Remicade


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infliximab

Remicade

Pharmacologic class: Monoclonal antibody

Therapeutic class: Antirheumatic, GI anti-inflammatory

Pregnancy risk category B

FDA Box Warning

• Patients treated with infliximab are at increased risk for developing serious infections, including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis), and infections due to other opportunistic pathogens (including Legionella and Listeria species), that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants (such as methotrexate or corticosteroids).

• Carefully consider risks and benefits of treatment with infliximab before starting therapy in patients with chronic or recurrent infection.

• TB includes active TB and reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before starting infliximab and during therapy. Treatment for latent infection should be started before initiating infliximab.

• Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.

• Closely monitor patients for signs and symptoms of infection during and after treatment with infliximab, including possible development of TB in patients who tested negative for latent TB before starting infliximab.

• Discontinue drug if patient develops a serious infection or sepsis.

• Lymphoma and other malignancies, some fatal, have been reported in children and adolescents treated with tumor necrosis factor (TNF) blockers, including infliximab. Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including infliximab. All cases occurred in patients with Crohn's disease and ulcerative colitis, the majority of whom were adolescent or young adult males. This rare, aggressive T-cell lymphoma is fatal. All of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with infliximab at or before diagnosis.

Action

Neutralizes and prevents activity of tumor necrosis factor-alpha (TNF-alpha) by binding to soluble and transmembrane forms of TNF and inhibiting its receptors, resulting in anti-inflammatory and antiproliferative activity. Reduces rate of joint destruction in rheumatoid arthritis and eases symptoms of Crohn's disease.

Availability

Powder for injection: 100 mg/vial

Indications and dosages

Rheumatoid arthritis (given with methotrexate)

Adults: Initially, 3 mg/kg I.V., followed by 3 mg/kg 2 and 6 weeks after initial dose, then q 8 weeks. In partial responders, dosage may be adjusted up to 10 mg/kg or treatment may be repeated as often as q 4 weeks.

Crohn's disease

Adults and children age 6 and older: 5 mg/kg I.V. as a single infusion, starting as induction regimen at 0, 2, and 6 weeks, then a maintenance regimen of 5 mg/kg q 8 weeks. For some adults patients who respond initially but then stop responding, dosage of 10 mg/kg may be warranted.

Ulcerative colitis

Adults and children age 6 and older: 5 mg/kg I.V. infusion given as induction therapy at 0, 2, and 6 weeks, followed by maintenance regimen of 5 mg/kg I.V. q 8 weeks thereafter

Ankylosing spondylitis

Adults: 5 mg/kg I.V. infusion at 0, 2, and 6 weeks, followed by maintenance regimen of 5 mg/kg q 6 weeks thereafter

Psoriatic arthritis

Adults: 5 mg/kg I.V. infusion (with or without methotrexate) given as induction therapy at 0, 2, and 6 weeks, followed by maintenance regimen of 5 mg/kg q 8 weeks thereafter

Plaque psoriasis

Adults: 5 mg/kg I.V. infusion given as induction therapy at 0, 2, and 6 weeks, followed by maintenance regimen of 5 mg/kg q 8 weeks thereafter

Off-label uses

• Sarcoidosis

Contraindications

• Hypersensitivity to drug, murine proteins, or other drug components
• Dosages above 5 mg/kg for patients with moderate to severe heart failure

Precautions

Use cautiously in:
• history of tuberculosis (TB), active infection, or exposure to TB; patients who have resided or traveled in areas of endemic TB or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis
• chronic or recurrent infection or underlying conditions that may predispose to infection; history of opportunistic infection; hepatitis B virus (HBV) carriers
• jaundice or marked liver enzyme elevations, cytopenias
• neurologic disorders (including CNS manifestation of systemic vasculitis, seizures), new-onset or exacerbation of demyelinating disorders (including multiple sclerosis and optic neuritis) and peripheral demyelinating disorders (including Guillain-Barré syndrome)
• male patients with Crohn's disease or ulcerative colitis who are receiving azathioprine or 6-mercaptopurine treatment
• concurrent use of live vaccines, tocilizumab (avoid use)
• concurrent use of anakinra or abatacept (use not recommended)
• when switching between biological disease-modifying antirheumatics (overlapping biological activity may further increase risk of infection)
• elderly patients
• pregnant or breastfeeding patients
• children younger than age 6 (safety not established).

