ORENCIA 125 mg solution for injection in pre-filled pen

  • Name:

    ORENCIA 125 mg solution for injection in pre-filled pen

  • Company:
    info
  • Active Ingredients:

    Abatacept

  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 17/04/19

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XPIL

Summary of Product Characteristics last updated on medicines.ie: 17/4/2019

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Bristol-Myers Squibb Pharma EEIG

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1 - 0 of 19 items.Total: Infinity pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 17 April 2019 PIL

Reasons for updating

  • Change to section 2 - use in children and adolescents
  • Change to section 3 - dose and frequency
  • Change to section 6 - marketing authorisation holder
  • Change to section 6 - date of revision

Updated on 17 April 2019 SmPC

Reasons for updating

  • Change to MA holder contact details

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Updated version to include the changes for the MAH details (section 7)

Updated on 16 April 2019 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

- In Section 4.2:

Special populations

Paediatric population

The safety and efficacy of ORENCIA solution for injection in pre-filled pen for subcutaneous administration in children below 18 years of age have not been established. No data are available.

ORENCIA powder for concentrate for solution for infusion is available for paediatric patients 6 years of age and older for the treatment of pJIA (see Summary of Product Characteristics for ORENCIA powder for concentrate for solution for infusion).

ORENCIA solution for injection pre-filled syringe for subcutaneous administration is available for paediatric patients 2 years of age and older for the treatment of pJIA (see Summary of Product Characteristics for ORENCIA Solution for Injection pre-filled syringe).

- In Section 4.5:

"ORENCIA" has been replaced with "abatacept"

- In section 4.6:

Pregnancy and women of childbearing potential

There are no adequate data from use of abatacept in pregnant women. In pre-clinical embryo-fetal development studies no undesirable effects were observed at doses up to 29-fold a human 10 mg/kg dose based on AUC. In a pre- and postnatal development study in rats, limited changes in immune function were observed at 11-fold higher than a human 10 mg/kg dose based on AUC (see section 5.3).

ORENCIA should not be used during pregnancy unless the clinical condition of the woman requires treatment with abatacept.

Women of childbearing potential have to use effective contraception during treatment and up to 14 weeks after the last dose of abatacept.

Breast-feeding

Abatacept has been shown to be present in rat milk.

It is unknown whether abatacept is excreted in human milk.

A risk to the newborns/infants cannot be excluded.

Breast-feeding should be discontinued during treatment with ORENCIA and for up to 14 weeks after the last dose of abatacept treatment.

- In Section 5.1:

Paediatric population

ORENCIA powder for concentrate for solution for infusion and ORENCIA solution for injection in pre-filled syringe are approved in the paediatric patients with pJIA. Please refer to the ORENCIA powder for concentrate for solution for infusion 250 mg and ORENCIA solution for injection in pre-filled syringe 125 mg, 87.5 mg and 50 mg SmPCs.

- In Section 10:

DATE OF REVISION OF THE TEXT 

08 April 2019

Updated on 22 February 2019 PIL

Reasons for updating

  • Change to section 6 - marketing authorisation holder
  • Change to section 6 - date of revision

Updated on 22 February 2019 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 7: Change to MAH Address

Updated on 7 August 2017 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable effects
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.1 has been updated with a new a indication

Psoriatic Arthritis

ORENCIA, alone or in combination with methotrexate (MTX), is indicated for the treatment of active psoriatic arthritis (PsA) in adult patients when the response to previous DMARD therapy including MTX has been inadequate and for whom additional systemic therapy for psoriatic skin lesions is not required.

 ​​

Section 4.2 has been updated with the method of administration

Psoriatic Arthritis

Adults

ORENCIA should be administered weekly at a dose of 125 mg by subcutaneous (SC) injection without the need for an intravenous (IV) loading dose.

Patients switching from ORENCIA intravenous therapy to subcutaneous administration should administer the first subcutaneous dose instead of the next scheduled intravenous dose.

