Remicade100 mg/20 ml

Remicade is a chimeric monoclonal antibody that inhibits tumor necrosis factor-alpha (TNF-alpha), administered by intravenous infusion for a range of chronic inflammatory and autoimmune conditions. Its uses are classified below by strength of evidence.

Established / FDA-Approved Uses

• Rheumatoid arthritis: Moderate-to-severe active rheumatoid arthritis, in combination with methotrexate, to reduce signs and symptoms, inhibit progression of structural damage, and improve physical function.
• Crohn's disease (adult and pediatric): Moderately-to-severely active Crohn's disease with an inadequate response to conventional therapy, and fistulizing Crohn's disease, to reduce the number of draining fistulas and maintain fistula closure.
• Ulcerative colitis (adult and pediatric): Moderately-to-severely active ulcerative colitis with an inadequate response to conventional therapy.
• Ankylosing spondylitis: Active ankylosing spondylitis, to reduce signs and symptoms.
• Psoriatic arthritis: Active psoriatic arthritis, to reduce signs and symptoms of active arthritis and inhibit progression of structural damage.
• Plaque psoriasis: Chronic severe (extensive and/or disabling) plaque psoriasis in adults who are candidates for systemic therapy.

Important Notes

• For rheumatoid arthritis, Remicade must be given in combination with methotrexate; it is not indicated as monotherapy for this indication.
• Remicade is generally reserved for patients who have had an inadequate response to conventional (non-biologic) therapy.

Each single-use vial contains Infliximab (a chimeric human-murine IgG1 monoclonal antibody) as a lyophilized powder for reconstitution, commonly supplied as 100 mg per vial, along with inactive excipients (such as sucrose, polysorbate 80, and buffering agents) used in the freeze-dried formulation.

Remicade is a biologic disease-modifying antirheumatic drug (DMARD) belonging to the tumor necrosis factor-alpha (TNF-alpha) inhibitor class. It is a chimeric (part-human, part-mouse) monoclonal antibody that binds specifically to both soluble and transmembrane forms of TNF-alpha, a key pro-inflammatory cytokine involved in the pathology of several chronic autoimmune and inflammatory diseases.

Remicade is supplied as a lyophilized powder that must be reconstituted and further diluted before being administered as a slow intravenous infusion under direct medical supervision. It is not an antibiotic; it is an immunosuppressant biologic agent used for long-term disease control in appropriately selected patients.

Remicade belongs to the therapeutic class of biologic disease-modifying antirheumatic drugs (DMARDs), specifically the tumor necrosis factor-alpha (TNF-alpha) inhibitor subclass of chimeric monoclonal antibodies.

Infliximab binds with high affinity to both the soluble and transmembrane forms of TNF-alpha, neutralizing its biological activity and preventing it from binding to its receptors. This blocks the downstream inflammatory cascade mediated by TNF-alpha, including the production of other pro-inflammatory cytokines (such as IL-1 and IL-6), reduces leukocyte migration and endothelial adhesion molecule expression, and can cause lysis of TNF-alpha-expressing cells through complement-mediated and antibody-dependent cytotoxicity.

These effects lead to reduced inflammation, decreased joint and tissue damage, and improvement in the signs and symptoms of the inflammatory and autoimmune conditions for which Infliximab is indicated. Pharmacokinetically, Infliximab has a serum half-life of approximately 7.7 to 9.5 days and is administered as a slow intravenous infusion because it is a protein that would be degraded by the gastrointestinal tract if given orally.

Remicade is administered only by a healthcare professional as a slow intravenous infusion (over at least 2 hours) in a clinical setting equipped to manage infusion reactions, using an in-line filter. It is never self-administered or given by any other route.

The following clinically significant interactions have been well established for Remicade:

• Other biologic DMARDs and TNF-alpha inhibitors (e.g., anakinra, abatacept, other TNF blockers): Concurrent use with Remicade is not recommended due to a significantly increased risk of serious infections without added clinical benefit.
• Live vaccines: Live or live-attenuated vaccines should not be given concurrently with Remicade because of the risk of clinical infection from the vaccine strain, due to Remicade's immunosuppressive effect.
• Methotrexate and other immunosuppressants (e.g., azathioprine): Combination with methotrexate is required for the rheumatoid arthritis indication and reduces immunogenicity (anti-drug antibody formation), but the combined immunosuppressive effect further increases infection risk and requires monitoring (see Precautions for infection risk).
• Cytochrome P450 substrates: TNF-alpha inhibition during chronic inflammation can alter cytochrome P450 enzyme activity; caution is advised when Remicade is used with CYP450 substrates that have a narrow therapeutic index (e.g., warfarin, cyclosporine), with monitoring of drug effect or levels as appropriate.

The most commonly reported side effects of Remicade include:

• Infusion-related reactions (fever, chills, itching, hives, chest pain, hypotension or hypertension, shortness of breath)
• Upper respiratory tract infections and sinusitis
• Headache
• Abdominal pain and nausea
• Cough
• Rash
• Fatigue

Serious but less common effects include serious infections (including reactivation of tuberculosis and hepatitis B), malignancies including lymphoma, heart failure exacerbation, demyelinating neurologic disease, lupus-like syndrome, and severe hepatic reactions (see Precautions and Warnings). Patients should seek prompt medical attention for signs of infection, unusual bruising or bleeding, jaundice, chest pain, or severe allergic reaction while receiving Remicade.