Administration

• Know that latent TB should be treated before infliximab therapy begins.
• To reconstitute, use 21G or smaller needle to add 10 ml of sterile water to each vial. To mix, swirl (don't shake). Solution may foam and appear clear or light yellow.
• Withdraw volume equal to amount of reconstituted drug from 250-ml polypropylene or polyolefin infusion bag or glass bottle of normal saline solution. Slowly add reconstituted drug to infusion bag or bottle, and gently mix. Use within 3 hours.
• Know that concentration of infusion should be 0.4 mg/ml to 4 mg/ml.
• Give I.V. infusion over at least 2 hours. Use polyethylene-lined infusion set equipped with in-line filter, with pore size of 1.2 microns or less.
• Premedicate with antihistamines, acetaminophen, and corticosteroids, as prescribed.

Watch for infusion reactions, especially after first infusion. Be aware that mild to moderate infusion reactions may improve after slowing or suspension of infusion. Upon resolution of reaction, restart infusion at lower infusion rate or administer antihistamines, acetaminophen, or corticosteroids. Discontinue drug in patients who don't tolerate infusion following these interventions; permanently discontinue drug in patients who have severe infusion-related hypersensitivity reactions.
• Discard unused portions of infusion solution.
• Don't give to patient with active infection.
• Be aware that patient who doesn't respond by week 14 isn't likely to respond, and therapy should cease.

Adverse reactions

CNS: fatigue, headache, anxiety, depression, dizziness, insomnia, CNS manifestation of systemic vasculitis, seizures, new-onset or exacerbation of demyelinating disorders (including multiple sclerosis, optic neuritis, Guillain-Barré syndrome)

CV: chest pain, hypertension, hypotension, tachycardia, peripheral edema, worsening of heart failure

EENT: conjunctivitis, rhinitis, sinusitis, laryngitis, pharyngitis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, flatulence, ulcerative stomatitis, intestinal obstruction

GU: dysuria, urinary frequency, urinary tract infection

Hematologic: hematoma, anemia, hemolytic anemia, pancytopenia

Hepatic: HBV reactivation, hepatotoxicity

Musculoskeletal: arthritis, joint pain, back pain, myalgia, involuntary muscle contractions

Respiratory: upper respiratory tract infection, bronchitis, cough, dyspnea

Skin: acne, diaphoresis, dry skin, bruising, eczema, erythema, flushing, pruritus, urticaria, rash, alopecia

Other: oral pain, tooth pain, moniliasis, chills, hot flashes, flulike symptoms, herpes simplex, herpes zoster, autoimmunity, lupuslike syndrome, serious infections, malignancies, infusion reactions, hypersensitivity reaction including anaphylaxis or serum sickness-like reactions

Interactions

Drug-drug.Abatacept, anakinra: increased risk of infections

Tocilizumab: increased immunosuppression and increased risk of infection

Vaccines: decreased antibody response to vaccine

Drug-diagnostic tests.Antinuclear antibodies: positive titer

Hepatic enzymes: increased values

Hemoglobin: decreased value

Patient monitoring

Stay alert for signs and symptoms of hypersensitivity and infusion reactions, including fever, chills, itching, rash, chest pain, dyspnea, facial flushing, and headache.

Watch for evidence of infection, especially in patients who have chronic infections or are receiving immunosuppressants. Drug increases risk of life-threatening opportunistic infections and TB.
• Monitor platelets and CBC with white cell differential.

Assess for heart failure in patients with history of cardiac disease.

Be aware that CNS disorders (such as seizures, new-onset or exacerbation of demyelinating disorders), malignancies including lymphoma, HBV reactivation, hepatotoxicity, and cytopenias may occur.

