Infliximab-Dyyb

Introduction Overview

Generic Name

infliximab-dyyb

Brand Name

Inflectra

Dosage Form

intravenous (infusion) injection

Drug Class

TNF alfa inhibitors

Pharmacokinetics

Absorption:
Infliximab-dyyb, administered as an intravenous infusion, bypasses the traditional absorption process associated with oral or subcutaneous drugs, resulting in 100% bioavailability immediately upon infusion. Because it is a large monoclonal antibody protein, it is not absorbed via the gastrointestinal tract and must be delivered directly into the systemic circulation. Upon intravenous administration over approximately 2 hours, peak plasma concentrations are typically achieved at the end of the infusion, ensuring rapid onset of action.

Distribution:
Following intravenous infusion, infliximab-dyyb distributes primarily within the vascular and interstitial fluid compartments. Given its large molecular size (~149 kDa), tissue penetration is limited predominantly to extracellular spaces and sites of inflammation, where the target antigen TNF-alpha is expressed. Infliximab exhibits a steady-state volume of distribution approximating the plasma volume, typically around 3.2 to 6.4 liters, reflecting limited extravascular distribution. Binding is highly specific for soluble and transmembrane TNF-alpha molecules, which are abundant in inflamed tissues of autoimmune diseases. This targeted distribution aids the drug’s ability to reduce inflammatory activity.

Metabolism:
As a chimeric monoclonal antibody, infliximab-dyyb undergoes proteolytic degradation via reticuloendothelial and cellular pathways rather than hepatic metabolism. It is catabolized by proteases into small peptides and amino acids, which are then reutilized or eliminated. Unlike small molecule drugs, cytochrome P450 enzymes are not involved in its metabolism, minimizing the risk of metabolic drug interactions. The presence of anti-drug antibodies may enhance clearance by promoting immunogenicity, potentially reducing drug levels and efficacy.

Elimination:
Infliximab-dyyb is eliminated primarily through reticuloendothelial-mediated degradation pathways. The mean terminal elimination half-life is approximately 7 to 12 days, with variability influenced by individual patient factors and development of anti-infliximab antibodies. Clearance rates are impacted by dose, disease activity, and individual immune responses. Because excretion via renal or hepatic pathways is negligible, renal or hepatic impairment typically does not necessitate dosage adjustment. The infusion schedule is generally based on maintaining therapeutic drug levels consistent with disease control, with infusions spaced every 6 to 8 weeks after induction.

Dosage Forms

Available Dosage Forms:
Inflectra is formulated exclusively as an intravenous infusion injection supplied as a single-dose vial containing 100 mg of infliximab-dyyb powder for reconstitution. No oral, subcutaneous, or other dosage forms are available for this drug. The drug must be reconstituted and diluted prior to administration by a healthcare professional.

Dosages for Adults and Adolescents:
- Crohn’s Disease (Adults and ≥6 years): 5 mg/kg intravenous infusion at weeks 0, 2, and 6, followed by maintenance infusions every 8 weeks. Dose escalation to 10 mg/kg may be considered in case of loss of response.
- Ulcerative Colitis (Adults and ≥6 years): Same dosing regimen as Crohn’s disease.
- Rheumatoid Arthritis (Adults): In combination with methotrexate, initial dose of 3 mg/kg intravenous infusion at weeks 0, 2, and 6, then every 8 weeks. Some patients may require doses up to 10 mg/kg or more frequent dosing (every 4 weeks).
- Ankylosing Spondylitis (Adults): 5 mg/kg intravenous infusion at weeks 0, 2, and 6, then every 6 weeks.
- Psoriatic Arthritis and Plaque Psoriasis (Adults): 5 mg/kg intravenous infusion at weeks 0, 2, and 6, then every 8 weeks.

Specific Patient Populations:
- Pediatric Patients: Approved for Crohn’s disease and ulcerative colitis in children aged 6 years and older, with dosing similar to adults (5 mg/kg induction and maintenance).
- No dosing data or established safety for children under 6 years.
- Dose adjustments may be necessary for patients losing therapeutic response or with elevated disease activity.
- Infusions should be administered under close medical supervision, with premedication considered to reduce infusion-related adverse events.
- No dosage adjustments based on renal or hepatic function due to proteolytic elimination.

Mechanism Of Action

Infliximab-dyyb exerts its therapeutic effects primarily through targeted inhibition of tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine implicated in the pathogenesis of multiple autoimmune and inflammatory diseases. TNF-alpha is produced mainly by activated macrophages and T-lymphocytes and plays a central role in regulating immune cells, inducing fever, apoptosis, and the synthesis of other inflammatory mediators.

At the molecular level, infliximab-dyyb is a chimeric IgG1 monoclonal antibody that specifically binds with high affinity to both soluble and transmembrane forms of TNF-alpha. By binding TNF-alpha, it prevents the cytokine from interacting with TNF receptors (TNFR1 and TNFR2) on cell surfaces, thereby blocking the downstream signaling pathways that would otherwise lead to expression of adhesion molecules, secretion of other inflammatory cytokines (such as IL-1 and IL-6), and recruitment of inflammatory cells.

