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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
ORENCIA (BLA-125118)
(ABATACEPT)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
01/19/2024 (SUPPL-249)
5 Warnings and Precautions
5.3 Infections
(Additions and/or revisions underlined)
Serious infections, including sepsis and pneumonia, have been reported in patients receiving ORENCIA (serious infections were reported in 3% and 1.9% of RA patients treated with intravenous ORENCIA and placebo, respectively) [see Adverse Reactions (6.1)]. Some of these infections have been fatal. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy which in addition to their underlying disease, could further predispose them to infection. A higher rate of serious infections has been observed in adult RA patients treated with concurrent TNF antagonists and ORENCIA compared to those treated with ORENCIA alone [see Warnings and Precautions (5.1)].
Healthcare providers should exercise caution when considering the use of ORENCIA in patients with a history of recurrent infections, underlying conditions which may predispose them to infections, or chronic, latent, or localized infections. Patients who develop a new infection while undergoing treatment with ORENCIA should be monitored closely. Administration of ORENCIA should be discontinued if a patient develops a serious infection.
Prior to initiating ORENCIA, patients should be screened for latent tuberculosis (TB) infection according to current TB guidelines. ORENCIA has not been studied in patients with a positive TB screen, and the safety of ORENCIA in individuals with latent TB infection is unknown. Patients testing positive in TB screening should be treated by standard medical practice prior to therapy with ORENCIA…
8 Use in Specific Populations
8.4 Pediatric Use
(Additions and/or revisions underlined)
…
Psoriatic Arthritis
Subcutaneous Administration
The safety and effectiveness of subcutaneous ORENCIA have been established for treatment of psoriatic arthritis in pediatric patients 2 to 17 years old.
Use of ORENCIA in this age group is supported by evidence from adequate and well-controlled studies of ORENCIA in adults with PsA, pharmacokinetic data from adult patients with RA, adult patients with PsA, and pediatric patients with pJIA, and safety data from clinical studies in pediatric patients 2 to 17 years old with pJIA using the subcutaneous formulation.
The observed pre-dose (trough) concentrations are generally comparable between adults with RA and PsA and pediatric patients with JIA with active polyarthritis, and the PK exposure is expected to be comparable between adult PsA and pediatric patients with PsA. [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.1, 14.2, 14.3)].
The safety and effectiveness of subcutaneous ORENCIA have not been established in pediatric patients less than 2 years old with psoriatic arthritis.
Intravenous Administration
The safety and effectiveness of intravenous ORENCIA in pediatric patients with psoriatic arthritis have not been established.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION ORENCIA (oh-REN-see-ah) (abatacept) injection, for intravenous or subcutaneous use
(Additions and/or revisions underlined)
What is ORENCIA?
ORENCIA is a prescription medicine that reduces signs and symptoms in:
adults with moderate to severe rheumatoid arthritis (RA), including those who have not been helped enough by other medicines for RA. ORENCIA may prevent further damage to your bones and joints and may help your ability to perform daily activities. In adults, ORENCIA may be used alone or with other RA treatments other than tumor necrosis factor (TNF) antagonists.
people 2 years of age and older with moderate to severe polyarticular juvenile idiopathic arthritis (pJIA). ORENCIA may be used alone or with methotrexate.
people 2 years of age and older with active psoriatic arthritis (PsA). In adults, ORENCIA can be used alone or with other PsA treatments. In children, ORENCIA can be used alone or with methotrexate.
ORENCIA is also used for the preventative treatment of acute graft versus host disease (aGVHD), in combination with a calcineurin inhibitor and methotrexate, in:
people 2 years of age and older undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated-donor.
It is not known if ORENCIA is safe and effective in children less than two years of age for the treatment of pJIA. It is not known if ORENCIA is safe and effective in children less than two years of age for the treatment of PsA.
…
How will I receive or use ORENCIA? For treatment of RA, pJIA or PsA:
You may receive ORENCIA given by a healthcare provider through a vein in your arm (intravenous infusion). It takes about 30 minutes to give you the full dose of medicine. You will then receive ORENCIA 2 weeks and 4 weeks after the first dose and then every 4 weeks. Intravenous administration of ORENCIA is not approved for pediatric patients with psoriatic arthritis.
