infliximab (Remicade, Inflectra, infliximab-dyyb)
Classes: Immunosuppressants; Monoclonal Antibodies; DMARDs, TNF Inhibitors; Antipsoriatics, Systemic; Inflammatory Bowel Disease Agents
Dosing and uses of Remicade, Inflectra (infliximab)
Adult dosage forms and strengths
injection, lyphilized powder for reconstitution
- 100mg/vial (Remicade, Inflectra)
Biosimilars to Remicade
- Inflectra (infliximab-dyyb)
Rheumatoid Arthritis
Remicade, Inflectra
Indicated for moderately-to-severely active rheumatoid arthritis in combination with methotrexate
3 mg/kg 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
Indicated for active psoriatic arthritis and chronic severe plaque psoriasis
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 IV at 0, 2, and 6 weeks, then every 8 weeks
May be used with methotrexate
Plaque Psoriasis
Remicade, Inflectra
Indicated for the treatment of adult patients with chronic severe (ie, extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and 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 IV at 0, 2, and 6 weeks, then every 8 weeks
Can be used with or without methotrexate
Crohn Disease
Remicade, Inflectra
Indicated for moderately-to-severely active Crohn disease in patients who have had inadequate response to conventional therapy
5 mg/kg 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
Ulcerative Colitis
Remicade, Inflectra
Indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adults with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy
5 mg/kg IV at 0, 2, and 6 weeks, then every 8 weeks
Ankylosing Spondylitis
Remicade, Inflectra
Indicated for active ankylosing spondylitis
5 mg/kg 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)
Idiopathic Pulmonary Fibrosis (Orphan)
Treatment of idiopathic pulmonary fibrosis
Orphan indication sponsor
- Foundation for Fatal Rare Diseases; Herrengasse 21; Furstentum Liechtenstein; Germany
Pediatric dosage forms and strengths
injection, lyphilized powder for reconstitution
- 100mg/vial (Remicade, Inflectra)
Biosimilars to Remicade
- Inflectra (infliximab-dyyb)
Crohn Disease
Remicade, Inflectra
Reduction of signs and symptoms and induction and maintenance of clinical remission in pediatric patients aged ≥6 yr with moderately to severely active Crohn disease who have had inadequate response to conventional therapy
5 mg/kg IV at 0, 2, and 6 weeks, then every 8 weeks
Ulcerative Colitis
Remicade
Treatment of moderately to severely active ulcerative colitis in children aged ≥6 yr who have had inadequate response to conventional therapy
5 mg/kg IV at 0, 2, and 6 weeks, then every 8 weeks
Dosing Considerations
Children should be current with immunizations before starting infliximaB
Do not administer live vaccines while patient is taking infliximaB
Juvenile Rheumatoid Arthritis (Orphan)
Orphan indication sponsor
- Centocor, Inc; 200 Great Valley Parkway; Malvern, PA 19355-1307
Remicade, Inflectra (infliximab) adverse (side) effects
>10%
Development of antinuclear antibodies (50%)
Infection (36%)
Upper respiratory tract infection (32%)
Abdominal pain (12%; 26% with Crohn disease)
Nausea (21%)
Infusion reaction (20%)
Headache (18%)
Development of antibodies to double-stranded DNA (17%)
Other respiratory infection (eg, sinusitis, cough) (12-14%)
Diarrhea (12%)
Elevated alanine transaminase (ALT; rarely >3 times upper limit of normal)
1-10% (selected)
Bronchitis (10%)
Dyspepsia (10%)
Rash (1-10%)
Fatigue (9%)
Back pain (8%)
Rhinitis (8%)
Urinary tract infection (8%)
Arthralgia (1-8%)
Fever (7%)
Hypertension (7%)
Pruritus (7%)
Dyspnea (6%)
Candidiasis (5%)
Lupuslike symptoms (<5%)
Postmarketing Reports
Anaphylacticlike reactions, including laryngeal/pharyngeal edema, severe bronchospasm, and seizure
Myocardial ischemia or infarction and transient visual loss have also been rarely reported during or within 2 hours of infusion
Serious infections and malignancies, including melanoma and Merkel cell carcinoma
Warnings
Black box warnings
Serious infection risk
- Increased risk for developing serious infections resulting in hospitalization or death; most patients were taking concomitant immunosuppressants (eg, methotrexate, corticosteroids)
- Patients older than 65 years may be at greater risk