This inhibition subsequently reduces inflammatory responses in tissues affected by diseases such as rheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. Furthermore, binding to membrane TNF-alpha can induce apoptosis of activated T cells and macrophages, contributing to immunomodulation and resolution of chronic inflammation.

Comparatively, infliximab-dyyb shares its mechanism with its reference biologic, Remicade (infliximab), and other biosimilars, offering similar clinical efficacy. Research and clinical trials have demonstrated that this mechanism effectively attenuates inflammatory cascades, improving symptoms and halting disease progression. The biosimilar status of infliximab-dyyb ensures no clinically meaningful differences in potency, efficacy, or safety relative to the original infliximab, facilitating broader access to therapy.

Pharmacological Actions

Selective binding and neutralization of tumor necrosis factor-alpha (TNF-alpha).
Inhibition of inflammatory cytokine cascade involved in autoimmune diseases.
Induction of apoptosis in activated T lymphocytes and macrophages expressing membrane-bound TNF-alpha.
Suppression of joint inflammation, swelling, and cartilage destruction in rheumatoid arthritis.
Reduction of intestinal inflammation in Crohn’s disease and ulcerative colitis.
Modulation of immune response leading to decreased activation and recruitment of immune cells.
Improvement of skin lesions in plaque psoriasis through immune regulation.
Decreased vascular adhesion molecule expression, reducing leukocyte migration.
Interference with granuloma formation, impacting infections such as tuberculosis.
Immunogenic modulation with potential formation of anti-drug antibodies.
Long elimination half-life allowing maintenance dosing every 6 to 8 weeks.
Minimal interaction with cytochrome P450 enzymes due to protein nature.
Potential immunosuppressive effects increasing susceptibility to infections.
May degrade binding TNF-alpha complexes and mediate antibody-dependent cell cytotoxicity.
Exerts therapeutic effects via intravenous administration with rapid systemic availability.

Therapeutic Or Clinical Uses

Treatment of moderately to severely active rheumatoid arthritis in adults, used concomitantly with methotrexate.
Management of Crohn’s disease in adults and children 6 years and older, especially for those not responding to other therapies.
Therapy for active ankylosing spondylitis in adults.
Treatment of psoriatic arthritis in adult patients.
Management of chronic, severe, and disabling plaque psoriasis in adults.
Indicated for moderately to severely active ulcerative colitis in adults and children aged 6 years and older.
Used to reduce signs and symptoms, inhibit progression of structural damage, and improve physical function in autoimmune diseases.
Option for patients intolerant or resistant to conventional therapies.
Appropriate for induction and maintenance therapy in inflammatory bowel diseases.
Utilized in combination regimens to enhance therapeutic efficacy in rheumatoid arthritis.
Employed in clinical settings requiring biologic agents blocking TNF-alpha mediated inflammation.
Part of biosimilar therapy providing cost-effective alternative to reference infliximab.
Approved for use in multiple autoimmune inflammatory conditions with demonstrated clinical benefit.
Provides immunomodulatory action to control chronic inflammatory disease activity.
Administered intravenously under medical supervision for targeted immunotherapy.

Side Or Adverse Effects

Increased risk of serious infections, including tuberculosis, bacterial, viral, and fungal infections due to immunosuppression.
Hypersensitivity reactions including anaphylaxis, infusion-related reactions such as fever, chills, rash, and chest pain.
Reactivation of latent hepatitis B virus leading to potentially fatal outcomes.
Potential induction or worsening of congestive heart failure symptoms.
Neurological adverse events including demyelinating disorders, seizures, numbness, and tingling.
Development of lupus-like syndrome characterized by rash, arthralgia, and serologic abnormalities.
Increased risk of malignancies including lymphoma, hepatosplenic T-cell lymphoma (especially in young males with inflammatory bowel disease), and skin cancers.
Hematologic abnormalities such as pancytopenia, leukopenia, and thrombocytopenia.
Hepatotoxicity manifested by liver enzyme elevations, jaundice, and right upper quadrant pain.
Psoriasis onset or exacerbation during treatment.
Common infusion reactions occurring during or within two hours post-infusion, including pruritus, hypotension or hypertension, and shortness of breath.
Respiratory infections such as sinusitis and upper respiratory tract infections.
Gastrointestinal complaints including abdominal pain and nausea.
Fatigue, headache, and flu-like symptoms.
Potential formation of anti-drug antibodies reducing efficacy and increasing adverse reactions.

Precautions

Perform careful screening for active or latent tuberculosis before initiating therapy.
Monitor closely for signs of infection throughout treatment and suspend therapy if serious infection develops.
Evaluate hepatitis B virus status prior to therapy and monitor periodically during treatment.
Assess patients for signs or history of congestive heart failure; use with caution and monitor symptomatology.
Avoid live vaccines during treatment and update immunizations prior to initiation.
Be vigilant for neurological symptoms suggestive of demyelinating disease or neuropathies.
Recognize and manage infusion-related and hypersensitivity reactions promptly.
Monitor complete blood counts regularly to detect hematologic abnormalities early.
Use caution in patients with pre-existing malignancies or increased cancer risk.
Consider risk-benefit in patients with chronic obstructive pulmonary disease due to increased cancer risk.
Inform females about potential risks for cervical cancer and screening during treatment.
Avoid concomitant administration with other biologic immunosuppressants such as Kineret, Orencia, or Actemra.
Pregnancy use only if clearly needed; inform infants about vaccination timing due to immunosuppression.
Ensure administration is performed by qualified healthcare professionals in appropriate clinical settings.

