Infliximab-Axxq

Introduction Overview

Generic Name

infliximab-axxq

Brand Name

Avsola

Dosage Form

intravenous (infusion) injection

Drug Class

TNF alfa inhibitors (tumor necrosis factor alpha inhibitors)

Pharmacokinetics

Absorption

Avsola is administered via intravenous infusion; therefore, it reaches systemic circulation directly, bypassing absorption barriers inherent to other routes such as oral or subcutaneous. Following infusion, infliximab-axxq circulates freely within the vascular compartment and penetrates tissues where TNF-alpha is expressed. Because Avsola is administered by IV route, bioavailability is effectively 100%.

Distribution

Infliximab-axxq, like other monoclonal antibodies, exhibits a limited volume of distribution, generally restricted to the plasma and extracellular fluid compartments. Distribution into tissues occurs based on vascular permeability and expression of TNF-alpha target sites. It has been shown that concentrations of the drug in synovial fluid and inflamed tissues can be substantial. The molecular size (~149 kDa) restricts passive diffusion, but binding to TNF-alpha in inflamed tissues promotes retention at the site of disease activity. The drug does not readily cross the blood-brain barrier. Binding to plasma proteins is mainly restricted to soluble TNF-alpha complexes, and unbound drug circulates in plasma.

Metabolism

Avsola is a chimeric monoclonal antibody and undergoes catabolism by proteolytic enzymes ubiquitously expressed in the reticuloendothelial system and various tissues. The metabolism does not involve hepatic cytochrome P450 enzymes. The degradation leads to smaller peptides and amino acids recycled or eliminated. Inflammatory states and immunogenicity may influence clearance due to anti-drug antibody formation, potentially increasing clearance rates.

Elimination

The clearance of infliximab-axxq depends on multiple factors including disease state, presence of anti-drug antibodies, and patient weight. The drug has a half-life of approximately 7 to 12 days. Elimination occurs via proteolytic catabolism rather than renal or biliary excretion. Dose and frequency are adjusted based on clinical factors and therapeutic response. The typical dosing interval is every 6 to 8 weeks for maintenance therapy. Immunogenicity may lead to reduced half-life and efficacy.

Dosage Forms

Adults

Avsola is available as a 100 mg single-dose vial for intravenous infusion. Recommended dosing varies by indication but generally involves an induction phase at weeks 0, 2, and 6, followed by maintenance therapy every 6 to 8 weeks. For example, rheumatoid arthritis treatment involves 3 mg/kg IV infusion combined with methotrexate every 8 weeks. Crohn's disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis typically use 5 mg/kg IV infusion at similar intervals. Dose escalation up to 10 mg/kg every 4 to 8 weeks may be considered if therapeutic response is inadequate.

Adolescents

Avsola is indicated for pediatric patients aged 6 years and older with moderately to severely active Crohn's disease and ulcerative colitis. The recommended dose is 5 mg/kg administered as an intravenous infusion at weeks 0, 2, and 6 during induction, followed by 5 mg/kg every 8 weeks as maintenance therapy. Safety and efficacy below 6 years have not been established. Dosage adjustments are recommended based on therapeutic response and tolerability in pediatric patients.

Special Populations

In patients with renal or hepatic impairment, no specific dosage adjustment is required due to the catabolic metabolism of monoclonal antibodies. For elderly patients, increased susceptibility to infections and malignancies has been observed; therefore, careful monitoring is advised, although dosing remains the same. Patients with congestive heart failure should be closely assessed; Avsola is generally avoided or used cautiously in moderate to severe heart failure. Immunogenicity could alter pharmacokinetics in patients with robust anti-drug antibody formation. Pregnancy and breastfeeding require thorough risk-benefit evaluation, with considerations for delayed live vaccines in infants exposed in utero.

Mechanism Of Action

Avsola (infliximab-axxq) is a chimeric monoclonal antibody that specifically binds with high affinity to tumor necrosis factor alpha (TNF-alpha), a pro-inflammatory cytokine pivotal in the pathogenesis of various autoimmune disorders. TNF-alpha exists both as a soluble and transmembrane cytokine; Avsola neutralizes its biological activity by preventing binding to TNF receptors (TNFR1 and TNFR2) on cell surfaces, thereby inhibiting downstream signaling pathways involved in inflammation and immune activation.

