infliximab (Remicade, Inflectra, infliximab-dyyb)

Dosing and uses of Remicade, Inflectra (infliximab)

• Adult
• Pediatric

 

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