IXIFI POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION 100 MG/ VIAL [SIN15948P]

Product Info

IXIFI POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION 100 MG/ VIAL

[SIN15948P]

4.1. Therapeutic indications

Rheumatoid Arthritis (RA)

IXIFI, in combination with methotrexate (MTX), is indicated for:
The reduction of signs and symptoms as well as the improvement in physical function in

• adult patients with active disease when the response to disease-modifying drugs, including MTX, has been inadequate.

• adult patients with severe, active and progressive disease not previously treated with MTX or other disease-modifying anti-rheumatic drugs (DMARDs).

In these patient populations, a reduction in the rate of the progression of joint damage, as measured by X-ray, has been demonstrated (see Section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Crohn’s Disease

IXIFI is indicated for:

• 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 an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies.

• Treatment of fistulizing 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).

Pediatric Crohn’s Disease

IXIFI is indicated for:
Treatment of severe, active Crohn’s disease, in pediatric patients aged 6 to 17 years, who have not responded to conventional therapy including a corticosteroid, an immunomodulator and primary nutrition therapy; or who are intolerant to or have contraindications for such therapies. Infliximab has been studied only in combination with conventional immunosuppressive therapy.

Ulcerative Colitis

IXIFI is indicated for:
Treatment of moderately to severely active ulcerative colitis (UC) in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies.

Pediatric Ulcerative Colitis

IXIFI is indicated for:
Reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active UC who have had an inadequate response to conventional therapy.

Ankylosing Spondylitis

IXIFI is indicated for:
Treatment of ankylosing spondylitis, in adult patients who have severe axial symptoms, elevated serological markers of inflammatory activity and who have responded inadequately to conventional therapy.

Psoriatic Arthritis

IXIFI, in combination with MTX, is indicated for:
Treatment of active and progressive psoriatic arthritis in adult patients who have responded inadequately to DMARDs.

Psoriasis

IXIFI is indicated for:
Treatment of moderate to severe plaque psoriasis in adults who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA (see Section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.2. Posology and method of administration

IXIFI treatment is to be administered under the supervision and monitoring of specialized physicians experienced in the diagnosis and treatment of rheumatoid arthritis, inflammatory bowel diseases, ankylosing spondylitis, psoriatic arthritis or psoriasis. IXIFI should be administered intravenously.

During IXIFI treatment, other concomitant therapies, e.g., corticosteroids and immunosuppressants should be optimized.

Posology

Dosage – Adults (≥ 18 years)

IXIFI is administered by intravenous infusion.

Rheumatoid Arthritis

3 mg/kg given as an intravenous infusion over a 2-hour period 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 MTX.

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 this time period.

Moderately to Severely, Active Crohn’s Disease

5 mg/kg given as an intravenous infusion over a 2-hour period. Available data do not support further infliximab treatment, in patients not responding within 2 weeks to the initial infusion.
In responding patients, the strategy for continued treatment is:

• Maintenance: Additional infusions of 5 mg/kg at 2 and 6 weeks after the initial dose, followed by infusions every eight weeks.

Fistulizing Crohn’s Disease

An initial 5 mg/kg infusion given over a 2-hour period is to be followed with additional 5 mg/kg infusion doses at 2 and 6 weeks after the first infusion. If a patient does not respond after these 3 doses, no additional treatment with infliximab should be given.

In responding patients, the strategies for continued treatment are:

• Additional infusions of 5 mg/kg every 8 weeks or

• Re-administration 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 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Ulcerative Colitis

5 mg/kg given as intravenous infusion over a 2-hour period 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 over a 2-hour period 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 intravenous infusion over a 2-hour period followed by additional 5 mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter. Efficacy and safety have been demonstrated in combination with MTX.

Psoriasis

5 mg/kg given as intravenous infusion over a 2-hour period 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 drug-free intervals of less than 1 year (see Sections 4.4 and 4.8, Delayed Hypersensitivity – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). After a drug-free interval of 16 weeks to 2 years, the risk of delayed hypersensitivity following re-administration is not known. Therefore, after a drug-free interval of 16 weeks, re-administration is not recommended.

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 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Re-administration for Psoriasis

Limited experience from retreatment 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 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Special populations

Pediatrics (6–17 years of age)

IXIFI has not been studied in children with Crohn’s disease or UC < 6 years of age. The pharmacokinetics of infliximab has been evaluated in pediatric patients with Crohn’s disease and UC (see Section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). The safety and effectiveness of IXIFI in pediatric patients with juvenile rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and plaque psoriasis have not been established.

Pediatric Crohn’s Disease

5 mg/kg given as intravenous infusion over a 2-hour period followed by additional 5 mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter. For some patients a longer dosing interval may be sufficient. Available data do not support further infliximab treatment in pediatric patients not responding within the first 10 weeks of treatment.

Pediatric Crohn’s disease patients who have had their dose adjusted to greater than 5 mg/kg every 8 weeks, may be at greater risk for adverse reactions. Continued therapy with the adjusted dose should be carefully considered in patients who show no evidence of additional therapeutic benefit after dose adjustment.

Pediatric Ulcerative Colitis

5 mg/kg given as intravenous infusion over a 2-hour period followed by additional 5 mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter.

Renal Impairment

IXIFI has not been studied in patients with renal impairment. No dose recommendations can be made (see Section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Hepatic Impairment

IXIFI has not been studied in patients with hepatic impairment. No dose recommendations can be made (see Section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Administration

IXIFI infusions should be administered by qualified healthcare professionals.

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. Prior to treatment, ensure appropriate personnel and medication, such as adrenaline, antihistamines and corticosteroids, and an artificial airway must be available to treat reactions (e.g., hypersensitivity, other reactions) that occur during infusion and shortly after infusion. Patients may be pre-treated with e.g., histamine-1 receptor antagonists, histamine-2 receptor antagonists, 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 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Discontinue the infusion if the mild to moderate reactions reoccur.

Discontinue the infusion if severe hypersensitivity reactions occur during the infusion.

Shortened Infusion 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.

For preparation and administration instructions, see Section 6.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

4.3. Contraindications

IXIFI is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab products or any of the inactive ingredients of IXIFI (see Section 6.1) or any murine proteins [severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness] (see Sections 4.4 and 4.8) – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

IXIFI is contraindicated in patients with moderate or severe heart failure (New York Heart Association [NYHA] Functional Class III/IV) (see Sections 4.4 and 4.8 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

IXIFI is contraindicated in patients with tuberculosis or other severe infections such as sepsis, abscesses, and opportunistic infections (see Section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).