Infliximab-Abda

Introduction Overview

Generic Name

infliximab-abda

Brand Name

Renflexis

Dosage Form

Intravenous (infusion) injection

Drug Class

Tumor Necrosis Factor (TNF) alfa inhibitors

Pharmacokinetics

Absorption:
Renflexis (infliximab-abda) is administered exclusively via intravenous infusion, bypassing the gastrointestinal tract and thus eliminating variability in absorption associated with oral administration. Following intravenous infusion, infliximab achieves immediate systemic bioavailability, with peak plasma concentrations occurring at the end of infusion. The infusions are typically delivered over approximately 2 hours to optimize tolerability and pharmacodynamic effect. Since Renflexis is a monoclonal antibody, traditional absorption parameters such as bioavailability and peak plasma concentration after oral dosing do not apply.

Distribution:
Once in systemic circulation, infliximab demonstrates a moderately large volume of distribution approximating plasma and extracellular fluid volumes, estimated at 3.5 to 6 L. The drug binds specifically to soluble and transmembrane tumor necrosis factor-alpha (TNF-α) molecules, forming stable complexes that may remain in circulation. Infliximab is an IgG1 monoclonal antibody and therefore exhibits limited tissue penetration beyond the vascular and interstitial spaces. The binding affinity for TNF-α is high, which facilitates rapid neutralization of this pro-inflammatory cytokine. The drug does not significantly cross the blood-brain barrier.

Metabolism:
Renflexis, like other monoclonal antibodies, is metabolized through proteolytic catabolism into small peptides and amino acids throughout the reticuloendothelial system and cellular lysosomes. It is degraded primarily by ubiquitous proteolytic enzymes rather than by cytochrome P450 enzymes typical for small molecules. Infliximab's metabolic clearance can be affected by the formation of anti-drug antibodies (ADAs), which may accelerate its clearance and reduce therapeutic efficacy. This immunogenicity is clinically relevant and may necessitate dose adjustments.

Elimination:
The elimination half-life of infliximab from Renflexis is approximately 8 to 10 days but can vary depending on patient factors including disease state, immunogenicity, and concurrent medications. Clearance occurs mainly through reticuloendothelial-mediated catabolism rather than renal or hepatic excretion. Because of its relatively long half-life, Renflexis is administered intermittently, with dosing intervals ranging from every 6 to 8 weeks depending on indication and clinical response. The drug is not eliminated via urine or feces in measurable amounts. Accumulation is minimal after repeated dosing, as steady-state concentrations are reached after approximately 3 dosing cycles.

Dosage Forms

Available Dosage Forms:
Renflexis is supplied as a sterile injectable solution for intravenous infusion. Specifically, it is available as a single-dose vial containing 100 mg of infliximab-abda. The formulation is preservative-free and contains inactive ingredients such as dibasic sodium phosphate heptahydrate, monobasic sodium phosphate monohydrate, polysorbate 80, and sucrose.

Dosages for Adults and Adolescents:
- Crohn’s Disease (Adults): 5 mg/kg at weeks 0, 2, and 6, then every 8 weeks. Dose escalation to 10 mg/kg may be considered for loss of response.
- Crohn’s Disease (Pediatric, ≥6 years): 5 mg/kg at weeks 0, 2, and 6, then every 8 weeks.
- Ulcerative Colitis (Adults and Pediatric ≥6 years): 5 mg/kg at weeks 0, 2, and 6, then every 8 weeks.
- Rheumatoid Arthritis (Adults, in combination with methotrexate): 3 mg/kg at weeks 0, 2, and 6, then every 8 weeks; dose increase up to 10 mg/kg or more frequent dosing (every 4 weeks) may be required.
- Ankylosing Spondylitis (Adults): 5 mg/kg at weeks 0, 2, and 6, then every 6 weeks.
- Psoriatic Arthritis and Plaque Psoriasis (Adults): 5 mg/kg at weeks 0, 2, and 6, then every 8 weeks.

Specific Patient Populations:
Dose adjustments may be necessary in patients with reduced response or increased immunogenicity. Pediatric dosing aligns with adult doses on a mg/kg basis starting from age 6. There are no established dosage adjustments for renal or hepatic impairment due to monoclonal antibody metabolism by proteolysis rather than organ clearance.

