RENFLEXIS- infliximab injection, powder, lyophilized, for solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

infliximab (UNII: B72HH48FLU) (infliximab - UNII:B72HH48FLU)

Available from:

Organon LLC

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

RENFLEXIS is indicated for: - reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn's disease (CD) who have had an inadequate response to conventional therapy. - reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing CD. RENFLEXIS 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 CD who have had an inadequate response to conventional therapy. RENFLEXIS is indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response to conventional therapy. RENFLEXIS 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. RENFLEXIS, in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis (RA). RENFLEXIS is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis (AS). RENFLEXIS is indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in adult patients with psoriatic arthritis (PsA). RENFLEXIS is indicated for the treatment of adult patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis (Ps) who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. RENFLEXIS should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician [see Boxed Warning, Warnings and Precautions (5)] . The use of RENFLEXIS at doses >5 mg/kg is contraindicated in patients with moderate or severe heart failure [see Warnings and Precautions (5.5) and Adverse Reactions (6.1)] . RENFLEXIS is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab products or any of the inactive ingredients of RENFLEXIS or any murine proteins [severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness] [see Warnings and Precautions (5.7) and Adverse Reactions (6.1)] . Risk Summary Available observational studies in pregnant women exposed to infliximab products showed no increased risk of major malformations among live births as compared to those exposed to non-biologics. However, findings on other birth and maternal outcomes were not consistent across studies of different study design and conduct [see Data] . Monoclonal antibodies such as infliximab products are transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant [see Clinical Considerations] . Because infliximab products do not cross-react with TNFα in species other than humans and chimpanzees, animal reproduction studies have not been conducted with infliximab products. In a developmental study conducted in mice using an analogous antibody, no evidence of maternal toxicity or fetal harm was observed [see Data] . All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Published data suggest that there is an increased risk of adverse pregnancy outcomes in women with inflammatory bowel disease or rheumatoid arthritis associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2.5 kg) and small for gestational age at birth. Fetal/Neonatal adverse reactions As with other IgG antibodies, infliximab products cross the placenta. Infliximab products have been detected in the serum of infants up to 6 months following birth. Consequently, these infants may be at increased risk of infection, including disseminated infection which can become fatal. At least a six month waiting period following birth is recommended before the administration of live vaccines (e.g., BCG vaccine or other live vaccines, such as the rotavirus vaccine) to these infants [see Warnings and Precautions (5.13)] . Cases of agranulocytosis in infants exposed in utero have also been reported [see Adverse Reactions (6.2)] . Data Human Data Two prospective cohort studies were conducted assessing birth outcomes as well as the health status of infants up to the age of one year in women exposed to infliximab compared to non-biologic comparators including methotrexate, azathioprine, 6-mercaptopurine and systemic corticosteroids used for the treatment of similar diseases. The first study was conducted in an IBD pregnancy registry in the United States and assessed pregnancy outcomes in 294 women with inflammatory bowel disease exposed to infliximab during pregnancy compared with 515 women on a non-biologic treatment. Infliximab exposure was not associated with increased rates of major congenital malformations, miscarriage/stillbirth, infants of low birth weight, small for gestational age, or infection in the first year of life. The second study among IBD and non-IBD patients in Sweden, Finland, and Denmark compared 97, 7, and 166 women exposed to infliximab to 2,693, 2,499 and 1,268 women on non-biologic systemic therapy, respectively. In this study, comparing pooled data across the three countries, exposure to infliximab was not associated with increased rates of congenital anomalies or infant death. Infliximab in combination with immunosuppressants (mainly systemic corticosteroids and azathioprine) was associated with increased rates of preterm birth, small for gestational age, low birth weight, and infant hospitalization for infection compared