10/30/2023 (SUPPL-250)
5 Warnings and Precautions
5.2 Hypersensitivity Reactions
Section title revised
5.3 Infections
Additions and/or revisions underlined:
…
Prior to initiating ORENCIA, patients should be screened for latent tuberculosis (TB) infection according to current TB guidelines.
…
8 Use in Specific Populations
8.4 Pediatric Use
Newly added subsection:
…
Psoriatic Arthritis
Subcutaneous Administration
The safety and effectiveness of subcutaneous ORENCIA have been established for treatment of psoriatic arthritis in pediatric patients 2 to 17 years old.
Use of ORENCIA in this age group is supported by evidence from adequate and well-controlled studies of ORENCIA in adults with PsA, pharmacokinetic data from adult patients with RA, adult patients with PsA, and pediatric patients with pJIA, and safety data from clinical studies in pediatric patients 2 to 17 years old with pJIA using the subcutaneous formulation.
The observed pre-dose (trough) concentrations are generally comparable between adults with RA and PsA and pediatric patients with JIA with active polyarthritis, and the PK exposure is expected to be comparable between adult PsA and pediatric patients with PsA. [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.1, 14.2, 14.3)].
The safety and effectiveness of subcutaneous ORENCIA have not been established in pediatric patients less than 2 years old with psoriatic arthritis.
Intravenous Administration
The safety and effectiveness of intravenous ORENCIA in pediatric patients with psoriatic arthritis have not been established.
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
Hypersensitivity Reactions
PATIENT INFORMATION
Additions and/or revisions underlined:
What is ORENCIA?
- people 2 years of age and older with active psoriatic arthritis (PsA). In adults, ORENCIA can be used alone or with other PsA treatments. In children, ORENCIA can be used alone or with methotrexate.
…
It is not known if ORENCIA is safe and effective in children less than two years of age for the treatment of PsA.
How will I receive or use ORENCIA?
For treatment of RA, pJIA or PsA:
- You may receive ORENCIA given by a healthcare provider through a vein in your arm (intravenous infusion). It takes about 30 minutes to give you the full dose of medicine. You will then receive ORENCIA 2 weeks and 4 weeks after the first dose and then every 4 weeks. Intravenous administration of Orencia is not approved for pediatric patients with psoriatic arthritis.
…
12/15/2021 (SUPPL-240)
5 Warnings and Precautions
5.1Increased Risk of Infection with Concomitant Use of TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors
…
The heading was revised, revision underlined.
5.4 Immunizations
Additions underlined
… In addition, there are clinical considerations for administering live vaccines to infants who were exposed to ORENCIA while in utero [see Use in Specific Populations (8.1)]. Based on its mechanism of action, ORENCIA may blunt the effectiveness of some immunizations.
5.5 Increased Risk of Adverse Reactions When Used in Patients with Chronic Obstructive Pulmonary Disease (COPD)
…
The heading was revised, revision underlined.
5.7 Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Reactivation in aGVHD Prophylaxis after Hematopoietic Stem Cell Transplant (HSCT)
New subsection added
Post-Transplant Lymphoproliferative Disorder (PTLD) occurred in patients who received ORENCIA for aGVHD prophylaxis during unrelated HSCT. Of 116 patients who received ORENCIA, 4 patients (3.4%) experienced PTLD. All the PTLD events were associated with Epstein-Barr virus (EBV) infection. Three of the four patients were EBV serology positive at baseline; one patient had negative baseline EBV serology with donor EBV serology unknown. Three of the 4 patients discontinued acyclovir prophylaxis at day 30 post-transplant. The range of time to onset of the events was 49 to 89 days post-transplant. Monitor patients for EBV reactivation in accordance with institutional practices. Provide prophylaxis for EBV infection for 6 months post-transplantation to prevent EBV-associated PTLD [see Dosage and Administration (2.4)].
Cytomegalovirus (CMV) invasive disease occurred in patients who received ORENCIA for aGVHD prophylaxis during unrelated HSCT. Of 116 patients who received ORENCIA, 7% experienced CMV invasive diseases up to day 225 post-transplant. All the patients who experienced CMV invasive disease were CMV serology positive at baseline. The median time to onset of the event was 91 days post-transplant. CMV invasive diseases predominantly involved the gastrointestinal tract [see Adverse Reactions (6.1)].