The binding of Avsola to TNF-alpha interrupts the cytokine's interaction with its receptors, effectively blocking the cascade that leads to NF-kB activation, cytokine production, upregulation of adhesion molecules, and recruitment of inflammatory cells. Additionally, Avsola can induce apoptosis of activated T-lymphocytes and monocytes expressing membrane-bound TNF-alpha, further reducing inflammation.

Clinically, the inhibition of TNF-alpha reduces synovial inflammation, joint destruction, and tissue damage in rheumatoid arthritis and other autoimmune conditions. It also downregulates the chronic inflammatory processes in Crohn’s disease, ulcerative colitis, and psoriasis by modulating immune cell responses and cytokine networks.

Compared to other TNF inhibitors, Avsola shares mechanism similarities being a biosimilar to infliximab, including the capacity for complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity, underpinning its wide therapeutic application. Clinical trials have demonstrated that the pharmacodynamic profiles and efficacy endpoints of Avsola are comparable to the reference infliximab product (Remicade), confirming biosimilarity with equivalent clinical outcomes.

Pharmacological Actions

Neutralizes and inhibits tumor necrosis factor alpha (TNF-alpha) activity
Reduces inflammatory cytokine cascade and immune cell recruitment
Induces apoptosis in activated T-cells and macrophages
Suppresses progression of autoimmune inflammatory processes
Decreases synovial inflammation and joint damage in rheumatoid arthritis
Modulates gut mucosal immune response in Crohn’s disease and ulcerative colitis
Reduces chronic skin inflammation in plaque psoriasis
Exerts immunomodulatory effects contributing to clinical symptom relief
Blocks leukocyte migration and vascular adhesion molecule expression
Displays complement-dependent cytotoxicity and antibody-dependent cytotoxicity against TNF-expressing cells
Improves endoscopic and histologic markers of inflammation in inflammatory bowel disease
Downregulates systemic inflammation markers such as C-reactive protein
Ameliorates symptoms of ankylosing spondylitis and psoriatic arthritis through TNF blockade

Therapeutic Clinical Uses

Treatment of moderately to severely active rheumatoid arthritis in combination with methotrexate
Management of moderately to severely active Crohn's disease in adults and children 6 years and older
Induction and maintenance therapy of moderately to severely active ulcerative colitis in adults and pediatric patients 6 years and older
Treatment of active ankylosing spondylitis in adults
Management of psoriatic arthritis in adults, with or without methotrexate
Treatment of chronic severe plaque psoriasis in adults
Useful for patients who have not responded adequately to conventional therapies in autoimmune conditions
Indicated in fistulizing Crohn’s disease to promote fistula closure
Off-label uses in other TNF-mediated inflammatory disorders based on physician discretion
Can be used as part of combination therapy with immunomodulators or corticosteroids
Provides anti-inflammatory effects to reduce symptoms and improve function
Employed in therapy to prevent structural joint damage progression

Side Or Adverse Effects

Serious infections including tuberculosis, bacterial, fungal, and viral infections
Reactivation of latent tuberculosis and hepatitis B virus
Infusion-related reactions such as fever, chills, rash, hypotension or hypertension, and dyspnea
Allergic or anaphylactic reactions including delayed hypersensitivity
Increased risk of malignancies including lymphoma and hepatosplenic T-cell lymphoma especially in young males
Development or worsening of congestive heart failure
Hepatotoxicity manifesting as jaundice, elevated liver enzymes, and liver failure
Hematologic abnormalities including leukopenia, neutropenia, anemia, and thrombocytopenia
Neurological disorders such as demyelinating disease, seizures, or neuropathies
Lupus-like syndrome with rash, joint pain, and serositis
Psoriasis induction or exacerbation
Headache and headache-related symptoms
Respiratory infections including sinusitis and pharyngitis
Abdominal pain and gastrointestinal disturbances
Injection site reactions and localized pain