Administration Notes:
Renflexis is administered by intravenous infusion over a minimum period of 2 hours. Pre-infusion medications (e.g., antihistamines, corticosteroids) may be used to reduce infusion-related reactions. Infusion rate adjustments or interruption may be needed in case of adverse reactions. The drug should only be administered by healthcare professionals in settings equipped to manage potential severe hypersensitivity reactions.

Mechanism Of Action

Renflexis (infliximab-abda) is a chimeric monoclonal antibody that specifically binds to tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine involved in the pathogenesis of various autoimmune and inflammatory diseases. By selectively targeting and binding both soluble and transmembrane forms of TNF-α, Renflexis prevents TNF-α from interacting with its cellular receptors (TNFR1 and TNFR2). This inhibits the downstream activation of pro-inflammatory signaling pathways that would normally lead to the expression of multiple inflammatory mediators.

At the cellular level, inhibition of TNF-α by Renflexis disrupts the cytokine cascade responsible for maintaining chronic inflammation, tissue destruction, and immune cell recruitment. It downregulates the activation of NF-κB, a transcription factor pivotal in upregulating inflammatory gene expression. This results in diminished infiltration of inflammatory cells, reduced expression of adhesion molecules, decreased production of other pro-inflammatory cytokines such as interleukins and interferons, and normalization of cartilage and bone remodeling processes.

Biochemically, infliximab can induce apoptosis of activated T lymphocytes and monocytes expressing membrane-bound TNF-α through complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity. This cellular depletion contributes to its anti-inflammatory and immunomodulatory effects.

Clinically, these molecular actions translate into mitigation of symptoms and progression in diseases such as rheumatoid arthritis, Crohn’s disease, ulcerative colitis, psoriasis, psoriatic arthritis, and ankylosing spondylitis. The biosimilar Renflexis shares this mechanism of action identically with the reference product Remicade, consistently neutralizing pathologic TNF-α activity and reducing inflammation. Comparative studies have demonstrated similar pharmacodynamic profiles and clinical efficacy, confirming that Renflexis effectively modulates TNF-α-mediated pathological processes the same way as infliximab originators. This mechanism underlies the therapeutic benefits as well as the risks such as immunosuppression, infection susceptibility, and potential malignancy linked to TNF blockade.

Pharmacological Actions

Monoclonal antibody targeting tumor necrosis factor-alpha (TNF-α) to inhibit its inflammatory activity.
Neutralizes both soluble and transmembrane forms of TNF-α, preventing receptor binding.
Suppresses the inflammatory cytokine cascade and downregulates NF-κB mediated gene expression.
Induces apoptosis of activated immune cells expressing membrane-bound TNF-α.
Reduces recruitment and activation of inflammatory cells within affected tissues.
Modulates immune response in autoimmune diseases, reducing tissue damage.
Exerts immunosuppressive effects, increasing susceptibility to infections.
Equivalent pharmacodynamic profile to originator infliximab, ensuring biosimilar efficacy.
Decreases expression of adhesion molecules, limiting leukocyte migration.
Ameliorates symptoms of inflammatory joint, skin, and gastrointestinal disorders.
Restores normal cartilage and bone remodeling processes in rheumatoid arthritis.
Interferes with granuloma formation and pathogen containment due to TNF-α blockade.
May impact immune surveillance leading to increased malignancy risk.
Potentially modulates B-cell and T-cell mediated autoimmune mechanisms.
Exerts dose-dependent effects correlating with clinical response.

Therapeutic Or Clinical Uses

Treatment of moderately to severely active rheumatoid arthritis in adults, in combination with methotrexate.
Management of Crohn’s disease in adults and pediatric patients aged 6 years and older with inadequate response to conventional therapy.
Treatment of moderately to severely active ulcerative colitis in adults and children aged 6 years and older.
Therapy for ankylosing spondylitis to reduce spinal inflammation and symptoms.
Management of psoriatic arthritis to decrease joint inflammation and prevent structural damage.
Treatment of chronic, severe, extensive, and/or disabling plaque psoriasis in adult patients.
Used in patients who have failed or are intolerant to other standard therapies for above conditions.
Off-label use in other autoimmune inflammatory conditions as determined by clinician judgment.
Reduction of signs and symptoms and inhibition of structural damage progression in rheumatoid arthritis.
Induction and maintenance of remission in inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis.
Used as part of combination therapy alongside immunomodulators or corticosteroids in certain cases.
Treatment option for patients with refractory psoriatic and spondyloarthropathies.
Therapeutic alternative offering cost savings as a biosimilar compared to original biologics.
Applicable in both adult and pediatric populations with specific dosing adjustments.
Used to modulate excessive immune activity by neutralizing a key inflammatory cytokine.