Monitor patients for CMV infection/reactivation for 6 months post-transplant regardless of the results of donor and recipient pre-transplant CMV serology. Consider prophylaxis for CMV infection/reactivation [see Dosage and Administration (2.4)].
6 Adverse Reactions
ADVERSE REACTIONS
Section revised, additions and/or revisions underlined
The following clinically significant adverse reactions are described elsewhere in the labeling:
Increased Risk of Infection with Concomitant Use with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors [see Warnings and Precautions (5.1)]
Hypersensitivity [see Warnings and Precautions (5.2)]
Infections [see Warnings and Precautions (5.3)]
Increased Risk of Adverse Reactions When Used in Patients with Chronic Obstructive Pulmonary Disease (COPD) [see Warnings and Precautions (5.5)]
Immunosuppression [see Warnings and Precautions (5.6)]
Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Reactivation in aGVHD Prophylaxis after Hematopoietic Stem Cell Transplant (HSCT) [see Warnings and Precautions (5.7)]
6.1 Clinical Trials Experience
Additions underlined
Adverse Reactions in Patients Undergoing Unrelated-Donor Hematopoietic Stem Cell Transplantation (HSCT) with Intravenous ORENCIA
The data described herein were from one clinical study of ORENCIA (GVHD-1) for aGVHD prophylaxis in patients 6 years and older with hematologic malignancies who were undergoing unrelated HSCT wherein all patients were receiving calcineurin inhibitor and methotrexate as the standard of care for aGVHD prophylaxis [see Clinical Studies (14.4)]. Two cohorts were studied at 10 mg/kg (maximum dose of 1,000 mg) as an intravenous infusion over 60 minutes on the day before transplantation (Day -1), followed by administration on Days 5, 14, and 28 after transplantation:
A single-arm cohort of ORENCIA-treated patients (n=43) who underwent 7 of 8 Human leukocyte antigen (HLA)-matched HSCT from unrelated donors (7 of 8 cohort) and
A randomized cohort comprised of ORENCIA-treated patients (n=73) and placebo-treated patients (n=69) who underwent 8 of 8 HLA-matched HSCT from unrelated donors (8 of 8 cohort).
Of the 116 patients who received ORENCIA, 27 (23%) were 6 to less than 17 years of age [see Use in Specific Populations (8.4)].
The safety information from the date of first dose of ORENCIA up to Day 225 post-transplantation from this study is presented below. The incidence of adverse reactions was determined based on pooled data of ORENCIA-treated patients from the 2 study cohorts (n=116).
Serious adverse reactions reported in > 5% of patients who received ORENCIA in combination with a calcineurin inhibitor and methotrexate included pyrexia (20%), pneumonia (8%), acute kidney injury (7%), diarrhea (6%), hypoxia (5%), and nausea (5%).
Permanent discontinuation of ORENCIA due to an adverse reaction occurred in two patients (1.7%) due to one case each of pneumonia and allergic reaction.
The most common (greater than or equal to10%) adverse reactions in the ORENCIA treated patients were anemia, hypertension, CMV reactivation/CMV infection, pyrexia, pneumonia, epistaxis, CD4 lymphocytes decreased, hypermagnesemia, and acute kidney injury.
Table 4 summarizes the frequency of adverse reactions reported in the study of ORENCIA in GVHD-1.
Please refer to label to view Table 4.
Clinically relevant adverse reactions in <10% of patients who received ORENCIA in combination with calcineurin inhibitor and methotrexate in Study GVHD-1 included EBV reactivation.
6.2 Immunogenicity
Additions underlined
…
Immunogenicity in Patients Treated for Prophylaxis of aGVHD with Intravenous ORENCIA
Immunogenicity was assessed in patients undergoing HSCT. Overall, immunogenicity incidence and associated antibody titers were low from the 4-dose intravenous ORENCIA regimen used in this study. Of the 114 immunogenicity evaluable subjects in the ORENCIA groups, none were positive during the ORENCIA treatment period (Day -1 to Day 28 following transplant). During the off-treatment period (Day 29 and up to Day 180 following transplant); 6 of 91 immunogenicity evaluable subjects (6.6%) were positive for CTLA4 and possibly Ig; 4 of the 6 positive subjects were found to have at least one positive sample with neutralization activity. In this study, immunogenicity positive subjects only had ADA positive samples on Day 180 (off-treatment period) and thus due to the timing of the response, the impact on PK, safety, or efficacy could not be determined.
