale brown. Do not use if the solution is cloudy, discoloured or contains visible particulate matter.

After use, place the pre-filled syringe/pre-filled syringe with automatic needle guard/pre-filled pen into a puncture resistant container and discard as required by local regulations. Do not recycle the injecting device. Always keep the medicinal product out of the sight and reach of children.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.