 

​​

​​

Section 4.8   has been updated with a summary of the summary of the safety profile in psoriatic arthritis

​​

In addition the reporting details for the yellow card scheme has been updated following update to Appendix 5

​​

Section 5.1 has been updated with Clinical efficacy and safety in adult psoriatic arthritis

​​

section 5.2  has been updated with the data from adults with psoriatic arthritis

​​

Section 10 has been updated with the date of revision - 25th July 2017

 

Updated on 7 August 2017 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 22 May 2017 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.4 - The patient numbers  and percentages from some of the clinical studies  have been updated

Section 4.5 -Changes to the frequencies of adverse events

Updated on 18 May 2017 PIL

Reasons for updating

  • New PIL for new product

Updated on 18 May 2017 PIL

Reasons for updating

  • Change to section 4 - possible side effects

Updated on 2 September 2016 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.       Clinical particulars

 

4.1     Therapeutic indications

 

 Rheumatoid arthritis

ORENCIA, in combination with methotrexate, is indicated for:

§    the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who responded inadequately to previous therapy with one or more disease-modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX) or a tumour necrosis factor (TNF)-alpha inhibitor.

§    the treatment of highly active and progressive disease in adult patients with rheumatoid arthritis not previously treated with methotrexate.

 

 

4.8     Undesirable effects

 

In Study SC-III, similar immunogenicity rates were seen in patients on treatment for the abatacept+MTX, and abatacept monotherapy groups (2.9% (3/103) and 5.0% (5/101), respectively) during the double-blind 12 month period. As in Study SC-I, there was no effect of immunogenicity on safety or efficacy.

 

In SC-III, increased rates of immunogenicity were observed in subjects tested during 6 months of complete drug withdrawal in the abatacept+MTX and abatacept monotherapy groups (37.7% [29/77] and 44.1% [27/59], respectively) with generally low titer antibody responses. No clinical impact of these antibody responses was detected, and no safety concerns were observed upon reinitiation of abatacept therapy.

 

 

5.       PHARMACOLOGICAL PROPERTIES

 

5.1     Pharmacodynamic properties

 

In Studies I, II, and V the efficacy and safety of abatacept compared to placebo were assessed in patients with an inadequate response to methotrexate and who continued on their stable dose of methotrexate. In addition, Study V investigated the safety and efficacy of abatacept or infliximab relative to placebo. In Study III the efficacy and safety of abatacept were assessed in patients with an inadequate response to a TNF-inhibitor, with the TNF-inhibitor discontinued prior to randomization; other DMARDs were permitted. Study IV primarily assessed safety in patients with active rheumatoid arthritis requiring additional intervention in spite of current therapy with non-biological and/or biological DMARDs; all DMARDs used at enrollment were continued. In Study VI, the efficacy and safety of abatacept were assessed in methotrexate-naive, Rheumatoid Factor (RF) and/or anti-Cyclic Citrullinated Peptide 2 (Anti-CCP2)-positive patients with early, erosive rheumatoid arthritis (≤ 2 years disease duration) who were randomized to receive abatacept plus methotrexate or methotrexate plus placebo. In Study SC-I, the goal was to demonstrate non-inferiority of the efficacy and comparability of the safety of abatacept subcutaneous relative to intravenous administration in subjects with moderate to severely active RA and experiencing inadequate response to MTX. Study SC-II investigated the relative efficacy and safety of abatacept and adalimumab, both given subcutaneously without an intravenous loading dose and with background MTX, in patients with moderate to severely active RA and an inadequate response to previous MTX therapy. In study SC-III, abatacept SC was evaluated in combination with methotrexate, or as abatacept monotherapy, and compared to MTX monotherapy in induction of remission following 12 months of treatment, and the possible maintenance of drug-free remission after complete drug withdrawal, in adult MTX-naive patients with highly active early rheumatoid arthritis (mean DAS28‑CRP of 5.4; mean symptom duration less than 6.7 months) with poor prognostic factors for rapidly progressive disease (e.g. anti-citrullinated protein antibodies [ACPA+], as measured by anti-CCP2 assay, and/or RF+, baseline joint erosions).

 

Studies I, II, III, IV, V, VI, SC-I, and SC-II, and SC-III evaluated 339, 638, 389, 1,441, 431, 509 1,371, and 646, and 351 adult patients, respectively.