Side Or Adverse Effects

Serious infections including tuberculosis, bacterial, viral, and fungal infections due to immunosuppression.
Infusion-related reactions such as fever, chills, flushing, chest pain, rash, hives, and hypotension or hypertension.
Increased risk of developing lymphoma and other malignancies including skin cancers.
Exacerbation or new onset of congestive heart failure; may worsen pre-existing heart conditions.
Hepatotoxicity presenting as jaundice, elevated liver enzymes, and liver failure in rare cases.
Hematologic abnormalities including pancytopenia, leukopenia, anemia, and thrombocytopenia.
Nervous system disorders such as demyelinating disease, seizures, numbness, tingling, and stroke.
Development of lupus-like syndrome with symptoms including rash, joint pain, and chest discomfort.
Worsening or new onset of psoriasis during therapy.
Allergic and delayed hypersensitivity reactions including serum sickness-like syndrome.
Injection or infusion site reactions with redness, swelling, or pain.
Gastrointestinal symptoms such as abdominal pain and potential development of fistulas or abscesses.
Potential reactivation of hepatitis B virus infection, leading to severe liver complications.
Fatigue, headache, and respiratory tract infections as common mild adverse effects.
Bone fractures and other musculoskeletal complaints reported in pediatric Crohn’s disease patients.

Precautions

Perform screening for latent tuberculosis and active infections prior to initiating therapy.
Monitor patients closely for development of infections during and after treatment.
Evaluate for history of chronic or recurrent infections before prescribing Renflexis.
Assess and monitor heart failure patients carefully; discontinue drug if symptoms worsen.
Screen for hepatitis B virus; monitor during treatment to detect viral reactivation.
Avoid concurrent use with other biologic immunomodulators such as anakinra, abatacept, or tocilizumab.
Be cautious in patients with pre-existing demyelinating diseases of the central nervous system.
Consider regular skin examinations given the increased risk of skin cancers.
Use caution and monitor patients with a history of malignancy, especially lymphoma or cervical cancer.
Advise patients on signs and symptoms of infection and instruct prompt reporting.
Vaccination status should be updated prior to therapy; live vaccines are contraindicated during treatment.
In pregnancy, weigh benefits against potential risks; infants exposed in utero may have immunosuppression.
Do not administer live vaccines to infants exposed to Renflexis in utero for at least 6 months post-birth.
Observe for infusion-related reactions and be prepared to manage anaphylaxis or other severe reactions.
Dose adjustments or discontinuation may be needed in case of severe adverse effects or loss of response.

Warnings

Serious and sometimes fatal infections including tuberculosis and opportunistic infections have occurred.
Potential development of malignancies, notably lymphoma and rare hepatosplenic T-cell lymphoma in young males.
Reports of worsening or new onset congestive heart failure; caution in patients with cardiac disease.
Risk of severe allergic or hypersensitivity reactions during or shortly after infusion.
Hepatitis B virus reactivation with possible fatal outcomes.
Possible induction of autoimmune phenomena such as lupus-like syndrome.
Neurologic events including multiple sclerosis-like demyelinating disorders and seizures.
Increased incidence of serious infections in elderly patients aged 65 and older.
Delayed hypersensitivity reactions may occur 3 to 12 days post-infusion.
Avoid live vaccines during treatment and certain periods post-exposure due to immunosuppression.
Monitor closely for signs of new or worsening psoriasis induced by infliximab products.
Not recommended to be used concomitantly with other TNF blockers or biologics targeting same pathway.
Use during pregnancy only if clearly needed; potential risk to the fetus due to immunosuppression.
Infusion reactions requiring interruption, slowing, or discontinuation of infusion have been observed.
There is a risk of serious cytopenias; monitor blood counts regularly during therapy.