Patient teaching

Instruct patient to report signs or symptoms of hypersensitivity reaction, such as fever, chills, itching, rash, chest pain, dyspnea, and facial flushing (may occur up to 12 days after therapy).

Tell patient to report infection symptoms, such as fever, burning on urination, cough, or sore throat.
• Advise patient to avoid potential infection sources, such as crowds and people with known infections.
• Advise patient not to receive live vaccines while receiving infliximab.

Instruct patient how to recognize and immediately report signs and symptoms of blood dyscrasias, hepatotoxicity, or other new or worsening symptoms.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

inFLIXimab

(in-flix-i-mab) ,

Remicade

(trade name)

Classification

Therapeutic: antirheumatics
Pharmacologic: monoclonal antibodies
Pregnancy Category: C

Indications

Active rheumatoid arthritis (moderate to severe, with methotrexate).Active Crohn’s disease (moderate to severe).Active psoriatic arthritis.Active ankylosing spondylitis.Active ulcerative colitis (moderate to severe) with inadequate response to conventional therapy: reducing signs and symptoms, and inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use.Plaque psoriasis (chronic severe).

Action

Neutralizes and prevents the activity of tumor necrosis factor-alpha (TNF-alpha), resulting in anti-inflammatory and antiproliferative activity.

Therapeutic effects

Decreased pain and swelling, decreased rate of joint destruction and improved physical function in ankylosing spondylitis, rheumatoid or psoriatic arthritis.
Reduction and maintenance of closure of fistulae in Crohn's disease.
Decreased symptoms, maintaining remission and mucosal healing with decreased corticosteroid use in ulcerative colitis.
Decrease in induration, scaling and erythema of psoriatic lesions.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Predominantly distributed within the vascular compartment.
Metabolism and Excretion: Unknown.
Half-life: 9.5 days.

Time/action profile (symptoms of Crohn’s disease)

ROUTEONSET PEAKDURATION
IV1–2 wkunknown12–48 wk†
†After infusion

Contraindications/Precautions

Contraindicated in: Hypersensitivity to infliximab, murine (mouse) proteins, or other components in the formulation;HF;Concurrent anakinra or abatacept; Lactation: Lactation.
Use Cautiously in: History of chronic or recurrent infection or underlying illness/treatment predisposing to infection;Patients being retreated after 2 yr without treatment (↑ risk of adverse reactions);History of tuberculosis or exposure (latent tuberculosis should be treated prior to infliximab therapy);History of opportunistic infection;Patients residing, or who have resided, where tuberculosis, histoplasmosis, coccidioidomycoses, or blastomycosis is endemic;Chronic obstructive pulmonary disease (↑ risk of malignancy); Geriatric: Geriatric patients; Obstetric: Use only if clearly needed; Pediatric: Children <6 yr (safety not established); ↑ risk of lymphoma (including hepatosplenic T-cell lymphoma [HSTCL] in patients with Crohn's disease or ulcerative colitis), leukemia, and other malignancies.

Adverse Reactions/Side Effects

Central nervous system

  • fatigue (most frequent)
  • headache (most frequent)
  • anxiety
  • depression
  • dizziness
  • insomnia

Ear, Eye, Nose, Throat

  • conjunctivitis

Respiratory

  • upper respiratory tract infection (most frequent)
  • bronchitis
  • cough
  • dyspnea
  • laryngitis
  • pharyngitis
  • respiratory tract allergic reaction
  • rhinitis
  • sinusitis

Cardiovascular

  • chest pain
  • hypertension
  • hypotension
  • pericardial effusion
  • tachycardia
  • HF

Gastrointestinal

  • abdominal pain (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • constipation
  • diarrhea
  • dyspepsia
  • flatulence
  • hepatotoxicity
  • intestinal obstruction
  • oral pain
  • tooth pain
  • ulcerative stomatitis

Genitourinary

  • dysuria
  • urinary frequency
  • urinary tract infection

Dermatologic

  • acne
  • alopecia
  • dry skin
  • ecchymosis
  • eczema
  • erythema
  • flushing
  • hematoma
  • hot flashes
  • pruritus
  • psoriasis
  • rash
  • sweating
  • urticaria

