Infliximab (Remicade)

Infliximabis used to treat certain types of arthritis (rheumatoid arthritis, arthritis of the spine, psoriatic arthritis), certain bowel diseases (Crohn's disease,ulcerative colitis), and a certain severe skin disease (chronicplaque psoriasis). In these conditions, the body's defense system (immune system) attacks healthy tissues. Infliximab works by blocking the actions of a certain natural substance (tumor necrosis factoralpha) in the body. This helps to decrease swelling (inflammation) and weaken your immune system, thereby slowing or stopping the damage from the disease.

Infliximab is available under the following different brand names:Remicade,Inflectra, infliximab-dyyb,Renflexis, and infliximab-abda.

Adult and Pediatric Dosage Forms and Strengths

Injection, lyophilized powder for reconstitution

100mg/vial (Remicade, Inflectra, Renflexis)

Biosimilars to Remicade

• Inflectra (infliximab-dyyb) Renflexis (infliximab-abda)

Dosage Considerations – Should be Given as Follows:

Rheumatoid Arthritis

Remicade, Inflectra, Renflexis

Indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately-to-severely active rheumatoid arthritis in combination withmethotrexate

3 mg/kg intravenously (IV) at 0, 2, and 6 weeks, then every 8 weeks

If incomplete response is noted, dose may be increased to 10 mg/kg or dosing frequency to every 4 weeks

Psoriatic Arthritis

Remicade, Inflectra, Renflexis

Indicated for reducing signs and symptoms in patients with active psoriatic arthritis

Indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis

5 mg/kg intravenously (IV) at 0, 2, and 6 weeks, then every 8 weeks

May be used with methotrexate

Plaque Psoriasis

Remicade, Inflectra, Renflexis

Indicated for the treatment of adult patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis who are candidates forsystemic therapyand when other systemic therapies are medically less appropriate

Should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician

5 mg/kg intravenously (IV) at 0, 2, and 6 weeks, then every 8 weeks

Can be used with or without methotrexate

Crohn's Disease

Remicade, Inflectra, Renflexis

Adult: Indicated for moderately-to-severely active Crohn's disease in patients who have had inadequate response to conventional therapy; also indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintainingfistulaclosure in adult patients with fistulizing Crohn's disease

5 mg/kg intravenously (IV) at 0, 2, and 6 weeks, then every 8 weeks; may be increased to 10 mg/kg

For adult patients who respond and then lose their response, consideration may be given to treatment with 10 mg/kg

Patients who do not respond by Week 14 are unlikely to respond with continued dosing and consideration should be given to discontinue

Pediatric: Reduction of signs and symptoms and induction and maintenance of clinicalremissionin pediatric patients aged 6 years and older with moderately to severely active Crohn's disease who have had inadequate response to conventional therapy

5 mg/kg intravenously (IV) at 0, 2, and 6 weeks, then every 8 weeks

Ulcerative Colitis

Remicade, Inflectra, Renflexis

Adult: Indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminatingcorticosteroiduse in adults with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy

5 mg/kg intravenously (IV) at 0, 2, and 6 weeks, then every 8 weeks

Pediatric: Treatment of moderately to severely active ulcerative colitis in children aged =6 yr who have had inadequate response to conventional therapy

Remicade 5 mg/kg intravenously (IV) at 0, 2, and 6 weeks, then every 8 weeks

Ankylosing Spondylitis

Remicade, Inflectra, Renflexis

Indicated for reducing signs and symptoms in patients with activeankylosingspondylitis

5 mg/kg intravenously (IV) at 0, 2, and 6 weeks, then every 6 weeks

Dosage Modifications

Moderate-to-severe (NYHA class III or IV) heart failure: Not to exceed 5 mg/kg/dose (see Contraindications)

Dosing Considerations, Pediatric

Children should be current with immunizations before starting infliximab

Do not administer livevaccineswhile patient is taking infliximab

Common side effects of infliximab include:

• Development of antinuclear antibodies
• Infection
• Upper respiratory tract infection
• Abdominal/stomach pain
• Nausea
• Infusion reaction
• Headache
• Development of antibodies to double-stranded DNA
• Other respiratory infection (e.g.,sinusitis, cough)
• Diarrhea
• Elevatedalaninetransaminase (ALT; rarely greater than 3 times upper limit of normal)
• Bronchitis
• Indigestion/heartburn
• Skin rash
• Fatigue
• Back pain
• Runny orstuffy nose
• Urinary tract infection
• Joint pain
• Fever
• High blood pressure(hypertension)
• Itching
• Yeast infection(candidiasis)
• Lupus-like symptoms
• Sinuspain
• Flushing (warmth, redness, or tingly feeling)

英夫利昔单抗的严重的副作用包括:

• Pain or swelling at injection site
• Swelling of ankles or feet
• Easy bruising or bleeding
• Vision changes
• Seizures
• Confusion
• Muscle weakness
• Numbness and tingling of arms or legs
• Butterfly-shaped facial rash
• Chest pain
• Pain/redness/swelling of arms or legs
• Shortness of breath
• Fast/slow/irregular heartbeat

Postmarketing side effects of infliximab reported include:

• Anaphylactic-like reactions, includinglaryngeal/pharyngealswelling, severe bronchospasm, and seizures
• Myocardialischemiaorinfarctionand transient visual loss have also been rarely reported during or within 2 hours of infusion
• Serious infections and malignancies, including melanoma andMerkel cell carcinoma

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

Infliximab has no known severe interactions with other drugs.

Infliximab has serious interactions with at least 68 different drugs.

Moderate interactions of infliximab include:

• astragalus
• belatacept
• cholera vaccine
• denosumab
• echinacea
• fingolimod
• hydroxyurea
• influenza virus vaccinequadrivalent,recombinant
• influenzavirus vaccine trivalent, recombinant
• maitake
• meningococcal group B vaccine
• mercaptopurine
• ocrelizumab
• sipuleucel-T

Mild interactions of infliximab include:

• cat's claw

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

Serious infection risk

• Increased risk for developing serious infections resulting in hospitalization or death; most patients were taking concomitant immunosuppressants (e.g., methotrexate, corticosteroids)
• Patients older than 65 years may be at greater risk
• Discontinue if patient develops serious infection orsepsis;报道感染包括de the following:
  • (1)Active tuberculosis, including reactivation oflatentdisease (frequently present with disseminated or extrapulmonary disease); test for latent tuberculosis before use and during therapy; treat latent infection before use
  • (2) Invasive fungal infections (e.g., histoplasmosis,coccidioidomycosis, candidiasis,aspergillosis,blastomycosis, pneumocystosis); may present with disseminated, rather than localized, disease;antigen/antibody testing for histoplasmosis may yield negative results in some patients with active infection; initiate empiricantifungaltherapy if severe systemic illness develops
  • (3) Infections caused by other opportunistic pathogens, including bacteria (e.g.,Legionella,Listeria),mycobacteria(e.g.,Mycobacterium tuberculosis), andviruses(e.g., hepatitisB virus)

Malignancy

• Lymphomaand other malignancies, some fatal, have been reported in children and adolescents treated with tumornecrosisfactor (TNF) blockers
• Manufacturer is required to report all malignancies to FDA for complete and consistent analysis

HepatosplenicT-cell lymphoma

• Hepatosplenic T-cell lymphoma (HSTCL) is an aggressive, rare type of T-cell lymphoma (usually fatal)
• Rare postmarketing cases of HSTCL are reported primarily in adolescent and young adult patients with Crohn's disease and ulcerative colitis treated with infliximab
• Reports have also included 1 patient being treated for psoriasis and 2 patients being treated for rheumatoid arthritis
• Most reported cases with infliximab have occurred with concomitant treatment withazathioprineor 6-mercaptopurine (6-MP), though cases have been reported in patients receiving azathioprine or 6-MP alone
• In the FDA Adverse Event Reporting System (AERS) database, the literature, and the HSTCL Cancer Survivors' Network, HSTCL cases have been identified in association with the following agents:
  • infliximab (20),
  • etanercept (1),
  • adalimumab(2),
  • infliximab/adalimumab (5),
  • certolizumab (0),
  • golimumab (0),
  • azathioprine (12), and
  • 6-MP (3)