 

Study SC-III: Induction of remission in methotrexate-naive RA patients

A randomized and double-blinded study evaluated abatacept SC in combination with methotrexate (abatacept + MTX), abatacept SC monotherapy, or methotrexate monotherapy (MTX group) in induction of remission following 12 months of treatment, and maintenance of drug-free remission after complete drug withdrawal in MTX-naive adult patients with highly active early rheumatoid arthritis with poor prognostic factors. Complete drug withdrawal led to loss of remission (return to disease activity) in all three treatment arms (abatacept with methotrexate, abatacept or methotrexate alone) in a majority of patients (Table 3).

 

Table 3:                       Remission Rates at End of Drug Treatment and Drug Withdrawal Phases in Study SC-III

Number of Patients

Abatacept SC+ MTX

n = 119

MTX

n = 116

Abatacept SC

n = 116

Proportion of Randomized Patients with Induction of Remission after 12 Months of Treatment

DAS28-Remissiona

Odds Ratio (95% CI) vs. MTX

P value

60.9%

2.01 (1.18, 3.43)

0.010

45.2%

N/A

N/A

42.5%

0.92 (0.55, 1.57)

N/A

SDAI Clinical Remissionb

Estimate of Difference (95% CI) vs. MTX

42.0%

17.02 (4.30, 29.73)

25.0%

N/A

29.3%

4.31 (-7.98, 16.61)

Boolean Clinical Remission

Estimate of Difference (95% CI) vs. MTX

37.0%

14.56 (2.19, 26.94)

22.4%

N/A

26.7%

4.31 (-7.62, 16.24)

Proportion of Randomized Patients in Remission at 12 Months and at 18 Months

(6 Months of Complete Drug Withdrawal)

DAS28-Remission a

Odds Ratio (95% CI) vs. MTX

P value

14.8%

2.51 (1.02, 6.18)

0.045

7.8%

N/A

N/A

12.4%

2.04 (0.81, 5.14)

N/A

a DAS28-defined remission (DAS28-CRP <2.6)

b SDAI criterion (SDAI 3.3)

 

In SC-III the safety profiles of the three treatment groups (abatacept + MTX, abatacept monotherapy, MTX group) were overall similar. During the 12-month treatment period, adverse reactions were reported in 44.5% (53/119), 41.4% (48/116), and 44.0% (51/116) and serious adverse reactions were reported in 2.5% (3/119), 2.6% (3/116) and 0.9% (1/116) of patients treated in the three treatment groups, respectively. Serious infections were reported in 0.8% (1/119), 3.4% (4/116) and 0% (0/116) patients.

 

Table 34:                     Mean Radiographic Changes Over 12 Months in Study II

 

In Study SC-III, structural joint damage was assessed by MRI. The abatacept + MTX group had less progression in structural damage compared with MTX group as reflected by mean treatment difference of the abatacept + MTX group versus MTX group (Table 5).

 

Table 5:                       Structural and Inflammatory MRI Assessment in Study SC-III

Mean Treatment Difference between Abatacept SC+MTX vs. MTX at 12 Months (95% CI)*

MRI Erosion Score

-1.22 (-2.20, -0.25)

MRI Osteitis/Bone Oedema Score

-1.43 (-2.68, -0.18)

MRI Synovitis Score

-1.60, (-2.42, -0.78)

* n = 119 for Abatacept SC + MTX; n = 116 for MTX

 

In Study SC-III, the proportion of subjects with a HAQ response as a measure of clinically meaningful improvement in physical function (reduction from baseline in HAQ-D1 score of > 0.3) was greater for the abatacept+ MTX group vs. the MTX group at Month 12 (65.5% vs 44.0%, respectively; treatment difference vs. MTX group of 21.6% [95% CI: 8.3, 34.9]).