Pregnancy

Data on Remicade use in pregnancy are limited but suggest it crosses the placenta, especially in the third trimester, and may be detectable in the infant's serum for up to 6 months after birth, which can affect the infant's response to live vaccines during that period. Remicade should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus; a physician should be consulted before use in pregnancy, and timing of doses relative to delivery should be discussed with the treating specialist.

Lactation

Limited data suggest Remicade is present in breast milk in very low amounts, with minimal expected oral absorption or systemic exposure in the breastfed infant. A physician should be consulted to weigh the benefits of breastfeeding against any potential risk before using Remicade while breastfeeding.

The following important precautions apply to the use of Remicade:

• Serious infections: Remicade increases the risk of serious infections, including bacterial, viral, fungal, and opportunistic infections, that may lead to hospitalization or death. Patients should be evaluated for tuberculosis (TB) and screened for latent hepatitis B virus infection before starting therapy, as Remicade can cause reactivation of latent TB or hepatitis B. Treatment should not be started in patients with an active, serious infection.
• Infusion reactions: Acute infusion reactions, including anaphylaxis and delayed hypersensitivity reactions, can occur; Remicade must be administered under medical supervision in a setting equipped to manage such reactions.
• Malignancy: TNF-alpha inhibitors, including Remicade, have been associated with an increased risk of lymphoma and other malignancies, including a rare hepatosplenic T-cell lymphoma reported mainly in adolescent and young adult males with inflammatory bowel disease, particularly when used with azathioprine or 6-mercaptopurine.
• Heart failure: Remicade should be used with caution in patients with heart failure and is contraindicated at doses above 5 mg/kg in moderate-to-severe (NYHA Class III/IV) heart failure, as it may cause worsening of the condition.
• Demyelinating disease: New onset or exacerbation of demyelinating central or peripheral nervous system disorders (e.g., multiple sclerosis-like syndromes, Guillain-Barré syndrome) has been reported; use with caution in patients with pre-existing or recent-onset demyelinating disease.
• Lupus-like syndrome: Discontinue Remicade if a lupus-like syndrome develops with persistent symptoms and positive antibodies against double-stranded DNA.
• Hepatotoxicity: Rare cases of severe liver injury, including liver failure, have been reported; monitor for signs and symptoms of liver dysfunction.
• Immunization: Avoid live vaccines during treatment (see Interactions).

There is limited clinical experience with overdose of Remicade, as it is administered under direct medical supervision. Single doses up to 20 mg/kg have been given without direct toxic effect. In the event of a suspected overdose or unexpected reaction, the infusion should be stopped immediately and the patient monitored closely; seek immediate medical attention. There is no specific antidote; management is supportive and symptomatic under medical care.

Store lyophilized vials under refrigeration at 2°C to 8°C (36°F to 46°F). Do not freeze. Protect from light by keeping in the original carton until time of reconstitution. Keep out of reach of children.

• Pediatric patients: Established for Crohn's disease and ulcerative colitis in children 6 years and older; safety and efficacy have not been established for other indications or in children younger than 6 years (see Pediatric Uses).
• Elderly patients: Use with caution due to a generally higher incidence of infections in the elderly population; no overall dose adjustment is established, but close monitoring for infection is advised.
• Renal/hepatic impairment: Not formally studied; no specific dose adjustment established. Avoid initiation in patients with active hepatic dysfunction (see Dosage and Administration).
• Patients with heart failure: Avoid doses above 5 mg/kg in moderate-to-severe heart failure (see Contraindications).

Remicade is generally used as long-term maintenance therapy, with infusions continued at regular intervals (typically every 4 to 8 weeks depending on indication) for as long as the patient continues to respond and tolerate treatment. The need for continued therapy, and periodic reassessment of dose or interval, should be determined by the treating physician based on clinical response and disease activity.

Each vial of Remicade lyophilized powder is reconstituted with 10 mL of Sterile Water for Injection, using a syringe with a 21-gauge or smaller needle, directing the stream of water to the wall of the vial and gently swirling (not shaking) to dissolve. The reconstituted solution is further diluted in 250 mL of 0.9% Sodium Chloride Injection to a final concentration before infusion. This must be performed by a trained healthcare professional using aseptic technique.

Biologic disease-modifying antirheumatic drugs (DMARDs); Tumor necrosis factor-alpha (TNF-alpha) inhibitors; Chimeric monoclonal antibodies; Immunosuppressants

Infliximab is a chimeric monoclonal antibody that binds with high affinity to both soluble and transmembrane forms of tumor necrosis factor-alpha (TNF-alpha), neutralizing its biological activity and blocking its interaction with cell surface TNF receptors. This interrupts the inflammatory cascade driven by TNF-alpha, reducing cytokine production, leukocyte infiltration, and tissue damage in the chronic inflammatory and autoimmune conditions for which it is indicated.

Remicade is approved for the treatment of moderately-to-severely active Crohn's disease and moderately-to-severely active ulcerative colitis in pediatric patients 6 years of age and older, using the same weight-based induction and maintenance dosing schedule as adults for these indications. Safety and efficacy of Remicade have not been established in children younger than 6 years, or in pediatric patients for rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or plaque psoriasis; use in these situations is not recommended.