8 Use in Specific Populations
8.1 PregnancyAdditions underlined
…
Risk Summary
The data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. However, there are clinical considerations for administering live vaccines to infants who were exposed to ORENCIA while in utero (see Clinical Considerations). In reproductive toxicology studies in rats and rabbits, no fetal malformations were observed with intravenous administration of ORENCIA during organogenesis at doses that produced exposures approximately 29 times the exposure at the maximum recommended human dose (MRHD) of 10 mg/kg/month on an AUC basis. However, in a pre- and postnatal development study in rats, ORENCIA altered immune function in female rats at 11 times the MRHD on an AUC basis.
Clinical Considerations
Infants and Administration of Live Vaccines
It is unknown if abatacept can cross the placenta into the fetus when a woman is treated with ORENCIA during pregnancy. Abatacept is an immunomodulatory agent. It is unknown if the immune response of an infant who was exposed in utero to abatacept and subsequently administered a live vaccine is impacted. Risks and benefits should be considered prior to vaccinating such infants [see Warnings and Precautions (5.4)].
…
Additions and/or revisions underlined
…
Acute Graft Versus Host Disease Prophylaxis
The safety and effectiveness of ORENCIA for the prophylaxis of acute graft versus host disease (aGVHD), in combination with a calcineurin inhibitor and methotrexate, in pediatric patients aged 2 years of age and older undergoing HSCT from a matched or 1 allele-mismatched unrelated donor have been established.Use of ORENCIA for this indication is supported by evidence from:
adequate and well-controlled studies in adults and pediatric patients aged 6 years and older administered a dose of 10 mg/kg intravenously on the day before transplantation followed by a dose of 10 mg/kg intravenously on Days 5, 14, and 28 after transplantation and
pharmacokinetic modeling and simulations of abatacept exposure in pediatric patients aged 2 to less than 6 years administered a dose of 15 mg/kg intravenously on the day before transplantation followed by a dose of 12 mg/kg intravenously on Days 5, 14, and 28 after transplantation.
Furthermore, the course of disease is sufficiently similar in pediatric patients aged 2 years to less than 6 years to that of patients aged 6 years and older to allow extrapolation of data to younger pediatric patients [see Clinical Pharmacology (12.3) and Clinical Studies (14.4)]. No new safety signals were observed in pediatric patients aged 6 years and older in Study GVHD-1.
The safety and effectiveness of ORENCIA for this indication have not been established in pediatric patients less than 2 years of age.
…
Additions underlined
…
Acute Graft Versus Host Disease Prophylaxis
Of the 116 patients in Study GVHD-1 who received ORENCIA at a dose of 10 mg/kg for the prophylaxis of aGVHD, 12 (10%) were 65 years of age and older, and 2 (2%) patients were 75 years of age and older [see Clinical Studies (14.4)]. Clinical studies of ORENCIA for aGVHD did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATIONAdditions underlined
…
Increased Risk of Infection with Concomitant Use With Immunosuppressants for RA
Inform patients that the concomitant use with other immunosuppressives (e.g., biologic DMARDs, JAK inhibitors) is not recommended [see Warnings and Precautions (5.1) and Drug Interactions (7.1)].
…
Extensive additions and revisions; please refer to label for complete information.
06/17/2020 (SUPPL-225)
5 Warnings and Precautions
(Extensive changes; please refer to label)
6 Adverse Reactions
(Extensive changes; please refer to label)
7 Drug Interactions
Immunosuppressants(Newly added section; please refer to label)
8 Use in Specific Populations
Geriatric Use(Additions and/or revisions underlined)
A total of 323 patients 65 years of age and older, including 53 patients 75 years and older, received ORENCIA in clinical studies. No overall differences in safety or effectiveness were observed between geriatric patients (patients aged 65 years of age and older) and younger adults, and other reported clinical experience has not identified differences in responses between geriatric patients and younger adults, but greater sensitivity of some geriatric patients cannot be ruled out. The frequency of serious infection and malignancy among ORENCIA-treated patients over age 65 was higher than for those under age 65. Because there is a higher incidence of infections and malignancies in the geriatric population in general, caution should be used when treating geriatric patients.