with non-biologic systemic treatment. Although the study did not show any associations with infliximab monotherapy, the analyses could have been underpowered to detect an association. There were additional methodological limitations with these studies that may account for the study findings in both studies: the concomitant use of other medications or treatments was not controlled and disease severity was not assessed; in the U.S. study, patient reported outcomes were collected without clinical validation. These methodological limitations hinder interpretation of the study results. Animal Data Because infliximab products do not cross-react with TNFα in species other than humans and chimpanzees, animal reproduction studies have not been conducted with infliximab products. An embryofetal development study was conducted in pregnant mice using cV1q anti-mouse TNFα, an analogous antibody that selectively inhibits the functional activity of mouse TNFα. This antibody administered in mice, during the period of organogenesis on gestation days (GDs) 6 and 12, at IV doses up to 40 mg/kg produced no evidence of maternal toxicity, fetal mortality, or structural abnormalities. Doses of 10 to 15 mg/kg in pharmacodynamic animal models with the anti-TNF analogous antibody produced maximal pharmacologic effectiveness. Analyses of fetal samples on GD 14 indicated placental transfer of the antibody and exposure of the fetuses during organogenesis. In a peri- and post-natal development study in mice, no maternal toxicity or adverse developmental effects in offspring were observed when dams were administered IV doses of 10 or 40 mg/kg of the analogous antibody on GDs 6, 12 and 18 and lactation days 3, 9 and 15. Risk Summary Published literature show that infliximab is present at low levels in human milk. Systemic exposure in a breastfed infant is expected to be low because infliximab products are largely degraded in the gastrointestinal tract. A U.S. multi-center study of 168 women treated with infliximab for inflammatory bowel disease (breast milk samples obtained, n=29) showed that infants exposed to infliximab through breast milk had no increase in rates of infections and developed normally. There are no data on the effects of infliximab products on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for RENFLEXIS and any potential adverse effects on the breastfed child from RENFLEXIS or from the underlying maternal condition. The safety and effectiveness of RENFLEXIS have been established in pediatric patients 6 to 17 years of age for induction and maintenance treatment of CD and UC [see Dosage and Administration (2.2, 2.4) and Adverse Reactions (6.1)] . However, the safety and effectiveness of RENFLEXIS in pediatric patients <6 years of age with CD or UC have not been established. The safety and effectiveness of RENFLEXIS in the treatment of pediatric patients with Ps and juvenile rheumatoid arthritis (JRA) have not been established. Pediatric Crohn's Disease The safety and effectiveness of RENFLEXIS have been established 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 CD who have had an inadequate response to conventional therapy. The use of RENFLEXIS for this indication is supported by RENFLEXIS's approval as a biosimilar to infliximab and evidence from a randomized, open-label pediatric CD study of infliximab in 112 pediatric patients aged 6 years and older [see Clinical Studies (14.2)] . Infliximab has been studied only in combination with conventional immunosuppressive therapy in pediatric CD. The longer term (greater than 1 year) safety and effectiveness of infliximab products in pediatric CD patients have not been established in clinical trials. Postmarketing cases of HSTCL have been reported in pediatric patients treated with TNF blockers including infliximab products. Due to the risk of HSTCL, a careful risk-benefit assessment should be made when RENFLEXIS is used in combination with other immunosuppressants in pediatric CD patients [see Boxed Warning, Warnings and Precautions (5.2)] . Pediatric Ulcerative Colitis The safety and effectiveness of RENFLEXIS for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients aged 6 years and older with moderately to severely active UC who have had an inadequate response to conventional therapy have been established. The use of RENFLEXIS for this indication is supported by RENFLEXIS's approval as a biosimilar to infliximab and evidence from adequate and well-controlled studies of infliximab in adults with additional safety and pharmacokinetic data from an open-label pediatric UC study in 60 pediatric patients aged 6 years and older [see Dosage and Administration (2.4), Adverse Reactions (6.1), and Clinical Studies (14.4)] . The effectiveness of infliximab in inducing and maintaining mucosal healing in pediatric UC was not established. Although 41 patients had a Mayo endoscopy subscore of 0 or 1 at the Week 8 endoscopy, the induction phase was open-label and lacked a control group. Only 9 patients had an optional endoscopy at Week 