Warnings

May cause serious and sometimes fatal infections due to immunosuppression.
Potential reactivation of latent tuberculosis and hepatitis B virus.
Increased risk of malignancies, including lymphoma and rare hepatosplenic T-cell lymphoma.
Use in patients with heart failure requires caution; may exacerbate condition and necessitate discontinuation.
Risk of severe infusion reactions including anaphylaxis.
Possibility of neurological adverse effects such as demyelinating disorders and seizures.
May induce lupus-like syndrome with arthralgia and rash.
Heightened risk of skin cancers and need for monitoring of skin changes.
Potential for hematologic toxicities resulting in bleeding or infection susceptibility.
Use during pregnancy requires careful consideration due to possible neonatal immunosuppression.
Live vaccines should be avoided during treatment and for several months after cessation.
Risk of new onset or worsening psoriasis during therapy.
Immunogenicity may lead to decreased drug efficacy or increased adverse reactions.
Close monitoring required for early identification and management of adverse events.
Infusion-related reactions can occur up to two hours post-infusion and need immediate attention.

Contraindication

Known hypersensitivity to infliximab products or any of the excipients in Inflectra.
Active, severe infections including sepsis, tuberculosis, or opportunistic infections.
Moderate to severe heart failure unless benefit outweighs risk and close monitoring is ensured.
Concurrent use with other biologic immunosuppressants such as Kineret (anakinra), Orencia (abatacept), or Actemra (tocilizumab).
Patients with a history of significant allergic reactions to murine or chimeric monoclonal antibodies.
Known demyelinating diseases like multiple sclerosis or Guillain-Barré syndrome, unless benefits clearly outweigh risks.
Use during active hepatitis B infection without appropriate antiviral therapy.
Administration with live vaccines during or immediately following therapy is contraindicated.
Hypersensitivity to any component including dibasic sodium phosphate dihydrate, monobasic sodium phosphate monohydrate, polysorbate 80, or sucrose.
Pediatric patients under 6 years of age due to unknown safety and efficacy.
Known history of malignancies where immunosuppression may exacerbate condition without adequate control.
Patients experiencing severe infusion reactions to prior infliximab infusions.
Uncontrolled or untreated latent infections.
Pregnant women unless benefits outweigh potential risks to fetus.

Drug Interactions

Concurrent use with other biologics targeting immune pathways (e.g., Kineret, Orencia, Actemra) increases risk of serious infections and immunosuppression.
May interact with immunosuppressive agents like methotrexate; monitoring required but often used in combination for therapeutic synergy.
Potential risk with live vaccines; live vaccines are contraindicated during treatment.
No significant metabolism via cytochrome P450 enzymes, reducing metabolic drug interactions.
Concomitant use with corticosteroids increases infection risk; requires careful monitoring.
Use with other agents that impair immune function may potentiate immunosuppression.
No known direct interaction with common CYP substrates, inducers, or inhibitors.
Limited data on interaction with anticoagulants; monitor patient for bleeding complications.
Potential interaction with drugs affecting TNF-alpha pathways; combination may exacerbate side effects.
May alter efficacy of vaccines due to immune suppression; vaccination schedules may need adjustment.
Interaction with phototherapy for psoriasis increases risk of skin cancer.
Co-administration with live or attenuated vaccines increases risk of infections.
Immunogenicity can be affected by concomitant medications affecting immune system activation.
Possible decreased formation of anti-drug antibodies when used with methotrexate, improving drug efficacy.
Monitor laboratory parameters when combining with other hepatotoxic or immunomodulating drugs.

Preparations Of The Drug

Single-dose vial containing 100 mg of infliximab-dyyb as a lyophilized powder.
Inactive ingredients include dibasic sodium phosphate dihydrate, monobasic sodium phosphate monohydrate, polysorbate 80, and sucrose.
No preservatives are present in the formulation.
Stored refrigerated at 2°C to 8°C (36°F to 46°F), protected from light.
Must be reconstituted with sterile water for injection, then diluted prior to intravenous infusion.
Prepared and administered by healthcare professionals only.
Diluted infusion solution must be used within specified time limits to maintain stability.
Single-use vials to prevent contamination; discard any unused portion.
Manufactured by Celltrion, Inc., South Korea.
Distributed by Pfizer Labs, Division of Pfizer Inc., New York, NY, USA.
Biosimilar product highly similar to the reference biologic Remicade with no clinically meaningful differences.
Compatible with standard infusion solutions such as 0.9% sodium chloride or 5% dextrose.
No oral or subcutaneous formulations available; intravenous administration only.
Supplied with package insert detailing reconstitution and administration guidelines.
Recommended freezing is contraindicated; maintain cold chain during transport and storage.