Hematologic

  • neutropenia

Musculoskeletal

  • arthralgia
  • arthritis
  • back pain
  • involuntary muscle contractions
  • myalgia

Neurologic

  • paresthesia

Miscellaneous

  • infections (including reactivation tuberculosis and other opportunistic infections due to bacterial, invasive fungal, viral, mycobacterial, and parasitic pathogens) (life-threatening)
  • malignancy (including lymphoma, HSTCL, leukemia, and skin cancer) (life-threatening)
  • fever (most frequent)
  • sarcoidosis (life-threatening)
  • infusion reactions (most frequent)
  • chills
  • flu-like syndrome
  • herpes simplex
  • herpes zoster
  • hypersensitivity reactions
  • lupus-like syndrome
  • moniliasis
  • pain
  • peripheral edema
  • vasculitis

Interactions

Drug-Drug interaction

Concurrent use with anakinra or abatacept ↑ risk of serious infections (not recommended).Concurrent use with azathioprine and/or methotrexate may ↑ risk of HSTCL.

Route/Dosage

Rheumatoid Arthritis

Intravenous (Adults) 3 mg/kg initially, then repeat at 2 and 6 wk after initial infusion, then repeat qy 8 wk; dose may be adjusted in partial responders up to 10 mg/kg or treatment as often as q 4 wk (to be used with methotrexate).

Crohn's Disease

Intravenous (Adults) 5 mg/kg initially, then repeat at 2 and 6 wk after initial infusion, then maintenance dose of 5 mg/kg q 8 wk; dose may be adjustedup to 10 mg/kg in patients who initially respond and then lose their response.
Intravenous (Children) 5 mg/kg initially, then repeat at 2 and 6 wk after initial infusion, then maintenance dose of 5 mg/kg q 8 wk.

Ankylosing Spondylitis

Intravenous (Adults) 5 mg/kg initially, then repeat at 2 and 6 wk after initial infusion, then maintenance dose of 5 mg/kg q 6 wk.

Psoriatic Arthritis

Intravenous (Adults) 5 mg/kg initially, then repeat at 2 and 6 wk after initial infusion, then maintenance dose of 5 mg/kg q 8 wk (to be used with or without methotrexate).

Ulcerative Colitis

Intravenous (Adults and Children ≥6 yr) 5 mg/kg initially, then repeat at 2 and 6 wk after initial infusion, then maintenance dose of 5 mg/kg q 8 wk.

Plaque Psoriasis

Intravenous (Adults) 5 mg/kg initially, then repeat at 2 and 6 wk after initial infusion, then maintenance dose of 5 mg/kg q 8 wk.

Availability

Powder for injection: 100 mg/vial

Nursing implications

Nursing assessment

  • Assess for infusion-related reactions (fever, chills, urticaria, pruritus) during and for 2 hr after infusion. Symptoms usually resolve when infusion is discontinued. Reactions are more common after 1st or 2nd infusion. Frequency of reactions may be reduced with immunosuppressant agents.
  • Monitor patients who develop a new infection while taking infliximab closely. Discontinue therapy in patients who develop a serious infection or sepsis. Do not initiate therapy in patients with active infections.
  • Assess for signs and symptoms of systemic infections (fever, malaise, weight loss, sweats, cough, dyspnea, pulmonary infiltrates, serious systemic illness with or without concomitant shock). Ascertain if patient lives in or has traveled to areas of endemic mycoses. Consider empiric antifungal treatment for patients at risk of histoplasmosis and other invasive fungal infections until the pathogens are identified. Consult with an infectious diseases specialist. Consider stopping infliximab until the infection has been diagnosed and adequately treated.
  • Assess for latent tuberculosis with a tuberculin skin test prior to initiation of therapy. Treatment of latent tuberculosis should be initiated prior to therapy with infliximab.
  • Observe patient for hypersensitivity reactions (urticaria, dyspnea, hypotension) during infusion. Discontinue infliximab if severe reaction occurs. Have medications (antihistamines, acetaminophen, corticosteroids, epinephrine) and equipment readily available in the event of a severe reaction.
  • Rheumatoid Arthritis: Assess pain and range of motion prior to and periodically during therapy.
  • Crohn’s Disease and Ulcerative Colitis: Assess for signs and symptoms before, during, and after therapy.
  • Psoriasis: Assess lesions periodically during therapy.
  • Lab Test Considerations: May cause ↑ in positive ANA. Frequency may be decreased with baseline immunosuppressant therapy.
    • Monitor liver function tests periodically during therapy. May cause mild to moderate AST and ALT ↑ without progressing to liver dysfunction. If patient develops jaundice or liver enzyme elevations ≥5 times the upper limits of normal, discontinue infliximab.
    • Monitor CBC with differential periodically during therapy. May cause leukopenia, neutropenia, thrombocytopenia, and pancytopenia. Discontinue infliximab if symptoms of blood dyscrasias (persistent fever) occur.