54. Approximately half of the patients were on concomitant immunomodulators (AZA, 6-MP, MTX) at study start. Due to the risk of HSTCL, a careful risk-benefit assessment should be made when RENFLEXIS is used in combination with other immunosuppressants in pediatric UC patients [see Boxed Warning and Warnings and Precautions (5.2)]. The longer term (greater than 1 year) safety and effectiveness of infliximab products in pediatric UC patients have not been established in clinical trials. Juvenile Rheumatoid Arthritis (JRA) The safety and effectiveness of RENFLEXIS in the treatment of pediatric patients with juvenile rheumatoid arthritis (JRA) have not been established. The safety and efficacy of RENFLEXIS in patients with JRA is based on RENFLEXIS's approval as a biosimilar to infliximab and evaluation of infliximab in a multicenter, randomized, placebo-controlled, double-blind study for 14 weeks, followed by a double-blind, all-active treatment extension, for a maximum of 44 weeks. Patients with active JRA between the ages of 4 and 17 years who had been treated with MTX for at least 3 months were enrolled. Concurrent use of folic acid, oral corticosteroids (≤ 0.2 mg/kg/day of prednisone or equivalent), NSAIDs, and/or disease modifying antirheumatic drugs (DMARDs) was permitted. Doses of 3 mg/kg infliximab or placebo were administered intravenously at Weeks 0, 2 and 6. Patients randomized to placebo crossed-over to receive 6 mg/kg infliximab at Weeks 14, 16, and 20, and then every 8 weeks through Week 44. Patients who completed the study continued to receive open-label treatment with infliximab for up to 2 years in a companion extension study. The study failed to establish the efficacy of infliximab in the treatment of JRA. Key observations in the study included a high placebo response rate and a higher rate of immunogenicity than what has been observed in adults. Additionally, a higher rate of clearance of infliximab was observed than had been observed in adults. Population pharmacokinetic analysis showed that in pediatric patients with JRA with a body weight of up to 35 kg receiving 6 mg/kg infliximab and pediatric patients with JRA with body weight greater than 35 kg up to adult body weight receiving 3 mg/kg infliximab, the steady state area under the concentration curve (AUCss ) was similar to that observed in adults receiving 3 mg/kg of infliximab. A total of 60 patients with JRA were treated with doses of 3 mg/kg and 57 patients were treated with doses of 6 mg/kg. The proportion of patients with infusion reactions who received 3 mg/kg infliximab was 35% (21/60) over 52 weeks compared with 18% (10/57) in patients who received 6 mg/kg over 38 weeks. The most common infusion reactions reported were vomiting, fever, headache, and hypotension. In the 3 mg/kg infliximab group, 4 patients had a serious infusion reaction and 3 patients reported a possible anaphylactic reaction (2 of which were among the serious infusion reactions). In the 6 mg/kg infliximab group, 2 patients had a serious infusion reaction, 1 of whom had a possible anaphylactic reaction. Two of the 6 patients who experienced serious infusion reactions received infliximab by rapid infusion (duration of less than 2 hours). Antibodies to infliximab developed in 38% (20/53) of patients who received 3 mg/kg infliximab compared with 12% (6/49) of patients who received 6 mg/kg. A total of 68% (41/60) of patients who received 3 mg/kg infliximab in combination with MTX experienced an infection over 52 weeks compared with 65% (37/57) of patients who received 6 mg/kg infliximab in combination with MTX over 38 weeks. The most commonly reported infections were upper respiratory tract infection and pharyngitis, and the most commonly reported serious infection was pneumonia. Other notable infections included primary varicella infection in 1 patient and herpes zoster in 1 patient. Of the total number of infliximab-treated patients in RA and Ps clinical studies, 256 (9.6%) were 65 years old and over, while 17 (0.6%) were 75 years old and over. In these trials, no overall differences in safety or effectiveness were observed between geriatric patients (patients ≥ 65 years old) and younger adult patients (patients 18 to 65 years old). However, the incidence of serious adverse reactions in geriatric patients was higher in both infliximab and control groups compared to younger adult patients. Of the total number of infliximab-treated patients in CD, UC, AS, and PsA clinical studies, 76 (3.2%) were 65 years old and over, while 9 (0.4%) were 75 years old and over. In the CD, UC, AS, and PsA studies, there were insufficient numbers of geriatric patients to determine whether they respond differently from younger adults. The incidence of serious infections in infliximab-treated geriatric patients was greater than in infliximab-treated younger adult patients; therefore close monitoring of geriatric patients for the development of serious infections is recommended [see Warnings and Precautions (5.1), and Adverse Reactions (6.1)] .