(Extensive changes; please refer to label)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION(Extensive changes; please refer to label)
(Additions and/or revisions underlined)
Some people treated with ORENCIA have developed skin cancer. Tell your healthcare provider if you
have a family or personal history of skin cancer, and if you see any growths or changes in the
appearance of your skin during or after your treatment with ORENCIA
You should not receive ORENCIA with certain types of vaccines (live vaccines). You
can receive non-live vaccines, such as pneumococcal and inactivated influenza (flu) vaccines.
03/21/2019 (SUPPL-224)
6 Adverse Reactions
6.6 Postmarketing ExperienceAddition of the following:
New or worsening psoriasis
06/30/2017 (SUPPL-209)
6 Adverse Reactions
6.5 Clinical Studies Experience in Adult PsA Patients(new subsection added)
The safety of ORENCIA was evaluated in 594 patients with psoriatic arthritis (341 patients on ORENCIA and 253 patients on placebo), in two randomized, double-blind, placebo-controlled trials. Of the 341 patients who received ORENCIA, 128 patients received intravenous ORENCIA (PsA-I) and 213 patients received subcutaneous ORENCIA (PsA-II). The safety profile was comparable between studies PsA-I and PsA-II and consistent with the safety profile in rheumatoid arthritis.
03/30/2017 (SUPPL-211)
6 Adverse Reactions
… and may not predict the rates observed in a broader patient population in clinical practice.
Addition of the following:
As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to abatacept in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.
6.1 Clinical Studies Experience in Adult RA Patients Treated with Intravenous ORENCIA
The data described herein reflect exposure to ORENCIA administered …
6.3 Clinical Studies Experience in Juvenile Idiopathic Arthritis
Patients Treated with Intravenous ORENCIA
Additions and/or revisions underlined:
In general, the adverse events in pediatric patients were similar …
Study JIA-1 was a three-part study including an open-label extension that assessed the safety and efficacy of intravenous ORENCIA in 190 pediatric patients, 6 to 17 years of age, with polyarticular juvenile idiopathic arthritis …
Newly added subsection:
Study JIA-2 was an open-label study with a 4-month short-term period and a long-term extension period that assessed the pharmacokinetics (PK), safety, and efficacy of subcutaneous ORENCIA in 205 pediatric patients, 2 to 17 years of age with juvenile idiopathic arthritis. The safety experience and immunogenicity for ORENCIA administered subcutaneously were consistent with the intravenous Study JIA-1.
There were no reported cases of hypersensitivity reactions. Local injection-site reactions occurred at a frequency of 4.4%.
8 Use in Specific Populations
8.1 PregnancyPLLR conversion, as below:
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ORENCIA during pregnancy. Healthcare professionals are encouraged to register patients and pregnant women are encouraged to enroll themselves by calling 1-877-311-8972.
Risk Summary
The data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. In reproductive toxicology studies in rats and rabbits, no fetal malformations were observed with intravenous administration of ORENCIA during organogenesis at doses that produced exposures approximately 29 times the exposure at the maximum recommended human dose (MRHD) of 10 mg/kg/month on an AUC basis. However, in a pre- and postnatal development study in rats, ORENCIA altered immune function in female rats at 11 times the MRHD on an AUC basis.
Data
Human Data
There are no adequate and well-controlled studies of ORENCIA use in pregnant women. The data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk.
Animal Data
Intravenous administration of abatacept during organogenesis to mice (10, 55, or mg/kg200 m/day), rats (10, 45, or 200 mg/kg/day), and rabbits (10, 45, or 200 mg/kg every 3 days) produced exposures in rats and rabbits that were approximately 29 times the MRHD on an AUC basis (at maternal doses of 200 mg/kg/day in rats and rabbits), and no embryotoxicity or fetal malformations were observed in any species.