Precautions

Screen for latent tuberculosis before initiation and monitor throughout therapy
Assess for hepatitis B infection and monitor viral status during treatment
Avoid use in patients with active infections
Monitor patients for signs of infection during treatment, especially elderly and immunocompromised
Use cautiously in patients with congestive heart failure or cardiac history
Advise patients about potential for allergic and infusion reactions
Avoid concomitant use with other biologic immunosuppressants to reduce infection risk
Evaluate for previous or current malignancy risk
Monitor blood counts regularly to detect hematologic abnormalities
Use in pediatric patients only if clearly indicated and with close surveillance
Educate patients on signs of nervous system disorders and lupus-like symptoms
Assess for COPD as patients may have increased cancer risk during therapy
Regular skin examinations for new or worsening skin lesions are advised
Coordinate vaccination status before initiation; avoid live vaccines during and shortly after treatment
Disclose all concurrent medications to avoid drug interactions

Warnings

Black box warning for serious infections including tuberculosis and invasive fungal infections
Increased risk of malignancies including lymphoma, especially in pediatric and adolescent patients
Potential for fatal infusion reactions requiring emergency treatment
Heart failure may worsen or develop during treatment
Hepatotoxicity, including fatal liver failure, has been reported
Risk of hematologic toxicity including pancytopenia and aplastic anemia
Possible development of demyelinating central and peripheral nervous system disorders
Reactivation of latent viral infections such as hepatitis B
Potential for inducing autoantibodies and lupus-like syndrome
Risk for opportunistic infections is heightened, especially among elderly patients
Avoid live vaccines concurrently due to impaired immune response
Delayed hypersensitivity reactions can occur days after infusion
Pregnant women exposure may increase infection risk in newborns
Infusion interruption or discontinuation may be required in severe adverse events
Careful consideration is needed in patients with history of malignancy

Contraindications

Known hypersensitivity to infliximab products or any component of Avsola
Active severe infections including sepsis, abscesses, or opportunistic infections
Moderate to severe heart failure (New York Heart Association Class III/IV) unless benefits outweigh risks
Hypersensitivity reactions to murine proteins (due to chimeric nature)
Concurrent therapy with other TNF blockers or biologic immunosuppressants such as anakinra, abatacept, or tocilizumab
Use in patients with active tuberculosis until adequate treatment course is completed
Patients with known hypersensitivity to polysorbate 80 or other inactive ingredients in Avsola
Pediatric patients under 6 years of age due to lack of safety and efficacy data
Patients with unresolved malignancy or history of certain hematologic cancers without oncologist approval

Drug Interactions

Increased risk of infections with concomitant use of other immunosuppressive agents including methotrexate
Avoid combination with biologics such as anakinra (Kineret), abatacept (Orencia), and tocilizumab (Actemra)
Potential interaction with live vaccines leading to increased risk of vaccine-related infections
Concomitant use with azathioprine or 6-mercaptopurine may increase hepatosplenic T-cell lymphoma risk especially in young males with inflammatory bowel disease
Possible alteration of cytochrome P450 enzyme activity due to cytokine modulation, affecting concurrent medications metabolized by CYP450
Increased risk of hematologic toxicity with certain chemotherapy agents
Reduced efficacy if anti-drug antibodies develop, potentially influenced by other immunomodulatory drugs
Monitoring recommended when used with corticosteroids due to additive immunosuppression
Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase infection risk when combined
Live vaccines contraindicated during and up to 6 months after treatment due to immunosuppression
Close monitoring if used with potent immunosuppressants for additive adverse effects

Preparations Of The Drug

Avsola single-dose vial, 100 mg infliximab-axxq for intravenous infusion
Provided as a sterile, preservative-free, lyophilized powder for reconstitution
Packaging includes diluent and instructions for preparation and administration
Available only as an intravenous infusion formulation to be administered under professional supervision
No oral, subcutaneous, or intramuscular forms of Avsola available
Reconstituted solution is clear to slightly opalescent, colorless to pale yellow
Must be stored refrigerated between 2°C to 8°C (36°F to 46°F) and protected from light
Once removed from refrigeration, stable at room temperature (up to 30°C) for up to 6 months but should not be returned to refrigerator
Similar biosimilars such as Remicade, Inflectra, Renflexis are also single-dose 100 mg vials for IV infusion
No preservative in formulation to reduce risk of hypersensitivity
Preparation and administration must be performed by trained healthcare professionals in controlled settings