Potential Nursing Diagnoses

Chronic pain (Indications)
Diarrhea (Indications)

Implementation

  • Do not confuse infliximab with rituximab.
  • Intravenous Administration
  • Intermittent Infusion: Calculate the total number of vials needed. Reconstitute each vial with 10 mL of sterile water for injection using a syringe with a 21-gauge needle or smaller. Direct stream to sides of vial. Do not use if vacuum is not present in vial. Gently swirl solution by rotating vial to dilute; do not shake. May foam on reconstitution; allow to stand for 5 min. Solution is colorless to light yellow and opalescent; a few translucent particles may develop because infliximab is a protein. Do not use if opaque particles, discoloration, or other particles occur. Diluent: Withdraw volume of total infliximab dose from infusion container containing 250 mL with 0.9% NaCl. Slowly add total dose of infliximab.Concentration: 0.4 to 4 mg/mL. Mix gently. Infusion should begin within 3 hr of preparation. Solution is incompatible with polyvinyl chloride equipment. Prepare in glass infusion bottle or polypropylene or polyolefin bags. Do not reuse or store any portion of infusion solution.
  • Rate: Administer over at least 2 hr through polyethylene-lined administration set with an in-line, sterile, nonpyrogenic, low protein-building filter with ≤1.2-micron pore size.
  • Y-Site Incompatibility: Do not administer concurrently in the same line with any other agents.

Patient/Family Teaching

  • Advise patient that adverse reactions (myalgia, rash, fever, polyarthralgia, pruritus) may occur 3–12 days after delayed (>2 yr) retreatment with infliximab. Symptoms usually decrease or resolve within 1–3 days. Instruct patient to notify health care professional if symptoms occur.
  • May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
  • Advise patient to notify health care professional promptly if symptoms of fungal infection occur.
  • Advise patient of risk of malignancies such as hepatosplenic T-cell lymphoma. Instruct patient to report signs and symptoms (splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss) to health care professional promptly.
  • Advise patient to examine skin periodically during therapy and notify health care professional of any changes in appearance of skin or growths on skin.

Evaluation/Desired Outcomes

  • Decreased pain and swelling with decreased rate of joint destruction and improved physical function in patients with ankylosing spondylitis, psoriatic, or rheumatoid arthritis.
  • Decrease in the signs and symptoms of Crohn’s disease and a decrease in the number of draining enterocutaneous fistulas. Decreased symptoms, maintaining remission and mucosal healing with decreased corticosteroid use in ulcerative colitis.
  • Decrease in induration, scaling and erythema of psoriatic lesions.
A chimeric monoclonal antibody which is used to manage psoriasis, rheumatoid arthritis, psoriatic arthritis, Crohn’s disease and ulcerative colitis ankylosing spondylitis

Remicade®

Avakine, cA2, CenTNF, infliximab Immunology An agent used to manage severe or mutilating rheumatoid arthritis, or severe or active–eg, fistulizing–Crohn's disease. See Rheumatoid arthritis.
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