In a study of pre- and postnatal development in rats (10, 45, or 200 mg/kg every 3 days from gestation day 6 through lactation day 21), alterations in immune function in female offspring, consisting of a 9-fold increase in T-cell-dependent antibody response relative to controls on postnatal day (PND) 56 and thyroiditis in a single female pup on PND 112, occurred at approximately 11 times the MRHD on an AUC basis (at a maternal dose of 200 mg/kg). No adverse effects were observed at approximately 3 times the MRHD (a maternal dose of
45 mg/kg). It is not known if immunologic perturbations in rats are relevant indicators of a risk for development of autoimmune diseases in humans exposed in utero to abatacept. Exposure to abatacept in the juvenile rat, which may be more representative of the fetal immune system state in the human, resulted in immune system abnormalities including inflammation of the thyroid and pancreas.
PLLR conversion. as below:
Risk Summary
There is no information regarding the presence of abatacept in human milk, the effects on the breastfed infant, or the effects on milk production. However, abatacept was present in the milk of lactating rats dosed with abatacept.
Additions and/or revisions underlined:
I In Study JIA-1, ORENCIA with intravenous administration was shown to reduce signs and symptoms of active polyarticular JIA in patients 6 to 17 years of age. ORENCIA with intravenous administration has not been studied in patients younger than 6 years of age.
In Study JIA-2, the PK and safety of ORENCIA prefilled syringe for subcutaneous injection have been studied in patients 2 to 17 years of age. The efficacy of ORENCIA for subcutaneous injection in children 2 to 17 years of age is based on pharmacokinetic exposure and extrapolation of established efficacy of intravenous ORENCIA in polyarticular JIA patients and subcutaneous ORENCIA in patients with RA. The safety and immunogenicity of ORENCIA for subcutaneous injection in children 2 to 17 years of age were assessed descriptively. ORENCIA may be used as monotherapy or concomitantly with methotrexate.
The safety and efficacy of ORENCIA ClickJect autoinjector for subcutaneous injection have not been studied in patients under 18 years of age.
Studies in juvenile rats exposed to ORENCIA … As the immune system of the rat is undeveloped in the first few weeks after birth, the relevance of these results to humans is unknown.
The safety and efficacy of ORENCIA in pediatric patients for uses other than juvenile idiopathic arthritis have not been established …
It is unknown if abatacept can cross the placenta into the fetus when the woman is treated with abatacept during pregnancy. Since abatacept is an immunomodulatory agent, the safety of administering live vaccines in infants exposed in utero to abatacept is unknown. Risk and benefits should be considered prior to vaccinating such infants.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATIONNewly added section following Subcutaneous Administration:
Disposal of Prefilled Syringes and ClickJect Autoinjectors
Advise patients to follow disposal instructions in the Instructions for Use. A puncture-resistant container for disposal of needles and syringes should be used. Instruct patients that they will need to follow their community guidelines for the correct way to dispose of their sharps disposal container. Instruct patients not to recycle their used sharps disposal container.
What is Orencia?
ORENCIA is a prescription medicine that reduces signs and symptoms in:
patients 2 years of age and older with moderate to severe polyarticular juvenile idiopathic arthritis (JIA).
It is not known if ORENCIA is safe and effective in children under 2 years of age.
Before you use ORENCIA, tell your healthcare provider about all of your medical conditions, including if you:
are pregnant or plan to become pregnant. It is not known if ORENCIA can harm your unborn baby. If you took ORENCIA during pregnancy, talk to your healthcare provider before your baby receives any vaccines.
are breastfeeding or plan to breastfeed. It is not known if ORENCIA passes into your breast milk. Talk to your healthcare provider should decide about the best way to feed your baby if you use ORENCIA or breastfeed. You should not do both.
How should I use ORENCIA?
You may also receive ORENCIA as an injection under your skin (subcutaneous). For home use, ORENCIA comes in a prefilled syringe or prefilled ClickJect autoinjector. Your healthcare provider will prescribe the type that is best for you. If your healthcare provider decides that you or a caregiver can give your injections of ORENCIA prefilled syringes or ORENCIA ClickJect autoinjectors at home, you or your caregiver should receive training on the right way to …