DrugindexOnline^{2nd edition}

Pronouncation: (in-FLIX-i-mab)
Class: Immunomodulator

Trade Names:
Remicade
- Powder for injection 100 mg (contains 500 mg sucrose)

Mechanism of Action

Pharmacology

Neutralizes the biological activity of tumor necrosis factor alpha (TNFα) by binding to its soluble and transmembrane forms and inhibits TNFα receptor binding.

Pharmacokinetics

Distribution

Distributed primarily within the vascular compartment.

Elimination

The t _½ is 8 to 9.5 days.

Indications and Usage

Reduce signs and symptoms and induce and maintain clinical remission of moderate to severe Crohn disease; reduce number of draining enterocutaneous and rectovaginal fistulas and maintain fistula closure in fistulizing Crohn disease; in combination with methotrexate to reduce signs and symptoms, inhibit progression of structural damage, and improve physical function in patients with moderately to severely active rheumatoid arthritis who have had inadequate response to methotrexate; reduce signs and symptoms of active ankylosing spondylitis; reduce signs and symptoms of active psoriatic arthritis; treatment of chronic severe plaque psoriasis in patients who are candidates for systemic therapy; reduce signs and symptoms, achieve clinical remission and mucosal healing, and eliminate corticosteroid use in patients with moderately to severely active ulcerative colitis.

Unlabeled Uses

Treatment of psoriasis and juvenile arthritis.

Contraindications

Hypersensitivity to murine proteins or other components of product; administration of more than 5 mg/kg to patients with moderate or severe CHF.

Dosage and Administration

Ankylosing Spondylitis
Adults

IV 5 mg/kg infusion followed by additional 5 mg/kg at 2 and 6 wk after the first infusion, then every 6 wk thereafter.

Moderate to Severe or Fistulizing Crohn Disease
Adults and Children 6 yr of age and older

IV 5 mg/kg as an induction regimen at 0, 2, and 6 wk, followed by a maintenance regimen of 5 mg/kg every 8 wk. In adult patients who respond and then lose response, consider treatment with 10 mg/kg.

Psoriatic Arthritis, Plaque Psoriasis
Adults

IV 5 mg/kg infusion followed by additional 5 mg/kg at 2 and 6 wk after the first infusion, then every 8 wk.

Rheumatoid Arthritis
Adults

IV 3 mg/kg infusion followed by additional 3 mg/kg doses at 2 and 6 wk after the first infusion, then every 8 wk thereafter in combination with methotrexate. For patients with incomplete response, may give up to 10 mg/kg or treat as often as every 4 wk.

Ulcerative Colitis
Adults

IV 5 mg/kg as an induction regimen at 0, 2, and 6 wk followed by a maintenance regimen of 5 mg/kg every 8 wk thereafter.

General Advice

• For administration by IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, or intra-arterial administration.
• Begin infusion of diluted solution within 3 h of preparation.
• Administer by IV infusion over a period of not less than 2 h through an infusion set with an in-line, sterile, nonpyrogenic, low-protein-binding filter with pore size of 1.2 mcm or less.
• Do not infuse infliximab concomitantly in the same IV line with any other agent.
• Discard any unused infusion solution. Do not save unused solution for later administration.

Storage/Stability

Store vials of powder for injection in refrigerator (36° to 46°F). Do not freeze.

Drug Interactions

Anakinra, etanercept

Risk of serious infection and neutropenia may be increased.

Vaccines

Do not coadminister live vaccines.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (7%); arrhythmia, bradycardia, cardiac arrest, chest pain, circulatory failure, hypotension, myocardial infarction, new and worsening heart failure, pulmonary embolism, syncope, tachycardia, thrombophlebitis; pericardial effusion, systemic and cutaneous vasculitis (postmarketing).

CNS

Headache (18%); fatigue (9%); confusion, dizziness, meningitis, neuritis, peripheral neuropathy, seizures, suicide attempt.

Dermatologic

Rash (10%); pruritus (7%); flushing, sweating, ulceration, urticaria; erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrosis (postmarketing).

GI

Nausea (21%); abdominal pain, diarrhea (12%); dyspepsia (10%); blood in stool, constipation, GI hemorrhage, ileus, intestinal obstruction, pancreatitis, perforation and stenosis, peritonitis, proctalgia.

Genitourinary

UTI (8%); menstrual irregularity, renal calculus, renal failure.

Hematologic

Anemia, hemolytic anemia, leukopenia, lymphadenopathy, lymphoma, pancytopenia, thrombocytopenia; idiopathic thrombocytopenic purpura, neutropenia, thrombotic thrombocytopenic purpura (postmarketing).

Hepatic

Biliary pain, cholecystitis, cholelithiasis, elevated ALT and AST; acute liver failure, cholestasis, hepatitis, jaundice (postmarketing).

Metabolic

Dehydration, edema.

Musculoskeletal

Arthralgia, back pain (8%); bone fracture; transverse myelitis (postmarketing).