- Discontinue if patient develops serious infection or sepsis; reported infections include the following:
- (1) Active tuberculosis, including reactivation of latent disease (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 (eg, 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 empiric antifungal therapy if severe systemic illness develops
- (3) Infections caused by other opportunistic pathogens, including bacteria (eg, Legionella, Listeria), mycobacteria (eg, Mycobacterium tuberculosis), and viruses (eg, hepatitis B virus)
Malignancy
- Lymphoma and other malignancies, some fatal, have been reported in children and adolescents treated with tumor necrosis factor (TNF) blockers
- Manufacturer is required to report all malignancies to FDA for complete and consistent analysis
Hepatosplenic T-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 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 with azathioprine or 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)
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
Cautions
Worsening or new onset congestive heart failure reported with TNF blockers; Exercise caution when using in patients who have heart failure; TNFalpha inhibitors should only be considered in patients with HF if there are no other reasonable treatment options, and then consider only in patients with compensated HF
Caution in neurologic disorder
Moderate-to-severe chronic obstructive pulmonary disease (COPD)
History of malignancy
Elderly
Monitor closely for signs and symptoms of demyelinating disease (eg, confusion, numbness, vision changes); consider termination of therapy if significant CNS reactions develop
Risk of tuberculosis, histoplasmosis, and other opportunistic infections, as well as hepatitis B reactivation; test for HBV 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 acute liver failure, jaundice, hepatitis, cholestasis); see Black box 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 (eg, leukopenia, thrombocytopenia, neutropenia, pancytopenia)
Consider discontinuance if lupuslike symptoms occur
Increased risk of lymphoma and other cancers is reported in children and adolescents
Skin cancer (eg, melanoma, Merkel cell carcinoma) is reported with TNF blockers
Occurrence of leukemia and new-onset psoriasis is reported in patients treated with TNF blockers
Readministration after period of no treatment resulted in higher incidence of infusion reactions than was seen with regular maintenance treatment (4% vs <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 are endemic
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
Pregnancy category: B
Lactation: Unknown whether drug is excreted in breast milk; discontinue drug, or do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Remicade, Inflectra (infliximab)
Mechanism of action
Recombinant humanized monoclonal anti-TNF-α antibody; prevents synovial and intestinal inflammation
Absorption
Onset: 2 wk (Crohn disease)
Duration: 12 wk
Distribution
Vd: 3-6 L
Metabolism
Unknown
Elimination
Half-life: 7-12 days
Excretion: Unknown
Administration
IV Incompatibilities
Do not infuse with other agents
IV Preparation
Reconstitute vials aseptically with 10 mL SWI; swirl vial gently to dissolve powder, and do not shake
Allow solution to stand for 5 minutes
Dilute total volume of reconstituted infliximab solution dose to 250 mL with sterile 0.9% sodium chloride injection, USP, by withdrawing a volume equal to volume of reconstituted infliximab from 0.9% sodium chloride injection, USP, 250 mL bottle or bag; do not dilute reconstituted infliximab solution with any other diluent; slowly add the total volume of reconstituted infliximab solution to 250 mL infusion bottle or bag; gently mix; the resulting infusion concentration should range between 0.4 mg/mL and 4 mg/mL
Discard if particulate matter is present or discoloration observed
Begin infusion within 3 hours of preparation (product contains no preservatives)
IV Administration
Infuse over ≥2 hours
Use in-line filter
Drug should not be infused in same line as other drugs
Discontinue if infusion reaction occurs
Storage
Store vials at 2-8°C (36-46°F)
Do not freeze
Product does not contain preservative