Product summary:

How Supplied Each RENFLEXIS® (infliximab-abda) for injection is supplied as one single-dose vial individually packaged in a carton (NDC 78206-162-01). Each single-dose vial contains 100 mg of infliximab-abda as a sterile, preservative-free, white lyophilized powder for reconstitution and dilution (more than one vial may be needed for a full dose) [see Dosage and Administration (2.11)] . Storage and Handling Store unopened RENFLEXIS® vials in a refrigerator at 2°C to 8°C (36°F to 46°F). If needed, unopened RENFLEXIS vials may be stored at room temperatures up to a maximum of 30°C (86°F) for a single period of up to 6 months but not exceeding the original expiration date. Once removed from the refrigerator, RENFLEXIS cannot be returned to the refrigerator. For storage conditions of the reconstituted and diluted product for administration, see Dosage and Administration (2.11) .

Authorization status:

Biologic Licensing Application

Patient Information leaflet

Organon LLC
----------
MEDICATION GUIDE
RENFLEXIS® (REN-FLEK-SIS) (INFLIXIMAB-ABDA)
FOR INJECTION, FOR INTRAVENOUS USE
This Medication Guide has been approved by the U.S. Food and Drug
Administration.
Revised: December 2023
Read the Medication Guide that comes with RENFLEXIS before you receive
the first treatment, and
before each time you get a treatment of RENFLEXIS. This Medication
Guide does not take the place of
talking with your doctor about your medical condition or treatment.
What is the most important information I should know about RENFLEXIS?
RENFLEXIS may cause serious side effects, including:
1. Risk of infection
RENFLEXIS is a medicine that affects your immune system. RENFLEXIS can
lower the ability of your
immune system to fight infections. Serious infections have happened in
patients receiving RENFLEXIS.
These infections include tuberculosis (TB) and infections caused by
viruses, fungi or bacteria that have
spread throughout the body. Some patients have died from these
infections.
•
Your doctor should test you for TB before starting RENFLEXIS.
•
Your doctor should monitor you closely for signs and symptoms of TB
during treatment with
RENFLEXIS.
Before starting RENFLEXIS, tell your doctor if you:
•
think you have an infection. You should not start receiving RENFLEXIS
if you have any kind of
infection.
•
are being treated for an infection.
•
have signs of an infection, such as a fever, cough, flu-like symptoms.
•
have any open cuts or sores on your body.
•
get a lot of infections or have infections that keep coming back.
•
have diabetes or an immune system problem. People with these
conditions have a higher chance
for infections.
•
have TB, or have been in close contact with someone with TB.
•
live or have lived in certain parts of the country (such as the Ohio
and Mississippi River valleys)
where there is an increased risk for getting certain kinds of fungal
infections (histoplasmosis,
coccidioidomycosis, or blastomycosis). These infections may develop or
become more severe if
yo

Summary of Product characteristics

RENFLEXIS- INFLIXIMAB INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
ORGANON LLC
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
RENFLEXIS SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR RENFLEXIS.
RENFLEXIS (INFLIXIMAB-ABDA) FOR INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2017
RENFLEXIS (INFLIXIMAB-ABDA) IS BIOSIMILAR TO REMICADE (INFLIXIMAB).
WARNING: SERIOUS INFECTIONS AND MALIGNANCY
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
INCREASED RISK OF SERIOUS INFECTIONS LEADING TO HOSPITALIZATION OR
DEATH, INCLUDING
TUBERCULOSIS (TB), BACTERIAL SEPSIS, INVASIVE FUNGAL INFECTIONS (SUCH
AS
HISTOPLASMOSIS) AND INFECTIONS DUE TO OTHER OPPORTUNISTIC PATHOGENS.
(5.1)
DISCONTINUE RENFLEXIS IF A PATIENT DEVELOPS A SERIOUS INFECTION.
PERFORM TEST FOR LATENT TB; IF POSITIVE, START TREATMENT FOR TB PRIOR
TO STARTING
RENFLEXIS. MONITOR ALL PATIENTS FOR ACTIVE TB DURING TREATMENT, EVEN
IF INITIAL LATENT
TB TEST IS NEGATIVE. (5.1)
LYMPHOMA AND OTHER MALIGNANCIES, SOME FATAL, HAVE BEEN REPORTED IN
CHILDREN AND
ADOLESCENT PATIENTS TREATED WITH TUMOR NECROSIS FACTOR (TNF) BLOCKERS,
INCLUDING
INFLIXIMAB PRODUCTS. (5.2)
POSTMARKETING CASES OF FATAL HEPATOSPLENIC T-CELL LYMPHOMA (HSTCL)
HAVE BEEN
REPORTED IN PATIENTS TREATED WITH TNF BLOCKERS INCLUDING INFLIXIMAB
PRODUCTS. ALMOST
ALL HAD RECEIVED AZATHIOPRINE OR 6- MERCAPTOPURINE CONCOMITANTLY WITH
A TNF BLOCKER
AT OR PRIOR TO DIAGNOSIS. THE MAJORITY OF CASES WERE REPORTED IN
PATIENTS WITH CROHN'S
DISEASE OR ULCERATIVE COLITIS, MOST OF WHOM WERE ADOLESCENT OR YOUNG
ADULT MALES.
(5.2)
RECENT MAJOR CHANGES
Dosage and Administration (2.11)
12/2023
Contraindications (4)
12/2023
Warnings and Precautions: Heart Failure (5.5)
12/2023
Warnings and Precautions: Vaccinations and Use of Live Vaccines/
Therapeutic
Infectious Agents (5.13)
12/2023
INDICATIONS AND USAGE
RENFLEXIS is a tumor necrosis factor (TNF) blocker indicated for:
_Crohn's Disease:_
reducing signs and symptoms and inducing a