Contraindication

Known hypersensitivity to infliximab, Renflexis, or any of its excipients.
Patients with active, severe infections including sepsis, tuberculosis, or opportunistic infections.
Concurrent treatment with other biologic immunomodulators such as anakinra (Kineret), abatacept (Orencia), or tocilizumab (Actemra).
Moderate to severe heart failure (New York Heart Association class III/IV) unless carefully assessed and monitored.
Known hypersensitivity reactions including anaphylaxis to infliximab products.
Use of live vaccines during treatment with Renflexis and for some time after discontinuation.
Severe hepatic impairment or liver failure without close medical supervision.
Pregnancy when the drug is not clearly indicated and benefits do not outweigh potential risks.
Patients with history of demyelinating conditions unless benefits outweigh risks and under close monitoring.
Pre-existing or active malignancies where TNF blockade could worsen prognosis unless otherwise advised.
Patients with uncontrolled or severe hematologic abnormalities prior to initiation.
Inability to comply with screening and monitoring requirements for infection and malignancy risks.
Current or recent infections requiring systemic antimicrobial treatment until resolution.
Patients with known sensitivity to murine proteins as infliximab is a chimeric antibody with murine component.
Use in combination with other TNF-α inhibitors due to increased risk of adverse events.

Drug Interactions

Concomitant use with other biologic agents such as anakinra, abatacept, or tocilizumab increases risk of serious infections and is not recommended.
Immunosuppressive agents like methotrexate may modulate immunogenicity and pharmacokinetics of infliximab.
Vaccines: Live vaccines are contraindicated during and following treatment due to immunosuppression.
Concomitant use with corticosteroids can increase infection risk but may be necessary in some clinical scenarios.
No significant interaction with cytochrome P450 metabolized drugs as infliximab is catabolized proteolytically.
Potential interaction with drugs affecting immune system function which may alter infection risk.
Use with caution when combined with other disease-modifying antirheumatic drugs (DMARDs) to avoid overlapping toxicities.
No direct pharmacokinetic interference with oral medications, but systemic immunosuppression may alter drug response.
Significant interaction not reported with anticoagulants, but cautious monitoring advised as infections can affect coagulation.
Affected by immunogenicity: Development of anti-drug antibodies may reduce efficacy and interact with immunosuppressants.
Potential interactions with antibiotics and antifungals due to increased risk of infection need clinical monitoring.
Live viral vaccines should be avoided in patients receiving Renflexis and immunocompromised contacts.
No reports of direct interactions with herbal supplements, though these may affect immune function indirectly.
Combination with other TNF blockers significantly increases adverse events; such regimens are contraindicated.
Consideration for timing and management when switching between biosimilars or originator infliximab products.

Preparations Of The Drug

Renflexis is supplied as a sterile, preservative-free, clear to slightly opalescent, colorless to pale yellow solution for intravenous infusion.
Available in single-dose vials containing 100 mg of infliximab-abda per vial.
Formulation includes inactive components: dibasic sodium phosphate heptahydrate, monobasic sodium phosphate monohydrate, polysorbate 80, and sucrose.
The product requires reconstitution and dilution before intravenous administration according to protocols.
Stored refrigerated between 2ºC to 8ºC (36ºF to 46ºF); may be stored at room temperature up to 30ºC (86ºF) for a single period not exceeding 6 months but must not exceed original expiration date.
Once removed from refrigeration, Renflexis should not be returned to the refrigerator.
Must be administered by intravenous infusion over approximately 2 hours by healthcare professionals.
Prefilled syringes and autoinjector forms are not available for Renflexis; only intravenous infusion format is approved.
Packaging designed for single use; discard any unused portion to avoid contamination.
Manufactured by Samsung Bioepis Co., Ltd., Incheon, Republic of Korea.
No preservatives are present in the formulation, necessitating aseptic handling.
Accompanying the product is a prescribing information sheet outlining preparation and administration guidelines.
Compatible infusion fluids include sterile 0.9% sodium chloride injection or 5% dextrose injection for dilution.
Avoid shaking the vial to prevent denaturation; gently invert to mix if necessary.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.