Respiratory

Upper respiratory tract infection (32%); sinusitis (14%); coughing, pharyngitis (12%); bronchitis (10%); rhinitis (8%); adult respiratory distress syndrome, bronchitis, dyspnea, pleurisy, pulmonary edema, respiratory insufficiency; interstitial pneumonitis/fibrosis (postmarketing).

Miscellaneous

Infusion reactions (20%); antibodies to infliximab (10%); pain (8%); fever (7%); moniliasis (5%); abscess, allergic reaction, anaphylactic reactions (including laryngeal/pharyngeal edema and severe bronchospasm), cellulitis, chills, diaphragmatic hernia, infections, intervertebral disk herniation, lupus-like syndrome, myalgia, neoplasms (eg, blood cell, breast), sepsis, serum sickness, surgical/procedural sequela, tendon disorder; Guillain-Barré syndrome, neuropathies (postmarketing).

Precautions

Warnings Infection Serious infections, including tuberculosis (frequently disseminated or extrapulmonary), invasive fungal infections, sepsis, and other opportunistic infections, may occur. Do not initiate treatment in patients with active infection; exercise caution in those with chronic infection or history of recurrent infection. Evaluate patients for latent tuberculosis infection with a tuberculin skin test. Patients should also be evaluated for tuberculosis risk factors. Hepatosplenic T-cell lymphoma Rare cases have been reported in adolescent and young adult patients with Crohn disease treated with infliximab. All the hepatosplenic T-cell lymphomas with infliximab have occurred in patients on concomitant treatment with azathioprine or 6-mercaptopurine.

Monitor Monitor patients for signs and symptoms of infection during or after infliximab treatment Monitor chronic carriers of hepatitis B. Monitor patients with heart failure during therapy.

Pregnancy

Category B .

Lactation

Undetermined.

Children

Crohn disease: Safety and efficacy not established in children younger than 6 yr of age. Juvenile rheumatoid arthritis, ulcerative colitis, or plaque psoriasis: Safety and efficacy not established.

Elderly

Use with caution because of higher incidence of infection in the elderly.

Hypersensitivity

Reactions vary in their time of onset. Urticaria, dyspnea, and hypotension have occurred during or within 2 h of infliximab infusion; however, serum sickness–like reactions have been observed in Crohn disease patients 3 to 12 days after infliximab treatment.

Autoimmunity

May result in autoantibody formation and, rarely, development of a lupus-like syndrome.

CHF

Preliminary results of ongoing trials of patients with moderate to severe CHF have reported higher incidences of hospitalization and mortality for worsening heart failure in patients receiving infliximab. Do not administer doses greater than 5 mg/kg in patients with CHF (New York Heart Association class ΙΙΙ/ΙV).

Hematologic

Leukopenia, neutropenia, pancytopenia, and thrombocytopenia, sometimes fatal, have been reported.

Hepatitis B virus reactivation

Has occurred in patients who are chronic carriers of this virus.

Hepatotoxicity

Autoimmune hepatitis and severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis, have been reported.

Immunogenicity

Treatment can be associated with development of antibodies to infliximab. The incidence in patients given a 3-dose induction regimen followed by maintenance dosing is about 10%.

Malignancy

Patients with long duration of Crohn disease or rheumatoid arthritis and chronic exposure to immunosuppressant therapies are more prone to develop lymphomas.

Neurologic events

Rarely, optic neuritis, seizure, and new onset or exacerbation of clinical symptoms or radiographic evidence of CNS demyelinating disorders, including multiple sclerosis, may occur.

Vaccinations

Bring children with Crohn disease up to date with all vaccinations prior to starting infliximab therapy. It is recommended that live vaccines not be given concurrently.

Patient Information

• Advise patient or caregiver that medication will be prepared and administered by a health care provider in a medical setting.
• Advise patient or caregiver to review the Medication Guide before each treatment infusion session.
• Review treatment infusion schedule with patient or caregiver (eg, 2 and 6 wk after initial infusion, then every 6 wk thereafter when treating ankylosing spondylitis, or every 8 wk thereafter when treating rheumatoid arthritis or Crohn disease).
• Advise patient to notify health care provider immediately of any of the following: bleeding or unusual bruising; change in vision; dark, brown-colored urine; difficulty breathing or unexplained shortness of breath; difficulty swallowing; fever or other signs of infection; flu-like symptoms; new or worsening headache; new or worsening joint or muscle pain; numbness or tingling in any part of the body; paleness; rash, hives, or itching; right upper stomach pain; sore throat; swelling of hands or face; unexplained cough; unexplained tiredness; weakness in arms or legs; or yellowing of skin or eyes.
• Advise patient with heart failure to notify health care provider immediately if new or worsening symptoms of heart failure (eg, shortness of breath, swelling of ankles or feet) develop.
• Warn patient not to receive live vaccines while undergoing infliximab therapy.