 

10.     DATE OF REVISION OF THE TEXT

 

August 2016

 

 

Updated on 1 September 2016 PIL

Reasons for updating

  • Change to date of revision
  • Changes to therapeutic indications

Updated on 21 June 2016 PIL

Reasons for updating

  • Change to date of revision
  • Addition of manufacturer

Updated on 12 April 2016 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.8       Undesirable effects

Immunogenicity in adults treated with subcutaneous abatacept

Study SC-I compared the immunogenicity to abatacept following subcutaneous or intravenous administration as assessed by ELISA assay. During the initial double blind 6 months period (short-term period), the overall immunogenicity frequency to abatacept was 1.1% (8/725) and 2.3% (16/710) for the subcutaneous and intravenous groups, respectively. The rate is consistent with previous experience, and there was no effect of immunogenicity on pharmacokinetics, safety, or efficacy.

 

Immunogenicity to abatacept following long-term subcutaneous administration was assessed by a new ECL assay. Comparison of incidence rates across different assays is not appropriate, as the ECL assay was developed to be more sensitive and drug tolerant than the previous ELISA assay. The cumulative immunogenicity frequency to abatacept by the ECL assay with at least one positive sample in the short-term and long-term periods combined was 15.7% (215/1369) while on abatacept, with a mean duration of exposure of 48.8 months, and 17.3% (194/1121) after discontinuation (> 21 days up to 168 days after last dose). The exposure adjusted incidence rate (expressed per 100 person-years) remained stable over the treatment duration.

 

Consistent with previous experience, titers and persistence of antibody responses were generally low and did not increase upon continued dosing (6.8% subjects were seropositive on 2 consecutive visits), and there was no apparent correlation of antibody development to clinical response, adverse events, or PK.



5.       PHARMACOLOGICAL PROPERTIES

 

5.1     Pharmacodynamic properties

In the open‑label extension of Studies I, II, III, VI, and SC-I durable and sustained ACR 20, 50, and 70 responses have been observed through 7 years, 5 years, 5 years, 2 years, and 5 years, respectively, of abatacept treatment. In study I, ACR responses were assessed at 7 years in 43 patients with 72% ACR 20 responses, 58% ACR 50 responses, and 44% ACR 70 responses. In study II, ACR responses were assessed at 5 years in 270 patients with 84% ACR 20 responses, 61% ACR 50 responses, and 40% ACR 70 responses. In study III, ACR responses were assessed at 5 years in 91 patients with 74% ACR 20 responses, 51% ACR 50 responses, and 23% ACR 70 responses. In study VI, ACR responses were assessed at 2 years in 232 patients with 85% ACR 20 responses, 74% ACR 50 responses, and 54% ACR 70 responses. In study SC-I, ACR responses were assessed at 5 years with 85% (356/421) ACR 20 responses, 66% (277/423) ACR 50 responses, and 45% (191/425) ACR 70 responses.



10.     DATE OF REVISION OF THE TEXT

 

April 2016

Updated on 23 December 2015 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.2     Posology and method of administration

 

Patients switching from ORENCIA intravenous therapy to subcutaneous administration should administer the first subcutaneous dose instead of the next scheduled intravenous dose.




 

4.6     Fertility, pregnancy and lactation

 

Pregnancy and Women of childbearing potential

There are no adequate data from use of abatacept in pregnant women. In pre-clinical embryo‑fetal development studies no undesirable effects were observed at doses up to 29‑fold a human 10 mg/kg dose based on AUC. In a pre‑ and postnatal development study in rats limited changes in immune function were observed at 11‑fold higher than a human 10 mg/kg dose based on AUC (see section 5.3). ORENCIA should not be used in pregnant women unless clearly necessary. Women of child‑bearing potential should use effective contraception during treatment with ORENCIA and up to 14 weeks after the last dose of abatacept treatment.

 

Abatacept may cross the placenta into the serum of infants born to women treated with abatacept during pregnancy. Consequently, these infants may be at increased risk of infection. The safety of administering live vaccines to infants exposed to abatacept in utero is unknown. Administration of live vaccines to infants exposed to abatacept in utero is not recommended for 14 weeks following the mother’s last exposure to abatacept during pregnancy.




10.     DATE OF REVISION OF THE TEXT

 

December 2015

Updated on 22 December 2015 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to information about pregnancy or lactation
  • Change to date of revision

Updated on 13 May 2015 SmPC

Reasons for updating

  • New SPC for medicines.ie

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

None provided

Updated on 13 May 2015 PIL

Reasons for updating

  • New PIL for medicines.ie