This medication contains infliximab. Do not take Remicade, Inflectra, infliximab-dyyb, Renflexis, or infliximab-abda if you are allergic to infliximab or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

Active serious infections

Documented hypersensitivity

Doses exceeding 5 mg/kg should not be administered to patients with moderate-to-severe heart failure; treatment with 10 mg/kg was associated with an increased incidence of death and hospitalization due to worsening heart failure

Effects of Drug Abuse

None.

Short-Term Effects

• See "What Are Side Effects Associated with Using Infliximab?"

Long-Term Effects

Long-termopioiduse may cause secondaryhypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, andosteoporosis.

• See "What Are Side Effects Associated with Using Infliximab?"

Cautions

Worsening or new onset congestive heart failure reported with TNF blockers; Exercise caution when using in patients who have heart failure; TNF alpha inhibitors should only be considered in patients with heart failure if there are no other reasonable treatment options, and then consider only in patients with compensated heart failure.

Caution in neurologic disorder.

Moderate-to-severechronic obstructive pulmonary disease(COPD).

History of malignancy.

Elderly.

密切监控民主党的症状和体征yelinating disease (e.g., confusion, numbness, vision changes); consider termination of therapy if significant中枢神经系统(CNS) reactions develop.

Risk of tuberculosis, histoplasmosis, and other opportunistic infections, as well as hepatitis B reactivation; test for乙型肝炎病毒infection before starting infliximab; monitor HBV carriers during and several months after therapy.

Live vaccines or therapeutic infectious agents should not be given with infliximab; bring pediatric patients up to date with all vaccinations prior to initiating therapy; at least a six month waiting period following birth is recommended before administration of live vaccines to infants exposed in utero to infliximab.

Immunizations should be current before therapy is initiated.

Administration of live virus vaccines should be delayed or avoided while patient is taking infliximab.

Increased risk of lymphoma (including hepatosplenic T-cell lymphoma (HSTCL), especially if given with azathioprine or 6-MP), pneumonia, hepatotoxicity (including acuteliver failure, jaundice, hepatitis,cholestasis); see Warnings.

Enhanced safety surveillance requirements to capture malignancy data: Manufacturer is required to report all malignancies to FDA for complete and consistent analysis.

Consider discontinuance if hematologic disorder occurs (e.g.,leukopenia, thrombocytopenia, neutropenia,pancytopenia).

Consider discontinuance if lupus-like symptoms occur.

Increased risk of lymphoma and other cancers is reported in children and adolescents.

Skin cancer (e.g., melanoma, Merkel cellcarcinoma) is reported with TNF blockers.

Occurrence ofleukemiaand new-onset psoriasis is reported in patients treated with TNF blockers.

Re-administration after period of no treatment resulted in higher incidence of infusion reactions than was seen with regular maintenance treatment (4% vs less than 1%).

Coadministration of TNF blockers with abatacept is associated with greater risk of serious infection than use of TNF blockers alone; concurrent use is not recommended.

Consider empiric antifungal therapy for patients who develop a systemic illness on infliximab and reside or travel to regions where mycoses areendemic.

Due to the risk of HSTCL, carefully assess the risk/benefit especially if the patient has Crohn's disease or ulcerative colitis, is male, and is receiving azathioprine or 6-mercaptopurine treatment.

Rare severe hepatic reactions reported; some fatal or necessitating liver transplantation; stop therapy in cases of jaundice and/or marked liver enzyme elevations.

Pregnancy and Lactation

Infliximab may be acceptable for use during pregnancy. Either animal studies show no risk but human studies are not available or animal studies showed minor risks and human studies were done and showed no risk.

It is unknown whether infliximab is excreted in breast milk; discontinue the drug, or do not nurse.